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Sample records for el-4 thymoma cells

  1. Opioid binding site in EL-4 thymoma cell line

    International Nuclear Information System (INIS)

    Fiorica, E.; Spector, S.

    1988-01-01

    Using EL-4 thymoma cell-line we found a binding site similar to the k opioid receptor of the nervous system. The Scatchard analysis of the binding of [ 3 H] bremazocine indicated a single site with a K/sub D/ = 60 +/- 17 nM and Bmax = 2.7 +/- 0.8 pmols/10 6 cells. To characterize this binding site, competition studies were performed using selective compounds for the various opioid receptors. The k agonist U-50,488H was the most potent displacer of [ 3 H] bremazocine with an IC 50 value = 0.57μM. The two steroisomers levorphanol and dextrorphan showed the same affinity for this site. While morphine, [D-Pen 2 , D-Pen 5 ] enkephalin and β-endorphin failed to displace, except at very high concentrations, codeine demonstrated a IC 50 = 60μM, that was similar to naloxone. 32 references, 3 figures, 2 tables

  2. Opioid binding site in EL-4 thymoma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Fiorica, E.; Spector, S.

    1988-01-01

    Using EL-4 thymoma cell-line we found a binding site similar to the k opioid receptor of the nervous system. The Scatchard analysis of the binding of (/sup 3/H) bremazocine indicated a single site with a K/sub D/ = 60 +/- 17 nM and Bmax = 2.7 +/- 0.8 pmols/10/sup 6/ cells. To characterize this binding site, competition studies were performed using selective compounds for the various opioid receptors. The k agonist U-50,488H was the most potent displacer of (/sup 3/H) bremazocine with an IC/sub 50/ value = 0.57..mu..M. The two steroisomers levorphanol and dextrorphan showed the same affinity for this site. While morphine, (D-Pen/sup 2/, D-Pen/sup 5/) enkephalin and ..beta..-endorphin failed to displace, except at very high concentrations, codeine demonstrated a IC/sub 50/ = 60..mu..M, that was similar to naloxone. 32 references, 3 figures, 2 tables.

  3. Differential downstream functions of protein kinase Ceta and -theta in EL4 mouse thymoma cells.

    Science.gov (United States)

    Resnick, M S; Kang, B S; Luu, D; Wickham, J T; Sando, J J; Hahn, C S

    1998-10-16

    Sensitive EL4 mouse thymoma cells (s-EL4) respond to phorbol esters with growth inhibition, adherence to substrate, and production of cytokines including interleukin 2. Since these cells express several of the phorbol ester-sensitive protein kinase C (PKC) isozymes, the function of each isozyme remains unclear. Previous studies demonstrated that s-EL4 cells expressed substantially more PKCeta and PKCtheta than did EL4 cells resistant to phorbol esters (r-EL4). To examine potential roles for PKCeta and PKCtheta in EL4 cells, wild type and constitutively active versions of the isozymes were transiently expressed using a Sindbis virus system. Expression of constitutively active PKCeta, but not PKCtheta, in s- and r-EL4 cells altered cell morphology and cytoskeletal structure in a manner similar to that of phorbol ester treatment, suggesting a role for PKCeta in cytoskeletal organization. Prolonged treatment of s-EL4 cells with phorbol esters results in inhibition of cell cycling along with a decreased expression of most of the PKC isozymes, including PKCtheta. Introduction of virally expressed PKCtheta, but not PKCeta, overcame the inhibitory effects of the prolonged phorbol ester treatment on cell cycle progression, suggesting a possible involvement of PKCtheta in cell cycle regulation. These results support differential functions for PKCeta and PKCtheta in T cell activation.

  4. The effects of tributyltin oxide and deoxynivalenol on the transcriptome of the mouse thymoma cell line EL-4

    NARCIS (Netherlands)

    Schmeits, P.J.M.; Kol, S.; Loveren, van H.; Peijnenburg, A.A.C.M.; Hendriksen, P.J.M.

    2014-01-01

    The main goal of this study was to assess the potential of the mouse thymoma EL-4 cell line in screening for chemical induced immunotoxicity. Therefore, EL-4 cells were exposed to two well-known immunotoxicants, organotin compound tributyltin oxide (TBTO, 0.5 and 1 µM for 3 or 6 h) and the mycotoxin

  5. Proteomic analysis of mouse thymoma EL4 cells treated with bis (tri-n-butyltin)oxide (TBTO)

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    Osman, A.M.; Kol, S.; Peijnenburg, A.A.C.M.; Blokland, M.H.; Pennings, J.L.A.; Kleinjans, J.C.S.; Loveren, van H.

    2009-01-01

    Here, we report the results of proteomic analysis of the mouse thymoma EL4 cell line exposed to bis(tri-n-butylin)oxide (TBTO), an immunotoxic organotin compound. The objective of the work was to examine whether TBTO affects the expression of proteins in this cell line and to compare the

  6. Mechanism of phorbol ester-mediated protein kinase C activation in EL4 thymoma cells

    International Nuclear Information System (INIS)

    Huang, F.L.; Arora, P.K.; Hanna, E.E.; Huang, K.P.

    1987-01-01

    Mouse thymoma EL4 cells respond to phorbol 12-myristate 13-acetate (PMA) in interleukin-2 secretion and growth inhibition. A rapid translocation of protein kinase C (PKC) from cytosol to the particulate fraction and followed by proteolytic degradation occur when EL4 cells are incubated with PMA. In the present study the translocated membrane-associated PKC (PP-PKC) was solubilized by buffer containing NP-40 and its behavior on column chromatography, molecular weight, and kinetic properties were compared to the cytosolic PKC (CS-PKC) from untreated cells. From DE-52 cellulose column, CS-PKC could be eluted by buffer containing 0.1 M KCl, whereas PP-PKC was eluted with buffer containing 0.25 M KCl and 0.2% NP-40. On gel filtration the partially purified PP-PKC from DE-52 was separated into two species: a high Mr species, which was a complex of 82KDa PKC, PMA, and lipid as evidenced by immunoblot analysis and labeling with [ 3 H]PMA and [ 3 H]myristic acid, and a 82KDa species, which was free of PMA and lipid. This 82KDa PP-PKC, though similar to the CS-PKC in molecular weight, is distinguishable from the CS-PKC in having lower Ka values for both Ca 2+ and PS and no longer requires diacylglycerol for maximum activation. These results indicate that upon PMA treatment of EL4 cells, the CS-PKC was modified through enhancing the kinase activity and affinity for membrane lipid. The modification results in the translocation and complexing of PKC with membrane lipid and PMA and subsequent degradation

  7. Deficient tyrosine phosphorylation of c-Cbl and associated proteins in phorbol ester-resistant EL4 mouse thymoma cells.

    Science.gov (United States)

    Luo, X; Sando, J J

    1997-05-02

    Two tyrosine phosphoproteins in phorbol ester-sensitive EL4 (S-EL4) mouse thymoma cells have been identified as the p120 c-Cbl protooncogene product and the p85 subunit of phosphatidylinositol 3-kinase. Tyrosine phosphorylation of p120 and p85 increased rapidly after phorbol ester stimulation. Phorbol ester-resistant EL4 (R-EL4) cells expressed comparable amounts of c-Cbl and phosphatidylinositol 3-kinase protein but greatly diminished tyrosine phosphorylation. Co-immunoprecipitation experiments revealed complexes of c-Cbl with p85, and of p85 with the tyrosine kinase Lck in phorbol ester-stimulated S-EL4 but not in unstimulated S-EL4 or in R-EL4 cells. In vitro binding of c-Cbl with Lck SH2 or SH3 domains was detected in both S-EL4 and R-EL4 cells, suggesting that c-Cbl, p85, and Lck may form a ternary complex. In vitro kinase assays revealed phosphorylation of p85 by Lck only in phorbol ester-stimulated S-EL4 cells. Collectively, these results suggest that Cbl-p85 and Lck-p85 complexes may form in unstimulated S-EL4 and R-EL4 cells but were not detected due to absence of tyrosine phosphorylation of p85. Greatly decreased tyrosine phosphorylation of c-Cbl and p85 in the complexes may contribute to the failure of R-EL4 cells to respond to phorbol ester.

  8. Phosphorylation of paxillin via the ERK mitogen-activated protein kinase cascade in EL4 thymoma cells.

    Science.gov (United States)

    Ku, H; Meier, K E

    2000-04-14

    Intracellular signals can regulate cell adhesion via several mechanisms in a process referred to as "inside-out" signaling. In phorbol ester-sensitive EL4 thymoma cells, phorbol-12-myristate 13-acetate (PMA) induces activation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases and promotes cell adhesion. In this study, clonal EL4 cell lines with varying abilities to activate ERKs in response to PMA were used to examine signaling events occurring downstream of ERK activation. Paxillin, a multifunctional docking protein involved in cell adhesion, was phosphorylated on serine/threonine residues in response to PMA treatment. This response was correlated with the extent and time course of ERK activation. PMA-induced phosphorylation of paxillin was inhibited by compounds that block the ERK activation pathway in EL4 cells, primary murine thymocytes, and primary murine splenocytes. Paxillin was phosphorylated in vitro by purified active ERK2. Two-dimensional electrophoresis revealed that PMA treatment generated a complex pattern of phosphorylated paxillin species in intact cells, some of which were generated by ERK-mediated phosphorylation in vitro. An ERK pathway inhibitor interfered with PMA-induced adhesion of sensitive EL4 cells to substrate. These findings describe a novel inside-out signaling pathway by which the ERK cascade may regulate events involved in adhesion.

  9. Effects of protein kinase C activators on phorbol ester-sensitive and -resistant EL4 thymoma cells.

    Science.gov (United States)

    Sansbury, H M; Wisehart-Johnson, A E; Qi, C; Fulwood, S; Meier, K E

    1997-09-01

    Phorbol ester-sensitive EL4 murine thymoma cells respond to phorbol 12-myristate 13-acetate with activation of ERK mitogen-activated protein kinases, synthesis of interleukin-2, and death, whereas phorbol ester-resistant variants of this cell line do not exhibit these responses. Additional aspects of the resistant phenotype were examined, using a newly-established resistant cell line. Phorbol ester induced morphological changes, ERK activation, calcium-dependent activation of the c-Jun N-terminal kinase (JNK), interleukin-2 synthesis, and growth inhibition in sensitive but not resistant cells. A series of protein kinase C activators caused membrane translocation of protein kinase C's (PKCs) alpha, eta, and theta in both cell lines. While PKC eta was expressed at higher levels in sensitive than in resistant cells, overexpression of PKC eta did not restore phorbol ester-induced ERK activation to resistant cells. In sensitive cells, PKC activators had similar effects on cell viability and ERK activation, but differed in their abilities to induce JNK activation and interleukin-2 synthesis. PD 098059, an inhibitor of the mitogen activated protein (MAP)/ERK kinase kinase MEK, partially inhibited ERK activation and completely blocked phorbol ester-induced cell death in sensitive cells. Thus MEK and/or ERK activation, but not JNK activation or interleukin-2 synthesis, appears to be required for phorbol ester-induced toxicity. Alterations in phorbol ester response pathways, rather than altered expression of PKC isoforms, appear to confer phorbol ester resistance to EL4 cells.

  10. The effect of medium composition on interleukin-2 production by murine EL-4 thymoma cells

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    Galesi A. L. L.

    2004-01-01

    Full Text Available Due to the role of interleukin-2 (IL-2 in the mediation of immune response, this cytokine has been used in the treatment of some types of cancer and infectious diseases. However, relatively high levels of this cytokine are required to achieve significant activity. The aim of this work was to study a culture medium composition designed to increase the production of IL-2 by suspended murine EL-4 cells. The cultivations were carried out aiming at producing IL-2 in stirred bioreactors. The effects of concentration of glutamine, phorbol-12-myristate-13-acetate (PMA, concanavalin A (Con A, Pluronic F68, and fetal calf serum (FCS on cell viability and IL-2 production were evaluated. PMA alone was more efficient in IL-2 production than it was in association with Con A. The maximum IL-2 production was around 162 ng/mL with 856 ng/mL PMA and 1.45% (v/v FCS.

  11. Selective up-regulation of protein kinase C eta in phorbol ester-sensitive versus -resistant EL4 mouse thymoma cells.

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    Resnick, M S; Luo, X; Vinton, E G; Sando, J J

    1997-06-01

    Stimulation of sensitive EL4 mouse thymoma cells (s-EL4) with phorbol esters results in production of interleukin 2 (IL-2), adherence to a plastic substrate, and growth inhibition, whereas a phorbol ester-resistant variant (r-EL4) fails to respond. Previous studies revealed substantially decreased expression of protein kinase C (PKC) epsilon in the r-EL4 versus s-EL4 cells. This work has been extended to examine the more recently described PKC isozymes. Western and Northern analyses revealed a marked decrease in PKC eta and theta in r-EL4 as compared to s-EL4 cells. Treatment of these lines with phorbol ester for 24 h resulted in down-regulation of all PKC isozymes examined except PKC eta, which was up-regulated in the s-EL4 cells at the time of maximal IL-2 production. Two newly isolated EL4 clones, resistant to phorbol ester-induced growth inhibition but still exhibiting the phorbol ester-induced adherence and IL-2 production, both expressed PKC eta and theta. Collectively, these observations suggest a dissociation of growth inhibition from adherence and IL-2 production pathways and a potential role for PKC eta in the latter.

  12. Proteomic analysis of mouse thymoma EL4 cells treated with bis(tri-n-butyltin)oxide (TBTO).

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    Osman, Ahmed M; van Kol, Sandra; Peijnenburg, Ad; Blokland, Marco; Pennings, Jeroen L A; Kleinjans, Jos C S; van Loveren, Henk

    2009-09-01

    Here, we report the results of proteomic analysis of the mouse thymoma EL4 cell line exposed to bis(tri-n-butylin)oxide (TBTO), an immunotoxic organotin compound. The objective of the work was to examine whether TBTO affects the expression of proteins in this cell line and to compare the differentially expressed proteins with the corresponding mRNA expression data. The identified proteins were quantified using a label-free quantitative method based on counting the observed peptides as an index of protein abundance. The calculation of the ratio of peptides obtained from exposed and control samples allowed us to evaluate the effect of TBTO on protein expression and to compare these results to those obtained in gene expression profiling studies. Correlation of some of the differentially expressed proteins and their corresponding mRNAs was observed. The analysis of the protein ratios revealed that 12 proteins were significantly affected. These proteins included cytoskeleton proteins myosin-9, spectrin beta 2 and plectin 8. The first two proteins were down-regulated 3-fold, whereas the third was up-regulated 2-fold. Ras-related Rab1, a GTP binding protein and T-complex protein-1 subunit alpha, a chaperonin, were decreased 2- and 3.6-fold, respectively. The ribosomal S10 and eukaryotic translation factor (eIf4G1), which are involved in protein synthesis, were down-regulated 2.6- and 3.7-fold, respectively. Also, proteins involved in splicing of pre-mRNA and in transcription, splicing factor arginine/serine-rich 2 and chromodomain-helicase-DNA binding protein 4 (Chd4), were decreased 2.6- and 4.5 times, respectively. Nuclear RNA helicase II was reduced 2.8-fold. Finally, prothymosin-alpha (ProTalpha), an essential protein for cell proliferation, and a protein similar to ProTalpha, (with a molecular weight and a pI (3.54) comparable to that of ProTalpha) were also down-regulated 6-and 8-fold, respectively. We propose that the observed down-regulation of the expression

  13. Effects of phorbol ester on mitogen-activated protein kinase kinase activity in wild-type and phorbol ester-resistant EL4 thymoma cells.

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    Gause, K C; Homma, M K; Licciardi, K A; Seger, R; Ahn, N G; Peterson, M J; Krebs, E G; Meier, K E

    1993-08-05

    Phorbol ester-sensitive and -resistant EL4 thymoma cell lines differ in their ability to activate mitogen-activated protein kinase (MAPK) in response to phorbol ester. Treatment of wild-type EL4 cells with phorbol ester results in the rapid activations of MAPK and pp90rsk kinase, a substrate for MAPK, while neither kinase is activated in response to phorbol ester in variant EL4 cells. This study examines the activation of MAPK kinase (MAPKK), an activator of MAPK, in wild-type and variant EL4 cells. Phosphorylation of a 40-kDa substrate, identified as MAPK, was observed following in vitro phosphorylation reactions using cytosolic extracts or Mono Q column fractions prepared from phorbol ester-treated wild-type EL4 cells. MAPKK activity coeluted with a portion of the inactive MAPK upon Mono Q anion-exchange chromatography, permitting detection of the MAPKK activity in fractions containing both kinases. This MAPKK activity was present in phorbol ester-treated wild-type cells, but not in phorbol ester-treated variant cells or in untreated wild-type or variant cells. The MAPKK from wild-type cells was able to activate MAPK prepared from either wild-type or variant cells. MAPKK activity could be stimulated in both wildtype and variant EL4 cells in response to treatment of cells with okadaic acid. These results indicate that the failure of variant EL4 cells to activate MAP kinase in response to phorbol ester is due to a failure to activate MAPKK. Therefore, the step that confers phorbol ester resistance to variant EL4 cells lies between the activation of protein kinase C and the activation of MAPKK.

  14. Internalization of interleukin 1 (IL 1) correlates with IL 1-induced IL 2 receptor expression and IL 2 secretion of EL4 thymoma cells

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    Von Hoegen, I.; Falk, Werner; Kojouharoff, G.; Krammer, P. H.

    1989-01-01

    The cytokine interleukin 1 (IL 1) plays an important role in the induction of IL 2 secretion and high-affinity IL 2 receptor (IL 2R) expression by T cells. The events that follow binding of IL 1 to IL 1R, however, are still unknown. In this study we describe two variants of the murine thymoma EL4 (5D3 and D6/76) that express comparable numbers of cell surface IL 1 receptors and bind IL 1 with the same affinity, but show distinct IL 1-dependent IL 2 secretion and IL 2R expression. In the prese...

  15. Interleukin-1 beta induced synthesis of protein kinase C-delta and protein kinase C-epsilon in EL4 thymoma cells: possible involvement of phosphatidylinositol 3-kinase.

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    Varley, C L; Royds, J A; Brown, B L; Dobson, P R

    2001-01-01

    We present evidence here that the proinflammatory cytokine, interleukin-1 beta (IL-1 beta) stimulates a significant increase in protein kinase C (PKC)-epsilon and PKC-delta protein levels and increases PKC-epsilon, but not PKC-delta, transcripts in EL4 thymoma cells. Incubation of EL4 cells with IL-1 beta induced protein synthesis of PKC-epsilon (6-fold increase) by 7 h and had a biphasic effect on PKC-delta levels with peaks at 4 h (2-fold increase) and 24 h (4-fold increase). At the level of mRNA, PKC-epsilon, but not PKC-delta levels, were induced after incubation of EL4 cells with IL-1 beta. The signalling mechanisms utilized by IL-1 beta to induce the synthesis of these PKC isoforms were investigated. Two phosphatidylinositol (PI) 3-kinase-specific inhibitors, wortmannin and LY294002, inhibited IL-1 beta-induced synthesis of PKC-epsilon. However, the PI 3-kinase inhibitors had little effect on the IL-1 beta-induced synthesis of PKC-delta in these cells. Our results indicate that IL-1 beta induced both PKC-delta and PKC-epsilon expression over different time periods. Furthermore, our evidence suggests that IL-1 beta induction of PKC-epsilon, but not PKC-delta, may occur via the PI 3-kinase pathway. Copyright 2001 S. Karger AG, Basel

  16. Staurosporine, but not Ro 31-8220, induces interleukin 2 production and synergizes with interleukin 1alpha in EL4 thymoma cells.

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    Mahon, T M; Matthews, J S; O'Neill, L A

    1997-07-01

    Protein kinase C (PKC) has been implicated in interleukin 1 (IL1) signal transduction in a number of cellular systems, either as a key event in IL1 action or as a negative regulator. Here we have examined the effects of two PKC inhibitors, staurosporine and the more selective agent Ro 31-8220, on IL1 responses in the murine thymoma line EL4.NOB-1. A 1 h pulse of staurosporine was found to strongly potentiate the induction of IL2 by IL1alpha in these cells. In contrast, neither a pulse nor prolonged incubation with Ro 31-8220 affected the response to IL1alpha. Both agents blocked the response to PMA, however. A 1 h pulse of staurosporine was also found to induce IL2 production on its own, activate the transcription factor nuclear factor kappaB (NFkappaB) and increase the expression of a NFkappaB-linked reporter gene. It synergized with IL1alpha in all of these responses. Ro 31-8220 was again without effect, although both staurosporine and Ro 31-8220 blocked the activation of NFkappaB by PMA. Finally, staurosporine caused the translocation of PKC-alpha and -epsilon, and to a lesser extent PKC-beta, but not PKC-θ or -zeta, from the cytosol to the membrane, although a similar effect was observed with Ro 31-8220. The results suggest that PKC is not involved in IL1alpha signalling in EL4 cells. Furthermore, the potentiating effect of staurosporine on IL1alpha action does not involve PKC inhibition, and is likely to be at the level of NFkappaB activation.

  17. Binding of human beta 2-microglobulin to murine EL4 thymoma cells upregulates MHC class I heavy-chain epitopes, inhibits IL-2 secretion and induces resistance to killing by natural killer cells

    DEFF Research Database (Denmark)

    Claësson, M H; Nissen, Mogens Holst

    1994-01-01

    line (ABLS-8), X63 B-lymphoma cells and YAC cells did not bind h beta 2m. In two of the T lymphomas, EL4 and BW5147, binding of h beta 2m led to an increase in major histocompatibility complex class I (MHC-I) heavy-chain epitope expression as measured by anti-H-2K/D antibody binding and FACS analysis....... EL4 cells which had bound h beta 2m decreased their rate of constitutive IL-2 secretion and became resistant to activated natural killer (NK) cell killing. The present data suggest the binding of h beta 2m to mouse T cells leads to conformational changes of MHC-I heavy chains which influence both...

  18. Squamous cell carcinoma following radiation therapy for the infiltrative thymoma

    International Nuclear Information System (INIS)

    Ozawa, Shinji; Kitao, Takeshi

    1992-01-01

    This report represents one case of infiltrative thymoma followed by squamous cell carcinoma of the lungs. A 69-year-old man suffered from infiltrative thymoma which reduced by the radiation therapy. Seven years later its replase and the onset of squamous cell carcinoma were found simultaneously. Infiltrative thymoma metastasized not only to the mediastinum but also to the liver and bronchus. Squamous cell carcinoma developed in the right upper lobe. In spite of chemotherapy against them, the patient died. There are many cases in which infiltrative thymoma is accompanied by squamous cell carcinoma of the lung simultaneously; however, secondary onset of squamous cell carcinoma after the radiation therapy of infiltrative thymoma is rare. Secondary carcinogenesis of this case was considered to be closely related with immunological abnormalities caused by thymoma, effects of radiation, smoking and so on. (author)

  19. Analysis of interleukin (IL)-1 beta and transforming growth factor (TGF)-beta-induced signal transduction pathways in IL-2 and TGF-beta secretion and proliferation in the thymoma cell line EL4.NOB-1.

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    Siese, A; Jaros, P P; Willig, A

    1999-02-01

    In the present study we investigated the interleukin (IL)-1beta and transforming growth factor-beta1 (TGF-beta1)-mediated proliferation, and production of IL-2 and TGF-beta, in the murine T-cell line, EL4.NOB-1. This cell line is resistant to TGF-beta concerning growth arrest but not autoinduction or suppression of IL-1-induced IL-2 production. When cocultured with IL-1beta, TGF-beta showed growth-promoting activity that could be antagonized by adding the phosphatidyl choline-dependent phospholipase C (PC-PLC) inhibitor, D609. Using specific enzyme inhibitors of protein kinases (PK) C and A, mitogen-activated protein kinase (MAPK), phospholipase A2 (PLA2), phosphatidylinositol-dependent (PI)-PLC and PC-PLC, we showed that IL-1beta-induced IL-2 synthesis was dependent on all investigated kinases and phospholipases, except PC-PLC. TGF-beta1 was able to inhibit IL-2 synthesis by the activation of PKA and MAPK. The same kinases are involved in TGF-beta autoinduction that is accompanied by a secretion of the active but not the latent growth factor and is antagonized by IL-1beta. Addition of the PI-PLC inhibitor, ET 18OCH3, or the PLA2 inhibitor (quinacrine) alone, resulted in secretion of latent TGF-beta and, in the case of ET 18OCH3, active TGF-beta. These data implicate a role for PI-PLC and PLA2 in the control of latency and secretion. Analysis of specific tyrosine activity and c-Fos expression showed synergistic but no antagonistic effects. These events are therefore not involved in IL- and TGF-beta-regulated IL-2 and TGF-beta production, but might participate in IL-1/TGF-beta-induced growth promotion.

  20. Pure red cell aplasia following irradiation of an asymptomatic thymoma

    International Nuclear Information System (INIS)

    Shibata, Kazuo; Masaoka, Akira; Mizuno, Takeo; Ichimura, Hideki

    1982-01-01

    An unusual case of pure red-cell aplasia (PRCA) developed sixteen days after irradiation of an asymptomatic thymoma. After removal of the encapsulated thymoma there was no improvement in the anemia, and no response to adrenocortical and anabolic steroid hormones or immunosuppressive agents. (author)

  1. The stimulation of EL-4 cells to produce interleukin-2 and its potential use in immunocytotoxicity testing

    International Nuclear Information System (INIS)

    Lasek, W.; Steer, S.; Clothier, R.; Balls, M.

    1989-01-01

    The ability of EL-4 thymoma cells to produce interleukin-2 (IL-2) following exposure to phorbol-12-myristate 13-acetate (PMA) and Concanavalin A (Con A) has been studied in vitro using medium containing either 10% or 1% fetal calf serum (FCS). The potent stimulatory effect of PMA on IL-2 production by EL-4 cells has been confirmed by measuring 3H-thymidine incorporation by the IL-2-dependent T cell line, CTLL-2, in the presence of conditioned medium (CM) from stimulated cultures. EL-4 cells produced several times more IL-2 when cultured in medium containing 10% FCS than when only 1% FCS was present. Added together, PMA and Con A acted synergistically in some EL-4 cell cultures. The ability of E:-4 cells to produce IL-2 was maintained after further incubation without stimulants. CM with IL-2 activity from stimulated EL-4 cells could prove useful in immunotoxicity testing

  2. Pure Red Cell Aplasia and Hypogammaglobulinemia in a Patient with Thymoma

    Directory of Open Access Journals (Sweden)

    Chen-Sung Lin

    2009-01-01

    Full Text Available Both pure red cell aplasia (PRCA and hypogammaglobulinemia are rarer conditions than myasthenia gravis (MG in thymoma patients. Several articles have discussed the relation between PRCA and thymoma or hypogammaglobulinemia and thymoma, and their proper treatments. Instances of both PRCA and hypogammaglobulinemia in a thymoma patient are few and reported sporadically in the literature. We discuss a 46-year-old woman with thymoma and simultaneous PRCA and hypogammaglobulinemia who achieved complete remission from PRCA after perioperative steroid administration and extended thymectomy, and review the literature.

  3. Expression and activity of multidrug resistance protein 1 in a murine thymoma cell line

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    Echevarria-Lima, Juliana; Kyle-Cezar, Fernanda; Leite, Daniela F P; Capella, Luiz; Capella, Márcia A M; Rumjanek, Vivian M

    2005-01-01

    Multidrug resistance proteins [MRPs and P-glycoprotein (Pgp)] are members of the family of ATP-binding cassette (ABC) transport proteins, originally described as being involved in the resistance against anti-cancer agents in tumour cells. These proteins act as ATP-dependent efflux pumps and have now been described in normal cells where they exert physiological roles. The aim of this work was to investigate the expression and activity of MRP and Pgp in the thymoma cell line, EL4. It was observed that EL4 cells expressed mRNA for MRP1, but not for MRP2, MRP3 or Pgp. The activity of ABC transport proteins was evaluated by using the efflux of the fluorescent probes carboxy-2′-7′-dichlorofluorescein diacetate (CFDA) and rhodamine 123 (Rho 123). EL4 cells did not retain CFDA intracellularly, and MRP inhibitors (probenecid, indomethacin and MK 571) decreased MRP1 activity in a concentration-dependent manner. As expected, EL4 cells accumulated Rho 123, and the presence of cyclosporin A and verapamil did not modify this accumulation. Most importantly, when EL4 cells were incubated in the presence of the MRP1 inhibitors indomethacin and MK 571 for 6 days, they started to express CD4 and CD8 molecules on their surface, producing double-positive cells and CD8 single-positive cells. Our results suggest that MRP activity is important for the maintenance of the undifferentiated state in this cell type. This finding might have implications in the physiological process of normal thymocyte maturation. PMID:15804283

  4. Systemic treatment with n-6 polyunsaturated fatty acids attenuates EL4 thymoma growth and metastasis through enhancing specific and non-specific anti-tumor cytolytic activities and production of TH1 cytokines.

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    Salem, Mohamed Labib

    2005-06-01

    Recently, there has been a great interest in the effects of different types of n-6 polyunsaturated acids (n-6 PUFAs) upon the immune system and cancer development. However, the effects of n-6 PUFAs are still controversial and as yet undefined. The present study aimed to investigate the anti-tumor effects of n-6 PUFAs against EL4 thymoma and the associated immune mechanisms. To this, sesame oil, a vegetable oil enriched with n-6 PUFAs, or free linoleic acid (LA) were administered intraperitoneally into C57BL/6 mice before and after challenge with EL4 lymphoma cells. Treatment with either sesame oil or LA attenuated the growth and metastasis of EL4 lymphoma. The anti-tumor effect of LA was superior to that of sesame oil, and associated with an increase in the survival rate of the tumor-bearing mice. In addition, both sesame oil and LA showed dose-dependent anti-lymphoma growth in vitro. Treatment with LA generated significant increases in the anti-lymphoma cytolytic and cytostatic activities of T cells and macrophages, respectively, and enhanced production of IL-2 and IFN-gamma while decreased production of IL-4, IL-6 and IL-10. In summation, the results suggest that n-6 PUFAs, represented by LA, can attenuate EL4 lymphoma growth and metastasis through enhancing the specific and non-specific anti-tumor cytolytic activities and production of TH1 cytokines. These findings might be of great importance for a proper design of systemic nourishment with PUFAs emulsions for cancer patients.

  5. Canine thymoma

    International Nuclear Information System (INIS)

    Aronsohn, M.

    1985-01-01

    Thymoma is an uncommon canine neoplasm of thymic epithelial cells. It is seen in various breeds but may occur more frequently in German Shepherd Dogs. Middle-aged or older dogs can be affected and no sex predilection exists. A paraneoplastic syndrome of myasthenia gravis, nonthymic malignant tumors, and/or polymyositis occurs in a significant number of dogs with thymoma. Clinical signs are variable and are related to a space-occupying cranial mediastinal mass and/or manifestations of the paraneo-plastic syndrome. Dyspnea is the most common presenting clinical sign. Thoracic radiographs usually show a cranial mediastinal mass. Lymphoma is the main differential diagnosis. A definitive diagnosis may be made by closed biopsy but is more likely to be confirmed by thoracotomy. Thymomas may be completely contained within the thymic capsule or may spread by local invasion or metastasis. A staging system allows for an accurate prognosis and a therapeutic plan. Surgical removal of encapsulated thymomas may result in long-term survival or cure. Invasive or metastatic thymomas carry a guarded prognosis. Manifestations of the paraneoplastic syndrome complicate treatment. Adjuvant radiation and chemotherapy may be of value for advanced cases; however, adequate clinical trials have not been done in the dog

  6. Diagnosis and treatment of thymoma associated with pure red cell aplasia: three cases report

    International Nuclear Information System (INIS)

    Wang Wencai; Xu Wuyin

    2000-01-01

    Objective: To discuss how to diagnose and treat thymoma associated with pure red cell aplasia (PRCA). Methods: Three patients of thymoma associated with PRCA were treated with thymothymectomy, and the local radiotherapy was conducted after operation for avoiding the thymoma reproduction. Determining of their peripheral blood hemoglobin was used to evaluate the postoperation result in PRCA. If PRCA can not be relieved, oral prednisone and cyclosporin A were given. Results: One patient with PRCA was cured, the second patient remained in remission by treatment with prednisone and CsA, and the third patient was in progress. Conclusion: The treatment by means of 'thymothymectomy-local radiotherapy-use of prednisone and CsA', is effective for thymoma associated with PRCA

  7. Metaplastic thymoma with myasthenia gravis presumably caused by an accumulation of intratumoral immature T cells: a case report.

    Science.gov (United States)

    Tajima, Shogo; Yanagiya, Masahiro; Sato, Masaaki; Nakajima, Jun; Fukayama, Masashi

    2015-01-01

    Among human neoplasms, thymomas are well known for their association with paraneoplastic autoimmune diseases such as myasthenia gravis. However, regarding rare metaplastic thymoma, only one case of an association with myasthenia gravis has been reported. Here, we present the second case of a 44-year-old woman with metaplastic thymoma associated with myasthenia gravis. In metaplastic thymoma, intratumoral terminal deoxynucleotidyl transferase-positive T-cells (immature T-cells) are generally scarce, while they were abundant in the present case. We believe that these immature T-cells could be related to the occurrence of myasthenia gravis.

  8. Thymoma calcification: Is it clinically meaningful?

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    Alkaied Homam

    2011-08-01

    Full Text Available Abstract Among anterior mediastinal lesions, thymoma is the most common. Thymomas are tumors of thymic epithelial cell origin that are distinguished by inconsistent histological and biologic behavior. Chest imaging studies typically show a round or lobulated tumor in the anterior mediastinum. Calcifications in thymomas are classically punctuate or amorphous, positioned within the lesion. Chest computed tomography (CT features suggesting higher risk thymoma consist of tumor heterogeneity, vascular involvement, lobulation, pulmonary nodules, lymphadenopathy, and pleural manifestations. Imaging findings have an imperfect ability to predict stage and prognosis for thymoma patients. Our objective is to highlight the clinical implications of thymoma calcifications on the diagnosis, clinical manifestation and prognosis. A pubmed and google search was performed using the following words: thymoma calcification, calcified thymus, mediastinal calcification, anterior mediastinal calcification, and calcified thymoma. After reviewing 370 articles, 32 eligible articles describing thymoma calcifications were found and included in this review. Although the presence of thymus calcifications was more common in patients with invasive thymomas, they were present in significant portion of non-invasive thymomas. The presence of calcifications was not a significant factor in differentiating between benign and malignant thymoma. As a result, the type, location, size or other characteristics of thymus gland calcifications were not relevant features in clinical and radiologic diagnosis of thymoma. The histopathological diagnosis is still the only possible way to confirm the neoplastic nature of thymoma. All types of thymomas should be evaluated and managed independently of the presence of calcifications.

  9. CD4 expression on EL4 cells as an epiphenomenon of retroviral transduction and selection.

    Science.gov (United States)

    Logan, Grant J; Spinoulas, Afroditi; Alexander, Stephen I; Smythe, Jason A; Alexander, Ian E

    2004-04-01

    The EL4 murine tumour cell line, isolated from a chemically induced lymphoma over 50 years ago, has been extensively exploited in immunological research. The conclusions drawn from many of these studies have been based on the presumption that EL4 cells maintain a stable phenotype during experimental manipulation. To the contrary, we have observed 100-fold greater expression of cell surface CD4 (CD4(high)) on a subpopulation of EL4 cells following retroviral transduction and G418 selection when compared with unmodified populations. Although the mechanism responsible for this effect remains to be elucidated, the unexpected expression of CD4, a molecule that functions as both a coreceptor with the T-cell receptor and ligand for the pro-inflammatory cytokine IL-16, has the potential to influence experimental outcomes. Upregulation of CD4 should be excluded when EL4 cells are utilized in experiments requiring a consistent immuno-phenotype.

  10. [Regulatory T cells inhibit proliferation of mouse lymphoma cell line EL4 in vitro].

    Science.gov (United States)

    Zhang, Chen; Kong, Yan; Guo, Jun; Ying, Zhi-Tao; Yuan, Zhi-Hong; Zhang, Yun-Tao; Zheng, Wen; Song, Yu-Qin; Li, Ping-Ping; Zhu, Jun

    2010-10-01

    This study was aimed to investigate the effect of regulatory T (Treg) cells on the T cell lymphoma EL4 cells and its mechanism in vitro. C57BL/6 mouse Treg cells were isolated by magnetic cell sorting (MACS). The purity of Treg cells and their expression of Foxp3 were identified by flow cytometry (FCM) and PT-PCR respectively. The suppression of Treg cells on EL4 cells was detected by 3H-TdR method. At the same time, enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of cytokine TGF-β1 and IL-10. The results showed that CD4+CD25+ T cells could be successfully isolated by MACS with the purity reaching 94.52% and the expression of Foxp3 reaching 84.72%. After sorting, the expression of Foxp3 mRNA could be detected by RT-PCR. 3H-TdR assay confirmed that regulatory T cells could suppress the proliferation of EL4 cells with or without antigen presenting cells (APC) or dendritic cells (DC), APC or DC might effectively enhance the suppression. In addition, DC alone also suppressed the proliferation. TGF-β1 and IL-10 could be detected in the supernatant by ELISA. It is concluded that the Treg cells can obviously suppress the proliferation of T cell lymphoma cells in vitro, APC or DC can enhance this suppressive effect, while the DC alone also can suppress the proliferation of EL4 cells, the TGF-β1 and IL-10 cytokine pathway may be one of the mechanisms of suppression.

  11. Cannabinoid inhibition of adenylate cyclase-mediated signal transduction and interleukin 2 (IL-2) expression in the murine T-cell line, EL4.IL-2.

    Science.gov (United States)

    Condie, R; Herring, A; Koh, W S; Lee, M; Kaminski, N E

    1996-05-31

    Cannabinoid receptors negatively regulate adenylate cyclase through a pertussis toxin-sensitive GTP-binding protein. In the present studies, signaling via the adenylate cyclase/cAMP pathway was investigated in the murine thymoma-derived T-cell line, EL4.IL-2. Northern analysis of EL4.IL-2 cells identified the presence of 4-kilobase CB2 but not CB1 receptor-subtype mRNA transcripts. Southern analysis of genomic DNA digests for the CB2 receptor demonstrated identical banding patterns for EL4.IL-2 cells and mouse-derived DNA, both of which were dissimilar to DNA isolated from rat. Treatment of EL4.IL-2 cells with either cannabinol or Delta9-THC disrupted the adenylate cyclase signaling cascade by inhibiting forskolin-stimulated cAMP accumulation which consequently led to a decrease in protein kinase A activity and the binding of transcription factors to a CRE consensus sequence. Likewise, an inhibition of phorbol 12-myristate 13-acetate (PMA)/ionomycin-induced interleukin 2 (IL-2) protein secretion, which correlated to decreased IL-2 gene transcription, was induced by both cannabinol and Delta9-THC. Further, cannabinoid treatment also decreased PMA/ionomycin-induced nuclear factor binding to the AP-1 proximal site of the IL-2 promoter. Conversely, forskolin enhanced PMA/ionomycin-induced AP-1 binding. These findings suggest that inhibition of signal transduction via the adenylate cyclase/cAMP pathway induces T-cell dysfunction which leads to a diminution in IL-2 gene transcription.

  12. [Establishment and identification of mouse lymphoma cell line EL4 expressing red fluorescent protein].

    Science.gov (United States)

    Li, Yan-Jie; Cao, Jiang; Chen, Chong; Wang, Dong-Yang; Zeng, Ling-Yu; Pan, Xiu-Ying; Xu, Kai-Lin

    2010-02-01

    This study was purposed to construct a lentiviral vector encoding red fluorescent protein (DsRed) and transfect DsRed into EL4 cells for establishing mouse leukemia/lymphoma model expressing DsRed. The bicistronic SIN lentiviral transfer plasmid containing the genes encoding neo and internal ribosomal entry site-red fluorescent protein (IRES-DsRed) was constructed. Human embryonic kidney 293FT cells were co-transfected with the three plasmids by liposome method. The viral particles were collected and used to transfect EL4 cells, then the cells were selected by G418. The results showed that the plasmid pXZ208-neo-IRES-DsRed was constructed successfully, and the viral titer reached to 10(6) U/ml. EL4 cells were transfected by the viral solution efficiently. The transfected EL4 cells expressing DsRed survived in the final concentration 600 microg/ml of G418. The expression of DsRed in the transfected EL4 cells was demonstrated by fluorescence microscopy and flow cytometry. In conclusion, the EL4/DsRed cell line was established successfully.

  13. Calcium signals and caspase-12 participated in paraoxon-induced apoptosis in EL4 cells.

    Science.gov (United States)

    Li, Lan; Cao, Zhiheng; Jia, Pengfei; Wang, Ziren

    2010-04-01

    In order to investigate whether calcium signals participate in paraoxon (POX)-induced apoptosis in EL4 cells, real-time laser scanning confocal microscopy (LSCM) was used to detect Ca(2+) changes during the POX application. Apoptotic rates of EL4 cells and caspase-12 expression were also evaluated. POX (1-10nM) increased intracellular calcium concentration ([Ca(2+)]i) in EL4 cells in a dose-dependent manner at early stage (0-2h) of POX application, and apoptotic rates of EL4 cells after treatment with POX for 16h were also increased in a dose-dependent manner. Pre-treatment with EGTA, heparin or procaine attenuated POX-induced [Ca(2+)]i elevation and apoptosis. Additionally, POX up-regulated caspase-12 expression in a dose-dependent manner, and pre-treatment with EGTA, heparin or procaine significantly inhibited POX-induced increase of caspase-12 expression. Our results suggested that POX induced [Ca(2+)]i elevation in EL4 cells at the early stage of POX-induced apoptosis, which might involve Ca(2+) efflux from the endoplasmic reticulum (ER) and Ca(2+) influx from extracellular medium. Calcium signals and caspase-12 were important upstream messengers in POX-induced apoptosis in EL4 cells. The ER-associated pathway possibly operated in this apoptosis. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  14. Review on thymoma and thymoma-associated autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Yue-min LI

    2014-10-01

    Full Text Available Thymic carcinomas are tumors of the anterior mediastinum derived from the epithelial cells of the thymus gland. Malignancies linked to thymoma lead to the loss of self-tolerance leading to autoimmune diseases, including myasthenia gravis, pure red cell aplastic anemia, systemic lupus erythematosus and pemphigus etc. In recent years, three main mechanisms have been proposed to elucidate these interactions, such as immature T cell theory, tumor-gene theory and the combination mechanism of cellular and humoral immunity. In fact, the resection of the thymoma is beneficial to many patients of thymoma related autoimmune diseases. DOI: 10.11855/j.issn.0577-7402.2014.08.16

  15. Cytotoxic T lymphocyte recognition of HLA-A/B antigens introduced into EL4 cells by cell-liposome fusion.

    Science.gov (United States)

    Engelhard, V H; Powers, G A; Moore, L C; Holterman, M J; Correa-Freire, M C

    1984-01-01

    HLA-A2 and -B7 antigens were introduced into EL4 (H-2b) cells by cell-liposome fusion and were used as targets or stimulators for cytotoxic T lymphocytes (CTL) generated in C57B1/6 (H-2b) mice. It was found that such EL4-HLA cells were not recognized by CTL that had been raised against either a human cell line bearing these HLA antigens or the purified HLA-A2 and -B7 antigens reconstituted into liposomes. In addition, EL4-HLA cells were not capable of inducing CTL that could recognize a human cell line bearing HLA-A2 and -B7 antigens. Instead, EL4-HLA cells induced CTL that specifically lysed EL4-HLA cells and not human cells expressing HLA-A2 and -B7. CTL recognition required the presence of HLA antigens on the EL4 cell surface and was inhibited by antibodies against either H-2b or HLA-A/B. Monoclonal antibody binding studies showed that the expected polymorphic determinants of the HLA-A2 and -B7 antigens were still present on EL4-HLA cells. However, the specificity of CTL or their precursors that are capable of recognizing HLA-A2 or -B7 was altered after these antigens became associated with the EL4 surface. Possible explanations for these results are discussed.

  16. Regulation of Id2 expression in EL4 T lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Weigent, Douglas A

    2009-01-01

    In previous studies, we have shown that overexpression of growth hormone (GH) in cells of the immune system upregulates proteins involved in cell growth and protects from apoptosis. Here, we report that overexpression of GH in EL4 T lymphoma cells (GHo) also significantly increased levels of the inhibitor of differentiation-2 (Id2). The increase in Id2 was suggested in both Id2 promoter luciferase assays and by Western analysis for Id2 protein. To identify the regulatory elements that mediate transcriptional activation by GH in the Id2 promoter, promoter deletion analysis was performed. Deletion analysis revealed that transactivation involved a 301-132bp region upstream to the Id2 transcriptional start site. The pattern in the human GHo Jurkat T lymphoma cell line paralleled that found in the mouse GHo EL4 T lymphoma cell line. Significantly less Id2 was detected in the nucleus of GHo EL4 T lymphoma cells compared to vector alone controls. Although serum increased the levels of Id2 in control vector alone cells, no difference was found in the total levels of Id2 in GHo EL4 T lymphoma cells treated with or without serum. The increase in Id2 expression in GHo EL4 T lymphoma cells measured by Id2 promoter luciferase expression and Western blot analysis was blocked by the overexpression of a dominant-negative mutant of STAT5. The results suggest that in EL4 T lymphoma cells overexpressing GH, there is an upregulation of Id2 protein that appears to involve STAT protein activity.

  17. Increase in colony-forming efficiency in soft agar of thymus cells from radiation-induced thymomas of NIH Swiss mice

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    Mori, Nobuko; Takamori, Yasuhiko; Hori, Yasuharu [Radiation Center of Osaka Prefecture, Sakai (Japan)

    1982-03-01

    Colony-forming efficiency in soft agar of radiation-induced thymoma in NIH Swiss mice was determined in the presence of cultured medium of reticulo-epitherial cells from normal thymus of NIH Swiss mouse as conditioned medium. A similar experiment was done with thymomas spontaneously developed in AKR mice. Most of colonies developed in soft agar were not composed of thymic lymphoma cells, but of macrophage-like cells. The ratio of the number of colonies to that of the seeded cells significantly increased in thymomas comparing with that in normal thymus. This result corresponded with the increased number of macrophages in thymoma, as determined by counting phagocytic cells of adherent cells.

  18. Recurrence of thymoma with pleural invasion in a patient with myasthenia gravis and pure red blood cell aplasia: a case report

    International Nuclear Information System (INIS)

    Rodriguez, Sonia Pilar; Zuluaga, Claudia Patricia; Uriza, Luis Felipe C; Sanchez M, Jully Mariana

    2008-01-01

    Thymoma are thymic tumors that arise from epithelial cells, they have different morphological characteristics. It is known for its association with autoimmune diseases such as myasthenia gravis, pure red cell aplasia, systemic lupus erythematosus, or hipogamaglobulinemia pemphigus foliaceus. The association thymoma-myasthenia gravis-pure red cell aplasia is a rare one; there will be a case report with the corresponding discussion and review of the literature

  19. Ultrasound guided electrochemotherapy for the treatment of a clear cell thymoma in a cat

    Directory of Open Access Journals (Sweden)

    Enrico Pierluigi Spugnini

    2017-03-01

    Full Text Available A twelve-year-old male castrated domestic shorthair cat was presented for rapidly progressing respiratory distress. The cat was depressed, tachypneic and moderately responsive. Ultrasonography showed a mediastinal mass associated with a significant pleural effusion that needed tapping every five to seven days. Ultrasound guided biopsy yielded a diagnosis of clear cell thymoma upon histopathology. After complete staging procedures, the owner elected to treat the cat with electrochemotherapy (ECT using systemic bleomycin. Two sessions of ultrasound guided ECT were performed at two week intervals with trains of biphasic electric pulses applied using needle electrodes until complete coverage of the area was achieved. The treatment was well tolerated and resulted in partial remission (PR. Additional sessions were performed on a monthly basis. The cat is still in PR after fourteen months. ECT resulted in improved local control and should be considered among the available adjuvant treatments in pets carrying visceral tumors.

  20. The short term effects of Low-dose-rate Radiation on EL4 Lymphoma Cell

    International Nuclear Information System (INIS)

    Bong, Jin Jong; Kang, Yu Mi; Shin, Suk Chull; Choi, Moo Hyun; Choi, Seung Jin; Kim, Hee Sun; Lee, Kyung Mi

    2012-01-01

    To determine the biological effects of low-dose-rate radiation ( 137 Cs, 2.95 mGy/h) on EL4 lymphoma cells during 24 h, we investigated the expression of genes related to apoptosis, cell cycle arrest, DNA repair, iron transport, and ribonucleotide reductase. EL4 cells were continuously exposed to low-dose-rate radiation (total dose: 70.8 mGy) for 24 h. We analyzed cell proliferation and apoptosis by trypan blue exclusion and flow cytometry, gene expression by real-time PCR, and protein levels with the apoptosis ELISA kit. Apoptosis increased in the Low-dose-rate irradiated cells, but cell number did not differ between non- (Non-IR) and Low-dose-rate irradiated (LDR-IR) cells. In concordance with apoptotic rate, the transcriptional activity of ATM, p53, p21, and Parp was upregulated in the LDR-IR cells. Similarly, Phospho-p53 (Ser15), cleaved caspase 3 (Asp175), and cleaved Parp (Asp214) expression was upregulated in the LDR-IR cells. No difference was observed in the mRNA expression of DNA repair-related genes (Msh2, Msh3, Wrn, Lig4, Neil3, ERCC8, and ERCC6) between Non-IR and LDR-IR cells. Interestingly, the mRNA of Trfc was upregulated in the LDR-IR cells. Therefore, we suggest that short-term Low-dose-rate radiation activates apoptosis in EL4 lymphoma cells.

  1. The short term effects of Low-dose-rate Radiation on EL4 Lymphoma Cell

    Energy Technology Data Exchange (ETDEWEB)

    Bong, Jin Jong; Kang, Yu Mi; Shin, Suk Chull; Choi, Moo Hyun; Choi, Seung Jin; Kim, Hee Sun [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd, Seoul (Korea, Republic of); Lee, Kyung Mi [Global Research Lab, BAERI Institute, Dept. of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of)

    2012-06-15

    To determine the biological effects of low-dose-rate radiation ({sup 137}Cs, 2.95 mGy/h) on EL4 lymphoma cells during 24 h, we investigated the expression of genes related to apoptosis, cell cycle arrest, DNA repair, iron transport, and ribonucleotide reductase. EL4 cells were continuously exposed to low-dose-rate radiation (total dose: 70.8 mGy) for 24 h. We analyzed cell proliferation and apoptosis by trypan blue exclusion and flow cytometry, gene expression by real-time PCR, and protein levels with the apoptosis ELISA kit. Apoptosis increased in the Low-dose-rate irradiated cells, but cell number did not differ between non- (Non-IR) and Low-dose-rate irradiated (LDR-IR) cells. In concordance with apoptotic rate, the transcriptional activity of ATM, p53, p21, and Parp was upregulated in the LDR-IR cells. Similarly, Phospho-p53 (Ser15), cleaved caspase 3 (Asp175), and cleaved Parp (Asp214) expression was upregulated in the LDR-IR cells. No difference was observed in the mRNA expression of DNA repair-related genes (Msh2, Msh3, Wrn, Lig4, Neil3, ERCC8, and ERCC6) between Non-IR and LDR-IR cells. Interestingly, the mRNA of Trfc was upregulated in the LDR-IR cells. Therefore, we suggest that short-term Low-dose-rate radiation activates apoptosis in EL4 lymphoma cells.

  2. Differential Expression of Ccn4 and Other Genes Between Metastatic and Non-metastatic EL4 Mouse Lymphoma Cells

    OpenAIRE

    S. CHAHAL, MANPREET; TERESA KU, H.; ZHANG, ZHIHONG; M. LEGASPI, CHRISTIAN; LUO, ANGELA; M. HOPKINS, MANDI; E. MEIER, KATHRYN

    2016-01-01

    Background: Previous work characterized variants of the EL4 murine lymphoma cell line. Some are non-metastatic, and others metastatic, in syngenic mice. In addition, metastatic EL4 cells were stably transfected with phospholipase D2 (PLD2), which further enhanced metastasis. Materials and Methods: Microarray analyses of mRNA expression was performed for non-metastatic, metastatic, and PLD2-expressing metastatic EL4 cells. Results: Many differences were observed between non-metastatic and meta...

  3. RasGRP1 confers the phorbol ester-sensitive phenotype to EL4 lymphoma cells.

    Science.gov (United States)

    Han, Shujie; Knoepp, Stewart M; Hallman, Mark A; Meier, Kathryn E

    2007-01-01

    The murine EL4 lymphoma cell line exists in variants that are either sensitive or resistant to the tumor promoter phorbol 12-myristate 13-acetate (PMA). In sensitive EL4 cells, PMA causes robust Erk mitogen-activated protein kinase activation that results in growth arrest. In resistant cells, PMA induces minimal Erk activation, without growth arrest. PMA stimulates IL-2 production in sensitive, but not resistant, cells. The role of RasGRP1, a PMA-activated guanine nucleotide exchange factor for Ras, in EL4 phenotype was examined. Endogenous RasGRP1 protein is expressed at much higher levels in sensitive than in resistant cells. PMA-induced Ras activation is observed in sensitive cells but not in resistant cells lacking Ras-GRP1. PMA induces down-regulation of RasGRP1 protein in sensitive cells but increases RasGRP1 in resistant cells. Transfection of RasGRP1 into resistant cells enhances PMA-induced Erk activation. In the reverse experiment, introduction of small interfering RNA (siRNA) for RasGRP1 suppresses PMA-induced Ras and Erk activations in sensitive cells. Sensitive cells incubated with siRNA for RasGRP1 exhibit the PMA-resistant phenotype, in that they are able to proliferate in the presence of PMA and do not secrete IL-2 when stimulated with PMA. These studies indicate that the PMA-sensitive phenotype, as previously defined for the EL4 cell line, is conferred by endogenous expression of RasGRP1 protein.

  4. Pretreatment of low dose radiation reduces radiation-induced apoptosis in mouse lymphoma (EL4) cells.

    Science.gov (United States)

    Kim, J H; Hyun, S J; Yoon, M Y; Ji, Y H; Cho, C K; Yoo, S Y

    1997-06-01

    Induction of an adaptive response to ionizing radiation in mouse lymphoma (EL4) cells was studied by using cell survival fraction and apoptotic nucleosomal DNA fragmentation as biological end points. Cells in early log phase were pre-exposed to low dose of gamma-rays (0.01 Gy) 4 or 20 hrs prior to high dose gamma-ray (4, 8 and 12 Gy for cell survival fraction analysis; 8 Gy for DNA fragmentation analysis) irradiation. Then cell survival fractions and the extent of DNA fragmentation were measured. Significant adaptive response, increase in cell survival fraction and decrease in the extent of DNA fragmentation were induced when low and high dose gamma-ray irradiation time interval was 4 hr. Addition of protein or RNA synthesis inhibitor, cycloheximide or 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRFB), respectively during adaptation period, the period from low dose gamma-ray irradiation to high dose gamma-ray irradiation, was able to inhibit the induction of adaptive response, which is the reduction of the extent DNA fragmentation in irradiated EL4 cells. These data suggest that the induction of adaptive response to ionizing radiation in EL4 cells required both protein and RNA synthesis.

  5. Basic study on apoptosis induction into cancer cells U-937 and EL-4 by ultrasound exposure.

    Science.gov (United States)

    Takeuchi, Shinichi; Udagawa, Yoshiko; Oku, Yumiko; Fujii, Takuma; Nishimura, Hiroyuki; Kawashima, Norimichi

    2006-12-22

    Recently, the low invasive cancer treatments with small aftereffects have been considered. We are studying on the suppression methods of cancer cell proliferation with ultrasound. Cancer cells of mouse T lymphoma (EL-4) have been used in our study. The human histitocytic lymphoma cells (U-937) was used in this time. The cancer cells were cultured in a culture medium of RPMI1640. The standing wave acoustic field was formed in a water tank of our ultrasound exposure system by a vibrating plate driven with a Langevine type transducer. The U-937 and EL-4 were exposed to ultrasound in the acoustic field with spatial average acoustic intensity of 350 mW/cm(2) at 150 kHz. The viable rate of EL-4 decreased with the lapse of culture time after ultrasound exposure. U-937 did not show the remarkable decrease tendency. The proliferation of U-937 which exposed to ultrasound with 700 mW/cm(2) was suppressed. It can be thought that apoptosis was induced in the cancer cells in this condition. We observed the morphological change on the U-937 exposed to ultrasound with this condition. The morphological changes by apoptosis like the shrink of cells, formation of apoptotic bodies etc. can be observed with an optical microscope and a phase contrast microscope.

  6. Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells

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    Manpreet S. Chahal

    2010-07-01

    Full Text Available Phospholipase D2 (PLD2 generates phosphatidic acid through hydrolysis of phosphatidylcholine. PLD2 has been shown to play a role in enhancing tumorigenesis. The epidermal growth factor receptor (EGFR can both activate and interact with PLD2. Murine lymphoma EL4 cells lacking endogenous PLD2 present a unique model to elucidate the role of PLD2 in signal transduction. In the current study, we investigated effects of PLD2 on EGF response. Western blotting and RT-PCR were used to establish that both parental cells and PLD2 transfectants express endogenous EGFR. Levels of EGFR protein are increased in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. EGF stimulates proliferation of EL4 cells transfected with active PLD2, but not parental cells or cells transfected with inactive PLD2. EGF-mediated proliferation in cells expressing active PLD2 is dependent on the activities of both the EGFR and the PI3K/Akt pathway, as demonstrated by studies using protein kinase inhibitors. EGF-induced invasion through a synthetic extracellular matrix is enhanced in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. Taken together, the data suggest that PLD2 acts in concert with EGFR to enhance mitogenesis and invasion in lymphoma cells.

  7. Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells.

    Science.gov (United States)

    Chahal, Manpreet S; Brauner, Daniel J; Meier, Kathryn E

    2010-07-02

    Phospholipase D2 (PLD2) generates phosphatidic acid through hydrolysis of phosphatidylcholine. PLD2 has been shown to play a role in enhancing tumorigenesis. The epidermal growth factor receptor (EGFR) can both activate and interact with PLD2. Murine lymphoma EL4 cells lacking endogenous PLD2 present a unique model to elucidate the role of PLD2 in signal transduction. In the current study, we investigated effects of PLD2 on EGF response. Western blotting and RT-PCR were used to establish that both parental cells and PLD2 transfectants express endogenous EGFR. Levels of EGFR protein are increased in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. EGF stimulates proliferation of EL4 cells transfected with active PLD2, but not parental cells or cells transfected with inactive PLD2. EGF-mediated proliferation in cells expressing active PLD2 is dependent on the activities of both the EGFR and the PI3K/Akt pathway, as demonstrated by studies using protein kinase inhibitors. EGF-induced invasion through a synthetic extracellular matrix is enhanced in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. Taken together, the data suggest that PLD2 acts in concert with EGFR to enhance mitogenesis and invasion in lymphoma cells.

  8. Doxorubicin attached to HPMA copolymer via amide bond modifies the glycosylation pattern of EL4 cells.

    Science.gov (United States)

    Kovar, Lubomir; Etrych, Tomas; Kabesova, Martina; Subr, Vladimir; Vetvicka, David; Hovorka, Ondrej; Strohalm, Jiri; Sklenar, Jan; Chytil, Petr; Ulbrich, Karel; Rihova, Blanka

    2010-08-01

    To avoid the side effects of the anti-cancer drug doxorubicin (Dox), we conjugated this drug to a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer backbone. Dox was conjugated via an amide bond (Dox-HPMA(AM), PK1) or a hydrazone pH-sensitive bond (Dox-HPMA(HYD)). In contrast to Dox and Dox-HPMA(HYD), Dox-HPMA(AM) accumulates within the cell's intracellular membranes, including those of the Golgi complex and endoplasmic reticulum, both involved in protein glycosylation. Flow cytometry was used to determine lectin binding and cell death, immunoblot to characterize the presence of CD7, CD43, CD44, and CD45, and high-performance anion exchange chromatography with pulsed amperometric detector analysis for characterization of plasma membrane saccharide composition. Incubation of EL4 cells with Dox-HPMA(AM) conjugate, in contrast to Dox or Dox-HPMA(HYD), increased the amounts of membrane surface-associated glycoproteins, as well as saccharide moieties recognized by peanut agglutinin, Erythrina cristagalli, or galectin-1 lectins. Only Dox-HPMA(AM) increased expression of the highly glycosylated membrane glycoprotein CD43, while expression of others (CD7, CD44, and CD45) was unaffected. The binding sites for galectin-1 are present on CD43 molecule. Furthermore, we present that EL4 treated with Dox-HPMA(AM) possesses increased sensitivity to galectin-1-induced apoptosis. In this study, we demonstrate that Dox-HPMA(AM) treatment changes glycosylation of the EL4 T cell lymphoma surface and sensitizes the cells to galectin-1-induced apoptosis.

  9. TGF-beta1 expression in EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Farmer, John T; Weigent, Douglas A

    2006-03-01

    Our previous studies show that growth hormone overexpression (GHo) upregulates the expression of the IGF-1R and IGF-2R resulting in the protection of the EL4 lymphoma cell line from apoptosis. In this study, we report that GHo also increases TGF-beta1 protein expression measured by luciferase promoter assay, Western analysis, and ELISA. Further, the data show that antibody to TGF-betaR2 decreases TGF-beta1 promoter activity to the level of vector alone control cells. GHo cells treated with (125)I-rh-latent TGF-beta1 showed increased activation of latent TGF-beta1 as measured by an increase in the active 24kDa, TGF-beta1 compared to vector alone control cells. The ability of endogenous GH to increase TGF-beta1 expression is blocked in EL4 cells by antisense but not sense oligodeoxynucleotides or in cells cultured with antibody to growth hormone (GH). The data suggest that endogenous GH may protect from apoptosis through the IGF-1R receptor while limiting cellular growth through increased expression and activation of TGF-beta1.

  10. The inhibition of apoptosis in EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Arnold, Robyn E; Weigent, Douglas A

    2004-01-01

    The antiapoptotic action of exogenous growth hormone (GH) has been reported for several lymphoid cell lines; however, the potential role of endogenous GH in apoptosis has not been thoroughly investigated. This study was designed to investigate the effects of endogenous GH on apoptosis induced by methyl methanesulfonate (MMS) in a T cell lymphoma overexpressing GH (GHo). The results of these experiments have shown that in EL4 lymphoma cells, overexpression of GH sustained viability after exposure to MMS compared to control cells. The extent of DNA fragmentation measured by ladder formation on agarose gels was reduced in GHo cells following treatment with MMS, when compared to control cells. Adding exogenous GH to control cells and treatment of GHo cells with antibodies to GH had no effect on MMS-induced DNA ladder formation. In further studies, DNA microarray analysis suggested a marked decrease in the constitutive expression of bax, BAD, and caspases 3, 8, and 9 in GHo cells compared to controls. In addition, after treatment with MMS, the activities of caspases 2, 3, 6, 8, and 9 were all lower than control in GHo cells. Western blot analysis detected an increase in Bcl-2 while the levels of nuclear factor kappa B (NFkappaB) remained unchanged in GHo cells. Treatment of EL4 cells with antisense deoxyoligonucleotides to GH and specific inhibitors of NFkappaB (SN-50) increased DNA fragmentation. GHo cells show increased levels of phosphorylated Akt and GSK-3, suggesting inactivation of this proapoptotic protein. The results, taken together with our previous data which showed increased nitric oxide formation in GHo cells, suggest a possible mechanism for the antiapoptotic effects of endogenous GH through the production of nitric oxide and support the idea that endogenous GH may play an important role in the survival of lymphocytes exposed to stressful stimuli. Copyright 2004 S. Karger AG, Basel

  11. Paraoxon induces apoptosis in EL4 cells via activation of mitochondrial pathways.

    Science.gov (United States)

    Saleh, A M; Vijayasarathy, C; Masoud, L; Kumar, L; Shahin, A; Kambal, A

    2003-07-01

    The toxicity of organophosphorus compounds, such as paraoxon (POX), is due to their anticholinesterase action. Recently, we have shown that, at noncholinergic doses (1 to 10 nM), POX (the bioactive metabolite of parathion) causes apoptotic cell death in murine EL4 T-lymphocytic leukemia cell line through activation of caspase-3. In this study, by employing caspase-specific inhibitors, we extend our observations to elucidate the sequence of events involved in POX-stimulated apoptosis. Pretreatment of EL4 cells with the caspase-9-specific inhibitor zLEHD-fmk attenuated POX-induced apoptosis in a dose-dependent manner, whereas the caspase-8 inhibitor zIETD-fmk had no effect. Furthermore, the activation of caspase-9, -8, and -3 in response to POX treatment was completely inhibited in the presence of zLEHD-fmk, implicating the involvement of caspase 9-dependent mitochondrial pathways in POX-stimulated apoptosis. Indeed, under both in vitro and in vivo conditions, POX triggered a dose- and time-dependent translocation of cytochrome c from mitochondria into the cytosol, as assessed by Western blot analysis. Investigation of the mechanism of cytochrome c release revealed that POX disrupted mitochondrial transmembrane potential. Neither this effect nor cytchrome c release was dependent on caspase activation, since the general inhibitor of the caspase family zVAD-fmk did not influence both processes. Finally, POX treatment also resulted in a time-dependent up-regulation and translocation of the proapoptotic molecule Bax to mitochondria. Inhibition of this event by zVAD-fmk suggests that the activation and translocation of Bax to mitochondria is subsequent to activation of the caspase cascades. The results indicate that POX induces apoptosis in EL4 cells through a direct effect on mitochondria by disrupting its transmembrane potential, causing the release of cytochrome c into the cytosol and subsequent activation of caspase-9. Inhibition of this specific pathway might provide

  12. Integrated modulation of phorbol ester-induced Raf activation in EL4 lymphoma cells.

    Science.gov (United States)

    Han, Shujie; Meier, Kathryn E

    2009-05-01

    The EL4 murine lymphoma cell line exists in variant phenotypes that differ with respect to responses to the tumor promoter phorbol 12-myristate 13-acetate (PMA1). Previous work showed that "PMA-sensitive" cells, characterized by a high magnitude of PMA-induced Erk activation, express RasGRP, a phorbol ester receptor that directly activates Ras. In "PMA-resistant" and "intermediate" EL4 cell lines, PMA induces Erk activation to lesser extents, but with a greater response in intermediate cells. In the current study, these cell lines were used to examine mechanisms of Raf-1 modulation. Phospho-specific antibodies were utilized to define patterns and kinetics of Raf-1 phosphorylation on several sites. Further studies showed that Akt is constitutively activated to a greater extent in PMA-resistant than in PMA-sensitive cells, and also to a greater extent in resistant than intermediate cells. Akt negatively regulates Raf-1 activation (Ser259), partially explaining the difference between resistant and intermediate cells. Erk activation exerts negative feedback on Raf-1 (Ser289/296/301), thus resulting in earlier termination of the signal in cells with a higher level of Erk activation. RKIP, a Raf inhibitory protein, is expressed at higher levels in resistant cells than in sensitive or intermediate cells. Knockdown of RKIP increases Erk activation and also negative feedback. In conclusion, this study delineates Raf-1 phosphorylation events occurring in response to PMA in cell lines with different extents of Erk activation. Variations in the levels of expression and activation of multiple signaling proteins work in an integrated fashion to modulate the extent and duration of Erk activation.

  13. Activation of macrophages for microbicidal and tumoricidal effector functions by soluble factors from EL-4, a continuous T cell line.

    OpenAIRE

    Nacy, C A; James, S L; Benjamin, W R; Farrar, J J; Hockmeyer, W T; Meltzer, M S

    1983-01-01

    Macrophages treated with culture fluids from EL-4 cells, a continuous T cell line, were activated to kill mKSA-TU-5 fibrosarcoma cells, amastigotes of Leishmania tropica, and schistosomula of Schistosoma mansoni. Active EL-4 factors eluted from Sephadex G-100 in two distinct regions: molecular weight 45,000 (activities induced killing of unrelated intracellular and extracellular targets) and molecular weight 23,000 (activities induced killing of extracellular targets only). These results conf...

  14. The inhibition of superoxide production in EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Arnold, Robyn E; Weigent, Douglas A

    2003-05-01

    A substantial body of research exists to support the production of growth hormone by cells of the immune system. However, the function and mechanism of action of lymphocyte-derived growth hormone remain largely unelucidated. Since, it has been found that exogenous growth hormone (GH) primes neutrophils for the production of reactive oxygen intermediates (ROI) and in particular superoxide (O2-), we investigated the role of GH on the production of O2- in T cells. Furthermore, we examined whether endogenous and exogenous GH act similarly. Our studies show that overexpression of GH in EL4, a T-cell lymphoma cell line, results in a decrease in the production of O2- compared to control cells, as detected using the fluorescent dye, dihydroethidium. O2- production in control cells was not affected by treatment with inhibitors of xanthine oxidase or a non-specific NADPH-oxidase inhibitor. However, treatment with diallyl sulfide, an inhibitor of cytochrome P450 2E1 mimicked the reduction in O2- production seen in cells overexpressing GH. Although no significant change could be detected in CYP2E1 protein levels, CYP2E1 activity was found to be greater in control EL4 than in cells overexpressing GH. Both the decrease in O2- production and the lower CYP2E1 activity in GH overexpressing cells could be abrogated by treatment with N(G)-monomethyl-L-arginine, an inhibitor of nitric oxide synthase. The overexpression of GH protects cells from apoptosis induced by isoniazid, a CYP2E1 inducer, suggesting a role for nitric oxide as a mediator in the regulation of xenobiotic metabolism and apoptosis-protection by lymphocyte GH.

  15. Differential expression of FAK and Pyk2 in metastatic and non-metastatic EL4 lymphoma cell lines.

    Science.gov (United States)

    Zhang, Zhihong; Knoepp, Stewart M; Ku, Hsun; Sansbury, Heather M; Xie, Yuhuan; Chahal, Manpreet S; Tomlinson, Stephen; Meier, Kathryn E

    2011-08-01

    The murine EL4 lymphoma cell line exists in variants that are either sensitive or resistant to phorbol 12-myristate 13-acetate (PMA). In sensitive cells, PMA causes Erk MAPK activation and Erk-mediated growth arrest. In resistant cells, PMA induces a low level of Erk activation, without growth arrest. A relatively unexplored aspect of the phenotypes is that resistant cells are more adherent to culture substrate than are sensitive cells. In this study, the roles of the protein tyrosine kinases FAK and Pyk2 in EL4 phenotype were examined, with a particular emphasis on the role of these proteins in metastasis. FAK is expressed only in PMA-resistant (or intermediate phenotype) EL4 cells, correlating with enhanced cell-substrate adherence, while Pyk2 is more highly expressed in non-adherent PMA-sensitive cells. PMA treatment causes modulation of mRNA for FAK (up-regulation) and Pyk2 (down-regulation) in PMA-sensitive but not PMA-resistant EL4 cells. The increase in Pyk2 mRNA is correlated with an increase in Pyk2 protein expression. The roles of FAK in cell phenotype were further explored using transfection and knockdown experiments. The results showed that FAK does not play a major role in modulating PMA-induced Erk activation in EL4 cells. However, the knockdown studies demonstrated that FAK expression is required for proliferation and migration of PMA-resistant cells. In an experimental metastasis model using syngeneic mice, only FAK-expressing (PMA-resistant) EL4 cells form liver tumors. Taken together, these studies suggest that FAK expression promotes metastasis of EL4 lymphoma cells.

  16. Autophagy contributes to apoptosis in A20 and EL4 lymphoma cells treated with fluvastatin.

    Science.gov (United States)

    Qi, Xu-Feng; Kim, Dong-Heui; Lee, Kyu-Jae; Kim, Cheol-Su; Song, Soon-Bong; Cai, Dong-Qing; Kim, Soo-Ki

    2013-11-08

    Convincing evidence indicates that statins stimulate apoptotic cell death in several types of proliferating tumor cells in a cholesterol-lowering-independent manner. However, the relationship between apoptosis and autophagy in lymphoma cells exposed to statins remains unclear. The objective of this study was to elucidate the potential involvement of autophagy in fluvastatin-induced cell death of lymphoma cells. We found that fluvastatin treatment enhanced the activation of pro-apoptotic members such as caspase-3 and Bax, but suppressed the activation of anti-apoptotic molecule Bcl-2 in lymphoma cells including A20 and EL4 cells. The process was accompanied by increases in numbers of annexin V alone or annexin V/PI double positive cells. Furthermore, both autophagosomes and increases in levels of LC3-II were also observed in fluvastatin-treated lymphoma cells. However, apoptosis in fluvastatin-treated lymphoma cells could be blocked by the addition of 3-methyladenine (3-MA), the specific inhibitor of autophagy. Fluvastatin-induced activation of caspase-3, DNA fragmentation, and activation of LC3-II were blocked by metabolic products of the HMG-CoA reductase reaction, such as mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). These results suggest that autophagy contributes to fluvastatin-induced apoptosis in lymphoma cells, and that these regulating processes require inhibition of metabolic products of the HMG-CoA reductase reaction including mevalonate, FPP and GGPP.

  17. Effect of ionizing radiation in combination with 5-flurouracil on cell cycle uncoupling of EL-4 cell line

    International Nuclear Information System (INIS)

    Liu Yang; Sun Yanhong; Zhang Xuan; Gong Shouliang; Zhang Wei; Li Song

    2009-01-01

    Objective: To observe the dose-and time-effect of ionizing radiation in combination with 5-flurouracil(5-FU) on the cell cycle uncoupling of EL-4 cell line. Methods: EL-4 cells were collected after irradiation with 0,1.0,2.0 and 4.0 Gy X-irradiation and treatment with 5-FU(0.001,0.010,0.100 and 1.000 mg·L -1 ) for 0,4,8,16,24 and 48 h.The regularity in the polyloid cells was analyzed by flow cytometry(FCM) following staining cells with propidium iodide(PI). Results: As compared with sham-irradiation group,the percentage of diploid EL-4 cells increased significantly at 8-24 h and returned to normal level at 48 h after irradiation with 2.0 Gy X-rays(P -1 group, the percentage of diploid cells decreased obviously at 16-48 h after treatment with 0.100 mg·L -1 5-FU(P -1 group, the percentage of diploid cells decreased significantly 16 h after treatment with different doses 5-FU(P -1 ; the percentage of octoploid cells increased significantly after treatment with 0.010 and 0.100 mg·L -1 5-Fu(P -1 5-FU. (authors)

  18. Kinetics of apoptotic markers in exogeneously induced apoptosis of EL4 cells.

    Science.gov (United States)

    Jessel, Robert; Haertel, Steffen; Socaciu, Carmen; Tykhonova, Svetlana; Diehl, Horst A

    2002-01-01

    We investigated the time-dependence of apoptotic events in EL4 cells by monitoring plasma membrane changes in correlation to DNA fragmentation and cell shrinkage. We applied three apoptosis inducers (staurosporine, tubericidine and X-rays) and we looked at various markers to follow the early-to-late apoptotic events: phospholipid translocation (identified through annexin V-fluorescein assay and propidium iodide), lipid package (via merocyanine assay), membrane fluidity and anisotropy (via fluorescent measurements), DNA fragmentation by the fluorescence-labeling test and cell size measurements. The different apoptotic inducers caused different reactions of the cells: staurosporine induced apoptosis most rapidly in a high number of cells, tubercidine triggered apoptosis only in the S phase cells, while X-rays caused a G2/M arrest and subsequently apoptosis. Loss of lipid asymmetry is promptly detectable after one hour of incubation time. The phosphatidylserine translocation, decrease of lipid package and anisotropy, and the increase of membrane fluidity appeared to be based on the same process of lipid asymmetry loss. Therefore, the DNA fragmentation and the cell shrinkage appear to be parallel and independent processes running on different time scales but which are kinetically inter-related. The results indicate different signal steps to apoptosis dependent on inducer characteristics but the kinetics of "early-to-late" apoptosis appears to be a fixed program.

  19. Phorbol esters induce interleukin 2 mRNA in sensitive but not in resistant EL4 cells

    International Nuclear Information System (INIS)

    Harrison, J.R.; Lynch, K.R.; Sando, J.J.

    1986-01-01

    Phorbol ester (PE) sensitive EL4 cells are growth-inhibited and produce interleukin 2 (IL2) when treated with PE. Resistant EL4 cells lack both responses. To determine whether the defect in resistant cells occurs pre or post-transcriptionally, an assay for IL2 mRNA was developed using a synthetic oligonucleotide to mouse IL2 as a probe. Total RNA (15 μg) from cells +/- PE was electrophoresed, blotted onto a cationic nylon membrane, and probed with radiolabeled oligomer. This probe hybridized to a 1.1 kb band in RNA from PE-treated sensitive cells. This RNA was detectable within 3h of PE administration, was clearly visible by 6h, and peaked by 9 to 12h. No bands hybridizing with the IL2 probe were detected in RNA isolated from unstimulated cells or from resistant EL4 cells at any time following PE stimulation. Since levels of the protooncogene c-myc have been shown to decrease in a number of cell lines during differentiation and growth inhibition, total RNA from EL4 cells was probed with a nick-translated plasmid containing the protein coding region of the c-myc gene. In PE sensitive cells, levels of c-myc RNA are markedly reduced by 3h. In a pilot experiment with resistant cells, c-myc levels appeared to remain constant. These results demonstrate that PE induced IL2 mRNA in PE sensitive but not resistant EL4 cells. Sensitive and resistant EL4 cell lines provide a useful model for the investigation of the regulation of gene expression by PE

  20. The production of nitric oxide in EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Arnold, Robyn E; Weigent, Douglas A

    2003-01-01

    Growth hormone (GH) is produced by immunocompetent cells and has been implicated in the regulation of a multiplicity of functions in the immune system involved in growth and activation. However, the actions of endogenous or lymphocyte GH and its contribution to immune reactivity when compared with those of serum or exogenous GH are still unclear. In the present study, we overexpressed lymphocyte GH in EL4 lymphoma cells, which lack the GH receptor (GHR), to determine the role of endogenous GH in nitric oxide (NO) production and response to genotoxic stress. Western blot analysis demonstrated that the levels of GH increased approximately 40% in cells overexpressing GH (GHo) when compared with cells with vector alone. The results also show a substantial increase in NO production in cells overexpressing GH that could be blocked by N(G)-monomethyl-L-arginine (L-NMMA), an L-arginine analogue that competitively inhibits all three isoforms of nitric oxide synthase (NOS). No evidence was obtained to support an increase in peroxynitrite in cells overexpressing GH. Overexpression of GH increased NOS activity, inducible nitric oxide synthase (iNOS) promoter activity, and iNOS protein expression, whereas endothelial nitric oxide synthase and neuronal nitric oxide synthase protein levels were essentially unchanged. In addition, cells overexpressing GH showed increased arginine transport ability and intracellular arginase activity when compared with control cells. GH overexpression appeared to protect cells from the toxic effects of the DNA alkylating agent methyl methanesulfonate. This possibility was suggested by maintenance of the mitochondrial transmembrane potential in cells overexpressing GH when compared with control cells that could be blocked by L-NMMA. Taken together, the data support the notion that lymphocyte GH, independently of the GH receptor, may play a key role in the survival of lymphocytes exposed to stressful stimuli via the production of NO.

  1. Inactivation of the small GTP binding protein Rho induces multinucleate cell formation and apoptosis in murine T lymphoma EL4.

    Science.gov (United States)

    Moorman, J P; Bobak, D A; Hahn, C S

    1996-06-01

    The small G-protein Rho regulates the actin microfilament-dependent cytoskeleton. Exoenzyme C3 of Clostridium botulinum ADP-ribosylates Rho at Asn41, a modification that functionally inactivates Rho. Using a Sindbis virus-based transient gene expression system, we studied the role of Rho in murine EL4 T lymphoma cells. We generated a double subgenomic infectious Sindbis virus (dsSIN:C3) recombinant which expressed C3 in >95% of EL4 cells. This intracellular C3 resulted in modification and inactivation of virtually all endogenous Rho. dsSIN:C3 infection led to the formation of multinucleate cells, likely by inhibiting the actin microfilament-dependent step of cytokinesis. Intriguingly, in spite of the inhibition of cytokinesis, karyokinesis continued, with the result that cells containing a nuclear DNA content as high as 16N (eight nuclei) were observed. In addition, dsSIN:C3-mediated inactivation of Rho was a potent activator of apoptosis in EL4 cells. To discern whether the formation of multinucleate cells was responsible for the activation of apoptosis, 5-fluorouracil (5-FUra) was used to induce cell cycle arrest. As expected, EL4 cells treated with 5-FUra were prevented from forming multinucleate cells upon infection with dsSIN:C3. dsSIN:C3 infection, however, still caused marked apoptosis in 5-FUra-treated cells, indicating that this activation of apoptosis was independent of multinucleate cell formation.

  2. Molecular analysis of thymoma.

    Directory of Open Access Journals (Sweden)

    Sunil Badve

    Full Text Available Histologic classification of thymomas has significant limitations with respect to both subtype definitions and consistency. In order to better understand the biology of the disease processes, we performed whole genome gene expression analysis. RNA was extracted from fresh frozen tumors from 34 patients with thymomas and followup data was available. Using the Illumina BeadStudio® platform and Human Ref-8 Beadchip, gene expression data was analyzed with Partek Genomics Suite®, and Ingenuity Pathways Analysis (IPA. Unsupervised clustering of gene expression data, representing one of the largest series in literature, resulted in identification of four molecular clusters of tumors (C1-C4, which correlated with histology (P = 0.002. However, neither histology nor clusters correlated with clinical outcomes. Correlation of gene expression data with clinical data showed that a number of genes were associated with either advanced stage at diagnosis or development of recurrence or metastases. The top pathways associated with metastases were amino acid metabolisms, biosynthesis of steroids and glycosphingolipids, cell cycle checkpoint proteins and Notch signaling. The differential expression of some of the top genes related to both metastases and stage was confirmed by RT-PCR in all cases of metastases and matched nonmetastatic cases. A number of potential candidates for therapeutics were also identified.

  3. Effect of RNAi p21 gene on uncoupling of EL-4 cells induced by X-irradiation

    International Nuclear Information System (INIS)

    Ju Guizhi; Yan Fengqin; Fu Shibo; Shen Bo; Sun Shilong; Yang Ying; Li Pengwu

    2008-01-01

    Objective: To investigate the effect of RNAi p21 gene on uncoupling of EL-4 cells induced by X-irradiation. Methods: Construction of RNAi p21 plasmid of pSileneer3.1-H1 neo-p21 was performed. Lipofectamine transfection assay was used to transfer the p21siBNA into EL-4 cells. Fluorescent staining and flow cytometry (FCM) analysis were employed for measurement of protein expression. Fluorescent staining of propidium iodide (PI) and FCM were used for measurement of potyploid cells. Results: In dose-effect experiment it was found that the expression of P21 protein of EL-4 cells increased significantly 24 h after X- irradiation with different doses compared with sham-inadiated control. In time course experiment it was found that the expression of P21 protein of EL-4 cells increased significantly at 8 h to 72 h after 4.0 Gy X-irradiation compared with sham-irradiated control. The results showed that the number of polyploid cells in EL-4 cells was not changed markedly after X-irradiation with doses of 0.5-6.0 Gy. After RNA interference with p21 gene, the expression of P21 protein of EL-4 cells decreased significantly 24 h and 48 h after 4.0 Gy X-irradiation in transfection of plasmid of pSilencer3.1-H1 neo-p21 compared with transfection of plasmid of pSilencer3.1-H1 nco control. And at the same time, the number of polyploid cells in EL-4 cells was increased significantly in transfection of plasmid of pSilencer3.1-H1 neo-p21 compared with transfection of plasmid of pSilencer3.1-H1 nco control. Conclusions: Uncoupling could be induced by X-irradiation in EL-4 cells following BNAi p21 gene, suggesting that P21 protein may play an important role in uncoupling induced by X-rays. (authors)

  4. CT of thymoma

    International Nuclear Information System (INIS)

    Sone, Shusuke; Higashihara, Tokuro; Morimoto, Shizuo; Ikezoe, Junpei; Arisawa, Jun

    1982-01-01

    Based on 17 patients with thymoma (8 with myasthenia gravis and 9 free from it); 1. The effectiveness of CT, conventional radiography and pneumomediastinography in the detection of thymomas was determined and the results compared. 2. The CT findings of thymomas were discussed and the CT features which seemed to suggest malignant thymomas were evaluated. The results were as follows: 1. Of the 17 cases with thymomas, 13 were diagnosed from p-a films, 13 from lateral films, and 16 from CT. Of the 16 thymomas, 14 were diagnosed from lateral tomography. Mass densities were shown in all 15 cases in which pneumomediastinography were performed. 2. Benign thymomas showed round or oval smoothly marginated mass. The fatty plane between the mass and the mediastinal structures was nicely preserved. 3. Malignant thymoma frequently showed a plaque-like mass with more or less irregular or lobulated contoures with obliteration of the fatty planes of the cardiovascular structures. Tumor calcification was shown in 4 of 10 malignant thymomas. 4. Slight tumor invasion to the mediastinal pleura and lung was difficult to predict from the CT images. (author)

  5. CT of thymoma

    Energy Technology Data Exchange (ETDEWEB)

    Sone, S.; Higashihara, T.; Morimoto, S.; Ikezoe, J.; Arisawa, J. (Osaka Univ. (Japan). Faculty of Medicine)

    1982-08-01

    Based on 17 patients with thymoma (8 with myasthenia gravis and 9 free from it); 1. The effectiveness of CT, conventional radiography and pneumomediastinography in the detection of thymomas was determined and the results compared. 2. The CT findings of thymomas were discussed and the CT features which seemed to suggest malignant thymomas were evaluated. The results were as follows: 1. Of the 17 cass with thymomas, 13 were diagnosed from p-a films, 13 from lateral films, and 16 from CT. Of the 16 thymomas, 14 were diagnosed from lateral tomography. Mass densities were shown in all 15 cases in which pneumomediastinography were performed. 2. Benign thymomas showed round or oval smoothly marginated mass. The fatty plane between the mass and the mediastinal structures was nicely preserved. 3. Malignant thymoma frequently showed a plaque-like mass with more or less irregular or lobulated contours with obliteration of the fatty planes of the cardiovascular structures. Tumor calcification was shown in 4 of 10 malignant thymomas. 4. Slight tumor invasion to the mediastinal pleura and lung was difficult to predict from the CT images.

  6. Lysosomal processing of sialoglycoconjugates in a wheat germ agglutinin resistant variant of EL4 murine leukemia cells

    International Nuclear Information System (INIS)

    Devino, N.L.

    1989-01-01

    Metabolic studies were undertaken in EL4 murine leukemia in WB6, a wheat germ agglutinin-resistant variant of EL4, in order to identify any differences in lysosomal processing of sialoglyco-conjugates. Five lysosomal acid hydrolases, acetylesterase, acid phosphatase, β-galactosidase, α-mannosidase, and neuraminidase, were studied using fluorescent 4-methylumbelliferyl substrates. No significant differences were found in the total activity of any of these enzymes in EL4 and WB6. Cells were incubated in the presence of N-acetylmannosamine, the metabolic precursor of sialic acid (N-acetylneuraminic acid). Free sialic acid accumulated in the lysosomes of WB6 but not of EL4. The accumulation of lysosomal free sialic acid in WB6 showed a dependence on the concentration of N-acetylmannosamine in the growth medium. Metabolic labelling with [6- 3 H]-N-acetylmannosamine showed that WB6 accumulated lysosomal free sialic acid even at very low concentrations of N-acetylmannosamine. The two cell lines differed in their distribution of radiolabelled neutral sugars, free sialic acid, and sialoglycoproteins. The velocity of 3 H-sialic acid release was 3.7-fold lower in WB6 than in EL4, suggesting that WB6 has a defect in lysosomal sialic acid transport. The metabolic consequences of this defect are examined, in light of other biochemical and immunological data on these cells

  7. Differential Expression of FAK and Pyk2 in Metastatic and Non-metastatic EL4 Lymphoma Cell Lines

    OpenAIRE

    Zhang, Zhihong; Knoepp, Stewart M.; Ku, Hsun; Sansbury, Heather M.; Xie, Yuhuan; Chahal, Manpreet S.; Tomlinson, Stephen; Meier, Kathryn E.

    2011-01-01

    The murine EL4 lymphoma cell line exists in variants that are either sensitive or resistant to phorbol 12-myristate 13-acetate (PMA). In sensitive cells, PMA causes Erk MAPK activation and Erk-mediated growth arrest. In resistant cells, PMA induces a low level of Erk activation, without growth arrest. A relatively unexplored aspect of the phenotypes is that resistant cells are more adherent to culture substrate than are sensitive cells. In this study, the roles of the protein tyrosine kinases...

  8. Evaluation of the Cytotoxic Effect of the Brittle Star (Ophiocoma Erinaceus) Dichloromethane Extract and Doxorubicin on EL4 Cell Line.

    Science.gov (United States)

    Afzali, Mahbubeh; Baharara, Javad; Nezhad Shahrokhabadi, Khadijeh; Amini, Elaheh

    2017-01-01

    Leukemia is a blood disease that creates from inhibition of differentiation and increased proliferation rate. The nature has been known as a rich source of medically useful substances. High diversity of bioactive molecules, extracted from marine invertebrates, makes them as ideal candidates for cancer research. The study has been done to investigate cytotoxic effects of dichloromethane brittle star extract and doxorubicin on EL4 cancer cells. Blood cancer EL4 cells were cultured and treated at different concentrations of brittle star ( Ophiocoma erinaceus ) dichloromethane extract at 24, 48 and 72 h. Cell toxicity was studied using MTT assay. Cell morphology was examined using an invert microscope. Further, apoptosis was examined using Annexin V-FITC, propodium iodide, DAPI, and Acridine orange/propodium iodide staining. Eventually, the apoptosis pathways were analyzed using measurement of Caspase-3 and -9 activity. The statistical analysis was performed using SPSS, ANOVA software, and Tukey's test. P EL4 proliferation as IC 50 =32 µg/mL. All experiments related to apoptosis analysis confirmed that dichloromethane brittle star extract and doxorubicin have a cytotoxic effect on EL4 cells inIC 50 concentration. The study showed that dichloromethane brittle star extract is as an adjunct to doxorubicin in treatment of leukemia cells.

  9. Proteomic Signatures of Thymomas.

    Directory of Open Access Journals (Sweden)

    Linan Wang

    Full Text Available Based on the histological features and outcome, the current WHO classification separates thymomas into A, AB, B1, B2 and B3 subtypes. It is hypothesized that the type A thymomas are derived from the thymic medulla while the type B thymomas are derived from the cortex. Due to occasional histological overlap between the tumor subtypes creating difficulties in their separation, the aim of this study was to provide their proteomic characterization and identify potential immunohistochemical markers aiding in tissue diagnosis. Pair-wise comparison of neoplastic and normal thymus by liquid chromatography tandem mass spectrometry (LC-MS/MS of formalin fixed paraffin embedded tissue revealed 61 proteins differentially expressed in thymomas compared to normal tissue. Hierarchical clustering showed distinct segregation of subtypes AB, B1 and B2 from that of A and B3. Most notably, desmoyokin, a protein that is encoded by the AHNAK gene, was associated with type A thymomas and medulla of normal thymus, by LC-MS/MS and immunohistochemistry. In this global proteomic characterization of the thymoma, several proteins unique to different thymic compartments and thymoma subtypes were identified. Among differentially expressed proteins, desmoyokin is a marker specific for thymic medulla and is potentially promising immunohistochemical marker in separation of type A and B3 thymomas.

  10. CT image of thymoma

    Energy Technology Data Exchange (ETDEWEB)

    Morioka, Nobuo; Shudo, Yuji; Jahana, Masanobu; Matsuki, Tsutomu; Kotani, Kazuhiko (Tottori Univ., Yonago (Japan). School of Medicine)

    1983-10-01

    Computor tomographic images of 11 patients who had had thymectomy for myasthenia gravis or thymoma were studied retrospectively. Of those 11 patients, malignant thymoma and benign condition including normal thymus were 6 and 5 respectively. On CT, calcification and lobulation with irregular margin seem to be reliable findings of malignancy. Defect or abscence of fatty plane and non-homogenous density are ancillary.

  11. CT image of thymoma

    International Nuclear Information System (INIS)

    Morioka, Nobuo; Shudo, Yuji; Jahana, Masanobu; Matsuki, Tsutomu; Kotani, Kazuhiko

    1983-01-01

    Computor tomographic images of 11 patients who had had thymectomy for myasthenia gravis or thymoma were studied retrospectively. Of those 11 patients, malignant thymoma and benign condition including normal thymus were 6 and 5 respectively. On CT, calcification and lobulation with irregular margin seem to be reliable findings of malignancy. Defect or abscence of fatty plane and non-homogenous density are ancillary. (author)

  12. B7-2 Expressed on EL4 Lymphoma Suppresses Antitumor Immunity by an Interleukin 4–dependent Mechanism

    OpenAIRE

    Stremmel, C.; Greenfield, E.A.; Howard, E.; Freeman, G.J.; Kuchroo, V.K.

    1999-01-01

    For T cells to become functionally activated they require at least two signals. The B7 costimulatory molecules B7-1 and B7-2 provide the “second signal” pivotal for T cell activation. In this report, we studied the relative roles of B7-1 and B7-2 molecules in the induction of antitumor immunity to the T cell thymoma, EL4. We generated EL4 tumor cells that expressed B7-1, B7-2, and B7-1+B7-2 by transfecting murine cDNAs. Our results demonstrate that EL4–B7-1 cells are completely rejected in sy...

  13. RRR-alpha-tocopheryl succinate inhibits EL4 thymic lymphoma cell growth by inducing apoptosis and DNA synthesis arrest.

    Science.gov (United States)

    Yu, W; Sanders, B G; Kline, K

    1997-01-01

    RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) treatment of murine EL4 T lymphoma cells induced the cells to undergo apoptosis. After 48 hours of VES treatment at 20 micrograms/ml, 95% of cells were apoptotic. Evidence for the induction of apoptosis by VES treatments is based on staining of DNA for detection of chromatin condensation/fragmentation, two-color flow-cytometric analyses of DNA content, and end-labeled DNA and electrophoretic analyses for detection of DNA ladder formation. VES-treated EL4 cells were blocked in the G1 cell cycle phase; however, apoptotic cells came from all cell cycle phases. Analyses of mRNA expression of genes involved in apoptosis revealed decreased c-myc and increased bcl-2, c-fos, and c-jun mRNAs within three to six hours after treatment. Western analyses showed increased c-Jun, c-Fos, and Bcl-2 protein levels. Electrophoretic mobility shift assays showed increased AP-1 binding at 6, 12, and 24 hours after treatment and decreased c-Myc binding after 12 and 24 hours of VES treatment. Treatments of EL4 cells with VES+RRR-alpha-to-copherol reduced apoptosis without effecting DNA synthesis arrest. Treatments of EL4 cells with VES+rac-6-hydroxyl-2, 5,7,8-tetramethyl-chroman-2-carboxylic acid, butylated hydroxytoluene, or butylated hydroxyanisole had no effect on apoptosis or DNA synthesis arrest caused by VES treatments. Analyses of bcl-2, c-myc, c-jun, and c-fos mRNA levels in cells receiving VES + RRR-alpha-tocopherol treatments showed no change from cells receiving VES treatments alone, implying that these changes are correlated with VES treatments but are not causal for apoptosis. However, treatments with VES + RRR-alpha-tocopherol decreased AP-1 binding to consensus DNA oligomer, suggesting AP-1 involvement in apoptosis induced by VES treatments.

  14. Differential Expression of Ccn4 and Other Genes Between Metastatic and Non-metastatic EL4 Mouse Lymphoma Cells.

    Science.gov (United States)

    Chahal, Manpreet S; Ku, H Teresa; Zhang, Zhihong; Legaspi, Christian M; Luo, Angela; Hopkins, Mandi M; Meier, Kathryn E

    Previous work characterized variants of the EL4 murine lymphoma cell line. Some are non-metastatic, and others metastatic, in syngenic mice. In addition, metastatic EL4 cells were stably transfected with phospholipase D2 (PLD2), which further enhanced metastasis. Microarray analyses of mRNA expression was performed for non-metastatic, metastatic, and PLD2-expressing metastatic EL4 cells. Many differences were observed between non-metastatic and metastatic cell lines. One of the most striking new findings was up-regulation of mRNA for the matricellular protein WNT1-inducible signaling pathway protein 1 (CCN4) in metastatic cells; increased protein expression was verified by immunoblotting and immunocytochemistry. Other differentially expressed genes included those for reproductive homeobox 5 (Rhox5; increased in metastatic) and cystatin 7 (Cst7; decreased in metastatic). Differences between PLD2-expressing and parental cell lines were limited but included the signaling proteins Ras guanyl releasing protein 1 (RGS18; increased with PLD2) and suppressor of cytokine signaling 2 (SOCS2; decreased with PLD2). The results provide insights into signaling pathways potentially involved in conferring metastatic ability on lymphoma cells. Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

  15. Expression of Caspase-3, P53 in EL-4 cells induced by ionizing radiation and its biological implications

    International Nuclear Information System (INIS)

    Ju Guizhi; Shen Bo; Sun Shilong; Yan Fengqin; Fu Shibo; Li Pengwu

    2006-01-01

    Objective: To investigate the effect of ionizing radiation on the expressions of Caspase-3 and P53 proteins in EL-4 cells and its implications in the induction of apoptosis and polyploid cells. Methods: EL- 4 cells were irradiated with 4.0 Gy X-rays (180 kV, 15 mA, 0.287 Gy/min). Fluorescent staining and flow cytometry analysis were used to measure protein expression, apoptosis and polyploid cells. Results: It was found that the expression of Caspase-3 protein was increased significantly at 8 h and 12 h after the irradiation compared with sham-irradiated control (P<0.05), and the expression of P53 protein was also increased significantly at 2,4,8,12 and 24 h after the irradiation compared with sham-irradiated control (P<0.05 or P<0.01). The results showed that apoptosis of EL-4 cells was increased significantly at 2,4,8,12,24,48, and 72 h after 4.0 Gy irradiation compared with sham-irradiated control (P<0.05 or P<0.01 or P<0.001). However, no significant change in the number of polyploidy cells was found during the period from 2 to 48 h after the irradiation with 4.0 Gy X-rays. Conclusions: It is indicated that the expressions of Caspase-3 and P53 protein in EL-4 cells can be induced by ionizing radiation, and play an important role in the induction of apoptosis; the molecular pathway for polyploid formation might be P53-independent. (authors)

  16. Scintiscanning demonstration of thymoma

    International Nuclear Information System (INIS)

    Yuzuriha, Hideki; Morimoto, Masami; Inokawa, Koichi; Hikita, Hitoshi; Iida, Futoshi; Nakanishi, Fumiko; Sone, Shunsuke

    1986-01-01

    Thymus scintigraphy was performed using 201 Tl-chloride, 67 Ga-citrate and 75 Se-selenomethionine on 30 thymoma patients with or without myasthenia gravis. Mass negativity was observed in 6 out of 17 (35.3 per cent) and 3 out of 13 cases (23.1 per cent), respectively. A rate of 70 per cent (21 cases out of 30) of mass positivity was observed by thymus scan using 201 Tl. With regard to the relation between thymus scan and cell type, 201 Tl-scan exhibited a high rate of mass positivity, regardless of the cell type while the 75 Se-scan showed a trend toward mass positivity in epithelial cell predominant cases. With 201 Tl, mass positivity was observed when the CPM/g ratio for tumors and blood exceeded 3.0. This trend can serve as an index for the suitability of supplementary chemo- and radiotherapies, as well as for prognosis in cases of relapse, and in those for whom excision was not complete. (author)

  17. B7-2 Expressed on EL4 Lymphoma Suppresses Antitumor Immunity by an Interleukin 4–dependent Mechanism

    Science.gov (United States)

    Stremmel, C.; Greenfield, E.A.; Howard, E.; Freeman, G.J.; Kuchroo, V.K.

    1999-01-01

    For T cells to become functionally activated they require at least two signals. The B7 costimulatory molecules B7-1 and B7-2 provide the “second signal” pivotal for T cell activation. In this report, we studied the relative roles of B7-1 and B7-2 molecules in the induction of antitumor immunity to the T cell thymoma, EL4. We generated EL4 tumor cells that expressed B7-1, B7-2, and B7-1+B7-2 by transfecting murine cDNAs. Our results demonstrate that EL4–B7-1 cells are completely rejected in syngeneic mice. Unlike EL4–B7-1 cells, we find that EL4–B7-2 cells are not rejected but progressively grow in the mice. A B7-1– and B7-2–EL4 double transfectant was generated by introducing B7-2 cDNA into the EL4–B7-1 tumor line that regressed in vivo. The EL4–B7-1+B7-2 double transfectant was not rejected when implanted into syngeneic mice but progressively grew to produce tumors. The double transfectant EL4 cells could costimulate T cell proliferation that could be blocked by anti–B7-1 antibodies, anti–B7-2 antibodies, or hCTLA4 immunoglobulin, showing that the B7-1 and B7-2 molecules expressed on the EL4 cells were functional. In vivo, treatment of mice implanted with double-transfected EL4 cells with anti–B7-2 monoclonal antibody resulted in tumor rejection. Furthermore, the EL4–B7-2 and EL4–B7-1+B7-2 cells, but not the wild-type EL4 cells, were rejected in interleukin 4 (IL-4) knockout mice. Our data suggests that B7-2 expressed on some T cell tumors inhibits development of antitumor immunity, and IL-4 appears to play a critical role in abrogation of the antitumor immune response. PMID:10075975

  18. B7-2 expressed on EL4 lymphoma suppresses antitumor immunity by an interleukin 4-dependent mechanism.

    Science.gov (United States)

    Stremmel, C; Greenfield, E A; Howard, E; Freeman, G J; Kuchroo, V K

    1999-03-15

    For T cells to become functionally activated they require at least two signals. The B7 costimulatory molecules B7-1 and B7-2 provide the "second signal" pivotal for T cell activation. In this report, we studied the relative roles of B7-1 and B7-2 molecules in the induction of antitumor immunity to the T cell thymoma, EL4. We generated EL4 tumor cells that expressed B7-1, B7-2, and B7-1+B7-2 by transfecting murine cDNAs. Our results demonstrate that EL4-B7-1 cells are completely rejected in syngeneic mice. Unlike EL4-B7-1 cells, we find that EL4-B7-2 cells are not rejected but progressively grow in the mice. A B7-1- and B7-2-EL4 double transfectant was generated by introducing B7-2 cDNA into the EL4-B7-1 tumor line that regressed in vivo. The EL4-B7-1+B7-2 double transfectant was not rejected when implanted into syngeneic mice but progressively grew to produce tumors. The double transfectant EL4 cells could costimulate T cell proliferation that could be blocked by anti-B7-1 antibodies, anti-B7-2 antibodies, or hCTLA4 immunoglobulin, showing that the B7-1 and B7-2 molecules expressed on the EL4 cells were functional. In vivo, treatment of mice implanted with double-transfected EL4 cells with anti-B7-2 monoclonal antibody resulted in tumor rejection. Furthermore, the EL4-B7-2 and EL4-B7-1+B7-2 cells, but not the wild-type EL4 cells, were rejected in interleukin 4 (IL-4) knockout mice. Our data suggests that B7-2 expressed on some T cell tumors inhibits development of antitumor immunity, and IL-4 appears to play a critical role in abrogation of the antitumor immune response.

  19. Adaptive response of apoptosis in EL-4 lymphoma cells induced by low dose radiation and its mechanism

    International Nuclear Information System (INIS)

    Liu Shuchun; Gong Pingsheng; Wang Zhicheng; Sun Liguang; Gong Shouliang

    2008-01-01

    EL-4 lymphoma cells were irradiated with the inductive doses (D1: 25-200 mGy, dose rate: 12.5mGy/min) and the challenging dose (D2:0.5-3.0 Gy, dose rate: 287 mGy/min), and the time interval between D1 and D2 was 6 h. The percentage of cell apoptosis and the expressive levels of cell apoptosis-associated gene pro- reins were measured with flow cytometry. The percentages of cell apoptosis in the D1 + D2 group with 25-100 mGy (D1) and 1.5 Gy (D2) or 75 mGy (D1) and 25-200 mGy (D2) were significantly lower than those in the D2 group. As compared with the D2 group, the positive percentage of cell Bcl-2 protein expression increased somewhat, and Bax decreased significantly, meanwhile the ratio of Bcl-2/Bax increased significantly and p53 decreased somewhat in D1 + D2 group with 25-100 mGy (D1) and 1.5 Gy (D2). The adaptive response of EL-4 lymphoma cell apoptosis could be induced by pre-irradiation with 25-100 mGy. Meantime, the expressive levels of cell apoptosis-associated gene Bcl-2, Bax and p53 proteins could change accordingly with cell apoptosis. These gene protein changes may play an important role in the mechanism of the adaptive response. (authors)

  20. Minimal-change nephropathy and malignant thymoma.

    Science.gov (United States)

    Varsano, S; Bruderman, I; Bernheim, J L; Rathaus, M; Griffel, B

    1980-05-01

    A 56-year-old man had fever, precordial pain, and a mediastinal mass. The mass disappeared two months later and the patient remained asymptomatic for 2 1/2 years. At that time a full-blown nephrotic syndrome developed, with minimal-change glomerulopathy. The chest x-ray film showed the reappearance of a giant mediastinal mass. On biopsy of the mass, malignant thymoma was diagnosed. Association between minimal-change disease and Hodgkin's disease is well known, while the association with malignant thymoma has not been previously reported. The relationship between malignant thymoma and minimal-change disease is discussed, and a possible pathogenic mechanism involving cell-mediated immunity is proposed.

  1. Expression of insulin-like growth factor-2 receptors on EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Farmer, John T; Weigent, Douglas A

    2007-01-01

    In the present study, we report the upregulation of functional IGF-2Rs in cells overexpressing growth hormone (GH). EL4 lymphoma cells stably transfected with an rGH cDNA overexpression vector (GHo) exhibited an increase in the binding of (125)I-IGF-2 with no change in the binding affinity compared to vector alone controls. An increase in the expression of the insulin-like growth factor-2 receptor (IGF-2R) in cells overexpressing GH was confirmed by Western blot analysis and IGF-2R promoter luciferase assays. EL4 cells produce insulin-like growth factor-2 (IGF-2) as detected by the reverse transcription-polymerase chain reaction (RT-PCR); however, no IGF-2 protein was detected by Western analysis. The increase in the expression of the IGF-2R resulted in greater levels of IGF-2 uptake in GHo cells compared to vector alone controls. The data suggest that one of the consequences of the overexpression of GH is an increase in the expression of the IGF-2R.

  2. Transcriptomic analysis of mouse EL4 T cells upon T cell activation and in response to protein synthesis inhibition via cycloheximide treatment

    OpenAIRE

    Lim, Pek Siew; Hardy, Kristine; Peng, Kaiman; Shannon, Frances M.

    2015-01-01

    T cell activation involves the recognition of a foreign antigen complexed to the major histocompatibility complex on the antigen presenting T cell to the T cell receptor. This leads to activation of signaling pathways, which ultimately leads to induction of key cytokine genes responsible for eradication of foreign antigens. We used the mouse EL4 T cell as a model system to study genes that are induced as a result of T cell activation using phorbol myristate acetate (PMA) and calcium ionomycin...

  3. Transcriptomic analysis of mouse EL4 T cells upon T cell activation and in response to protein synthesis inhibition via cycloheximide treatment

    Directory of Open Access Journals (Sweden)

    Pek Siew Lim

    2016-03-01

    Full Text Available T cell activation involves the recognition of a foreign antigen complexed to the major histocompatibility complex on the antigen presenting T cell to the T cell receptor. This leads to activation of signaling pathways, which ultimately leads to induction of key cytokine genes responsible for eradication of foreign antigens. We used the mouse EL4 T cell as a model system to study genes that are induced as a result of T cell activation using phorbol myristate acetate (PMA and calcium ionomycin (I as stimuli. We were also interested to examine the importance of new protein synthesis in regulating the expression of genes involved in T cell activation. Thus we have pre-treated mouse EL4 T cells with cycloheximide, a protein synthesis inhibitor, and left the cells unstimulated or stimulated with PMA/I for 4 h. We performed microarray expression profiling of these cells to correlate the gene expression with chromatin state of T cells upon T cell activation [1]. Here, we detail further information and analysis of the microarray data, which shows that T cell activation leads to differential expression of genes and inducible genes can be further classified as primary and secondary response genes based on their protein synthesis dependency. The data is available in the Gene Expression Omnibus under accession number GSE13278. Keywords: EL4 T cell, Microarray, T cell activation, Inducible genes

  4. EL4 cell-based colorimetric toxin neutralization activity assays for determination of neutralizing anti-ricin antibodies.

    Science.gov (United States)

    Lindsey, Changhong Y; Brown, J Edward; Torabazar, Nahid R; Smith, Leonard A

    2013-01-01

    A recombinant ricin toxin A-chain 1-33/44-198 vaccine (RVEc), developed at the United States Army Medical Research Institute of Infectious Diseases as a vaccine candidate, is under investigation in a phase 1 clinical study. To effectively evaluate the immunogenicity of this ricin vaccine and to eliminate the use of radioactive material, an EL4 cell-based colorimetric toxin neutralization activity (TNA) assay using a CellTiter 96 AQueous One Solution Cell Proliferation Assay Reagent has been developed, optimized, and applied in the vaccine efficacy studies. The TNA assay measures the protective neutralizing anti-ricin antibodies in animal sera by determining the cell viability after ricin exposure in the assay system and comparing it to a purified mouse polyclonal antiricin IgG standard curve. The standard curve of the anti-ricin TNA assay closely fits a four-parameter logistic regression model. The unknown test sample concentration was expressed as microg/mL, but not the 50% effective concentration (EC50), which was determined by most TNA assays. The neutralizing endpoint titers, not the 50% effective dilution (ED50), of human specimens were measured with the TNA assay in support of the clinical study of the RVEc vaccine. The optimal amount of ricin toxin, EL4 cells, and concentration of standards used in the assay system was established to minimize false-negative and false-positive results of serum specimens from the nonclinical and clinical studies of RVEc. The testing conditions were adjusted to optimize assay performance. The colorimetric TNA assay replaced a radioactive TNA assay previously used in the ricin vaccine studies.

  5. TNF induction of EL4 hyposensitivity to lysis by recombinant (soluble) and membrane-associated TNFs: TNF binding, internalization, and degradation.

    Science.gov (United States)

    Fishman, M; Costlow, M

    1994-04-01

    EL4 mouse thymoma cells sensitive to TNF-mediated lysis only in the presence of cycloheximide (S-EL4) or in the presence or absence of cycloheximide (N-EL4) were used in these experiments. Murine tumor cell line (S-EL4) sensitivity to TNF cytotoxicity is augmented when cycloheximide is added together with TNF or when cycloheximide is added 1 hr before or after TNF. No enhanced sensitivity is observed when target cells are incubated with cycloheximide 2-4 hr before or after the addition of TNF. In the absence of cycloheximide, S-EL4 cells preexposed to murine TNF are less susceptible to lysis by TNF and TNF receptor-conjugated TNF but are lysed by integral membrane TNF. TNF-induced hyposensitivity is partially reversed by actinomycin D or by culturing the preexposed cells for 4 hr prior to TNF lytic assay. TNF preincubation of N- and S-EL4 cells results in an immediate decrease in 125I-TNF binding due to TNF receptor occupancy. Recovery of TNF-R occupancy and TNF internalization were subsequently noted.

  6. Dose-rate effect of adaptive response of apoptosis and cell cycle progression induced by low-dose ionizing radiation in EL-4 lymphoma cells in vitro

    International Nuclear Information System (INIS)

    Liu Shuchun; Lu Zhe; Li Yanbo; Kang Shunai; Gong Shouliang; Zhao Wenju

    2008-01-01

    Objective: To observe the dose-rate effect of adaptive response of apoptosis and cell cycle progression induced by low-dose ionizing radiation in EL-4 lymphoma cells in vitro in order to reveal the possible mechanism of biological effect and adaptive response induced by low dose radiation. Methods: The experiment was divided into D2 (challenging dose), D1 (inductive dose) + D2 and sham-irradiation groups. EL-4 lymphoma cells were irradiated with D1 (75 mGy, 6.25-200.00 mGy·mm -1 ) and D2(1.5 Gy, 287 mGy·min -1 ), the time interval between D1 and D2 was 6 h. The percentage of apoptosis and each cell cycle phase were measured with flow cytometry. Results: When the dose rates of D1 were 6.25-50.00 mGy·min -1 , the percentages of apoptosis in the D1 + D2 group were significantly lower than those in the D2 group (P 0 /G 1 phase cells decreased significantly (P -1 , D2 is 1.5 Gy (287 mGy·min -1 ), and the time interval between D1 and D2 is 6 h, the adaptive response of apoptosis and cell cycle progression in EL-4 lymphoma cells in vitro could be induced. (authors)

  7. Heterogenous populations of cytotoxic cells in the peritoneal cavity of BALB/c mice immunized with allogeneic EL4 leukemia cells

    International Nuclear Information System (INIS)

    Zighelboim, J.; Bonavida, B.; Fahey, J.L.

    1974-01-01

    Adherent cells, presumably macrophages, obtained from the peritoneal cavity shortly after rejection of the allogeneic leukemia EL4, produced effective cell-mediated cytotoxicity (CMC) in vitro. These cytotoxic cells were sensitive to anti-macrophage serum and resistant to anti-thymocyte serum and 10,000 roentgen irradiation. In contrast, a second population of specifically cytotoxic cells were nonadherent, sensitive to x-rays and anti-thymocyte serum, but not to anti-macrophage serum. The two cell populations had a cooperative cytotoxic effect in vitro against allogeneic tumor cells

  8. Radioresponse of thymomas verified with histologic reponse

    Energy Technology Data Exchange (ETDEWEB)

    Ohara, Kiyoshi; Tatsuzaki, Hideo; Okumura, Toshiyuki; Itai, Yuji [Dept. of Radiology, Tsukuba Univ., Tsukuba City (Japan)]|[Inst. of Clinical Medicine, Tsukuba Univ., Tsukuba City (Japan); Fuji, Hiroshi [Dept. of Radiology, Tsukuba Univ., Tsukuba City (Japan); Sugahara, Shinji [Dept. of Radiology, Hitachi General Hospital, Hitachi City (Japan); Akaogi, Eiichi; Onizuka, Masataka; Ishikawa, Shigemi; Mitsui, Kiyofumi [Dept. of Surgery, Tsukuba Univ., Tsukuba City (Japan)]|[Inst. of Clinical Medicine, Tsukuba Univ., Tsukuba City (Japan)

    1998-12-31

    Patterns of radiologic response of 10 thymomas treated by preoperative radiotherapy (RT) (18-20 Gy/2 weeks) were determined in conjunction with histologic response. Changes in tumor volume were evaluated with CT scans obtained 5 to 36 days before and 14 to 24 days after the initiation of RT and before surgery. The extent of tumor volume reduction (TR) varied widely (40-78%), while the mean daily volume decrement expressed as a percentage of the pre-RT tumor volume correlated significantly with the pre-RT tumor volume. Histologically, the tumors, all of which were resected 17 to 33 days after RT initiation, generally consisted of predominant fibrous tissues, rare necrotic foci, and few epithelial cells. The TR did not correlate with pre-RT tumor volume, observation period, histologic subtype, or quantity of remaining epithelial cells. The TR of thymomas does not predict RT impact on tumor cells but does reflect the quantity of inherent tumor stroma. (orig.)

  9. Radioresponse of thymomas verified with histologic reponse

    International Nuclear Information System (INIS)

    Ohara, Kiyoshi; Tatsuzaki, Hideo; Okumura, Toshiyuki; Itai, Yuji; Fuji, Hiroshi; Sugahara, Shinji; Akaogi, Eiichi; Onizuka, Masataka; Ishikawa, Shigemi; Mitsui, Kiyofumi

    1998-01-01

    Patterns of radiologic response of 10 thymomas treated by preoperative radiotherapy (RT) (18-20 Gy/2 weeks) were determined in conjunction with histologic response. Changes in tumor volume were evaluated with CT scans obtained 5 to 36 days before and 14 to 24 days after the initiation of RT and before surgery. The extent of tumor volume reduction (TR) varied widely (40-78%), while the mean daily volume decrement expressed as a percentage of the pre-RT tumor volume correlated significantly with the pre-RT tumor volume. Histologically, the tumors, all of which were resected 17 to 33 days after RT initiation, generally consisted of predominant fibrous tissues, rare necrotic foci, and few epithelial cells. The TR did not correlate with pre-RT tumor volume, observation period, histologic subtype, or quantity of remaining epithelial cells. The TR of thymomas does not predict RT impact on tumor cells but does reflect the quantity of inherent tumor stroma. (orig.)

  10. Multiple Thymoma with Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Dong Hyun Seo

    2017-02-01

    Full Text Available The actual incidence of multiple thymoma is unknown and rarely reported because it remains controversial whether the cases represent a disease of multicentric origin or a disease resulting from intrathymic metastasis. In this case, a patient underwent total thymectomy for multiple thymoma with myasthenia gravis via bilateral video-assisted thoracic surgery. A well-encapsulated multinodular cystic mass, measuring 57 mm×50 mm×22 mm in the right lobe of the thymus, and a well-encapsulated mass, measuring 32 mm×15 mm×14 mm in the left lobe, were found. Both tumors were type B2 thymoma. Few cases of multiple thymoma with myasthenia gravis have ever been reported in the literature. We report a case of synchronous multiple thymoma associated with myasthenia gravis.

  11. Transcriptomic analysis of mouse EL4 T cells upon T cell activation and in response to protein synthesis inhibition via cycloheximide treatment.

    Science.gov (United States)

    Lim, Pek Siew; Hardy, Kristine; Peng, Kaiman; Shannon, Frances M

    2016-03-01

    T cell activation involves the recognition of a foreign antigen complexed to the major histocompatibility complex on the antigen presenting T cell to the T cell receptor. This leads to activation of signaling pathways, which ultimately leads to induction of key cytokine genes responsible for eradication of foreign antigens. We used the mouse EL4 T cell as a model system to study genes that are induced as a result of T cell activation using phorbol myristate acetate (PMA) and calcium ionomycin (I) as stimuli. We were also interested to examine the importance of new protein synthesis in regulating the expression of genes involved in T cell activation. Thus we have pre-treated mouse EL4 T cells with cycloheximide, a protein synthesis inhibitor, and left the cells unstimulated or stimulated with PMA/I for 4 h. We performed microarray expression profiling of these cells to correlate the gene expression with chromatin state of T cells upon T cell activation [1]. Here, we detail further information and analysis of the microarray data, which shows that T cell activation leads to differential expression of genes and inducible genes can be further classified as primary and secondary response genes based on their protein synthesis dependency. The data is available in the Gene Expression Omnibus under accession number GSE13278.

  12. Membrane Raft Organization Is More Sensitive to Disruption by (n-3) PUFA Than Nonraft Organization in EL4 and B Cells123

    OpenAIRE

    Rockett, Benjamin Drew; Franklin, Andrew; Harris, Mitchel; Teague, Heather; Rockett, Alexis; Shaikh, Saame Raza

    2011-01-01

    Model membrane and cellular detergent extraction studies show (n-3) PUFA predominately incorporate into nonrafts; thus, we hypothesized (n-3) PUFA could disrupt nonraft organization. The first objective of this study was to determine whether (n-3) PUFA disrupted nonrafts of EL4 cells, an extension of our previous work in which we discovered an (n-3) PUFA diminished raft clustering. EPA or DHA treatment of EL4 cells increased plasma membrane accumulation of the nonraft probe 1,1′-dilinoleyl-3,...

  13. Effect of X-irradiation on DNA binding activity of NF-kB in EL-4 cells

    International Nuclear Information System (INIS)

    He Shujie; Jin Shunzi; Liu Shuzheng

    2002-01-01

    Changes in time course of the DNA-binding activity of NF-κB as well as the subcellular localization of p65 subunit and expression of IκBα in EL-4 cells after irradiation with 2 Gy and 0.075 Gy X-rays were examined using electrophoresis mobility shift assay (EMSA) and immunohistochemistry (IHC), respectively. Results showed that the increases in DNA-binding activity of NF-κB p50/p50 and p50/p65 were induced by both 0.075 Gy and 2 Gy X-rays. However, the amplitude of the increase in activity of the two dimers was different after irradiation with the two doses of X-rays. After irradiation with 0.075 Gy, the increase in p50/p65 activity was higher than that of p50/p50 activity. After irradiation with 2 Gy, the situation was reversed. Irradiation with both 2 Gy and 0.075 Gy induced an increase in the rate of p65 nuclear translocation and the degradation of IκBα before the increase of its expression, but the degree of these changes after different dose irradiation was different. These results suggest that the transcriptional regulation of NF-κB changes with irradiation dose, resulted in the difference in responses of cells

  14. Membrane raft organization is more sensitive to disruption by (n-3) PUFA than nonraft organization in EL4 and B cells.

    Science.gov (United States)

    Rockett, Benjamin Drew; Franklin, Andrew; Harris, Mitchel; Teague, Heather; Rockett, Alexis; Shaikh, Saame Raza

    2011-06-01

    Model membrane and cellular detergent extraction studies show (n-3) PUFA predominately incorporate into nonrafts; thus, we hypothesized (n-3) PUFA could disrupt nonraft organization. The first objective of this study was to determine whether (n-3) PUFA disrupted nonrafts of EL4 cells, an extension of our previous work in which we discovered an (n-3) PUFA diminished raft clustering. EPA or DHA treatment of EL4 cells increased plasma membrane accumulation of the nonraft probe 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate by ~50-70% relative to a BSA control. Förster resonance energy transfer imaging showed EPA and DHA also disrupted EL4 nanometer scale nonraft organization by increasing the distance between nonraft molecules by ~25% compared with BSA. However, changes in nonrafts were due to an increase in cell size; under conditions where EPA or DHA did not increase cell size, nonraft organization was unaffected. We next translated findings on EL4 cells by testing if (n-3) PUFA administered to mice disrupted nonrafts and rafts. Imaging of B cells isolated from mice fed low- or high-fat (HF) (n-3) PUFA diets showed no change in nonraft organization compared with a control diet (CD). However, confocal microscopy revealed the HF (n-3) PUFA diet disrupted lipid raft clustering and size by ~40% relative to CD. Taken together, our data from 2 different model systems suggest (n-3) PUFA have limited effects on nonrafts. The ex vivo data, which confirm previous studies with EL4 cells, provide evidence that (n-3) PUFA consumed through the diet disrupt B cell lipid raft clustering.

  15. Membrane Raft Organization Is More Sensitive to Disruption by (n-3) PUFA Than Nonraft Organization in EL4 and B Cells123

    Science.gov (United States)

    Rockett, Benjamin Drew; Franklin, Andrew; Harris, Mitchel; Teague, Heather; Rockett, Alexis; Shaikh, Saame Raza

    2011-01-01

    Model membrane and cellular detergent extraction studies show (n-3) PUFA predominately incorporate into nonrafts; thus, we hypothesized (n-3) PUFA could disrupt nonraft organization. The first objective of this study was to determine whether (n-3) PUFA disrupted nonrafts of EL4 cells, an extension of our previous work in which we discovered an (n-3) PUFA diminished raft clustering. EPA or DHA treatment of EL4 cells increased plasma membrane accumulation of the nonraft probe 1,1′-dilinoleyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate by ~50–70% relative to a BSA control. Förster resonance energy transfer imaging showed EPA and DHA also disrupted EL4 nanometer scale nonraft organization by increasing the distance between nonraft molecules by ~25% compared with BSA. However, changes in nonrafts were due to an increase in cell size; under conditions where EPA or DHA did not increase cell size, nonraft organization was unaffected. We next translated findings on EL4 cells by testing if (n-3) PUFA administered to mice disrupted nonrafts and rafts. Imaging of B cells isolated from mice fed low- or high-fat (HF) (n-3) PUFA diets showed no change in nonraft organization compared with a control diet (CD). However, confocal microscopy revealed the HF (n-3) PUFA diet disrupted lipid raft clustering and size by ~40% relative to CD. Taken together, our data from 2 different model systems suggest (n-3) PUFA have limited effects on nonrafts. The ex vivo data, which confirm previous studies with EL4 cells, provide evidence that (n-3) PUFA consumed through the diet disrupt B cell lipid raft clustering. PMID:21525263

  16. The mouse tumor cell lines EL4 and RMA display mosaic expression of NK-related and certain other surface molecules and appear to have a common origin.

    Science.gov (United States)

    Gays, F; Unnikrishnan, M; Shrestha, S; Fraser, K P; Brown, A R; Tristram, C M; Chrzanowska-Lightowlers, Z M; Brooks, C G

    2000-05-15

    As a potential means for facilitating studies of NK cell-related molecules, we examined the expression of these molecules on a range of mouse tumor cell lines. Of the lines we initially examined, only EL4 and RMA expressed such molecules, both lines expressing several members of the Ly49 and NKRP1 families. Unexpectedly, several of the NK-related molecules, together with certain other molecules including CD2, CD3, CD4, CD32, and CD44, were often expressed in a mosaic manner, even on freshly derived clones, indicating frequent switching in expression. In each case examined, switching was controlled at the mRNA level, with expression of CD3zeta determining expression of the entire CD3-TCR complex. Each of the variable molecules was expressed independently, with the exception that CD3 was restricted to cells that also expressed CD2. Treatment with drugs that affect DNA methylation and histone acetylation could augment the expression of at least some of the variable molecules. The striking phenotypic similarity between EL4 and RMA led us to examine the state of their TCRbeta genes. Both lines had identical rearrangements on both chromosomes, indicating that RMA is in fact a subline of EL4. Overall, these findings suggest that EL4 is an NK-T cell tumor that may have retained a genetic mechanism that permits the variable expression of a restricted group of molecules involved in recognition and signaling.

  17. THYMOMA (REVIEW OF THE LITERATURE

    Directory of Open Access Journals (Sweden)

    O. A. Alexandrov

    2017-01-01

    Full Text Available Objective. We aimed to systematically review the literature dealing with the epidemiology, classification, clinical course, diagnosis and treatment of thymoma. Material and methods. We reviewed retrospective and prospective randomized trials using Medline and Elibrary databases. Results. The classification system, prognostic factors, paraneoplastic syndromes and their incidence in patients with thyoma were described. The diagnostic value of computed tomography, magnetic resonance imaging and positron emission tomography was evaluated and the methods of morphologic verification were described. The main attention was paid to multimodality treatment of thymoma, including surgery and intraoperative radiotherapy. Conclusion. Thymoma is a rare tumor. The accumulation of long-term follow-up results prompted the changes in clinical management of thymoma. Predisposition to late recurrence even after radical surgery determined multimodality treatment strategies.

  18. The effect of mesenchymal stem cells on the p53 methylation in irradiation-induced thymoma in C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Hai B Zheng

    2015-01-01

    Conclusion: MSCs decrease the incidence of irradiation-induced thymoma, which may be mediated by improving thymus microenvironment and changing the methylation of p53 promoter, and subsequently maintaining genome′s stability.

  19. Growth of the parvovirus minute virus of mice MVMp3 in EL4 lymphocytes is restricted after cell entry and before viral DNA amplification: cell-specific differences in virus uncoating in vitro.

    OpenAIRE

    Previsani, N; Fontana, S; Hirt, B; Beard, P

    1997-01-01

    Two murine parvoviruses with genomic sequences differing only in 33 nucleotides (8 amino acids) in the region coding for the capsid proteins show different host cell specificities: MVMi grows in EL4 T lymphocytes and MVMp3 grows in A9 fibroblasts. In this study we compared the courses of infections with these two viruses in EL4 cells in order to investigate at which step(s) the infection process of MVMp3 is interrupted. The two viruses bound equally well to EL4 cells, and similar amounts of M...

  20. Nicotine promotes cell proliferation and induces resistance to cisplatin by α7 nicotinic acetylcholine receptor‑mediated activation in Raw264.7 and El4 cells.

    Science.gov (United States)

    Wang, Yan Yan; Liu, Yao; Ni, Xiao Yan; Bai, Zhen Huan; Chen, Qiong Yun; Zhang, Ye; Gao, Feng Guang

    2014-03-01

    Although nicotine is a risk factor for carcinogenesis and atherosclerosis, epidemiological data indicate that nicotine has therapeutic benefits in treating Alzheimer's disease. Our previous studies also showed that nicotine-treated dendritic cells have potential antitumor effects. Hence, the precise effects of nicotine on the biological characterizations of cells are controversial. The aim of the present study was to assess the roles of α7 nicotinic acetylcholine receptors (nAChRs), Erk1/2-p38-JNK and PI3K-Akt pathway in nicotine-mediated proliferation and anti-apoptosis effects. The results firstly showed that nicotine treatment clearly augmented cell viability and upregulated PCNA expression in both Raw264.7 and El4 cells. Meanwhile, nicotine afforded protection against cisplatin-induced toxicity through inhibiting caspase-3 activation and upregulating anti-apoptotic protein expression. Further exploration demonstrated that nicotine efficiently abolished cisplatin-promoted mitochondria translocation of Bax and the release of cytochrome c. The pretreatment of α-bungarotoxin and tubocurarine chloride significantly attenuated nicotine-augmented cell viability, abolished caspase-3 activation and α7 nAChR upregulation. Both Erk-JNK-p38 and PI3K-Akt signaling pathways could be activated by nicotine treatment in Raw264.7 and El4 cells. Notably, when Erk-JNK and PI3K-Akt activities were inhibited, nicotine-augmented cell proliferation and anti-apoptotic effects were abolished accordingly. The results presented here indicate that nicotine could achieve α7 nAChR-mediated proliferation and anti-apoptotic effects by activating Erk-JNK and PI3K-Akt pathways respectively, providing potential therapeutic molecules to deal with smoking-associated human diseases.

  1. Synergistic effect of EMF-BEMER-type pulsed weak electromagnetic field and HPMA-bound doxorubicin on mouse EL4 T-cell lymphoma

    Czech Academy of Sciences Publication Activity Database

    Říhová, Blanka; Etrych, Tomáš; Šírová, Milada; Tomala, Jakub; Ulbrich, Karel; Kovář, Marek

    2011-01-01

    Roč. 19, č. 10 (2011), s. 890-899 ISSN 1061-186X R&D Projects: GA AV ČR IAA400200702 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z40500505 Keywords : EL4 T-cell lymphoma * athymic mice * DOX(HYD)-HPMA Subject RIV: EC - Immunology Impact factor: 2.696, year: 2011

  2. Expression of insulin-like growth factor-1 and insulin-like growth factor-1 receptors in EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Weigent, Douglas A; Arnold, Robyn E

    2005-03-01

    Almost all of the previous studies with growth hormone (GH) have been done with exogenously supplied GH and, therefore, involve actions of the hormone through its receptor. However, the actions of endogenous or lymphocyte GH are still unclear. In a previous study, we showed that overexpression of GH (GHo) in a lymphoid cell line resulted in protection of the cells to apoptosis mediated by nitric oxide (NO). In the present study, we show that the protection from apoptosis could be transferred to control cells with culture fluids obtained from GHo cells and blocked by antibodies to the insulin-like growth factor-1 (IGF-1) or antibodies to the IGF-1-receptor (IGF-1R). Northern and Western blot analysis detected significantly higher levels of IGF-1 in cells overexpressing GH. An increase in the expression of the IGF-1R in GHo cells was also detected by Western blot analysis, (125)I-IGF-1 binding and analysis of IGF-1R promoter luciferase constructs. Transfection of GHo cells with a dominant negative IGF-1R mutant construct blocked the generation of NO and activation of Akt seen in GHo cells compared to vector alone control EL4 cells. The results suggest that one of the consequences of the overexpression of GH, in cells lacking the GH receptor, is an increase in the expression of IGF-1 and the IGF-1R which mediate the protection of EL4 lymphoma cells from apoptosis.

  3. Aero thermal test results obtained on the n. C 5 EL 4 Cluster in the atmospheric pressure cell

    International Nuclear Information System (INIS)

    Gasc, B.

    1964-01-01

    In the framework of thermal studies on the EL-4 cluster, the full-scale tests at atmospheric pressure are designed to permit measurement of local values of the wall temperature, of the velocity and of the temperature in the fluid. The experimental results, obtained with the help of an original measuring apparatus, make it possible to follow the changes in these values along the cluster and to predict in much detail the in-pile thermal behaviour. In particular it is shown that changes in the wall temperature along the cluster are greatly influenced by disruption of the flow caused by grids and supports. (author) [fr

  4. Effects of active and inactive phospholipase D2 on signal transduction, adhesion, migration, invasion, and metastasis in EL4 lymphoma cells.

    Science.gov (United States)

    Knoepp, Stewart M; Chahal, Manpreet S; Xie, Yuhuan; Zhang, Zhihong; Brauner, Daniel J; Hallman, Mark A; Robinson, Stephanie A; Han, Shujie; Imai, Masaki; Tomlinson, Stephen; Meier, Kathryn E

    2008-09-01

    The phosphatidylcholine-using phospholipase D (PLD) isoform PLD2 is widely expressed in mammalian cells and is activated in response to a variety of promitogenic agonists. In this study, active and inactive hemagglutinin-tagged human PLD2 (HA-PLD2) constructs were stably expressed in an EL4 cell line lacking detectable endogenous PLD1 or PLD2. The overall goal of the study was to examine the roles of PLD2 in cellular signal transduction and cell phenotype. HA-PLD2 confers PLD activity that is activated by phorbol ester, ionomycin, and okadaic acid. Proliferation and Erk activation are unchanged in cells transfected with active PLD2; proliferation rate is decreased in cells expressing inactive PLD2. Basal tyrosine phosphorylation of focal adhesion kinase (FAK) is increased in cells expressing active PLD2, as is phosphorylation of Akt; inactive PLD2 has no effect. Expression of active PLD2 is associated with increased spreading and elongation of cells on tissue culture plastic, whereas inactive PLD2 inhibits cell spreading. Inactive PLD2 also inhibits cell adhesion, migration, and serum-induced invasion. Cells expressing active PLD2 form metastases in syngeneic mice, as do the parental cells; cells expressing inactive PLD2 form fewer metastases than parental cells. In summary, active PLD2 enhances FAK phosphorylation, Akt activation, and cell invasion in EL4 lymphoma cells, whereas inactive PLD2 exerts inhibitory effects on adhesion, migration, invasion, and tumor formation. Overall, expression of active PLD2 enhances processes favorable to lymphoma cell metastasis, whereas expression of inactive PLD2 inhibits metastasis.

  5. Synergistic effect of EMF-BEMER-type pulsed weak electromagnetic field and HPMA-bound doxorubicin on mouse EL4 T-cell lymphoma.

    Science.gov (United States)

    Říhová, Blanka; Etrych, Tomáš; Šírová, Milada; Tomala, Jakub; Ulbrich, Karel; Kovář, Marek

    2011-12-01

    We have investigated the effects of low-frequency pulsed electromagnetic field (LF-EMF) produced by BEMER device on experimental mouse T-cell lymphoma EL4 growing on conventional and/or athymic (nude) mice. Exposure to EMF-BEMER slowed down the growth of tumor mass and prolonged the survival of experimental animals. The effect was more pronounced in immuno-compromised nude mice compared to conventional ones. Acceleration of tumor growth was never observed. No measurable levels of Hsp 70 or increased levels of specific anti-EL4 antibodies were detected in the serum taken from experimental mice before and at different intervals during the experiment, i.e. before solid tumor appeared, at the time of its aggressive growth, and at the terminal stage of the disease. A significant synergizing antitumor effect was seen when EL4 tumor-bearing mice were simultaneously exposed to EMF-BEMER and treated with suboptimal dose of synthetic HPMA copolymer-based doxorubicin, DOX(HYD)-HPMA. Such a combination may be especially useful for heavily treated patients suffering from advanced tumor and requiring additional aggressive chemotherapy which, however, at that time could represent almost life-threatening way of medication.

  6. Invasive thymoma; Radiologic evaluation by computed tomography

    International Nuclear Information System (INIS)

    Yoon, Choon Sik; Choe, Kyu Ok

    1985-01-01

    In 6 cases of invasive thymoma proved histologically from 1981 to 1984 in Yonsei University Medical Center, the CT findings and pattern were analysed. The results were as follows; 1. Of 6 cases, 4 were males and 2 were females. All cases were between 40-64 years and the average was 51 year old. 2. Of 6 cases, 2 female patients were associated with myasthenia gravis. 3. By the histological examination, 2 were confirmed as mixed cell type, 2 spindle cell type, 1 lymphocytic type and 1 epithelial cell type. 4. CT findings of invasive thymoma were 1) A discrete but lobulated and irregular marginated soft tissue mass in the superoanterior mediastinum replacing the normal mediastinal fat tissue. 2) Usually irregular low density areas within the mass suggesting central necrosis or calcification in 1 of 6 cases was noted. 3) Local invasiveness of the mass shown as obliteration of the normal fat plans surrounding great vessels, irregular thickening or nodular shadows of the pleura, diagphragm and pericardium and irregular and ragged tumor-lung interfaces if the tumor invade to the structures. 4) Frequent extension of tumor to middle and post. mediastinum along pericardium or mediastinal pleura with resultant extrinsic indentation and/or invasion of the hilar region. 5). Extensive tumor infiltration to middle and post. mediastinum in 1 case, indistinguishable from lymphoma. 6) Low attenuation numbered area of brain in another 1 case, but not confirmed histologically

  7. Invasive thymoma; Radiologic evaluation by computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Choon Sik; Choe, Kyu Ok [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1985-04-15

    In 6 cases of invasive thymoma proved histologically from 1981 to 1984 in Yonsei University Medical Center, the CT findings and pattern were analysed. The results were as follows; 1. Of 6 cases, 4 were males and 2 were females. All cases were between 40-64 years and the average was 51 year old. 2. Of 6 cases, 2 female patients were associated with myasthenia gravis. 3. By the histological examination, 2 were confirmed as mixed cell type, 2 spindle cell type, 1 lymphocytic type and 1 epithelial cell type. 4. CT findings of invasive thymoma were 1) A discrete but lobulated and irregular marginated soft tissue mass in the superoanterior mediastinum replacing the normal mediastinal fat tissue. 2) Usually irregular low density areas within the mass suggesting central necrosis or calcification in 1 of 6 cases was noted. 3) Local invasiveness of the mass shown as obliteration of the normal fat plans surrounding great vessels, irregular thickening or nodular shadows of the pleura, diagphragm and pericardium and irregular and ragged tumor-lung interfaces if the tumor invade to the structures. 4) Frequent extension of tumor to middle and post. mediastinum along pericardium or mediastinal pleura with resultant extrinsic indentation and/or invasion of the hilar region. 5). Extensive tumor infiltration to middle and post. mediastinum in 1 case, indistinguishable from lymphoma. 6) Low attenuation numbered area of brain in another 1 case, but not confirmed histologically.

  8. Calcium plays a key role in paraoxon-induced apoptosis in EL4 cells by regulating both endoplasmic reticulum- and mitochondria-associated pathways.

    Science.gov (United States)

    Li, Lan; Du, Yi; Ju, Furong; Ma, Shunxiang; Zhang, Shengxiang

    2016-01-01

    Paraoxon (POX) is one of the most toxic organophosphorus pesticides, but its toxic mechanisms associated with apoptosis remain unclear. The aim of this study was to investigate calcium-associated mechanisms in POX-induced apoptosis in EL4 cells. EL4 cells were exposed to POX for 0-16 h. EGTA was used to chelate Ca(2+ ) in extracellular medium, and heparin and procaine were used to inhibit Ca(2+ )efflux from the endoplasmic reticulum (ER). Z-ATAD-FMK was used to inhibit caspase-12 activity. The apoptotic rate assay, western blotting and immunocytochemistry (ICC) were used to reveal the mechanisms of POX-induced apoptosis. POX significantly increased the expression and activation of caspase-12 and caspase-3, enhanced expression of calpain 1 and calpain 2, and induced the release of cyt c, but did not change the expression of Grp 78. Inhibiting caspase-12 activity alleviated POX-induced upregulation of calpain 1 and caspase-3, promoted POX-induced upregulation of calpain 2, and reduced POX-induced cyt c release, suggesting that there was a cross-talk between the ER-associated pathway and mitochondria-associated apoptotic signals. Attenuating intracellular calcium concentration with EGTA, heparin or procaine decreased POX-induced upregulation of calpain 1, calpain 2, caspase-12 and caspase-3, and reduced POX-induced cyt c release. After pretreatment with EGTA or procaine, POX significantly promoted expression of Grp 78. Calcium played a key role in POX-induced apoptosis in EL4 cells by regulating both ER- and mitochondria-associated pathways. The cross-talk of ER- and mitochondria-associated pathways was accomplished through calcium signal.

  9. CD44 standard and CD44v10 isoform expression on leukemia cells distinctly influences niche embedding of hematopoietic stem cells

    OpenAIRE

    Erb, Ulrike; Megaptche, Amelie Pajip; Gu, Xiaoyu; Büchler, Markus W; Zöller, Margot

    2014-01-01

    Background A blockade of CD44 is considered a therapeutic option for the elimination of leukemia initiating cells. However, anti-panCD44 can interfere with hematopoiesis. Therefore we explored, whether a CD44 variant isoform (CD44v)-specific antibody can inhibit leukemia growth without attacking hematopoiesis. As a model we used CD44v10 transfected EL4 thymoma cells (EL4-v10). Methods The therapeutic efficacy of anti-panCD44 and anti-CD44v10 was evaluated after intravenous application of EL4/...

  10. Multiple thymoma in a patient with myasthenia gravis: case report

    International Nuclear Information System (INIS)

    Ko, Eun Sook; Jeon, Kyung Nyeo; Bae, Kyung Soo; Yoo, Jin Jong; Kang, Duk Sik

    2004-01-01

    A thymoma often occurs in patients with myasthenia gravis, but the development of multiple thymoma is very rare. The authors report the radiologic and pathologic findings of multiple invasive thymoma in a 59-year-old male with myasthenia gravis

  11. Multiple thymoma in a patient with myasthenia gravis: case report

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Eun Sook; Jeon, Kyung Nyeo; Bae, Kyung Soo; Yoo, Jin Jong [College of Medicine, Gyeongsang National Univ., Jinju (Korea, Republic of); Kang, Duk Sik [College of Medicine, Kyungpook National Univ., Daegu (Korea, Republic of)

    2004-02-01

    A thymoma often occurs in patients with myasthenia gravis, but the development of multiple thymoma is very rare. The authors report the radiologic and pathologic findings of multiple invasive thymoma in a 59-year-old male with myasthenia gravis.

  12. Proteomic characterization of EL4 lymphoma-derived tumors upon chemotherapy treatment reveals potential roles for lysosomes and caspase-6 during tumor cell death in vivo.

    Science.gov (United States)

    Kramer, David A; Eldeeb, Mohamed A; Wuest, Melinda; Mercer, John; Fahlman, Richard P

    2017-06-01

    The murine mouse lymphoblastic lymphoma cell line (EL4) tumor model is an established in vivo apoptosis model for the investigation of novel cancer imaging agents and immunological treatments due to the rapid and significant response of the EL4 tumors to cyclophosphamide and etoposide combination chemotherapy. Despite the utility of this model system in cancer research, little is known regarding the molecular details of in vivo tumor cell death. Here, we report the first in-depth quantitative proteomic analysis of the changes that occur in these tumors upon cyclophosphamide and etoposide treatment in vivo. Using a label-free quantitative proteomic approach a total of 5838 proteins were identified in the treated and untreated tumors, of which 875 were determined to change in abundance with statistical significance. Initial analysis of the data reveals changes that may have been predicted, such as the downregulation of ribosomes, but demonstrates the robustness of the dataset. Analysis of the dataset also reveals the unexpected downregulation of caspase-3 and an upregulation of caspase-6 in addition to a global upregulation of lysosomal proteins in the bulk of the tumor. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Thymoma - prognostic factors and treatment results

    International Nuclear Information System (INIS)

    Gripp, S.; Hilgers, K.; Schmitt, G.

    1997-01-01

    Purpose/Objective: To assess the prognostic factors and treatment results of thymoma with emphasis on surgery and radiotherapy. Materials and Methods: Thymoma patients treated at Duesseldorf University Hospital from 1954 to 1991 were studied in this retrospective analysis. Depending on stage and residual disease, treatment was surgery (sternotomy or thoracotomy) with and without radiotherapy and chemotherapy (Holoxan, Endoxan, Vinblastin, Adriamycin, Bleomycin, CDDP, Vepesid). 70 patients (38f, 32m) were enrolled in this study. The mean age was 46,5 years. At presentation the median Karnofsky's index was 90%. In 19% thymoma was accidentally diagnosed, 81% presented symptoms at diagnosis. Masaoka's staging system was used (I: intact capsule; II: invasion of the capsule; III: invasion of neighboring organs; IV: dissemination). Stage at presentation was I:21%; II: 26%; III: 43%; IV: 10%. All histologic slices were peer reviewed. Histologic classification according to Lewis (predominantly lymphocytic: 36%; predominantly epithelial: 23%; mixed type: 33%, spindle cell thymoma: 9%) was applied. All available paraffin embedded specimens (36) were studied with DNA cytometric analysis after Feulgen staining. Occasionally thymoma was accompanied by Myasthenia gravis (23%) or other paraneoplastic syndromes (19%). Statistical analysis was performed using the Kaplan-Meier method and logrank-tests. Multivariate analysis was also performed. Results: From 70 patients treated surgically, 68% were radically resected (R0), 26% incompletely resected (R1,2) and 6% had biopsy only. The median cause specific survival (CSS) was 132 months. All patients with localized disease (stage I and II) were completely resected and received no further therapy, whereas only 50% (15 pat) in stage III and 0% in stage IV were amenable to radical resection. 36% (25 pat) received an additional therapy (CMT): 31% (22 pat) postoperative irradiation and 4% (3 pat) combined radio-chemotherapy. The radiation

  14. Growth of the parvovirus minute virus of mice MVMp3 in EL4 lymphocytes is restricted after cell entry and before viral DNA amplification: cell-specific differences in virus uncoating in vitro.

    Science.gov (United States)

    Previsani, N; Fontana, S; Hirt, B; Beard, P

    1997-10-01

    Two murine parvoviruses with genomic sequences differing only in 33 nucleotides (8 amino acids) in the region coding for the capsid proteins show different host cell specificities: MVMi grows in EL4 T lymphocytes and MVMp3 grows in A9 fibroblasts. In this study we compared the courses of infections with these two viruses in EL4 cells in order to investigate at which step(s) the infection process of MVMp3 is interrupted. The two viruses bound equally well to EL4 cells, and similar amounts of MVMi and MVMp3 input virion DNA appeared in the nuclear fractions of EL4 cells 1 h after infection. However, double-stranded replicative-form (RF) DNA of the two viruses appeared at different times, at 10 h postinfection with MVMi and at 24 h postinfection with MVMp3. The amount of MVMp3 RF DNA detected at 24 h was very small because it was produced only in a tiny subset of the population of EL4 cells that proved to be permissive for MVMp3. Replication of double-stranded viral DNA in EL4 cells was measured after transfection of purified RF DNA, cloned viral DNA, and cloned viral DNA with a mutation preventing synthesis of the capsid proteins. In each of these cases, DNA replication was comparable for MVMi and MVMp3. Production of virus particles also appeared to be similar after transfection of the two types of RF DNA into EL4 cells. Conversion of incoming 32P-labeled single-stranded MVM DNA to 32P-labeled double-stranded RF DNA was detected only after RF DNA amplification, indicating that few molecules serve as templates for viral DNA amplification. We showed that extracts of EL4 cells contain a factor which can destabilize MVMi virions but not MVMp3 by testing the sensitivity of viral DNA to DNase and by CsCl gradient analyses of viral particles. We therefore conclude that the MVMp3 life cycle is arrested after the transport of virions to the nucleus and prior to the replication of RF DNA, most likely at the stage of viral decapsidation.

  15. Extracts of Crinum latifolium inhibit the cell viability of mouse lymphoma cell line EL4 and induce activation of anti-tumour activity of macrophages in vitro.

    Science.gov (United States)

    Nguyen, Hoang-Yen T; Vo, Bach-Hue T; Nguyen, Lac-Thuy H; Bernad, Jose; Alaeddine, Mohamad; Coste, Agnes; Reybier, Karine; Pipy, Bernard; Nepveu, Françoise

    2013-08-26

    Crinum latifolium L. (CL) leaf extracts have been traditionally used in Vietnam and are now used all over the world for the treatment of prostate cancer. However, the precise cellular mechanisms of the action of CL extracts remain unclear. To examine the effects of CL samples on the anti-tumour activity of peritoneal murine macrophages. The properties of three extracts (aqueous, flavonoid, alkaloid), one fraction (alkaloid), and one pure compound (6-hydroxycrinamidine) obtained from CL, were studied (i) for redox capacities (DPPH and bleaching beta-carotene assays), (ii) on murine peritoneal macrophages (MTT assay) and on lymphoma EL4-luc2 cells (luciferine assay) for cytotoxicity, (iii) on macrophage polarization (production of ROS and gene expression by PCR), and (iv) on the tumoricidal functions of murine peritoneal macrophages (lymphoma cytotoxicity by co-culture with syngeneic macrophages). The total flavonoid extract with a high antioxidant activity (IC50=107.36 mg/L, DPPH assay) showed an inhibitory action on cancer cells. Alkaloid extracts inhibited the proliferation of lymphoma cells either by directly acting on tumour cells or by activating of the tumoricidal functions of syngeneic macrophages. The aqueous extract induced mRNA expression of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin 6 (IL-6) indicating differentiation of macrophages into pro-inflammatory M1 polarized macrophages. The total flavonoid, alkaloid extracts and an alkaloid fraction induced the expression of the formyl peptide receptor (FPR) on the surface of the polarized macrophages that could lead to the activation of macrophages towards the M1 phenotype. Aqueous and flavonoid extracts enhanced NADPH quinine oxido-reductase 1 (NQO1) mRNA expression in polarized macrophages which could play an important role in cancer chemoprevention. All the samples studied were non-toxic to normal living cells and the pure alkaloid tested, 6-hydroxycrinamidine, was not

  16. Ectopic cervical thymoma mimicking as papillary thyroid carcinoma: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Thakur Abhijit

    2010-04-01

    Full Text Available Ectopic cervical thymomas are often confused with thyroid or parathyroid swellings due to their anatomical positioning. Predominant epithelial thymoma can be misdiagnosed as papillary thyroid carcinoma on fine needle aspiration and lymph node metastasis of epithelial tumor on frozen section. Predominantly lymphocytic thymomas have often been misinterpreted as Hashimoto′s thyroiditis or malignant lymphoma, either by fine needle aspiration or on frozen section analysis. If cytology is doubtful and is not correlating with clinical, anatomical and surgical findings; immunohistochemistry is a very important tool in such cases to give final answer. Thyroid cell specific proteins such as thyroglobulin, thyroid transcription factor-1, thyroperoxidase and dipeptidyl aminopeptidase-4, neuroendocrine markers chromogranin, calcitonin and parathyroid hormone could be used to rule out thyroid or parathyroid origin. We present such rare case of ectopic cervical thymoma mimicking as papillary thyroid carcinoma.

  17. The C-type lectin OCILRP2 costimulates EL4 T cell activation via the DAP12-Raf-MAP kinase pathway.

    Science.gov (United States)

    Lou, Qiang; Zhang, Wei; Liu, Guangchao; Ma, Yuanfang

    2014-01-01

    OCILRP2 is a typical Type-II transmembrane protein that is selectively expressed in activated T lymphocytes, dendritic cells, and B cells and functions as a novel co-stimulator of T cell activation. However, the signaling pathways underlying OCILRP2 in T cell activation are still not completely understood. In this study, we found that the knockdown of OCILRP2 expression with shRNA or the blockage of its activity by an anti-OCILRP2 antagonist antibody reduced CD3/CD28-costimulated EL4 T cell viability and IL-2 production, inhibit Raf1, MAPK3, and MAPK8 activation, and impair NFAT and NF-κB transcriptional activities. Furthermore, immunoprecipitation results indicated that OCILRP2 could interact with the DAP12 protein, an adaptor containing an intracellular ITAM motif that can transduce signals to induce MAP kinase activation for T cell activation. Our data reveal that after binding with DAP12, OCILRP2 activates the Raf-MAP kinase pathways, resulting in T cell activation.

  18. The C-type lectin OCILRP2 costimulates EL4 T cell activation via the DAP12-Raf-MAP kinase pathway.

    Directory of Open Access Journals (Sweden)

    Qiang Lou

    Full Text Available OCILRP2 is a typical Type-II transmembrane protein that is selectively expressed in activated T lymphocytes, dendritic cells, and B cells and functions as a novel co-stimulator of T cell activation. However, the signaling pathways underlying OCILRP2 in T cell activation are still not completely understood. In this study, we found that the knockdown of OCILRP2 expression with shRNA or the blockage of its activity by an anti-OCILRP2 antagonist antibody reduced CD3/CD28-costimulated EL4 T cell viability and IL-2 production, inhibit Raf1, MAPK3, and MAPK8 activation, and impair NFAT and NF-κB transcriptional activities. Furthermore, immunoprecipitation results indicated that OCILRP2 could interact with the DAP12 protein, an adaptor containing an intracellular ITAM motif that can transduce signals to induce MAP kinase activation for T cell activation. Our data reveal that after binding with DAP12, OCILRP2 activates the Raf-MAP kinase pathways, resulting in T cell activation.

  19. Thymoma and minimally invasive surgical treatment

    International Nuclear Information System (INIS)

    Krajc, T.; Spalek, P.; Lucenic, M.; Benej, R.; Harustiak, S.

    2011-01-01

    The authors review the current thymoma classification schemes, diagnosis and surgical treatment options. Many minimally invasive techniques do not provide sufficient extensiveness when compared to complete sternotomy. The Zieliński technique combines transcervical, subxiphoidal and bilateral thoracoscopic approach in a hybrid procedure (MMIT, maximal minimally invasive thymectomy) based on double sternal traction, and allows for removal of the thymus gland, the thymoma and all the relevant mediastinal adipose tissue, thus adhering to principles of oncological radicality. Of the 28 patients undergoing MMIT there were 7 with myasthenia associated thymoma (MGAT) and 5 with a thymoma and no myasthenia, tumors staged Masaoka I-II. Apart from one temporary recurrent nerve palsy there were no postoperative complications. The largest thymoma measured 70 x 65 x 55 mm. Adjuvant radiotherapy was applied in 5 patients. Ectopic thymic tissue was identified in 100 % of patients with thymoma and no myasthenia and in 42.9 % of MGAT patients. Until now there were no recurrences, however, the follow-up median is very short, the longest follow-up period being 30 months. MMIT is a safe technique suitable also for Masaoka I-II thymoma patients and for some specific cases with Masaoka III stage (lung parenchyma invasion). The authors approach all the anterior mediastinal tumors with no mediastinal lymphadenopathy and no myasthenia as a potential thymoma and always attempt the MMIT procedure starting as VATS procedure on the side of tumor. (author)

  20. Combining EL4-B5-based B-cell stimulation and phage display technology for the successful isolation of human anti-Scl-70 autoantibody fragments.

    Science.gov (United States)

    Weber, Malte; Weiss, Etienne; Engel, Alfred M

    2003-07-01

    Scl-70 is the major antigen recognised by autoantibodies in the sera of patients with systemic sclerosis (SSc). The autoantibodies that specifically react with Scl-70 are highly characteristic of the disease and represent valuable markers for the diagnosis of SSc. We describe a novel strategy for cloning autoantibody fragments starting with a small blood sample from an SSc patient. B cells isolated from the collected peripheral blood mononuclear cells (PBMCs) were cultured in vitro using the EL4-B5 system. Anti-Scl-70 IgG-producing cells were pooled for RNA preparation followed by the generation of phagemid libraries of approximately 10(7) independent single-chain Fvs (scFvs). The screening of these libraries by phage display allowed us to isolate four anti-Scl-70 scFvs following three rounds of biopanning. About 10 times more starting blood material was needed to generate scFv libraries of similar size from PBMCs of an SSc patient and only two anti-Scl-70 scFvs were isolated after three rounds of phage selection. Together, this work shows that functional autoantibody fragments can be advantageously cloned after in vitro expansion of B cells. The isolated anti-Scl-70 autoantibody fragments represent useful tools for calibrating SSc diagnostic assays.

  1. TIPE attenuates the apoptotic effect of radiation and cisplatin and promotes tumor growth via JNK and p38 activation in Raw264.7 and EL4 cells.

    Science.gov (United States)

    Liu, Yao; Ni, Xiao Yan; Chen, Rui Ling; Li, Juan; Gao, Feng Guang

    2018-06-01

    Tumor necrosis factor α‑induced protein 8 (TIPE) is highly expressed in many types of malignancies. Apoptosis is the process of programmed cell death which maintains the balance of cell survival and death. TIPE is involved in the carcinogenesis of many tumor types, yet the exact role of TIPE in defective apoptosis‑associated carcinogenesis remains uncertain. In the present study, TIPE‑overexpressing Raw264.7 and EL4 cells and vector control cells were treated with 4 mJ/cm2 ultraviolet radiation or 2 µg/ml cisplatin. Following ultraviolet irradiation, TIPE overexpression decreased the percentage of apoptotic cells as detected by flow cytometric and reversed the cisplatin‑mediated decrease in mitochondrial membrane potential by JC‑1 assay. Western blot analyses also revealed that TIPE overexpression inhibited cisplatin‑induced activation of caspase‑3 and ‑9 and PARP. Secondly, TIPE overexpression increased the levels of phosphorylated JNK, MEK and p38. Moreover, inhibition of JNK and p38, but not MEK, efficiently abolished the cell pro‑survival effect of TIPE. Most importantly, an in vivo tumor implantation model revealed that TIPE overexpression augmented the volume and weight of the implanted tumors, indicating that TIPE facilitated tumor formation. We found that TIPE exhibited an anti‑apoptotic effect via JNK and p38 activation, which ultimately promoted tumor. Hence, the present study revealed that activation of JNK and p38 kinases contribute to the TIPE‑mediated anti‑apoptotic effect, indicating that JNK and p38 may be potential therapeutic molecules for TIPE overexpression‑associated diseases.

  2. Role of nuclear factor of activated T-cells and activator protein-1 in the inhibition of interleukin-2 gene transcription by cannabinol in EL4 T-cells.

    Science.gov (United States)

    Yea, S S; Yang, K H; Kaminski, N E

    2000-02-01

    We previously reported that immunosuppressive cannabinoids inhibited interleukin (IL)-2 steady-state mRNA expression and secretion by phorbol-12-myristate-13-acetate plus ionomycin-activated mouse splenocytes and EL4 murine T-cells. Here we show that inhibition of IL-2 production by cannabinol, a modest central nervous system-active cannabinoid, is mediated through the inhibition of IL-2 gene transcription. Moreover, electrophoretic mobility shift assays demonstrated that cannabinol markedly inhibited the DNA binding activity of nuclear factor of activated T-cells (NF-AT) and activator protein-1 (AP-1) in a time- and concentration-dependent manner in activated EL4 cells. The inhibitory effects produced by cannabinol on AP-1 DNA binding were quite transient, showing partial recovery by 240 min after cell activation and no effect on the activity of a reporter gene under the control of AP-1. Conversely, cannabinol-mediated inhibition of NF-AT was robust and sustained as demonstrated by an NF-AT-regulated reporter gene. Collectively, these results suggest that decreased IL-2 production by cannabinol in EL4 cells is due to the inhibition of transcriptional activation of the IL-2 gene and is mediated, at least in part, through a transient inhibition of AP-1 and a sustained inhibition of NF-AT.

  3. Hyperpolarized [U-(2) H, U-(13) C]Glucose reports on glycolytic and pentose phosphate pathway activity in EL4 tumors and glycolytic activity in yeast cells.

    Science.gov (United States)

    Timm, Kerstin N; Hartl, Johannes; Keller, Markus A; Hu, De-En; Kettunen, Mikko I; Rodrigues, Tiago B; Ralser, Markus; Brindle, Kevin M

    2015-12-01

    A resonance at ∼181 ppm in the (13) C spectra of tumors injected with hyperpolarized [U-(2) H, U-(13) C]glucose was assigned to 6-phosphogluconate (6PG), as in previous studies in yeast, whereas in breast cancer cells in vitro this resonance was assigned to 3-phosphoglycerate (3PG). These peak assignments were investigated here using measurements of 6PG and 3PG (13) C-labeling using liquid chromatography tandem mass spectrometry (LC-MS/MS) METHODS: Tumor-bearing mice were injected with (13) C6 glucose and the (13) C-labeled and total 6PG and 3PG concentrations measured. (13) C MR spectra of glucose-6-phosphate dehydrogenase deficient (zwf1Δ) and wild-type yeast were acquired following addition of hyperpolarized [U-(2) H, U-(13) C]glucose and again (13) C-labeled and total 6PG and 3PG were measured by LC-MS/MS RESULTS: Tumor (13) C-6PG was more abundant than (13) C-2PG/3PG and the resonance at ∼181 ppm matched more closely that of 6PG. (13) C MR spectra of wild-type and zwf1Δ yeast cells showed a resonance at ∼181 ppm after labeling with hyperpolarized [U-(2) H, U-(13) C]glucose, however, there was no 6PG in zwf1Δ cells. In the wild-type cells 3PG was approximately four-fold more abundant than 6PG CONCLUSION: The resonance at ∼181 ppm in (13) C MR spectra following injection of hyperpolarized [U-(2) H, U-(13) C]glucose originates predominantly from 6PG in EL4 tumors and 3PG in yeast cells. © 2014 Wiley Periodicals, Inc.

  4. Seronegative myasthenia gravis associated with malignant thymoma.

    Science.gov (United States)

    Richards, Jason; Howard, James F

    2017-05-01

    Myasthenia gravis (MG) is generally caused by antibodies directed against the neuromuscular junction, including antibodies against the postsynaptic nicotinic acetylcholine receptor (AChR). Pathologic abnormalities of the thymus gland, including thymoma, are associated with MG. We report a 56-year-old woman who presented with double vision. Single fiber EMG confirmed myasthenia gravis. AChR, striational muscle and MuSK antibodies were absent in the serum. Chest CT demonstrated a malignant thymoma. We report the first case of seronegative myasthenia gravis associated with malignant thymoma. The case challenges the conventional wisdom that all patients with thymoma associated MG test positive for antibodies against AChR. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Sclerosing thymoma: case report Timoma esclerosante: relato de caso

    Directory of Open Access Journals (Sweden)

    Gesine Gregorio Siqueira

    2012-08-01

    Full Text Available We present a rare case of thymoma in a 36-year old woman, who was initially diagnosed with severe myasthenia gravis and subsequently undergone surgical resection. During surgery tumor was found at the anterior mediastinum, tightly attached to the phrenic nerve, pleura and pericardium. Histological assessment showed large areas of sclerosis and fibrous collagenous tissue as well as islands of epithelial and lymphoid cells. Sclerosing thymoma, which is a rare subtype of thymoma (Relatamos um caso raro de timoma em uma mulher de 36 anos de idade, com clínica e diagnóstico de miastenia gravis de difícil controle clínico, submetida à ressecção cirúrgica. No intraoperatório, observou-se tumor no mediastino anterior, firmemente aderido ao nervo frênico, à pleura e ao pericárdio. Ao exame histológico, foram evidenciadas extensas áreas de tecido fibrocolagenoso e esclerose, assim como ilhas de células epiteliais e células linfoides. Diagnosticado timoma esclerosante, subtipo raro de timoma (< 1%, sendo este o primeiro caso relatado no Brasil. A paciente apresentou melhora parcial dos sintomas associados à miastenia gravis.

  6. Thymoma

    Science.gov (United States)

    ... to Content ASCO.org Conquer Cancer Foundation ASCO Journals Donate eNews Signup f Cancer.net on Facebook t Cancer.net on Twitter q Cancer.net on YouTube g Cancer.net on Google Menu Home Types of Cancer Navigating Cancer Care Coping With Cancer Research and Advocacy Survivorship Blog About ...

  7. Docosahexaenoic acid modifies the clustering and size of lipid rafts and the lateral organization and surface expression of MHC class I of EL4 cells.

    Science.gov (United States)

    Shaikh, Saame Raza; Rockett, Benjamin Drew; Salameh, Muhammad; Carraway, Kristen

    2009-09-01

    An emerging molecular mechanism by which docosahexaenoic acid (DHA) exerts its effects is modification of lipid raft organization. The biophysical model, based on studies with liposomes, shows that DHA avoids lipid rafts because of steric incompatibility between DHA and cholesterol. The model predicts that DHA does not directly modify rafts; rather, it incorporates into nonrafts to modify the lateral organization and/or conformation of membrane proteins, such as the major histocompatibility complex (MHC) class I. Here, we tested predictions of the model at a cellular level by incorporating oleic acid, eicosapentaenoic acid (EPA), and DHA, compared with a bovine serum albumin (BSA) control, into the membranes of EL4 cells. Quantitative microscopy showed that DHA, but not EPA, treatment, relative to the BSA control diminished lipid raft clustering and increased their size. Approximately 30% of DHA was incorporated directly into rafts without changing the distribution of cholesterol between rafts and nonrafts. Quantification of fluorescence colocalization images showed that DHA selectively altered MHC class I lateral organization by increasing the fraction of the nonraft protein into rafts compared with BSA. Both DHA and EPA treatments increased antibody binding to MHC class I compared with BSA. Antibody titration showed that DHA and EPA did not change MHC I conformation but increased total surface levels relative to BSA. Taken together, our findings are not in agreement with the biophysical model. Therefore, we propose a model that reconciles contradictory viewpoints from biophysical and cellular studies to explain how DHA modifies lipid rafts on several length scales. Our study supports the notion that rafts are an important target of DHA's mode of action.

  8. Ectopic cervical thymoma in a patient with Myasthenia gravis

    Directory of Open Access Journals (Sweden)

    Chang Hung

    2011-07-01

    Full Text Available Abstract Ectopic cervical thymoma is rare and is often misdiagnosed as a thyroid tumor or other malignancy. Ectopic thymic tissue can be found along the entire thymic descent path during embryogenesis. However, a thymoma arising from such ectopic thymic tissue is extremely rare. Herein we report a patient with ectopic cervical thymoma and myasthenia gravis (MG and discuss the management.

  9. Differentiation of EL4 lymphoma cells by tumoral environment is associated with inappropriate expression of the large chondroitin sulfate proteoglycan PG-M and the tumor-associated antigen HTgp-175.

    Science.gov (United States)

    Rottiers, P; Verfaillie, T; Contreras, R; Revets, H; Desmedt, M; Dooms, H; Fiers, W; Grooten, J

    1998-11-09

    Progression to malignancy of transformed cells involves complex genetic alterations and aberrant gene expression patterns. While aberrant gene expression is often caused by alterations in individual genes, the contribution of the tumoral environment to the triggering of this gene expression is less well established. The stable but heterogeneous expression in cultured EL4/13 cells of a novel tumor-associated antigen, designated as HTgp-175, was chosen for the investigation of gene expression during tumor formation. Homogeneously HTgp-175-negative EL4/13 cells, isolated by cell sorting or obtained by subcloning, acquired HTgp-175 expression as a result of tumor formation. The tumorigenicity of HTgp-175-negative vs. HTgp-175-positive EL4 variants was identical, indicating that induction but not selection accounted for the phenotypic switch from HTgp-175-negative to HTgp-175-positive. Although mutagenesis experiments showed that the protein was not essential for tumor establishment, tumor-derived cells showed increased malignancy, linking HTgp-175 expression with genetic changes accompanying tumor progression. This novel gene expression was not an isolated event, since it was accompanied by ectopic expression of the large chondroitin sulfate proteoglycan PG-M and of normal differentiation antigens. We conclude that signals derived from the tumoral microenvironment contribute significantly to the aberrant gene expression pattern of malignant cells, apparently by fortuitous activation of differentiation processes and cause expression of novel differentiation antigens as well as of inappropriate tumor-associated and ectopic antigens.

  10. Netrin-1 receptor antibodies in thymoma-associated neuromyotonia with myasthenia gravis.

    Science.gov (United States)

    Torres-Vega, Estefanía; Mancheño, Nuria; Cebrián-Silla, Arantxa; Herranz-Pérez, Vicente; Chumillas, María J; Moris, Germán; Joubert, Bastien; Honnorat, Jérôme; Sevilla, Teresa; Vílchez, Juan J; Dalmau, Josep; Graus, Francesc; García-Verdugo, José Manuel; Bataller, Luis

    2017-03-28

    To identify cell-surface antibodies in patients with neuromyotonia and to describe the main clinical implications. Sera of 3 patients with thymoma-associated neuromyotonia and myasthenia gravis were used to immunoprecipitate and characterize neuronal cell-surface antigens using reported techniques. The clinical significance of antibodies against precipitated proteins was assessed with sera of 98 patients (neuromyotonia 46, myasthenia gravis 52, thymoma 42; 33 of them with overlapping syndromes) and 219 controls (other neurologic diseases, cancer, and healthy volunteers). Immunoprecipitation studies identified 3 targets, including the Netrin-1 receptors DCC (deleted in colorectal carcinoma) and UNC5A (uncoordinated-5A) as well as Caspr2 (contactin-associated protein-like 2). Cell-based assays with these antigens showed that among the indicated patients, 9 had antibodies against Netrin-1 receptors (7 with additional Caspr2 antibodies) and 5 had isolated Caspr2 antibodies. Only one of the 219 controls had isolated Caspr2 antibodies with relapsing myelitis episodes. Among patients with neuromyotonia and/or myasthenia gravis, the presence of Netrin-1 receptor or Caspr2 antibodies predicted thymoma ( p myasthenia gravis, and neuromyotonia, often with Morvan syndrome ( p = 0.009). Expression of DCC, UNC5A, and Caspr2 proteins was demonstrated in paraffin-embedded thymoma samples (3) and normal thymus. Antibodies against Netrin-1 receptors (DCC and UNC5a) and Caspr2 often coexist and associate with thymoma in patients with neuromyotonia and myasthenia gravis. This study provides Class III evidence that antibodies against Netrin-1 receptors can identify patients with thymoma (sensitivity 21.4%, specificity 100%). © 2017 American Academy of Neurology.

  11. The same drug but a different mechanism of action: comparison of free doxorubicin with two different N-(2-hydroxypropyl)methacrylamide copolymer-bound doxorubicin conjugates in EL-4 cancer cell line.

    Science.gov (United States)

    Kovár, Lubomír; Strohalm, Jirí; Chytil, Petr; Mrkvan, Tomás; Kovár, Marek; Hovorka, Ondrej; Ulbrich, Karel; Ríhová, Blanka

    2007-01-01

    Doxorubicin is one of the most potent anti-tumor drugs with a broad spectrum of use. To reduce its toxic effect and improve its pharmacokinetics, we conjugated it to an HPMA copolymer carrier that enhances its passive accumulation within solid tumors via the EPR effect and decreases its cytotoxicity to normal, noncancer cells. In this study, we compared the antiproliferative, pro-survival, and death signals triggered in EL-4 cancer cells exposed to free doxorubicin and doxorubicin conjugated to a HPMA copolymer carrier via either enzymatically (PK1) or hydrolytically (HYD) degradable bonds. We have previously shown that the intracellular distribution of free doxorubicin, HYD, and PK1 is markedly different. Here, we demonstrated that these three agents greatly differ also in the antiproliferative effect and cell death signals they trigger. JNK phosphorylation sharply increased in cells treated with HYD, while treatment with free doxorubicin moderately decreased and treatment with PK1 even strongly decreased it. On the other hand, treatment with free doxorubicin greatly increased p38 phosphorylation, while PK1 and HYD increased it slightly. PK1 also significantly increased ERK phosphorylation, while both the free doxorubicin and HYD conjugate slightly decreased it. Long-term inhibition of JNK significantly increased both proliferation and viability of EL-4 cells treated with free doxorubicin, showing that the JNK signaling pathway could be critical for mediating cell death in EL-4 cells exposed to free doxorubicin. Both activation of caspase 3 and decreased binding activity of the p50 subunit of NFkappaB were observed in cells treated with free doxorubicin and HYD, while no such effects were seen in cells incubated with PK1. Analysis of the expression of genes involved in apoptosis and regulation of the cell cycle demonstrated that free doxorubicin and HYD have very similar mechanisms of action, while PK1 has very different characteristics.

  12. Xenotropic type C virus expression in murine thymomas induced by radiation or 3-methylcholanthrene

    International Nuclear Information System (INIS)

    Mayer, A.; Duran-Reynals, M.L.

    1981-01-01

    Thymic lymphoma incidence and thymic expression of MuLV with xenotropic infectivity was monitored in AKR, RF, and reciprocal F 1 mice of the AKR X RF cross after treatment with either γ radiation or the chemical carcinogen 3-methylcholanthrene (MCA). These two inbred strains and the F 1 hybrids developed similary high incidences of thymoma, and lymphomatous cells from AKR mice and (ARK] X RF∫)F 1 mice were observed to be expressing MuLV with xenotropic host range. However, lymphoma cells from RF mice and (RF] X AKR∫)F 1 mice did not shed xenotropic MuLV. Thymic xenotropic virus expression was therefore not correlated with a high incidence of radiation or chemically induced thymoma, but rather appeared to be a phenotype genetically transmitted by AKR mice to F 1 mice of the AKR X RF cross as a dominant trait in induced thymomas. In addition, a maternal effect on thymic xenotropic virus expression in induced thymomas was observed by the comparison of reciprocal F 1 hybrids in this cross

  13. Transforming growth factor-beta 1 (TGF-beta1) promotes IL-2 mRNA expression through the up-regulation of NF-kappaB, AP-1 and NF-AT in EL4 cells.

    Science.gov (United States)

    Han, S H; Yea, S S; Jeon, Y J; Yang, K H; Kaminski, N E

    1998-12-01

    Transforming growth factor beta1 (TGF-beta1) has been previously shown to modulate interleukin 2 (IL-2) secretion by activated T-cells. In the present studies, we determined that TGF-beta1 induced IL-2 mRNA expression in the murine T-cell line EL4, in the absence of other stimuli. IL-2 mRNA expression was significantly induced by TGF-beta1 (0.1-1 ng/ml) over a relatively narrow concentration range, which led to the induction of IL-2 secretion. Under identical condition, we examined the effect of TGF-beta1 on the activity of nuclear factor AT (NF-AT), nuclear factor kappaB (NF-kappaB), activator protein-1 (AP-1) and octamer, all of which contribute to the regulation of IL-2 gene expression. Electrophoretic mobility shift assays showed that TGF-beta1 markedly increased NF-AT, NF-kappaB and AP-1 binding to their respective cognate DNA binding sites, whereas octamer binding remained constant, as compared with untreated cells. Employing a reporter gene expression system with p(NF-kappaB)3-CAT, p(NF-AT)3-CAT and p(AP-1)3-CAT, TGF-beta1 treatment of transfected EL4 cells induced a dose-related increase in chloramphenicol acetyltransferase activity that correlated well with the DNA binding profile found in the electrophoretic mobility shift assay studies. These results show that TGF-beta1, in the absence of any additional stimuli, up-regulates the activity of key transcription factors involved in IL-2 gene expression, including NF-AT, NF-kappaB and AP-1, to help promote IL-2 mRNA expression by EL4 cells.

  14. Caspr2 antibody limbic encephalitis is associated with Hashimoto thyroiditis and thymoma.

    Science.gov (United States)

    Lee, Chih-Hong; Lin, Jainn-Jim; Lin, Kun-Ju; Chang, Bao-Luen; Hsieh, Hsiang-Yao; Chen, Wei-Hsun; Lin, Kuang-Lin; Fung, Hon-Chung; Wu, Tony

    2014-06-15

    Contactin-associated protein 2 (Caspr2) antibody is a neuronal surface antibody (NSAb) capable of causing disorders involving central and peripheral nervous systems (PNS). Thymoma can be found in patients with Caspr2 antibodies and is most frequently associated with PNS symptoms. Myasthenia gravis can be found in these patients, but Hashimoto thyroiditis (HT) has not been reported. A 76-year-old woman presented with sub-acute-onset changes in mental status. Further investigations revealed thymoma and HT. The presence of NSAb was tested by immunofluorescence on human embryonic kidney-293 cells. Treatment included corticosteroids, azathioprine, thyroxine, plasmapheresis, and thymectomy. Caspr2 antibody was positive in serum but absent in CSF. Brain magnetic resonance imaging (MRI) showed diffuse cortical atrophy, but did not change significantly after treatments. Brain positron emission tomography (PET) revealed diffuse hypometabolism over the cerebral cortex. The patient's mental status only partially improved. In Caspr2 antibody-associated syndromes, thymoma can occur in patients presenting only with LE, and HT can be an accompanying disease. Brain MRI and PET may not show specific lesions in limbic area. Patients with Caspr2 antibodies and thymoma may not have good prognosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. THYMOMA -A Review of Fourteen Patients

    International Nuclear Information System (INIS)

    Kim, S. K.; Lee, H. S.; Cho, K. H.; Suh, C. O.; Kim, G. E.

    1985-01-01

    Between Jan. 1977 and Dec. 1984, 14 patients diagnosed of thymoma has been analyzed retrospectively. 6 patients(6/14 patients 43%) had myasthenia gravis. 12 patients (12/14 patients 86%) had invasive thymoma. Complete resection was carried out in 6 patients (43%), 2 patients had partial resection (14%) and 6 patients had only biopsy (43%). Postoperative or radical radiotherapy was given to 8 patients, of whom 5 patients was still alive (4 yr. 2.8 yr. 1.6 yr. 1.4 yr. 1.3 yr) and 3 patients died (1 yr. 0.6 yr. 0.6 yr). External irradiation ranges 1,950-7,000 rads (mean 4,500, median 4,000 rads)

  16. THYMOMA -A Review of Fourteen Patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, S. K.; Lee, H. S.; Cho, K. H.; Suh, C. O.; Kim, G. E. [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1985-06-15

    Between Jan. 1977 and Dec. 1984, 14 patients diagnosed of thymoma has been analyzed retrospectively. 6 patients(6/14 patients 43%) had myasthenia gravis. 12 patients (12/14 patients 86%) had invasive thymoma. Complete resection was carried out in 6 patients (43%), 2 patients had partial resection (14%) and 6 patients had only biopsy (43%). Postoperative or radical radiotherapy was given to 8 patients, of whom 5 patients was still alive (4 yr. 2.8 yr. 1.6 yr. 1.4 yr. 1.3 yr) and 3 patients died (1 yr. 0.6 yr. 0.6 yr). External irradiation ranges 1,950-7,000 rads (mean 4,500, median 4,000 rads)

  17. Effects of overexpression of IL-1 receptor-associated kinase on NFkappaB activation, IL-2 production and stress-activated protein kinases in the murine T cell line EL4.

    Science.gov (United States)

    Knop, J; Wesche, H; Lang, D; Martin, M U

    1998-10-01

    The association and activation of the IL-1 receptor-associated protein kinase (IRAK) to the IL-1 receptor complex is one of the earliest events detectable in IL-1 signal transduction. We generated permanent clones of the murine T cell line EL4 6.1 overexpressing human (h)IRAK to evaluate the role of this kinase in IL-1 signaling. Overexpression of hIRAK enhanced IL-1-stimulated activation of the transcription factor NFkappaB, whereas a truncated form (N-IRAK) specifically inhibited IL-1-dependent NFkappaB activity. In clones stably overexpressing hIRAK a weak constitutive activation of NFkappaB correlated with a low basal IL-2 production which was enhanced in an IL-1-dependent manner. Compared to the parental cell line the dose-response curve of IL-1-induced IL-2 production was shifted in both potency and efficacy. These results demonstrate that IRAK directly triggers NFkappaB-mediated gene expression in EL4 cells. Qualitatively different effects were observed for the IL-1-induced activation of stress-activated protein (SAP) kinases: permanent overexpression of IRAK did not affect the dose dependence but prolonged the kinetics of IL-1-induced activation of SAP kinases, suggesting that this signaling branch may be regulated by distinct mechanisms.

  18. Multimodality therapy and prognostic analysis of thymoma

    International Nuclear Information System (INIS)

    Chen Jie; Wang Ping; Song Yongchun

    2007-01-01

    Objective: The aim of this study is to draft the judicious treatment methods by analyzing the Long-term survival result of thymoma and evaluating the effect that prognosis analysis has on thymoma. Methods: Retrospective analysis of the clinical material of 142 patients with thymoma in the Tianjin Medical University Cancer Hospital from January 1954 to January 2001. Statistical analysis was performed using the SPSS software package. The Kaplan-Meier method was used single variable analysis, The Log-rank test was used to compare survival between groups, The Cox' s proportional hazards model was used to multi-factor analysis. Results: The 5- and 10-year survival rate of the 142 patients was 59.9% and 45.8%, respectively. Staging was adopted on the Masaoka's way, 5- and 10-year survival rates was: 93.8%, 79.2% in stage I; 79.3%, 55.2% in stage II; 53.1%, 34.4% in stage III; and 0 and 0 in stage IV. Among 30 patients associated with myasthenia gravis, 19 patients suffered from generalized myasthenia gravis and 11 patients of ocular myasthenia gravis, with 5- and 10-year survival rate of 83.3% and 60.0%, respectively. Three patients finally died of myasthenia gravis. The 5- and 10-year survival rate of 112 patients without myasthenia gravis was 53.6% and 42.0%, respectively. Among 116 patients, treated with surgery-, resection was carried out in 84 patients, palliative resection in 9 patients, and biopsy only in 23 patients. Eighty-nine patients were given radiotherapy and 55 patients had postoperative radiotherapy. Single variable analysis showed that Masaoka clinical staging, association with myasthenia gravis, histopathologic subtype and the method of treatment were prognostic factor's. Finally, drawing the conclusion through muhivariable analysis; Masaoka clinical staging, association with myasthenia gravis and the treatment method were prognostic factors. Conclusions: The diagnosis of thymoma is made clinically and pathologically. The treatment principle should be

  19. Protien expression profiling of mouse thymoma upon exposure to the tricothecene deoxynivalenol (DON) Implications for its mechanism of action

    NARCIS (Netherlands)

    Osman, A.M.; Pennings, J.L.A.; Blokland, M.H.; Peijnenburg, A.A.C.M.; Loveren, van H.

    2010-01-01

    The objective of this work was to investigate whether proteomic analysis of thymoma cells treated with the trichothecene deoxynivalenol (DON) as compared to non-treated (control) cells would reveal differential protein expression, and thus would contribute to a better understanding of the mechanisms

  20. Entire hemithorax irradiation for Masaoka stage IVa thymomas

    Science.gov (United States)

    Soares, André; Louro, Luís Vasco; Almeida, Marta; Sousa, Olga

    2012-01-01

    Thymomas are rare neoplasms that have an indolent growth with a preferentially intra-thoracic dissemination pattern. Surgery is currently the standard treatment of thymomas; however radiotherapy is often used in an adjuvant setting due to a high sensitivity of these tumors to such treatment. Postoperative entire hemithoracic irradiation has been used in selected Masaoka stage IVa cases after complete surgical excision of metastatic lesions. In the present article, the authors report three cases of Masaoka stage IVa thymoma that underwent entire hemithorax irradiation after surgical excision of metastatic lesions. The first two patients presented as stage IVa thymomas. The third case consisted of a pleural recurrence of a thymoma. Hemithoracic irradiation with low doses has been used by different authors; the available data shows that it is a well-tolerated treatment that could potentially lead to better loco-regional control and increased overall survival. PMID:24377042

  1. Transfer of in vitro expanded T lymphocytes after activation with dendritomas prolonged survival of mice challenged with EL4 tumor cells.

    Science.gov (United States)

    Li, Jinhua; Theofanous, Leigh; Stickel, Sara; Bouton-Verville, Hilary; Burgin, Kelly E; Jakubchak, Susan; Wagner, Thomas E; Wei, Yanzhang

    2007-07-01

    Adoptive T cell transfer after in vitro expansion represents an attractive cancer immunotherapy. The majority of studies so far have been focusing on the expansion of tumor infiltrated lymphocytes (TIL) and some have shown very encouraging results. Recently, we have developed a unique tumor immune response activator, dendritomas, by fusion of dendritic cells and tumor cells. Animal studies and early clinical trials have shown that dendritomas are able to activate tumor specific immune responses. In this study, we hypothesized that naïve T cells can be primed with dendritomas and expanded in vitro to develop an adoptive transfer therapy for patients who do not have solid tumors, such as leukemia. T cells were isolated and purified from lymph nodes of mice. The cells were then incubated with dendritomas made from syngeneic DCs and tumor cells and expanded in vitro using Dynabeads mouse CD3/CD28 T cell expander for approximately three weeks. The in vitro primed and expanded T cells showed tumor cell specific CTL activity and increased secretion of IFN-gamma. Tumor bearing mice receiving the in vitro expanded T cells survived significantly longer than control mice. Furthermore, the depletion of regulator T cells enhanced the survival of the mice that received the adoptive transfer therapy.

  2. CT differentiation of invasive thymoma and thymic carcinoma

    International Nuclear Information System (INIS)

    Lee, Eun Jung; Jung, Gyoo Sik; Kim, Seong Min; Huh, Jin Do; Joh, Young Duk; Shin, Mi Jung; Kim, Jung Sik; Suh, Soo Jhi

    1998-01-01

    In order to determine the differential points between them, we analyzed the CT findings of invasive thymoma and thymic carcinoma. We retrospectively reviewed the CT scans of 14 patients with invasive thymoma and 15 with thymic carcinoma, confirmed by surgery(n=3D19) or percutaneous needle aspiration(n=3D10) between 1988 and 1996. CT findings were evaluated in each group for intrathoracic spread(posterior, direct posterior, and anterolateral), obliteration of the fat plane between the mass and vascular structures, vessel encasement, invasion of adjacent mediastinal structures, pleural implants, mediastinal nodes and distant metastasis. Direct posterior spread was more common in thymic carcinoma than invasive thymoma;it was seen in one case (7%) of invasive thymoma and 12(80%) of thymic carcinoma(p=3D0.00). Posterior spread was seen in six cases (43%) of in vasive thymoma and nine (60%) of thymic carcinoma. Anterolateral spread was seen only in two cases (13%) of thymic carcinoma. Obliteration of the fat plane was seen in nine cases (64%) of invasive thymoma and 14 (93%) of thymic carcinoma, while vessel encasement was seen in two cases (14%) of invasive thymoma and 13(87%) of thymic carcinoma(p=3D0.00). Invasion of adjacent structures was seen in two cases (14%) of invasive thymoma and eight (53%) of thymic carcinoma. Pleural implants were more common in invasive thymoma than thymic carcinoma, being seen in six cases (43%) of the former and one (7%) of the latter(p=3D0.04). Mediastinal lymphadenopathy was seen in three cases (21%) of invasive thymoma and ten (67%) of thymic carcinoma. Distant metastases were observed only in six cases (40%) of thymic carcinoma(p=3D0.02). Although differentiation between invasive thymoma and thymic carcinoma is difficult on the basis of CT findings, there are certain differential points. Thymic carcinomas showed a higher rate of direct posterior intrathoracic spread, vessel encasement, mediastinal nodes and distant metastases than

  3. Syringolin A selectively labels the 20 S proteasome in murine EL4 and wild-type and bortezomib-adapted leukaemic cell lines.

    Science.gov (United States)

    Clerc, Jérôme; Florea, Bogdan I; Kraus, Marianne; Groll, Michael; Huber, Robert; Bachmann, André S; Dudler, Robert; Driessen, Christoph; Overkleeft, Herman S; Kaiser, Markus

    2009-11-02

    The natural product syringolin A (SylA) is a potent proteasome inhibitor with promising anticancer activities. To further investigate its potential as a lead structure, selectivity profiling with cell lysates was performed. At therapeutic concentrations, a rhodamine-tagged SylA derivative selectively bound to the 20 S proteasome active sites without detectable off-target labelling. Additional profiling with lysates of wild-type and bortezomib-adapted leukaemic cell lines demonstrated the retention of this proteasome target and subsite selectivity as well as potency even in clinically relevant cell lines. Our studies, therefore, propose that further development of SylA might indeed result in an improved small molecule for the treatment of leukaemia.

  4. Recurrent thymoma in the retroperitoneal space: a rare case report

    Directory of Open Access Journals (Sweden)

    Jun Yang

    2015-06-01

    Full Text Available Thymoma is an epithelial neoplasm of the thymus, which commonly lies in the anterior mediastinum and recurrences of thymoma generally are locally, and retroperitoneal recurrence is considered to be rare. A 46-year old Asian woman with invasive thymoma had undergone thymectomy 10 years ago. Computed tomography demonstrated a wellcircumscribed mass in the left retroperitoneal space. The patient had not any symptom including myasthenia gravis. Because on the anterior mediastinum area shows no sign of tumor recurrence and the mass adjacent to the vertebral body, neurogenic tumor was suspected. Surgical resection was performed using a retroperitoneal approach, which revealed the tumor adhering neighboring diaphragm. The tumor was histologically diagnosed to be type B1 thymoma according to the World Health Organization classification. The retroperitoneal mass was an unusual local recurrence after thymectomy. The patients whose had under invasive thymectomy should be evaluated carefully when finding retroperitoneal mass during follow-up.

  5. Clinical results of radiation therapy for thymoma

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-05-01

    From August 1968 to December 1989, 58 patients with thymoma were treated by radiotherapy using cobalt-60 gamma ray. Eleven cases were treated by radiothrapy alone, 1 by preoperative radiotheapy, 43 by postoperative radiotherapy, and 3 in combination with intraoperative radiotherapy. The following points were clarified: (a) Postoperative and intraoperative radiotherapy were effective; (b) For 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; (c) The patients with complicating myasthenia gravis had a longer survival time and better local control rate than those without it. Radiation pneumonitis was observed in 17 patients, and none of them died of this complication. In all cases in combination with intraoperative radiotherapy, dry desquamation was observed within the irradiated field. (author).

  6. Clinical results of radiation therapy for thymoma

    International Nuclear Information System (INIS)

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

    1992-01-01

    From August 1968 to December 1989, 58 patients with thymoma were treated by radiotherapy using cobalt-60 gamma ray. Eleven cases were treated by radiothrapy alone, 1 by preoperative radiotheapy, 43 by postoperative radiotherapy, and 3 in combination with intraoperative radiotherapy. The following points were clarified: (a) Postoperative and intraoperative radiotherapy were effective; (b) For 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; (c) The patients with complicating myasthenia gravis had a longer survival time and better local control rate than those without it. Radiation pneumonitis was observed in 17 patients, and none of them died of this complication. In all cases in combination with intraoperative radiotherapy, dry desquamation was observed within the irradiated field. (author)

  7. Management of stage III thymoma with postoperative radiation therapy

    International Nuclear Information System (INIS)

    Krueger, J.B.; Sagerman, R.H.; King, G.A.

    1987-01-01

    The results of postoperative radiation therapy in 12 patients with Stage III thymoma treated during the period 1966-1986 were reviewed. Surgical therapy consisted of total resection in one, subtotal resection in seven, and biopsy only in four. Megavoltage irradiation in the dose range of 3,000-5,600 cGy was employed, with the majority receiving a dose of at least 5,000 cGy. The local control rate was 67%. The actuarial 5-year observed and adjusted survival rates were 57% and 75%, respectively. These results indicate that postoperative radiation therapy is an effective therapeutic modality in the control of Stage III thymoma

  8. Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of thymoma: a preliminary report

    International Nuclear Information System (INIS)

    Liu Renshyan; Yeh Shinhwa; Huang Minhsiung; Wang Liangshun; Chu Leeshing; Chang Chenpei; Chu Yumkung; Wu Lingchi

    1995-01-01

    This study aimed to analyse the uptake patterns of fluorine-18 fluorodeoxyglucose (FDG) in thymomas of different stages. FDG positron emission tomography (PET) scan was performed in 12 patients suspected of having thymoma and in nine controls. Qualitative visual interpretation was used to detect the foci with FDG uptake higher than that of normal mediastinum. Tumour/lung ratio (TLR) was calculated from the counts of ROIs over the mass and over comparable normal lung tissue in thymoma patients. Mediastinum/lung ratio (MLR) was calculated from the counts of ROIs over the anterior mediastinum and lung in controls. The PET scan patterns of distribution of foci with FDG uptake and TLRs were correlated with the computed tomography (CT) of magnetic resonance imaging (MRI) findings, and staging of the thymomas. Thymectomy was performed in ten patients and thoracoscopy was done in two patients. The results revealed ten thymomas (two stage I tumours, two stage II, four stage III and two stage IV, according to the Masaoka classification), and two cases of thymic hyperplasia associated with myasthenia gravis. Myasthenia gravis was also noted in four thymoma patients. FDG studies showed (a) diffuse uptake in the widened anterior mediastinum in patients with thymic hyperplasia, (b) confined focal FDG uptake in the non-invasive or less invasive, stage I and II thymomas, and (c) multiple discrete foci of FDG uptake in the mediastinum and thoraci structures in stage III and IV advanced invasive thymomas. The thymomas had the highest TLRs, followed by the TLRs of thymic hyperplasia and the MLRs of control subjects. No significant difference was found between thymomas in different stages or between thymomas with and thymomas without myasthenia gravis. In comparison with CT and/or MRI, FDG/PET detected more lesions in patients with invasive thymomas and downgraded the staging of thymoma in four patients. (orig./MG)

  9. Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of thymoma: a preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Liu Renshyan [National PET/Cyclotron Center and Dept. of Nuclear Medicine, Taipei Veterans General Hospital and National Yang-Ming Univ. School of Medicine, Taipei (Taiwan, Province of China)]|[National Def. Medical Center, Taipei (Taiwan, Province of China); Yeh Shinhwa [National PET/Cyclotron Center and Dept. of Nuclear Medicine, Taipei Veterans General Hospital and National Yang-Ming Univ. School of Medicine, Taipei (Taiwan, Province of China); Huang Minhsiung [Div. of Thoracic Surgery, Taipei Veterans General Hospital and National Yang-Ming Univ. School of Medicine, Taipei (Taiwan, Province of China); Wang Liangshun [Div. of Thoracic Surgery, Taipei Veterans General Hospital and National Yang-Ming Univ. School of Medicine, Taipei (Taiwan, Province of China); Chu Leeshing [National PET/Cyclotron Center and Dept. of Nuclear Medicine, Taipei Veterans General Hospital and National Yang-Ming Univ. School of Medicine, Taipei (Taiwan, Province of China)]|[National Def. Medical Center, Taipei (Taiwan, Province of China); Chang Chenpei [National PET/Cyclotron Center and Dept. of Nuclear Medicine, Taipei Veterans General Hospital and National Yang-Ming Univ. School of Medicine, Taipei (Taiwan, Province of China); Chu Yumkung [National PET/Cyclotron Center and Dept. of Nuclear Medicine, Taipei Veterans General Hospital and National Yang-Ming Univ. School of Medicine, Taipei (Taiwan, Province of China); Wu Lingchi [National PET/Cyclotron Center and Dept. of Nuclear Medicine, Taipei Veterans General Hospital and National Yang-Ming Univ. School of Medicine, Taipei (Taiwan, Province of China)

    1995-12-01

    This study aimed to analyse the uptake patterns of fluorine-18 fluorodeoxyglucose (FDG) in thymomas of different stages. FDG positron emission tomography (PET) scan was performed in 12 patients suspected of having thymoma and in nine controls. Qualitative visual interpretation was used to detect the foci with FDG uptake higher than that of normal mediastinum. Tumour/lung ratio (TLR) was calculated from the counts of ROIs over the mass and over comparable normal lung tissue in thymoma patients. Mediastinum/lung ratio (MLR) was calculated from the counts of ROIs over the anterior mediastinum and lung in controls. The PET scan patterns of distribution of foci with FDG uptake and TLRs were correlated with the computed tomography (CT) of magnetic resonance imaging (MRI) findings, and staging of the thymomas. Thymectomy was performed in ten patients and thoracoscopy was done in two patients. The results revealed ten thymomas (two stage I tumours, two stage II, four stage III and two stage IV, according to the Masaoka classification), and two cases of thymic hyperplasia associated with myasthenia gravis. Myasthenia gravis was also noted in four thymoma patients. FDG studies showed (a) diffuse uptake in the widened anterior mediastinum in patients with thymic hyperplasia, (b) confined focal FDG uptake in the non-invasive or less invasive, stage I and II thymomas, and (c) multiple discrete foci of FDG uptake in the mediastinum and thoraci structures in stage III and IV advanced invasive thymomas. The thymomas had the highest TLRs, followed by the TLRs of thymic hyperplasia and the MLRs of control subjects. No significant difference was found between thymomas in different stages or between thymomas with and thymomas without myasthenia gravis. In comparison with CT and/or MRI, FDG/PET detected more lesions in patients with invasive thymomas and downgraded the staging of thymoma in four patients. (orig./MG)

  10. Management of invasive thymoma at Groote Schuur Hospital, Cape ...

    African Journals Online (AJOL)

    Fifteen patients (median age 55 years; range 23 - 69 years) with macroscopic invasive thymoma or thymic carcinoma were treated at Groote Schuur Hospital between 1969 and 1988. Stage 3 (macroscopically invasive) disease was present in 12 patients (80%) and stage 4 (metastatic disease) in 3 (20%). Ten of the patients ...

  11. A gene signature to determine metastatic behavior in thymomas.

    Directory of Open Access Journals (Sweden)

    Yesim Gökmen-Polar

    Full Text Available PURPOSE: Thymoma represents one of the rarest of all malignancies. Stage and completeness of resection have been used to ascertain postoperative therapeutic strategies albeit with limited prognostic accuracy. A molecular classifier would be useful to improve the assessment of metastatic behaviour and optimize patient management. METHODS: qRT-PCR assay for 23 genes (19 test and four reference genes was performed on multi-institutional archival primary thymomas (n = 36. Gene expression levels were used to compute a signature, classifying tumors into classes 1 and 2, corresponding to low or high likelihood for metastases. The signature was validated in an independent multi-institutional cohort of patients (n = 75. RESULTS: A nine-gene signature that can predict metastatic behavior of thymomas was developed and validated. Using radial basis machine modeling in the training set, 5-year and 10-year metastasis-free survival rates were 77% and 26% for predicted low (class 1 and high (class 2 risk of metastasis (P = 0.0047, log-rank, respectively. For the validation set, 5-year metastasis-free survival rates were 97% and 30% for predicted low- and high-risk patients (P = 0.0004, log-rank, respectively. The 5-year metastasis-free survival rates for the validation set were 49% and 41% for Masaoka stages I/II and III/IV (P = 0.0537, log-rank, respectively. In univariate and multivariate Cox models evaluating common prognostic factors for thymoma metastasis, the nine-gene signature was the only independent indicator of metastases (P = 0.036. CONCLUSION: A nine-gene signature was established and validated which predicts the likelihood of metastasis more accurately than traditional staging. This further underscores the biologic determinants of the clinical course of thymoma and may improve patient management.

  12. Recurrent invasive thymoma with pleural dissemination : disease management and treatment possibilities.

    Science.gov (United States)

    Konecna, J; Willemse, E; Lefebvre, Y; de Wind, R; Andry, G

    2014-01-01

    Thymoma is the most common benign neoplasm of the anterior mediastinum presenting often an agressive behaviour typical for the malignants tumors. The rate of invasive thymoma recurrency is relatively high. We present the case of a 55-year old man with a recurrent invasive thymoma with a pleural dissemination, detected on CT-imaging 2 years following his primary surgery. Since the first pre-operative imaging studies showed no invasion of the adjacent organs and a thymoma was suspected, a surgical resection was decided as a first line treatment. Per-operatively a number of adjacent structures were invaded and despite a macroscopical RO resection, the margins were microscopically positive. An invasive thymoma, WHO classification B3, Masaoka stage IVb was diagnosed and the patient received adjuvant radiotherapy. We highlight the role of multimodality treatement and disscus the potential of surgical, radiotherapeutical and systemic therapy in stage IV thymoma as well as in recurrent disease. Copyright© Acta Chirurgica Belgica.

  13. Marked cytoreduction of a lymphocyte-rich mediastinal thymoma with neoadjuvant chemotherapy in a cat

    Directory of Open Access Journals (Sweden)

    Linda J Tong

    2015-05-01

    Full Text Available Case summary A 15-year-old neutered female domestic shorthair cat presented with lethargy and acute-onset dyspnoea. Thoracic computed tomography (CT revealed a large, cranial mediastinal mass with an estimated volume of 180.7 cm 3 . Chemotherapy consisting of dexamethasone followed by L-asparaginase, prednisolone, vincristine and doxorubicin was commenced owing to the severity of disease and initial possibility of lymphoma. A diagnosis of lymphocyte-rich thymoma was made based upon histological examination, positive pancytokeratin staining, variable lymphocyte CD3 expression and T cell receptor gamma polyclonality. Thoracic CT performed 35 days after the commencement of chemotherapy showed a marked reduction in the size of the mass, with an estimated volume of 9.4 cm 3 . A median sternotomy and thymectomy were performed. No clinical signs have recurred 34 months after surgery. Conclusions and relevance The response to chemotherapy in this case was unusual, and is likely associated with the high non-neoplastic lymphoid component of the mass. The case demonstrates that preoperative chemotherapy can be used to reduce thymoma volume prior to surgery, potentially decreasing anaesthetic risk.

  14. Thymoma (World Health Organization type B3) with neuroendocrine differentiation in multiple endocrine neoplasia type 1

    OpenAIRE

    Tomita, Masaki; Ichiki, Nobuhiko; Ayabe, Takanori; Tanaka, Hiroyuki; Kataoka, Hiroaki; Nakamura, Kunihide

    2017-01-01

    Abstract Thymic epithelial tumors occur in 1?5% of patients with multiple endocrine neoplasia type 1 (MEN 1). Majority of these thymic epithelial tumors are thymic carcinoids and patients with thymoma in MEN 1 is rare. Furthermore, thymoma with neuroendocrine differentiation was also rarely reported. Herein, we report a 68-year-old man having type B3 thymoma with neuroendocrine differentiation in MEN 1 and to the best of our knowledge this is the first such case ever reported.

  15. Radiotherapy for invasive thymoma and thymic carcinoma. Clinicopathological review

    International Nuclear Information System (INIS)

    Mayer, R.; Stuecklschweiger, G.F.; Prettenhofer, U.; Stranzl, H.; Hackl, A.; Beham-Schmid, C.; Groell, R.; Smolle-Juettner, F.M.; Renner, H.; Quehenberger, F.

    1999-01-01

    All 33 patients were irradiated with a mean dose of 50 Gy after complete resection (16 patients), partial resection (9 patients) of biopsy (8 patients). Staging was done according to the Masaoka classification; there were 12 Stage II, 12 Stage III and 9 Stage IV patients. Results: In patients with invasive thymoma Stage II to IV (median follow-up 54.4 months) Kaplan-Meier estimates of overall survival (OS), disease-specific (DSS) and disease-free survival (DFS) at 5 years were 63.7% (95% confidence interval [CI], 42 to 84%), 88.3% (CI, 75 to 100%) and 77,4% (CI, 58 to 95%), respectively. Among the prognostic factors tested, such as age, myasthenia gravis, completeness of surgery and histologic subclassification, total radiation dose, and Masaoka Stage, the latter was the only significant predictor of improved survival (p=0.04). Considering local control, radiation dose was a significant prognostic factor (p=0.0006). In patients with thymic carcinoma (median follow-up 43.4 months) 5 year DSS, and DFS were 22.2% (CI, 0 to 60%) and 16.7% (CI, 0 to 46%), respectively. Thymoma as compared to thymic carcinoma had a statistically significant better DSS (p=0.007) and DFS (p=0.0007). Conclusion: Postoperative radiotherapy with sufficient doses plays an important role as adjuvant treatment in complete or incomplete resected invasive Stage II to III thymoma. In unresectable thymoma Stage III to IV as well as in thymic carcinoma a multimodality approach should be considered to improve survival. (orig.) [de

  16. Stages of Thymoma and Thymic Carcinoma

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... cancer cells have places where hormones can attach ( receptors ), drugs, surgery, or radiation therapy is used to ...

  17. Treatment Options for Thymoma and Thymic Carcinoma

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... cancer cells have places where hormones can attach ( receptors ), drugs, surgery, or radiation therapy is used to ...

  18. [Antitumor effects of matrix protein of vesicular stomatic virus on EL4 lymphoma mice].

    Science.gov (United States)

    Lin, Shi-jia; Yu, Qin-mei; Meng, Wen-tong; Wen, Yan-jun; Chen, Li-juan; Niu, Ting

    2011-03-01

    To explore antitumor effects of plasmid pcDNA3. 1-MP encoding matrix protein of vesicular stomatitis virus (VSV) complexed with cationic liposome (DOTAP:CHOL) in mice with EL4 lymphoma. C57BL/6 mouse model with EL4 lymphoma was established. Sixty mice bearing EL4 lymphoma were divided randomly into five groups including Lip-MP, Lip-pVAX, Lip, ADM and NS groups, which were intravenously injected with liposome-pcDNA 3. 1-MP complex, liposome-pVAX complex, empty liposome, Adriamycin and normal saline respectively every three days. Tumor volumes and survival time were monitored. Microvessel density and tumor proliferative index in tumor tissues were determined by CD31, Ki-67 immunohistochemistry staining, meanwhile the tumor apoptosis index was measured by TUNEL method. From 6 days after treatments on, the tumor volume in Lip-MP group was much smaller than that in Lip-pVAX, Lip and NS group (P EL4 tumor cells in vivo (P EL4 lymphoma, which may be related to the induction of tumor cell apoptosis, inhibition of tumor angiogenesis, and suppression of tumor cell proliferation.

  19. Clinical and pathological aspects of microscopic thymoma with myasthenia gravis and review of published reports.

    Science.gov (United States)

    Fukuhara, Mitsuro; Higuchi, Mitsunori; Owada, Yuki; Inoue, Takuya; Watanabe, Yuzuru; Yamaura, Takumi; Muto, Satoshi; Hasegawa, Takeo; Suzuki, Hiroyuki

    2017-06-01

    Microscopic thymomas, defined as epithelial proliferations smaller than 1 mm in diameter, characteristically occur in patients with myasthenia gravis without macroscopic thymic epithelial tumors. However, some clinical and pathological aspects of this entity are still unclear. This retrospective study includes five consecutive patients who had undergone extended thymectomy for myasthenia gravis at our institution from April 2007 to March 2016 and in whom microscopic thymomas were diagnosed by histopathological examination of the resected specimens. During the same period, we performed 32 extended transsternal thymothymectomies/thymectomies in patients with myasthenia gravis, including the above five cases. We here review 18 cases of microscopic thymoma, including our five cases and 13 previously reported cases. The incidence of previously undiagnosed microscopic thymoma in patients undergoing thymectomy for myasthenia gravis in our institution is 15.2%. Serum preoperative anti-acetylcholine receptor antibody (anti-AchR Ab) titers were abnormally high in all of our five cases h (74.4±53.3 nmol/L) and decreased significantly after surgery (11.7±13.5 nmol/L, P=0.037). We divided our cases into the following three groups: microscopic thymoma group (Group M), thymoma group (Group T) and non-thymic tumor group (Group N). The mean preoperative anti-AchR Ab titers of these groups were 74.4, 26.5, and 368 nmol/L, respectively. All these values decreased postoperatively. The mean anti-AchR Ab titer was significantly higher in Group M than in Group T (P=0.034). All five cases in Group M were found by post-operative pathological examination to have multifocal type A thymomas. Microscopic thymomas tend to be multifocal type A thymomas. Anti-AchR Ab titers decreased significantly in all groups. It is very important to both perform complete extended thymectomies in patients with myasthenia gravis and pathological examination of thin slices of thymic tissue to maximize detection

  20. MS4a4B, a CD20 homologue in T cells, inhibits T cell propagation by modulation of cell cycle.

    Directory of Open Access Journals (Sweden)

    Hui Xu

    2010-11-01

    Full Text Available MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural killer cells (NK and some T cell lines. But its expression in all malignant T cells, including thymoma and T hybridoma tested, was silenced. Interestingly, its expression was regulated during T cell activation. Viral vector-driven overexpression of MS4a4B in primary T cells and EL4 thymoma cells reduced cell proliferation. In contrast, knockdown of MS4a4B accelerated T cell proliferation. Cell cycle analysis showed that MS4a4B regulated T cell proliferation by inhibiting entry of the cells into S-G2/M phase. MS4a4B-mediated inhibition of cell cycle was correlated with upregulation of Cdk inhibitory proteins and decreased levels of Cdk2 activity, subsequently leading to inhibition of cell cycle progression. Our data indicate that MS4a4B negatively regulates T cell proliferation. MS4a4B, therefore, may serve as a modulator in the negative-feedback regulatory loop of activated T cells.

  1. MS4a4B, a CD20 homologue in T cells, inhibits T cell propagation by modulation of cell cycle.

    Science.gov (United States)

    Xu, Hui; Yan, Yaping; Williams, Mark S; Carey, Gregory B; Yang, Jingxian; Li, Hongmei; Zhang, Guang-Xian; Rostami, Abdolmohamad

    2010-11-01

    MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural killer cells (NK) and some T cell lines. But its expression in all malignant T cells, including thymoma and T hybridoma tested, was silenced. Interestingly, its expression was regulated during T cell activation. Viral vector-driven overexpression of MS4a4B in primary T cells and EL4 thymoma cells reduced cell proliferation. In contrast, knockdown of MS4a4B accelerated T cell proliferation. Cell cycle analysis showed that MS4a4B regulated T cell proliferation by inhibiting entry of the cells into S-G2/M phase. MS4a4B-mediated inhibition of cell cycle was correlated with upregulation of Cdk inhibitory proteins and decreased levels of Cdk2 activity, subsequently leading to inhibition of cell cycle progression. Our data indicate that MS4a4B negatively regulates T cell proliferation. MS4a4B, therefore, may serve as a modulator in the negative-feedback regulatory loop of activated T cells.

  2. Role of radiation therapy for stage III thymoma

    International Nuclear Information System (INIS)

    Chun, Ha Chung; Lee, Myung Za

    2001-01-01

    To evaluate the effectiveness and tolerance of the postoperative radiation therapy for patients with Stage III thymoma and to define the optimal radiotherapeutic regimen. We retrospectively analyzed the records of 24 patients with Stage III thymoma who were referred for postoperative radiation therapy in our institution from June, 1987 to May, 1999. Surgical therapy consisted of total resection in one patient, subtotal resection in seventeen, and biopsy alone in six patients. Age of the patients was ranged from 20 to 62 years with mean age of 47 years. Male to female ratio was 14 to 10. Radiation therapy was delivered with linear accelerator producing either 6 MeV or 10 MeV photons. The irradiated volume included anterior mediastinum and known residual disease. The supraclavicular fossae were not irradiated. The delivered total dose was ranged from 30 to 56 Gy. One patient received 30 Gy and eighteen patients received minimum of 50 Gy. Follow up period was ranged from 12 months to 8 years with median follow up of 40 months. The overall local control rate for entire group of patients was 67% at 5 years. The cumulative local failure rates at one, three and five year were 18%, 28% and 33%, respectively. In patients treated with subtotal resection and biopsy alone, local control rate was 76% and 33%, respectively. The actuarial observed survival rate at 5 years was 57%, and actuarial adjusted survival at 5 years was 72%. The difference between 5 year survival rates for patients treated with subtotal resection and biopsy alone was not statistically significant (62% vs 30%). We might conclude that postoperative radiation therapy was safe and effective treatment for patients with Stage III thymoma. Postoperative radiation therapy is recommended in cases where tumor margin is close or incomplete resection is accomplished

  3. A chondrosarcoma in the anterior mediastinum mimicking a thymoma

    International Nuclear Information System (INIS)

    Østergaard, Mia L; Petersen, Rene H; Kalhauge, Anna

    2015-01-01

    A chondrosarcoma in the anterior mediastinum is a rare finding with a relatively good prognosis. We describe a case of a 75-year-old man with a 2-year history of neck discomfort and weight loss. Imaging showed a homogenous tumor with a minor compression on the anterior part of the heart. It had close relation to the ribs, no surrounding fat, and a thymoma was suspected. Biopsy prior to surgery was impossible due to the location of the tumor. Unfortunately, final pathology from the surgical specimen revealed a chondrosarcoma

  4. Complete atrioventricular block following radiation therapy for malignant thymoma

    International Nuclear Information System (INIS)

    Nakao, Takeshi; Kanaya, Honin; Namura, Masanobu; Ohsato, Kazuo; Araki, Tsutomu; Ohka, Takio; Sugihara, Norihiko; Takeda, Ryoyu.

    1990-01-01

    Complete atrioventricular block following radiation is very rare. We present a case which developed after radiation therapy for malignant thymoma. The etiology of conduction disturbances due to radiation is unknown. In our case, serial electrocardiograms showed stepwise progression of the conduction disturbance, and his bundle electrocardiograms revealed new prolongation of the H-V interval. Endomyocardial biopsy specimens demonstrated occlusion in small arteries and diffuse degenerative changes in the myocardium. We therefore attributed the complete atrioventricular block in our patient to secondary damage to the conduction system, caused by radiation-induced occlusive changes in the small arteries supplying the conduction system. (author)

  5. Incidental invasive thymoma during coronary artery bypass surgery

    International Nuclear Information System (INIS)

    Al-Smady, Moaath M.; Hammdan, Farouq F.; Abu-Abeeleh, Mahmood M.; Massad, Islam M.

    2009-01-01

    We encountered 2 incidental cases of invasive thymomas at Jordan University Hospital, Amman, Jordan: during the routine coronary artery bypass graft surgery between 2005 and 2008 with an incidence of 0.6%. Both patients presented with angina pain. None of the 2 patients had pressure symptoms (cough, shortness of breath or superior vena cava syndrome) or Myasthenia Gravis symptoms. Total thyectomy with dissection of perithymic fat was performed on both cases. No radiotherapy was given. No recurrence of the tumor was seen in 2 years follow-up. These cases are presented to emphasize the occurrence of this tumor. (author)

  6. Total body irradiation for myasthenia gravis with thymoma: case report

    International Nuclear Information System (INIS)

    Kang, Ki Mun; Choi, Ihl Bohng; Kim, In Ah

    1999-01-01

    Myasthenia Gravis (MG) is relatively rare occuring as one of important autoimmune disease to affect neuromuscular junction. This study was clinically to evaluate total body irradiation (TBI) against two patients including 33-year and 39-year females for chronic MG with thymoma who hospitalized in the St. Mary's Hospital, Catholic University since 1994 as well as who showed no response by thymectomy, immunotherapy and hormonal therapy. TBI designed by the dose of 150-180 cGy consisting of 10 cGy per fraction, three times a week, for 5-6 weeks using linear accelerator of 6 MV. During the treatment of TBI, they did complain acute side effect such as vomiting and also appear improved physical condition from 4-6 weeks after TBI. Through the follow-up period of 18 or 42 months after TBI, they did not have any symptomatic recurrence. Consequently, the results suggest that TBI can be used as an alternative tool for the patients concurrently for MG with thymoma who had been refractory to various conventional therapies like thymectomy, immunotherapy and hormonal therapy

  7. Role of radiotherapy in the management of thymoma

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, Samon; Saito, Yasuo; Takashima, Tsutomu; Watanabe, Yoh (Kanazawa Univ. (Japan). School of Medicine)

    1983-08-01

    Twenty-five cases with thymoma were treated in the department of Radiology of Kanazawa University from January, 1968 to December, 1981. All the patients recieved radiation therapy with or without operation. The effects of radiotherapy for thymoma were studied. The results and conclusions obtained were as follows; 1) Eight cases with stage III that recieved irradiation postoperatively, six of the eight cases showed the local control within the period between six months to seven years, excluding other two cases in which occurred the mediastinal and pleural disseminations. Therefore postoperative irradiation of 40- 50 Gy/4-5 weeks is considered to be necessary in stage III cases. 2) In 11 inoperable advanced cases, seven cases showed marked tumor regression on chest X-ray film and five cases showed the local control within the period between nine months and four years two months. Therefore long term survival may be possible if curative irradiation of 50-60 Gy/5-6 weeks is given for inoperable cases. 3) Concerning the cause of death, the mediastinal and pleural disseminations were very common, and local tumor progression, respiratory insufficiency by myasthenia gravis and distant metastasis were less common.

  8. The role of radiotherapy in the management of thymoma

    International Nuclear Information System (INIS)

    Miyata, Samon; Saito, Yasuo; Takashima, Tsutomu; Watanabe, Yoh

    1983-01-01

    Twenty-five cases with thymoma were treated in the department of Radiology of Kanazawa University from January, 1968 to December, 1981. All the patients recieved radiation therapy with or without operation. The effects of radiotherapy for thymoma were studied. The results and conclusions obtained were as follows; 1) Eight cases with stage III that recieved irradiation postoperatively, six of the eight cases showed the local control within the period between six months to seven years, excluding other two cases in which occurred the mediastinal and pleural disseminations. Therefore postoperative irradiation of 40- 50 Gy/4-5 weeks is considered to be necessary in stage III cases. 2) In 11 inoperable advanced cases, seven cases showed marked tumor regression on chest X-ray film and five cases showed the local control within the period between nine months and four years two months. Therefore long term survival may be possible if curative irradiation of 50-60 Gy/5-6 weeks is given for inoperable cases. 3) Concerning the cause of death, the mediastinal and pleural disseminations were very common, and local tumor progression, respiratory insufficiency by myasthenia gravis and distant metastasis were less common. (author)

  9. Total body irradiation for myasthenia gravis with thymoma: case report

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Ki Mun; Choi, Ihl Bohng; Kim, In Ah [College of Medicine, Catholic Univ., Seoul (Korea, Republic of)

    1999-06-01

    Myasthenia Gravis (MG) is relatively rare occuring as one of important autoimmune disease to affect neuromuscular junction. This study was clinically to evaluate total body irradiation (TBI) against two patients including 33-year and 39-year females for chronic MG with thymoma who hospitalized in the St. Mary's Hospital, Catholic University since 1994 as well as who showed no response by thymectomy, immunotherapy and hormonal therapy. TBI designed by the dose of 150-180 cGy consisting of 10 cGy per fraction, three times a week, for 5-6 weeks using linear accelerator of 6 MV. During the treatment of TBI, they did complain acute side effect such as vomiting and also appear improved physical condition from 4-6 weeks after TBI. Through the follow-up period of 18 or 42 months after TBI, they did not have any symptomatic recurrence. Consequently, the results suggest that TBI can be used as an alternative tool for the patients concurrently for MG with thymoma who had been refractory to various conventional therapies like thymectomy, immunotherapy and hormonal therapy.

  10. Thymic epithelial tumors: Comparison of CT and MR imaging findings of low-risk thymomas, high-risk thymomas, and thymic carcinomas

    International Nuclear Information System (INIS)

    Sadohara, Junko; Fujimoto, Kiminori; Mueller, Nestor L.; Kato, Seiya; Takamori, Shinzo; Ohkuma, Kazuaki; Terasaki, Hiroshi; Hayabuchi, Naofumi

    2006-01-01

    Objective: To assess the CT and magnetic resonance (MR) imaging findings of thymic epithelial tumors classified according to the current World Health Organization (WHO) histologic classification and to determine useful findings in differentiating the main subtypes. Materials and methods: Sixty patients with thymic epithelial tumor who underwent both CT and MR imaging were reviewed retrospectively. All cases were classified according to the 2004 WHO classification. The following findings were assessed in each case on both CT and MRI: size of tumor, contour, perimeter of capsule; homogeneity, presence of septum, hemorrhage, necrotic or cystic component within tumor; presence of mediastinal lymphadenopathy, pleural effusion, and great vessel invasion. These imaging characteristics of 30 low-risk thymomas (4 type A, 12 type AB, and 14 type B1), 18 high-risk thymomas (11 type B2 and seven type B3), and 12 thymic carcinomas on CT and MR imaging were compared using the chi-square test. Comparison between CT and MR findings was performed by using McNemar test. Results: On both CT and MR imaging, thymic carcinomas were more likely to have irregular contours (P < .001), necrotic or cystic component (P < .05), heterogeneous contrast-enhancement (P < .05), lymphadenopathy (P < .0001), and great vessel invasion (P < .001) than low-risk and high-risk thymomas. On MR imaging, the findings of almost complete capsule, septum, and homogenous enhancement were more commonly seen in low-risk thymomas than high-risk thymomas and thymic carcinomas (P < .05). MR imaging was superior to CT in the depiction of capsule, septum, or hemorrhage within tumor (all comparison, P < .05). Conclusion: The presence of irregular contour, necrotic or cystic component, heterogeneous enhancement, lymphadenopathy, and great vessel invasion on CT or MR imaging are strongly suggestive of thymic carcinomas. On MR imaging, the findings of contour, capsule, septum, and homogenous enhancement are helpful in

  11. A rare case of thymoma in a 15-month-old girl

    Energy Technology Data Exchange (ETDEWEB)

    Boylan, Emma; Wyers, Mary; Jaffar, Reema [Children' s Memorial Hospital, Department of Medical Imaging, Chicago, IL (United States)

    2011-11-15

    We report a case of thymoma in a 15-month-old girl successfully treated with thymectomy. This case is unique due to the very young age of the child and a family history of thymoma in the father, who was treated with resection at age 10. Radiographic and CT findings mimicked thymic hyperplasia, and highlight the difficulty of distinguishing between these two conditions, since the latter is more common in children. The case is followed by a discussion of thymic hyperplasia and thymoma. (orig.)

  12. Improvement of macrophage dysfunction by administration of anti-transforming growth factor-beta antibody in EL4-bearing hosts.

    Science.gov (United States)

    Maeda, H; Tsuru, S; Shiraishi, A

    1994-11-01

    An experimental therapy for improvement of macrophage dysfunction caused by transforming growth factor-beta (TGF-beta) was tried in EL4 tumor-bearing mice. TGF-beta was detected in cell-free ascitic fluid from EL4-bearers, but not in that from normal mice, by western blot analysis. The ascites also showed growth-suppressive activity against Mv1Lu cells, and the suppressive activity was potentiated by transient acidification. To investigate whether the functions of peritoneal macrophages were suppressed in EL4-bearers, the abilities to produce nitric oxide and tumor necrosis factor-alpha (TNF-alpha) upon lipopolysaccharide (LPS) stimulation were measured. Both abilities of macrophages in EL4-bearing mice were suppressed remarkably on day 9, and decreased further by day 14, compared with non-tumor-bearing controls. TGF-beta activity was abrogated by administration of anti-TGF-beta antibody to EL4-bearing mice. While a large amount of TGF-beta was detected in ascitic fluid from control EL4-bearers, little TGF-beta was detectable in ascites from EL4-bearers given anti-TGF-beta antibody. Furthermore, while control macrophages exhibited little or no production of nitric oxide and TNF-alpha on LPS stimulation in vitro, macrophages from EL4-bearers administered with anti-TGF-beta antibody showed the same ability as normal macrophages. These results clearly indicate that TGF-beta contributes to macrophage dysfunction and that the administration of specific antibody for TGF-beta reverses macrophage dysfunction in EL4-bearing hosts.

  13. The diagnosis of thymoma and thymic atrophy in patients with myasthenia gravis

    International Nuclear Information System (INIS)

    Sund, K.K.; Skeie, G.O.; Gilhus, N.E.; Aarli, J.A.; Varhaug, J.E.

    1997-01-01

    The authors have compared clinical, immunological and radiological data in 20 patients with myasthenia gravis and thymoma and in 21 patients with myasthenia gravis and thymic atrophy. The median age at onset was 54 years in the thymoma group and 63 years in the thymic atrophy group. The severity of the disease was similar in the two groups, and there was no significant difference in the concentration of acetylcholine receptor antibodies. CA antibodies were demonstrated in 17/20 thymoma patients and in 6/21 with thymic atrophy, while 19/20 thymoma patients had antibodies to titin, compared with 9/21 among those with thymic atrophy. The diagnosis and treatment of patients with myasthenia gravis is based upon an evaluation of clinical, immunological and radiological data. 28 refs., 2 tabs

  14. Two Invasive Thymomas Incidentally Found during Coronary Artery Bypass Graft Surgery

    Directory of Open Access Journals (Sweden)

    Navid Omidifar

    2016-01-01

    Full Text Available Thymoma, the most common neoplasm of the anterior mediastinum, is a rare tumor of thymic epithelium that can be locally invasive. We reported 2 cases of invasive thymoma incidentally found during routine coronary artery bypass graft (CABG surgery at Faghihee Hospital of Shiraz University of Medical Sciences of Iran in a period of about 6 months. The 2 patients were male and above 60 years old. They had no clinical symptoms and radiological evidence of mediastinal mass before detection of the tumor during operation. For both patients mass was completely excised and sent to the laboratory. The ultimate pathological diagnosis of both masses was invasive thymoma (stage 2. There are few reports in which thymomas were found incidentally during cardiac surgery. In spite of rare coincidence, due to being asymptomatic and possibly invasive, special attention to thymus gland during cardiac surgery or other mediastinal surgery and preoperative imaging studies seem to be reasonable approach.

  15. Malignant Thymoma with Widespread Metastases in a Dog: Case Report and Brief Literature Review

    OpenAIRE

    Mitcham, S. A.; Clark, E. G.; Mills, J. H. L.

    1984-01-01

    A malignant thymoma of epithelial type with metastases to the liver, spleen and bone marrow in a 16 year old female Cocker Spaniel dog is described. Lesions were considered to be incidental findings at necropsy.

  16. Imaging and intervention for coronary artery disease following irradiation of malignant thymoma

    International Nuclear Information System (INIS)

    Fatimi, S.H.

    2012-01-01

    Thymomas are rare malignant epithelial growths, constituting 20% of mediastinal tumours. Resection followed by irradiation may be employed in all thymomas except for stage 1 thymomas. Mediastinal irradiation is associated with coronary artery disease. The mean duration of presentation of post-irradiation coronary artery disease is 16 years (range 3-29 years). In our patient coronary artery disease was found only a year post irradiation. A 55 year old male who presented with complaints of dyspnoea, retrosternal chest pain and heaviness since one year underwent resection for malignant thymoma followed by radiotherapy. He presented with coronary artery disease a year after undergoing mediastinal irradiation. On follow-up, patient was treated successfully by coronary artery bypass graft. This case is an unusual occurrence and suggests that mediastinal irradiation may result in significant coronary artery disease as early as within one year. (author)

  17. Radiotherapy for invasive thymoma and thymic carcinoma. Clinicopathological review

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, R.; Stuecklschweiger, G.F.; Prettenhofer, U.; Stranzl, H.; Hackl, A. [Univ. Graz (Austria). Dept. of Radiotherapy; Beham-Schmid, C. [Univ. Graz (Austria). Dept. of Pathology; Groell, R. [Univ. Graz (Austria). Dept. of Radiology; Smolle-Juettner, F.M.; Renner, H. [Univ. Graz (Austria). Dept. of Thoracic and Hyperbaric Surgery; Quehenberger, F. [Univ. Graz (Austria). Dept. of Medical Informatics, Statistics and Documentation

    1999-06-01

    All 33 patients were irradiated with a mean dose of 50 Gy after complete resection (16 patients), partial resection (9 patients) of biopsy (8 patients). Staging was done according to the Masaoka classification; there were 12 Stage II, 12 Stage III and 9 Stage IV patients. Results: In patients with invasive thymoma Stage II to IV (median follow-up 54.4 months) Kaplan-Meier estimates of overall survival (OS), disease-specific (DSS) and disease-free survival (DFS) at 5 years were 63.7% (95% confidence interval [CI], 42 to 84%), 88.3% (CI, 75 to 100%) and 77,4% (CI, 58 to 95%), respectively. Among the prognostic factors tested, such as age, myasthenia gravis, completeness of surgery and histologic subclassification, total radiation dose, and Masaoka Stage, the latter was the only significant predictor of improved survival (p=0.04). Considering local control, radiation dose was a significant prognostic factor (p=0.0006). In patients with thymic carcinoma (median follow-up 43.4 months) 5 year DSS, and DFS were 22.2% (CI, 0 to 60%) and 16.7% (CI, 0 to 46%), respectively. Thymoma as compared to thymic carcinoma had a statistically significant better DSS (p=0.007) and DFS (p=0.0007). Conclusion: Postoperative radiotherapy with sufficient doses plays an important role as adjuvant treatment in complete or incomplete resected invasive Stage II to III thymoma. In unresectable thymoma Stage III to IV as well as in thymic carcinoma a multimodality approach should be considered to improve survival. (orig.) [Deutsch] Alle 33 Patienten wurden nach kompletter Resektion (n=16), Teilresektion (n=9) oder Biopsie (n=8) mit einer mittleren Dosis von 50 Gy (30 bis 60 Gy) bestrahlt. Die Stadieneinteilung nach Masaoka ergab jeweils zwoelf Patienten in Stadium II und III sowie neun Patienten im Stadium IV. Ergebnisse: Patienten mit einem invasivem Thymom Masaoka-Stadium II bis IV (mediane Nachsorgezeit 54,4 Monate) hatten ein Fuenf-Jahres-Gesamtueberleben, krankheitsspezifisches und

  18. Analysis of the radiation therapy outcomes and prognostic factors of thymoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seok Ho; Lee, Kyu Chan; Choi, Jin Ho; Lee, Jae Ik; Sym, Sun Jin; Cho, Eun Kyung [Gil Medical Center, Gachon University of Medicine and Science, Incheon (Korea, Republic of)

    2010-11-15

    This retrospective study was performed to evaluate the efficacy of radiation therapy (RT) and to investigate the prognostic factors for thymoma when treated with RT. We analyzed 21 patients with thymoma and also received RT from March 2002 to January 2008. The median follow-up time was 37 months (range, 3 to 89 months). The median patient age was 57 years (range, 24 to 77 years) and the gender ratio of males to females was 4 : 3. Of the 21 patients, complete resections (trans-sternal thymectomy) and R2 resections were performed in 14 and 1 patient, respectively. A biopsy was performed in 6 patients (28.7%). The WHO cell types in the 21 patients were as follows: 1 patient (4.8%) had type A, 10 patients (47.6%) had type B1-3, and 10 patients (47.6%) had type C. Based on Masaoka staging, 10 patients (47.6%) were stage II, 7 patients (33.3%) were stage III, and 4 patients (19.1%) were stage IVa. Three-dimensional RT was administered to the tumor volume (planned target volume), including the anterior mediastinum and the residual disease. The total RT dose ranged from 52.0 to 70.2 Gy (median dose, 54 Gy). Consistent with the WHO criteria, the response rate was only analyzed for the 6 patients who received a biopsy only. The prognostic factors analyzed for an estimate of survival included age, gender, tumor size, tumor pathology, Masaoka stage, the possibility of treatment by performing surgery, the presence of myasthenia gravis, and RT dose. The 3-year overall survival rate (OS) and the progression free survival rate (PFS) were 80.7% and 78.2%, respectively. Among the 10 patients with WHO cell type C, 3 of 4 patients (75%) who underwent a complete resection and 3 of 6 patients (50%) who underwent a biopsy survived. Distant metastasis developed in 4 patients (19.1%). The overall response rate in the 6 patients who received biopsy only were as follows: partial remission in 4 patients (66.7%), stable disease in 1 patient (16.6%), and progressive disease in 1 patient (16

  19. Analysis of the radiation therapy outcomes and prognostic factors of thymoma

    International Nuclear Information System (INIS)

    Lee, Seok Ho; Lee, Kyu Chan; Choi, Jin Ho; Lee, Jae Ik; Sym, Sun Jin; Cho, Eun Kyung

    2010-01-01

    This retrospective study was performed to evaluate the efficacy of radiation therapy (RT) and to investigate the prognostic factors for thymoma when treated with RT. We analyzed 21 patients with thymoma and also received RT from March 2002 to January 2008. The median follow-up time was 37 months (range, 3 to 89 months). The median patient age was 57 years (range, 24 to 77 years) and the gender ratio of males to females was 4 : 3. Of the 21 patients, complete resections (trans-sternal thymectomy) and R2 resections were performed in 14 and 1 patient, respectively. A biopsy was performed in 6 patients (28.7%). The WHO cell types in the 21 patients were as follows: 1 patient (4.8%) had type A, 10 patients (47.6%) had type B1-3, and 10 patients (47.6%) had type C. Based on Masaoka staging, 10 patients (47.6%) were stage II, 7 patients (33.3%) were stage III, and 4 patients (19.1%) were stage IVa. Three-dimensional RT was administered to the tumor volume (planned target volume), including the anterior mediastinum and the residual disease. The total RT dose ranged from 52.0 to 70.2 Gy (median dose, 54 Gy). Consistent with the WHO criteria, the response rate was only analyzed for the 6 patients who received a biopsy only. The prognostic factors analyzed for an estimate of survival included age, gender, tumor size, tumor pathology, Masaoka stage, the possibility of treatment by performing surgery, the presence of myasthenia gravis, and RT dose. The 3-year overall survival rate (OS) and the progression free survival rate (PFS) were 80.7% and 78.2%, respectively. Among the 10 patients with WHO cell type C, 3 of 4 patients (75%) who underwent a complete resection and 3 of 6 patients (50%) who underwent a biopsy survived. Distant metastasis developed in 4 patients (19.1%). The overall response rate in the 6 patients who received biopsy only were as follows: partial remission in 4 patients (66.7%), stable disease in 1 patient (16.6%), and progressive disease in 1 patient (16

  20. Mutational status of EGFR and KIT in thymoma and thymic carcinoma.

    Science.gov (United States)

    Yoh, Kiyotaka; Nishiwaki, Yutaka; Ishii, Genichiro; Goto, Koichi; Kubota, Kaoru; Ohmatsu, Hironobu; Niho, Seiji; Nagai, Kanji; Saijo, Nagahiro

    2008-12-01

    This study was conducted to evaluate the prevalence of EGFR and KIT mutations in thymomas and thymic carcinomas as a means of exploring the potential for molecularly targeted therapy with tyrosine kinase inhibitors. Genomic DNA was isolated from 41 paraffin-embedded tumor samples obtained from 24 thymomas and 17 thymic carcinomas. EGFR exons 18, 19, and 21, and KIT exons 9, 11, 13, and 17, were analyzed for mutations by PCR and direct sequencing. Protein expression of EGFR and KIT was evaluated immunohistochemically. EGFR mutations were detected in 2 of 20 thymomas, but not in any of the thymic carcinomas. All of the EGFR mutations detected were missense mutations (L858R and G863D) in exon 21. EGFR protein was expressed in 71% of the thymomas and 53% of the thymic carcinomas. The mutational analysis of KIT revealed only a missense mutation (L576P) in exon 11 of one thymic carcinoma. KIT protein was expressed in 88% of the thymic carcinomas and 0% of the thymomas. The results of this study indicate that EGFR and KIT mutations in thymomas and thymic carcinomas are rare, but that many of the tumors express EGFR or KIT protein.

  1. Prognosis and therapeutic response according to the world health organization histological classification in advanced thymoma

    International Nuclear Information System (INIS)

    Tagawa, Tetsuzo; Kometani, Takuro; Yamazaki, Koji

    2011-01-01

    The clinical efficacy of the World Health Organization (WHO) classification of thymoma has been reported to be a prognostic factor for patients with thymomas. This study focuses on the relationship between the therapeutic response and the WHO histological classification in patients with advanced thymoma. A retrospective review was performed on 22 patients with Masaoka stage III and IV thymoma treated from 1975 to 2007. There were 1, 1, 7, 3, and 10 patients with WHO histological subtypes A, AB, B1, B2, and B3, respectively. Surgery was performed on 10 patients. There were 2 complete resections, 2 incomplete resections, and 6 exploratory thoracotomies. Of 18 patients with unresectable tumors, 8, 5, and 5 were treated with radiotherapy, chemotherapy, and chemoradiotherapy as the initial therapy, respectively. The response rate in 9 patients with type A-B2 was significantly better than that in 9 patients with type B3 regardless of treatment modality (100% vs 11.1%, P=0.0001). Only the WHO classification was significantly associated with survival, with type B3 having a worse prognosis than A-B2 (P=0.01). Type B3 thymoma showed a lower response rate to treatments and thus shorter survival. The WHO classification is a good predictive factor for therapeutic response in advanced thymoma. (author)

  2. [Experimental study of interleukin-12 gene vaccines in the treatment of low-load malignant lymphoma (EL4)].

    Science.gov (United States)

    Jiang, Q; Da, W; Ou, Y

    2001-11-01

    Two kinds of murine interleukin-12 (mIL-12) fusion gene vaccines were used to treat the murine low-load malignant T cell lymphoma EL4 as minimal residual disease (MRD) model. C57BL/6 synergistical mice were subcutaneously inoculated with 1 x 10(6) wild-type (wt) EL4 tumor cells as low-load lymphoma model treated with two mIL-12 gene vaccines. Package cell line PA317/12 producing mIL-12 retrovirus (RV) was used as in vivo vaccine and EL4 tumor cells transferred with mIL-12 gene as ex vivo vaccine. In both mIL-12 gene vaccine-treated groups, there was no tumor growth in 50% mice 60 days after inoculation. Nine of these no tumor growth mice were re-challenged with 5 x 10(5) wt EL4 cells, and 5 of them survived without tumors in another 60 days. All control mice died with tumors within one month after inoculation. Among those developed tumors in both vaccine-treated groups, the development of tumors was delayed, the survival period prolonged (P EL4 MRD in C57BL/6 mice.

  3. CD44 standard and CD44v10 isoform expression on leukemia cells distinctly influences niche embedding of hematopoietic stem cells.

    Science.gov (United States)

    Erb, Ulrike; Megaptche, Amelie Pajip; Gu, Xiaoyu; Büchler, Markus W; Zöller, Margot

    2014-03-31

    A blockade of CD44 is considered a therapeutic option for the elimination of leukemia initiating cells. However, anti-panCD44 can interfere with hematopoiesis. Therefore we explored, whether a CD44 variant isoform (CD44v)-specific antibody can inhibit leukemia growth without attacking hematopoiesis. As a model we used CD44v10 transfected EL4 thymoma cells (EL4-v10). The therapeutic efficacy of anti-panCD44 and anti-CD44v10 was evaluated after intravenous application of EL4/EL4-v10. Ex vivo and in vitro studies evaluated the impact of anti-panCD44 and anti-CD44v10 as well as of EL4 and EL4-v10 on hematopoietic stem cells (HSC) in cocultures with bone marrow stroma cells with a focus on adhesion, migration, cell cycle progression and apoptosis resistance. Intravenously injected EL4-v10 grow in bone marrow and spleen. Anti-panCD44 and, more pronounced anti-CD44v10 prolong the survival time. The higher efficacy of anti-CD44v10 compared to anti-panCD44 does not rely on stronger antibody-dependent cellular cytotoxicity or on promoting EL4-v10 apoptosis. Instead, EL4 compete with HSC niche embedding. This has consequences on quiescence and apoptosis-protecting signals provided by the stroma. Anti-panCD44, too, more efficiently affected embedding of HSC than of EL4 in the bone marrow stroma. EL4-v10, by catching osteopontin, migrated on bone marrow stroma and did not or weakly interfere with HSC adhesion. Anti-CD44v10, too, did not affect the HSC--bone marrow stroma crosstalk. The therapeutic effect of anti-panCD44 and anti-CD44v10 is based on stimulation of antibody-dependent cellular cytotoxicity. The superiority of anti-CD44v10 is partly due to blocking CD44v10-stimulated osteopontin expression that could drive HSC out of the niche. However, the main reason for the superiority of anti-CD44v10 relies on neither EL4-v10 nor anti-CD44v10 severely interfering with HSC--stroma cell interactions that, on the other hand, are affected by EL4 and anti-panCD44. Anti-panCD44

  4. Peculiarities of diagnosis and surgical treatment of mediastinal thymomas complicated by myasthenia

    International Nuclear Information System (INIS)

    Gagua, R.; Todua, F.; Kuchava, V.; Gzirishvili, L.; Tsivtsivadze, G.; Vashakidze, M.

    2013-01-01

    The aim of this work is to improve the results of diagnosis and surgical treatment of mediastinal thymomas. With this reason, 128 patients with the tumors of thymus have been undergone operations at the Thoracic Department of the National Cancer Centre (NCC) of Georgia. Material and methods: Out of 128 patients, type A thymomas were diagnosed in 7, type AB - in 14, type B1 - in 52, typer B2 - in 32, type B3 - in 18 patients. Myasthenia was revealed in 51 patients. Most frequently myasthenia was found in type B1 (48.1%) and in type B2 (40.8%) thymomas while in type A and type AB - in 28.6% and in 28.5% correspondingly, but in type B3 myasthenia was found in 16.7%. Results: Helical Computerized Tomography (CT) is leading in diagnosis of mediastinal thymomas. Surgical method in the volume of thymomtymectomy is the best choice of treatment of thymomas and it is performed basically by sternotomic approach. The effectiveness of surgical treatment depended upon the optimization of patients presurgical preparing and it often included steroidal therapy and plasmapheresis. The period of post surgical liquidation of myasthenia signs was between 1 - 14 months. The remote results of treatment depend on histological type of tumor and its stage. At I-II stages of A and AB type thymomas, 100% of patients survived 5 and more years after radical operation, while in III stage - 86%. 5-year survival rate was 95-97% in thymomas of B1-3 types stage I, but at stage III it was no more than 38%. (author)

  5. Role of Adjuvant Radiotherapy for Stage II Thymoma After Complete Tumor Resection

    International Nuclear Information System (INIS)

    Chen Yidong; Feng Qinfu; Lu Haizhen; Mao Yousheng; Zhou Zongmei; Ou Guangfei; Wang Mei; Zhao Jun; Zhang Hongxing; Xiao Zefen; Chen Dongfu; Liang Jun; Zhai Yirui; Wang Luhua; He Jie

    2010-01-01

    Purpose: To determine whether patients with Masaoka stage II thymoma benefit from adjuvant radiation therapy after complete tumor resection. Methods and Materials: A total of 107 patients with stage II thymoma who underwent complete resection of their tumors between September 1964 and October 2006 were retrospectively analyzed. Sixty-six patients were treated with adjuvant radiotherapy, and 41 patients received surgery alone. Results: Eight patients (7.5%) had a relapse of their disease, including two patients (4.5%) who had surgery alone, and 6 patients (9.5%) who had adjuvant radiation therapy. Disease-free survival rates at 5 and 10 years were 92.3% and 82.6%, respectively, for the surgery-plus-radiation group, and 97.6% and 93.1%, respectively, for the group that underwent surgery alone (p = 0.265). Disease-specific survival rates at 5 and 10 years were 96.4% and 89.3%, respectively, for the surgery-plus-radiation group and 97.5% and 97.5% for the surgery group (p = 0.973). On univariate analysis, patients with type B3 thymomas had the lowest disease-free survival rates among all subtypes (p = 0.001), and patients with large thymomas (>7 cm) had lower disease-specific survival rates than those with small tumors (<7 cm) (p = 0.017). On multivariate analysis, histological type (type B3) thymoma was a significant independent prognostic factor. Conclusions: Adjuvant radiotherapy after complete tumor resection for patients with stage II thymoma did not significantly reduce recurrence rates or improve survival rates. Histological type (type B3) thymoma was a significant independent prognostic factor. Further investigation should be carried out using a multicenter randomized or controlled study.

  6. Role of radiation therapy in locally advanced thymoma

    International Nuclear Information System (INIS)

    Urgesi, A.; Monetti, U.; Rossi, G.; Ricardi, U.; Casadio, C.

    1990-01-01

    The records of all patients treated for thymoma in the Department of Radiotherapy of Torino University between 1970 and 1988 were reviewed. There were 59 in stage 3 and 18 in stage 4a; 74 patients were operated before radiotherapy and 3 had a pre-operative irradiation followed by surgery and post-operative boost. Complete resection was possible in 55.9 per cent of stage 3 cases and in none with stage 4a. Subtotal resection was done in 36.6 per cent of stage 3 patients and 83.3 per cent in stage 4a. 8 patients had only biopsy: 5 in stage 3 (8.5 per cent) and 3 in stage 4a (16.6 per cent). Post-operative radiation doses ranged between 39.6 and 46 Gy to the whole mediastinum followed by a 10-16 Gy boost on smaller fields in cases presenting residual disease after surgery. The pre-operative dose was 30 Gy followed by a post-operative boost of 16-24 Gy. Conventional fraction sizes of 1.8-2 Gy were always used. The 10 years survival rate was 58.3 per cent. There was a significant difference between stage 3 (70.9 per cent) and stage 4a (26.3 per cent)(p<0.0004). Survival of patients in stage 3 was not significantly affected by the type of surgery. No significant difference in survival or recurrence rate was observed in patients with different histologies and in patients with or without myasthenia. Thoracic relapses occurred in 15. 2 per cent of stage 3 patients and in 50 per cent of stage 4a patients (p<0.01). Only 7 relapses (9.1 per cent) were within the limits of the radiation field. Radiotherapy seems to be effective in reducing the risk of local recurrence and prolonging survival in patients operated upon for locally advanced thymoma. More patients are alive and free of disease at 10 years than those who received radical surgery. (author). 26 refs.; 4 figs.; 5 tabs

  7. Characteristics and construction problems of EL 4; Caracteristiques et problemes de construction d'EL4

    Energy Technology Data Exchange (ETDEWEB)

    Carle, R; Schulhof, P [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires; Sevin, Ph [Electricite de France (EDF), 75 - Paris (France); Buttin, J [Societe INDATOM (France)

    1964-07-01

    EL 4 is the prototype of a new series of reactors moderated with heavy water and cooled by carbon dioxyde. It was studied with a double purpose: - to realize a sufficiently large and complete reactor for testing the problems of construction and operation of this type of reactors; - to keep in this installation the possibility of adapting the improvements (new materials, improved fuel elements) studied in the R. and D. program. The first objective could not be considered without a considerable volume of preliminary work. This work included particularly the construction and testing from 1962 to 1964 of several prototype channels, out of pile, but under the actual temperature and pressure conditions. These tests showed the proper behaviour of the materials under the severe mechanical and chemical conditions of the reactor. These installations will, furthermore, be available for testing further modifications before adapting them to the reactor. Important tests concerning the safety of the reactor in the event of an explosion of the CO{sub 2} circuit have also been carried out. Construction itself began in July 1962 under the double direction of the Commissariat a l'Energie Atomique and Electricite de France. The civil engineering work will be finished in 1964. The airtight containment (in which it was considered preferable to house the reactor because of its prototype character) was built in pre-stressed concrete, a method which appeared to be particularly rapid and easy. The main piece of the reactor is the heavy water tank. This tank is composed of two double end plates equipped with 216 tubes and joined by a steel cylinder. Some difficult welding problems according to the specifications were solved during the construction of these bottoms. A rigorous series of controls by radiographies and ultrasonic methods was adapted to a complicated geometry. The assembly of the reactor unit, and particularly of the array of tubes supplying the 216 channels, was studied in every

  8. Rare association of thymoma, myasthenia gravis and sarcoidosis : a case report

    Directory of Open Access Journals (Sweden)

    Kurukumbi Mohankumar

    2008-07-01

    Full Text Available Abstract Introduction The association of thymoma with myasthenia gravis (MG is well known. Thymoma with sarcoidosis however, is very rare. We presented an interesting case with coexisting thymoma, MG and sarcoidosis. Case presentation A 59-year-old female patient with a history of sarcoidosis was admitted to the hospital with a one-day history of sudden onset of right-sided partial ptosis and diplopia. Neurosarcoidosis with cranial nerve involvement was considered, but was ruled out by the clinical findings, and MG was confirmed by the positive tensilon test, electrophysiological findings and positive acetylcholine receptor binding antibodies. On further evaluation, a CT chest scan showed a left anterior mediastinal mass and bilateral lymphadenopathy. Post surgical diagnosis confirmed the thymoma and sarcoidosis in the lymph nodes. Conclusion When two or more diseases of undetermined origin are found together, several interesting questions are raised. It is important to first confirm the diagnoses individually. Immunologic mechanisms triggering the occurrence of these diagnoses together, are difficult to address. Although the coexistence of thymoma, MG and sarcoidosis may be coincidental, it is noteworthy to report this case because of the multiple interesting features observed as well as the rarity of occurrence.

  9. Specific anti-EL4-lymphoma immunity in mice cured 2 years earlier with doxorubicin and interleukin-2.

    Science.gov (United States)

    Ehrke, M J; Verstovsek, S; Zaleskis, G; Ho, R L; Ujházy, P; Maccubbin, D L; Mihich, E

    1996-05-01

    This laboratory has reported the conditions for an effective, non-toxic, chemoimmunotherapy utilizing doxorubicin in combination with prolonged administration of interleukin-2 and the identification of the critical role of activated CD8+ T cells in the therapeutic effect. Mice (C57BL/6) cured in those studies have been followed for the remainder of their life spans. These mice, approximately 2 months of age when initially inoculated with syngeneic EL4 lymphoma, survived for more than 2 years, the normal life span of C57BL/6 mice. Mice 4 months old reinoculated with the EL4 cells all survived. At about 1 year of age mice were sacrificed and the ability of their thymocytes and splenocytes to develop specific CD8+ anti-EL4 activity was as high as it had been at the time of tumor rejection. At about 2 years of age EL4 was reimplanted into mice; all of them survived. These surviving mice, at 2 years 2 months of age, as well as a group of 2-year-old mice not rechallenged, were killed and functional antitumor activity and phenotype characteristics of various lymphocyte populations were determined in comparison to those of young and age-matched control mice. The phenotyping of the lymphocytes from the cured mice indicated very notable differences in subset distribution and increased CD44 expression. Functionally they developed high levels of anti-EL4 activity, which was ablated by combined treatment with monoclonal antibodies against CD8 and CD44, indicating the role of memory cells. Consistent with cells from aged mice, these same cell populations had a very reduced allogeneic responsiveness. It appears that cured mice have developed an immune memory specific for EL4.

  10. Differential immunotoxic effects of ethanol on murine EL-4 lymphoma and normal lymphocytes is mediated through increased ROS production and activation of p38MAPK.

    Science.gov (United States)

    Premachandran, Sudha; Khan, Nazir M; Thakur, Vikas S; Shukla, Jyoti; Poduval, T B

    2012-08-01

    Ethanol has been used to achieve thymic depletion in myasthenia gravis patients. Ethanol (95%) has also been used widely in the therapy of many tumors including hepatocellular carcinoma. In light of these findings, we delineated the differential immunotoxic behavior and mechanism of lower concentration of ethanol towards murine EL-4 lymphoma and its normal counterpart lymphocytes. EL-4 lymphoma and normal lymphocytes were cultured with ethanol (0%-5%) for 6 h and cytotoxicity was measured by various methods. EL-4 cells treated with ethanol showed concentration-dependent loss of viability at 2%-5% ethanol concentration and exhibit proliferative arrest at preG1 stage. Acridine-orange and ethidium-bromide staining indicated that ethanol induced death in EL-4 cells, by induction of both apoptosis and necrosis which was further supported by findings of DNA-fragmentation and trypan blue dye exclusion test. However, treatment of lymphocytes with similar concentration of ethanol did not show any death-associated parameters. Furthermore, ethanol induced significantly higher ROS generation in EL-4 cells as compared to lymphocytes and caused PARP cleavage and activation of apoptotic proteins like p53 and Bax, in EL-4 cells and not in normal lymphocytes. In addition, ethanol exposure to EL-4 cells led to phosphorylation of p38MAPK, and upregulation of death receptor Fas (CD95). Taken together, these results suggest that ethanol upto a concentration of 5% caused no significant immunotoxicity towards normal lymphocytes and induced cell death in EL-4 cells via phosphorylation of p38MAPK and regulation of p53 leading to further activation of both extrinsic (Fas) and intrinsic (Bax) apoptotic markers.

  11. Use of azathioprine for non-thymoma myasthenia and risk of cancer

    DEFF Research Database (Denmark)

    Pedersen, E G; Pottegård, Anton; Hallas, J

    2013-01-01

    BACKGROUND AND PURPOSE: To evaluate the association between the use of azathioprine and risk of cancer in patients with non-thymoma myasthenia gravis (MG) in a nationwide setting. METHODS: Case-control study based on population-based registries. Cases were patients with MG with a first time...

  12. Paraneoplastic myasthenia gravis and polymyositis secondary to a thymoma in a young woman

    DEFF Research Database (Denmark)

    Ezzatian-Ahar, Shabnam; Pedersen, Emil Arnspang; Schrøder, Henrik Daa

    2016-01-01

    We present the case of a 33-year-old woman who within weeks developed severe swallowing difficulties and weakness in her limbs to an extent requiring hospitalization. Workup confirmed clinically suspected diagnoses of polymyositis and autoimmune myasthenia. A suspicion of malignant thymoma based ...

  13. Histo-blood group antigens in human fetal thymus and in thymomas

    DEFF Research Database (Denmark)

    Engel, P; Dabelsteen, Erik; Francis, D

    1996-01-01

    -y, Le-x and sialyl-Le-x) of the ABO-histo-blood group system was investigated in 19 normal fetal thymuses (gestational age 16 to 39 weeks) and in 19 thymomas in order to study possible tumor-associated changes in the glycosylation pattern. The material was investigated by immunochemical stainings...

  14. [Symptoms of myasthenia gravis in a patient with a history of thymectomy for invasive thymoma].

    Science.gov (United States)

    Giraldo, Lilliana María; Duque, Camilo; Uribe, Carlos Santiago; Hernández, Olga Helena

    2015-01-01

    Myasthenia gravis is an antibody-mediated autoimmune disease. Approximately 10-15% of patients present with a thymoma, the presence of which is associated with greater severity of symptoms, myasthenic crisis, and irresponsiveness to front-line therapy. A thymectomy is recommended in young patients with generalized myasthenia gravis and in all patients presenting with thymoma. The patient was a 43-year-old woman, who first showed symptoms of myasthenic crisis in 2005 and presented with invasive thymoma managed with thymectomy and radiotherapy. In the subsequent three years, the patient presented with severe symptoms and two myasthenic crises that required mechanical ventilation and immunoglobulin treatment. Contrast chest computed tomography examinations showed no recurrence. Between 2009 and 2012, the patient experienced decreased symptom severity. In 2013, the patient presented with an exacerbation of symptoms; a contrast chest magnetic resonance scan showed a lesion in the anterior mediastinum, previously observed in 2011, suggestive of residual tissue as opposed to fibrosis. Regular management was started with immunoglobulins; a positron emission tomography scan was inconclusive, requiring a new resection, which showed no evidence of tumor recurrence. Patients with myasthenia gravis and those with myasthenia-related thymoma both share thymectomy as an element of treatment. However, following the procedure, exacerbation or reappearance of symptoms does not necessarily represent new alterations in the thymus.

  15. Paraneoplastic myasthenia gravis and polymyositis secondary to a thymoma in a young woman

    DEFF Research Database (Denmark)

    Ezzatian-Ahar, Shabnam; Pedersen, Emil Arnspang; Schrøder, Henrik Daa

    2016-01-01

    We present the case of a 33-year-old woman who within weeks developed severe swallowing difficulties and weakness in her limbs to an extent requiring hospitalization. Workup confirmed clinically suspected diagnoses of polymyositis and autoimmune myasthenia. A suspicion of malignant thymoma based...

  16. Immune selection of tumor cells in TCR β-chain transgenic mice.

    Science.gov (United States)

    Silaeva, Yulia Yu; Grinenko, Tatyana S; Vagida, Murad S; Kalinina, Anastasia A; Khromykh, Ludmila M; Kazansky, Dmitry B

    2014-10-01

    The concept of immunological surveillance implies that immunogenic variants of tumor cells arising in the organism can be recognized by the immune system. Tumor progression is provided by somatic evolution of tumor cells under the pressure of the immune system. The loss of MHC Class I molecules on the surface of tumor cells is one of the most known outcomes of immune selection. This study developed a model of immune selection based on the immune response of TCR 1d1 single β-chain transgenic B10.D2(R101) (K(d)I(d)D(b)) mice to allogeneic EL4 (H-2(b)) thymoma cells. In wild-type B10.D2(R101) mice, immunization with EL4 cells induced a vigorous CTL response targeted to the H-2K(b) molecule and results in full rejection of the tumor cells. In contrast, transgenic mice developed a compromised proliferative response in mixed-lymphocyte response assays and were unable to reject transplanted allogeneic EL4 cells. During the immune response to EL4 cells, CD8(+) T-lymphocytes with endogenous β-chains accumulated predominantly in the spleen of transgenic mice and only a small part of the T-lymphocytes expressing transgenic β-chains became CD8(+)CD44(+)CD62L(-) effectors. Then, instead of a full elimination of tumor cells as in wild-type mice, a reproducible prolonged equilibrium phase and subsequent escape was observed in transgenic mice that resulted in death of 90% of the mice in 40-60 days after grafting. Prolonged exposure of tumor cells to the pressure of the immune system in transgenic mice in vivo resulted in a stable loss of H-2K(b) molecules on the EL4 cell surface. Genetic manipulation of the T-lymphocyte repertoire was sufficient to reproduce the classic pattern of interactions between tumor cells and the immune system, usually observed in reliable syngeneic models of anti-tumor immunity. This newly-developed model could be used in further studies of immunoregulatory circuits common for transplantational and anti-tumor immune responses.

  17. Retroperitoneal extension via the retrocrural space of malignant thymoma and malignant pleural mesothelioma. Retrospective evaluation by CT

    Energy Technology Data Exchange (ETDEWEB)

    Ohkawara, Kiyoshi; Furuse, Makoto; Mizutani, Yoshihide; Ohsawa, Tadashi; Fujii, Takeshi [Jichi Medical School, Minamikawachi, Tochigi (Japan)

    1995-01-01

    We reviewed CT findings of 31 patients with malignant thymoma and one patient with malignant pleural mesothelioma in our institution. Transdiaphragmatic extension into the retroperitoneum via the retrocrural space was observed in 10% of malignant thymomas. In the same way, this spread from chest to abdomen was demonstrated in the case of malignant pleural mesothelioma. CT is especially useful in assessing extent of these tumors and determining the optimal treatment plan. (author).

  18. Retroperitoneal extension via the retrocrural space of malignant thymoma and malignant pleural mesothelioma. Retrospective evaluation by CT

    International Nuclear Information System (INIS)

    Ohkawara, Kiyoshi; Furuse, Makoto; Mizutani, Yoshihide; Ohsawa, Tadashi; Fujii, Takeshi

    1995-01-01

    We reviewed CT findings of 31 patients with malignant thymoma and one patient with malignant pleural mesothelioma in our institution. Transdiaphragmatic extension into the retroperitoneum via the retrocrural space was observed in 10% of malignant thymomas. In the same way, this spread from chest to abdomen was demonstrated in the case of malignant pleural mesothelioma. CT is especially useful in assessing extent of these tumors and determining the optimal treatment plan. (author)

  19. Maxillary Sinus Kaposi Sarcoma: Case Report in an HIV-Negative Patient with Thymoma

    Directory of Open Access Journals (Sweden)

    Bernardo Carvalho Araújo

    2017-01-01

    Full Text Available Introduction. Kaposi sarcoma is an angioproliferative disorder that requires infection with human herpesvirus 8 (HHV-8 for its development. The majority of cases are associated with HIV infection or other immunocompromising conditions. Thymomas are occasionally associated to cytopenia, which may alter the patients’ immune responses. Methods. Case report using clinical records. Results. Case report of a 46-year-old male patient diagnosed with thymoma and myasthenia gravis. The patient was referred to an otolaryngology consultation with complaints of facial pain in the right malar region, interpreted as an acute sinusitis. Following examination, an expansive maxillary sinus mass was found, and endoscopic surgery was undertaken. After careful investigation, it was diagnosed as a Kaposi sarcoma. Conclusions. It is thought to be the first described case of a maxillary sinus Kaposi sarcoma in an HIV-negative patient. Thus, this entity has to be considered in the differential diagnosis of sinus masses, even in non-HIV patients.

  20. Diagnostic imaging and treatment of an invasive thymoma in myasthenia gravis

    International Nuclear Information System (INIS)

    Soetje, G.; Brinkmann, G.; Striepling, E.; Engemann, R.

    1991-01-01

    A 40-year old woman with an invasive thymoma and myasthenia gravis is described in this article. Chest-x-ray, CT and MRI of the mediastinum could not offer definite results on tumour malignancy. Radical surgical removal was the consequence. This revealed a tumour infiltration of the pleura and pericardium; hence an adjuvant irradiation must have been performed. Mestinon-treatment was afterwards gradually reduced. (orig.) [de

  1. Correlative Imaging in a Patient with Cystic Thymoma: CT, MR and PET/CT Comparison

    International Nuclear Information System (INIS)

    Romeo, Valeria; Esposito, Alfredo; Maurea, Simone; Camera, Luigi; Mainenti, Pier Paolo; Palmieri, Giovannella; Buonerba, Carlo; Salvatore, Marco

    2015-01-01

    Cystic thymoma is a rare variant of thymic neoplasm characterized by almost complete cystic degeneration with mixed internal structure. We describe a case of a 60 year-old woman with a cystic thymoma studied with advanced tomographic imaging stydies. CT, MRI and PET/CT with 18 F-FDG were performed; volumetric CT and MRI images provided better anatomic evaluation for pre-operative assessment, while PET/CT was helpful for lesion characterization based on 18 F-FDG uptake. Although imaging studies are mandatory for pre-operative evaluation of cystic thymoma, final diagnosis still remains surgical. A 60-year-old woman with recent chest pain and no history of previous disease was admitted to our departement to investigate the result of a previous chest X-ray that showed bilateral mediastinal enlargement; for this purpose, enhanced chest CT scan was performed using a 64-rows scanner (Toshiba, Aquilion 64, Japan) before and after intravenous bolus administration of iodinated non ionic contrast agent; CT images demonstrated the presence of a large mediastinal mass (11×8 cm) located in the anterior mediastinum who extended from the anonymous vein to the cardio-phrenic space, compressing the left atrium and causing medium lobe atelectasis; bilateral pleural effusion was also present. In conclusion, correlative imaging plays a foundamental role for the diagnostic evaluation of patient with cystic thymoma. In particular, volumetric CT and MRI studies can provide better anatomic informations regarding internal structure and local tumor spread for pre-operative assessment. Conversely, metabolic imaging using 18 F-FDG PET/CT is helpful for lesion characterization differentiating benign from malignant lesion on the basis of intense tracer uptake. The role of PET/MRI is still under investigation. However, final diagnosis still remains surgical even though imaging studies are mandatory for pre-operative patient management

  2. Analysis of prognosis of thymoma from long-term follow-up

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Hiroshi; Masaki, Norie; Nishiyama, Kinji; Inoue, Takehiro; Matayoshi, Yoshinobu; Kozuka, Takahiro; Nakahara, Kazuya; Hashimoto, Jumpei

    1988-03-01

    In order to determine the prognosis and the mode of recurrence, a total of 108 cases of thymoma which were treated at the Department of Radiology and First Department of Surgery, Osaka University Hospital, were analyzed. Of the cases with complete resection followed by postoperative radiotherapy by 40 Gy/4 weeks (76 cases), ten-year survival of 88 % was obtained, which was in contrast to that with incomplete resection. Of the cases with Stages III and IVa with incomplete resection, recurrence-free survival was 62 % at 10 years, and recurrence occurred even 12 years after initial therapy. Local recurrence was found most frequently and was in 9 out of 10 recurred cases from invasive thymoma. Most recurrent cases led to fatal due to tumor. Lower neck was involved in only 3 cases through the entire course and distant metastasis was rather frequent at terminal stage (10 out of 13), sites being lung parenchyma (7), bone (4), liver (2) and brain (2), in order. Radiotherapy to hemithorax had been withheld in a case with Stage IVa, until pleural recurrence was clinically evident 10 years later. Myasthenia gravis was seen in 62 % of the cases, and was even higher (77 %) in encapsulated cases. Prognosis did not differ from the cases without myasthenia gravis under the same surgical stage. No apparent dose-response relationship was found in the radiotherapy of thymoma.

  3. Analysis of prognosis of thymoma from long-term follow-up

    International Nuclear Information System (INIS)

    Ikeda, Hiroshi; Masaki, Norie; Nishiyama, Kinji; Inoue, Takehiro; Matayoshi, Yoshinobu; Kozuka, Takahiro; Nakahara, Kazuya; Hashimoto, Jumpei

    1988-01-01

    In order to determine the prognosis and the mode of recurrence, a total of 108 cases of thymoma which were treated at the Department of Radiology and First Department of Surgery, Osaka University Hospital, were analyzed. Of the cases with complete resection followed by postoperative radiotherapy by 40 Gy/4 weeks (76 cases), ten-year survival of 88 % was obtained, which was in contrast to that with incomplete resection. Of the cases with Stages III and IVa with incomplete resection, recurrence-free survival was 62 % at 10 years, and recurrence occurred even 12 years after initial therapy. Local recurrence was found most frequently and was in 9 out of 10 recurred cases from invasive thymoma. Most recurrent cases led to fatal due to tumor. Lower neck was involved in only 3 cases through the entire course and distant metastasis was rather frequent at terminal stage (10 out of 13), sites being lung parenchyma (7), bone (4), liver (2) and brain (2), in order. Radiotherapy to hemithorax had been withheld in a case with Stage IVa, until pleural recurrence was clinically evident 10 years later. Myasthenia gravis was seen in 62 % of the cases, and was even higher (77 %) in encapsulated cases. Prognosis did not differ from the cases without myasthenia gravis under the same surgical stage. No apparent dose-response relationship was found in the radiotherapy of thymoma. (author)

  4. Clinical and serologic parallels to APS-I in patients with thymomas, and autoantigen transcripts in their tumors1

    Science.gov (United States)

    Wolff, Anette S. B.; Kärner, Jaanika; Owe, Jone F.; Oftedal, Bergithe E.V.; Gilhus, Nils Erik; Erichsen, Martina M.; Kämpe, Olle; Meager, Anthony; Peterson, Pärt; Kisand, Kai; Willcox, Nick; Husebye, Eystein S.

    2014-01-01

    Patients with the autoimmune polyendocrine syndrome type I (APS-I), caused by mutations in the autoimmune regulator (AIRE) gene, and myasthenia gravis (MG) with thymoma, show intriguing but unexplained parallels. They include uncommon manifestations like autoimmune adrenal insufficiency (AI), hypoparathyroidism (HP), and chronic mucocutaneous candidiasis (CMC) plus autoantibodies neutralizing IL-17, IL-22 and type I interferons. Thymopoiesis in the absence of AIRE is implicated in both syndromes. To test whether these parallels extend further, we screened 247 patients with MG and/or thymoma for clinical features and organ-specific autoantibodies characteristic of APS-I patients, and assayed 26 thymoma samples for transcripts for AIRE and 16 peripheral tissue-specific autoantigens (TSAgs) by quantitative PCR. We found APS-I-typical autoantibodies and clinical manifestations, including CMC, AI and asplenia, respectively in 49/121 (40%) and 10/121 (8%) thymoma patients, but clinical features seldom co-occurred with the corresponding autoantibodies. Both were rare in other MG subgroups (N=126). In 38 APS-I patients, by contrast, we observed neither autoantibodies against muscle antigens nor any neuromuscular disorders. Whereas relative transcript levels for AIRE and 7 of 16 TSAgs showed the expected under-expression in thymomas, levels were increased for 4 of the 5 TSAgs most frequently targeted by these patients’ autoAbs. Hence the clinical and serologic parallels to APS-I in patients with thymomas are not explained purely by deficient TSAg transcription in these aberrant AIRE-deficient tumors. We therefore propose additional explanations for the unusual autoimmune biases they provoke. Thymoma patients should be monitored for potentially life-threatening APS-I manifestations such as AI and HP. PMID:25230752

  5. Clinical and serologic parallels to APS-I in patients with thymomas and autoantigen transcripts in their tumors.

    Science.gov (United States)

    Wolff, Anette S B; Kärner, Jaanika; Owe, Jone F; Oftedal, Bergithe E V; Gilhus, Nils Erik; Erichsen, Martina M; Kämpe, Olle; Meager, Anthony; Peterson, Pärt; Kisand, Kai; Willcox, Nick; Husebye, Eystein S

    2014-10-15

    Patients with the autoimmune polyendocrine syndrome type I (APS-I), caused by mutations in the autoimmune regulator (AIRE) gene, and myasthenia gravis (MG) with thymoma, show intriguing but unexplained parallels. They include uncommon manifestations like autoimmune adrenal insufficiency (AI), hypoparathyroidism, and chronic mucocutaneous candidiasis plus autoantibodies neutralizing IL-17, IL-22, and type I IFNs. Thymopoiesis in the absence of AIRE is implicated in both syndromes. To test whether these parallels extend further, we screened 247 patients with MG, thymoma, or both for clinical features and organ-specific autoantibodies characteristic of APS-I patients, and we assayed 26 thymoma samples for transcripts for AIRE and 16 peripheral tissue-specific autoantigens (TSAgs) by quantitative PCR. We found APS-I-typical autoantibodies and clinical manifestations, including chronic mucocutaneous candidiasis, AI, and asplenia, respectively, in 49 of 121 (40%) and 10 of 121 (8%) thymoma patients, but clinical features seldom occurred together with the corresponding autoantibodies. Both were rare in other MG subgroups (n = 126). In 38 patients with APS-I, by contrast, we observed neither autoantibodies against muscle Ags nor any neuromuscular disorders. Whereas relative transcript levels for AIRE and 7 of 16 TSAgs showed the expected underexpression in thymomas, levels were increased for four of the five TSAgs most frequently targeted by these patients' autoantibodies. Therefore, the clinical and serologic parallels to APS-I in patients with thymomas are not explained purely by deficient TSAg transcription in these aberrant AIRE-deficient tumors. We therefore propose additional explanations for the unusual autoimmune biases they provoke. Thymoma patients should be monitored for potentially life-threatening APS-I manifestations such as AI and hypoparathyroidism. Copyright © 2014 by The American Association of Immunologists, Inc.

  6. Study of pressure losses in the EL 4 cluster

    International Nuclear Information System (INIS)

    Berriaud, Ch.

    1964-01-01

    The evolution of research on the EL-4 cluster is examined here from the pressure losses point of view. These may be split up into separate pressure losses along the rode and in pressure losses corresponding to various particularities of the cluster. Tests have been carried out on series of three or four clusters placed in a channel. Water was first used, and then carbon dioxide at 60 bars. In all cases the following two parameters were varied: the Reynolds' number, and the rotation of a cluster around its axis with respect to the surrounding clusters. The influence of the gap between to successive clusters has also been studied. The first tests were carried out on clusters without jackets, the subsequent ones on clusters fitted with jackets. It was thus possible to study various types of element assemblies. The results are given in the form of curves representing: the evolution of the independent pressure loss coefficients as a function of the Reynolds number. (author) [fr

  7. Resveratrol (trans-3,5,4'-trihydroxystilbene) suppresses EL4 tumor growth by induction of apoptosis involving reciprocal regulation of SIRT1 and NF-κB.

    Science.gov (United States)

    Singh, Narendra P; Singh, Udai P; Hegde, Venkatesh L; Guan, Hongbing; Hofseth, Lorne; Nagarkatti, Mitzi; Nagarkatti, Prakash S

    2011-08-01

    Understanding the molecular mechanisms through which natural products and dietary supplements exhibit anticancer properties is crucial and can lead to drug discovery and chemoprevention. The current study sheds new light on the mode of action of resveratrol (RES), a plant-derived polyphenolic compound, against EL-4 lymphoma growth. Immuno-compromised NOD/SCID mice injected with EL-4 tumor cells and treated with RES (100 mg/kg body weight) showed delayed development and progression of tumor growth and increased mean survival time. RES caused apoptosis in EL4 cells through activation of aryl hydrocarbon receptor (AhR) and upregulation of Fas and FasL expression in vitro. Blocking of RES-induced apoptosis in EL4 cells by FasL mAb, cleavage of caspases and PARP, and release of cytochorme c, demonstrated the participation of both extrinsic and intrinsic pathways of apoptosis. RES also induced upregulation of silent mating type information regulation 2 homolog, 1 (SIRT1) and downregulation of nuclear factor kappa B (NF-κB) in EL4 cells. siRNA-mediated downregulation of SIRT1 in EL4 cells increased the activation of NF-κB but decreased RES-mediated apoptosis, indicating the critical role of SIRT1 in apoptosis via blocking activation of NF-κB. These data suggest that RES-induced SIRT1 upregulation promotes tumor cell apoptosis through negative regulation of NF-κB, leading to suppression of tumor growth. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. An ectopic hamartomatous thymoma compressing left jugular vein

    African Journals Online (AJOL)

    2014-05-07

    May 7, 2014 ... tumor and verifying its attachments to other vital structures. Because of the mixed cellular components including epithelial cells, spindle cells and adipose ... conventional mixed tumors of skin adnexal or salivary gland origin, synovial sarcoma, a peripheral nerve sheath tumor variant, and cystic teratoma.

  9. English Language for Teachers (EL4T): a course for EFL teachers

    OpenAIRE

    Shrestha, Prithvi

    2013-01-01

    This paper reports on the design and implementation of EL4T in a large-scale project. EL4T is a self-study mobile technology-based ESP course designed to enhance Bangladeshi school English language teachers’ English language skills and pedagogical practices. Key implications of developing this course for ESP in EFL contexts will be presented.

  10. Associação timoma e estrongiloidíase intestinal grave Thymoma and severe intestinal strongyloidiasis association

    OpenAIRE

    Pérsio Godoy; Christian Marcellus Camargos Campos; Guilherme Costa; Lúcia Porto Fonseca de Castro

    1998-01-01

    Os autores relatam o caso de um homem de 59 anos de idade com timoma e estrongiloidíase intestinal grave. São revistos aspectos da resposta imunitária relacionados ao tumor e, possivelmente, implicados no desenvolvimento da hiperinfecção pelo Strongyloides stercoralis.A 59-years-old man with thymoma and severe intestinal strongyloidiasis is reported. The authors pointed out a possible influence of immunological response related with thymoma in the development of hyperinfection by Strongyloide...

  11. Postoperative Survival for Patients with Thymoma Complicating Myasthenia Gravis
- Preliminary Retrospective Results of the ChART Database

    Directory of Open Access Journals (Sweden)

    Fangrui WANG

    2016-07-01

    Full Text Available Background and objective It is so far not clear that how myasthenia gravis (MG affected the prognosis of thymoma patients. The aim of this assay is to compare the postoperative survival between patients with thymoma only and those with both thymoma and MG. Methods The Chinese Alliance for Research in Thymomas (ChART registry recruited patients with thymoma from 18 centers over the country on an intention to treat basis from 1992 to 2012. Two groups were formed according to whether the patient complicated MG. Demographic and clinical data were reviewed, Patients were followed and their survival status were analyzed. Results There were 1,850 patients included in this study, including 421 with and 1,429 without MG. Complete thymectomy were done in 91.2% patients in MG group and 71.0% in non-MG group (P<0.05. There were more percentage of patients with the histology of thymoma AB, B1, or B2 (P<0.05 in MG group, and more percentage of patients with MG were in Masaoka stage I and II. The 5 year and 10 year OS rates were both higher in MG group (93% vs 88%; 83% vs 81%, P=0.034 respectively. The survival rate was significantly higher in patients with MG when the Masaoka staging was III/IV (P=0.003. Among patients with advanced stage thymoma (stage III, IVa, IVb, the constituent ratios of III, IVa, IVb were similar between MG and Non-MG group. Histologically, however, there were significantly more proportion of AB/B1/B2/B3 in the MG group while there were more C in the non-MG group (P=0.000. Univariate analyses for all patients showed that MG, WHO classification, Masaoka stage, surgical approach, chemotherapy and radiotherapy and resectability were significant factors, and multivariate analysis showed WHO Classification, Masaoka stage, and resectability were strong independent prognostic indicators. Conclusion Although MG is not an independent prognostic factor, the survival of patients with thymoma was superior when MG was present, especially in late

  12. Malignant thymomas – The experience of the Portuguese Oncological Institute, Porto, and literature review

    Directory of Open Access Journals (Sweden)

    Berta Sousa

    2007-07-01

    Full Text Available Introduction: Epithelial thymic tumours (ETT, which comprise the majority of thymomas, are neoplasias developed from the epithelial cells of the thymus and constitute around 30% of anterior mediastinal masses in adults. Thymomas consist of cells with no cytological characteristics of malignity; malignant behaviour is determined by invasion of the capsule and adjacent structures. These tumours present a broad spectrum of clinical and morphological characteristics and the small series of known patients makes establishing a standard treatment difficult. Material and methods: A retrospective study was made into thymoma diagnosed patients admitted to the Portuguese Oncology Institute in Porto (IPOPorto from 1983 to 2004. Clinical characteristics were analysed and a histological classification made in accordance with World Health Organization criteria, Masaoka staging, and their relation to treatment methods. A review of the clinical records of these patients was then made, as well as a review of histological material for classification in line with 1999 WHO criteria. Results: Twenty-eight ETT patients were treated at the IPO-Porto between 1983 and 2004. Of these, 21 had invasive thymomas and these are the subject of this study. Eleven subjects were male and 10 female, with a median age of 55 years (24-79 years. The WHO histological classification was as follows: 2 patients (9.5% type A, 6 (28.6% type AB, 4 (19% type B1, 2 (9.5% type B2, 7 (33.4% type B3. Masaoka staging was 9 patients (42.8% with stage II, 6 (28.6% with stage III and 6 (28.6% with stage IVa. The majority of patients had local symptoms, with only one subject diagnosed with erythrocyte aplasia and five with Myasthenia Gravis (MG.The 6 patients who were given complete surgical resection only showed no evidence of disease recurrence (2 type A-II, 2 type AB-II, 1 type B1-II, 1 type B2- IVa, with follow-up from 8-144 months. Ten patients with complete resection received adjuvant treatment

  13. [Establishment of EL4 tumor-bearing mouse models and investigation on immunological mechanisms of anti-tumor effect of melphalan].

    Science.gov (United States)

    Li, Mo-lin; Li, Chuan-gang; Shu, Xiao-hong; Jia, Yu-jie; Qin, Zhi-hai

    2006-03-01

    To establish mouse lymphoma EL4 tumor-bearing mouse models in wild type C57BL/6 mice and nude C57BL/6 mice respectively, and to further investigate the immunological mechanisms of anti-tumor effect of melphalan. Mouse lymphoma EL4 cells were inoculated subcutaneously into wild type C57BL/6 mice (immune-competent mice). Twelve days later, melphalan of different doses were administered intraperitoneally to treat these wild type C57BL/6 tuomr-bearing mice. Tumor sizes were observed and recorded subsequently to find out the minimal dose of melphalan that could cure the tuomr-bearing mice. Then the same amount of EL4 tumor cells were inoculated subcutaneously into wild type C57BL/6 mice and nude C57BL/6 mice (T cell-deficient mice) simultaneously, which had the same genetic background of C57BL/6. Twelve days later, melphalan of the minimal dose was given intraperitoneally to treat both the wild type and nude C57BL/6 tuomr-bearing mice. Tumor sizes were observed and recorded in these two different types of mice subsequently. A single dose of melphalan (7.5 mg/kg) could cure EL4 tumor-bearing wild type C57BL/6 mice, but could not induce tumor regression in EL4 tumor-bearing nude C57BL/6 mice. A single dose of melphalan has obvious anti-tumor effect on mouse lymphoma EL4 tumor-bearing wild type C57BL/6mice, which requires the involvement of T lymphocytes in the host probably related to their killing functions.

  14. [Study of the immunological mechanism of anti-tumor effects of 5-FU by establishing EL4 tumor-bearing mouse models].

    Science.gov (United States)

    Li, Mo-Lin; Li, Chuan-Gang; Shu, Xiao-Hong; Li, Ming-Xia; Jia, Yu-Jie; Qin, Zhi-Hai

    2007-11-01

    To investigate the immunological mechanism of anti-tumor effect of 5-FU by establishing lymphoma EL4 tumor-bearing mouse models in wild type C57BL/6 mice and nude C57BL/6 mice, respectively. The mouse lymphoma EL4 cells were inoculated subcutaneously into wild type C57BL/6 mice (immune-competent mice). Twelve days later, 5-FU of different doses was administered intraperitoneally to treat these wild type C57BL/6 tumor-bearing mice. The size of tumors in the wild type C57BL/6 mice was observed and recorded to explore the minimal dose of 5-FU that could cure the tumor-bearing mice. Then the same amount of EL4 tumor cells was inoculated subcutaneously into wild type C57BL/6 mice and nude C57BL/6 mice (T cell-deficient mice) simultaneously, which had the same genetic background of C57BL/6. Twelve days later, 5-FU of the minimal dose was given intraperitoneally to treat both the wild type and nude C57BL/6 tumor-bearing mice. The size of tumors in the two different types of mice was observed and recorded. A single dose of 5-FU (75 mg/kg) cured both the EL4 tumor-bearing wild type C57BL/6 mice and the EL4 tumor-bearing nude C57BL/6 mice in the first week. Two weeks after 5-FU treatment, all of the nude mice died of tumor relapse while most of the wild type C57BL/6 mice were fully recovered. A single dose of 5-FU has marked anti-tumor effects on lymphoma EL4 tumor-bearing C57BL/6 mice with or without T lymphocytes. The relapse of tumors after 5-FU treatment might be related to the function of T lymphocytes.

  15. Pure Red Cell Aplasia Associated with Good Syndrome

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    Masayuki Okui

    2017-04-01

    Full Text Available Pure red cell aplasia (PRCA and hypogammaglobulinemia are paraneoplastic syndromes that are rarer than myasthenia gravis in patients with thymoma. Good syndrome coexisting with PRCA is an extremely rare pathology. We report the case of a 50-year-old man with thymoma and PRCA associated with Good syndrome who achieved complete PRCA remission after thymectomy and postoperative immunosuppressive therapy, and provide a review of the pertinent literature.

  16. Impact of radiotherapy on myasthenia gravis in patients with malignant thymomas

    International Nuclear Information System (INIS)

    Hou Xiuyu; Xu Yonggang; Gao Hong; Li Ming; Li Gaofeng; Liu Mingyuan

    2006-01-01

    Objective: To evaluate the change of myasthenia gravis(MG) during radiotherapy for patients with malignant thymomas. Methods: Forty-five with malignant thymomas patients with were analyzed. The median total dose was DT54.2 Gy in 1.8-2.0 Gy/fraction, 5 clays a week. Anti-cholinesterase, such as pyridostigmine was used to control the MG symptoms. Results: Forty-five patients completed radiotherapy on schedule except one from whom the treatment was was with drawn because of respiratory muscle involvement. Among these 44 patients, myasthenic symptom was relieved in 4 to various degrees, 4 progressed, 34 no change and 2 developed cholinergic crisis. Myasthenic symptom was not changed in one patient for whom radiotherapy had been standed before operation nor during the course of postoperative radiotherapy. Conclusions: A course of radiotherapy of DT54.2 Gy, on fractionation of DT1.8-2.0 Gy modal would not aggravate myasthenia. However, proper use of anti-cholinesterase, careful observation and timely drug-adjustment are necessary. (authors)

  17. Survival Impact of Adjuvant Radiation Therapy in Masaoka Stage II to IV Thymomas: A Systematic Review and Meta-analysis

    International Nuclear Information System (INIS)

    Lim, Yu Jin; Kim, Eunji; Kim, Hak Jae; Wu, Hong-Gyun; Yan, Jinchun; Liu, Qin; Patel, Shilpen

    2016-01-01

    Purpose: To evaluate the survival impact of postoperative radiation therapy (PORT) in stage II to IV thymomas, using systematic review and meta-analysis. Methods and Materials: A database search was conducted with EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to August 2015. Thymic carcinomas were excluded, and studies comparing overall survival (OS) with and without PORT in thymomas were included. The hazard ratios (HRs) of OS were extracted, and a random-effects model was used in the pooled analysis. Results: Seven retrospective series with a total of 1724 patients were included and analyzed. Almost all of the patients underwent macroscopically complete resection, and thymoma histology was confirmed by the World Health Organization criteria. In the overall analysis of stage II to IV thymomas, OS was not altered with the receipt of PORT (HR 0.79, 95% confidence interval [CI] 0.58-1.08). Although PORT was not associated with survival difference in Masaoka stage II disease (HR 1.45, 95% CI 0.83-2.55), improved OS was observed with the addition of PORT in the discrete pooled analysis of stage III to IV (HR 0.63, 95% CI 0.40-0.99). Significant heterogeneity and publication bias were not found in the analyses. Conclusions: From the present meta-analysis of sole primary thymomas, we suggest the potential OS benefit of PORT in locally advanced tumors with macroscopically complete resection, but not in stage II disease. Further investigations with sufficient survival data are needed to establish detailed treatment indications.

  18. Survival Impact of Adjuvant Radiation Therapy in Masaoka Stage II to IV Thymomas: A Systematic Review and Meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Yu Jin; Kim, Eunji [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Hak Jae, E-mail: khjae@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Wu, Hong-Gyun [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Yan, Jinchun [Department of Radiation Oncology, Dalian Medical University, Liaoning (China); Department of Radiation Oncology, Fudan University Cancer Hospital, Shanghai (China); Liu, Qin [The Wistar Institute, Philadelphia, Pennsylvania (United States); Patel, Shilpen [Department of Radiation Oncology, University of Washington Medical Center, Seattle, Washington (United States)

    2016-04-01

    Purpose: To evaluate the survival impact of postoperative radiation therapy (PORT) in stage II to IV thymomas, using systematic review and meta-analysis. Methods and Materials: A database search was conducted with EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to August 2015. Thymic carcinomas were excluded, and studies comparing overall survival (OS) with and without PORT in thymomas were included. The hazard ratios (HRs) of OS were extracted, and a random-effects model was used in the pooled analysis. Results: Seven retrospective series with a total of 1724 patients were included and analyzed. Almost all of the patients underwent macroscopically complete resection, and thymoma histology was confirmed by the World Health Organization criteria. In the overall analysis of stage II to IV thymomas, OS was not altered with the receipt of PORT (HR 0.79, 95% confidence interval [CI] 0.58-1.08). Although PORT was not associated with survival difference in Masaoka stage II disease (HR 1.45, 95% CI 0.83-2.55), improved OS was observed with the addition of PORT in the discrete pooled analysis of stage III to IV (HR 0.63, 95% CI 0.40-0.99). Significant heterogeneity and publication bias were not found in the analyses. Conclusions: From the present meta-analysis of sole primary thymomas, we suggest the potential OS benefit of PORT in locally advanced tumors with macroscopically complete resection, but not in stage II disease. Further investigations with sufficient survival data are needed to establish detailed treatment indications.

  19. Modulation of IL-33/ST2-TIR and TLR signalling pathway by fingolimod and analogues in immune cells.

    Science.gov (United States)

    Rüger, K; Ottenlinger, F; Schröder, M; Zivković, A; Stark, H; Pfeilschifter, J M; Radeke, H H

    2014-12-01

    For the immune modulatory drug fingolimod (FTY720), lymphocyte sequestration has been extensively studied and accepted as mode of action. Further, direct effects on immune cell signalling are incompletely understood. Herein, we used the parent drug and newly synthesized analogues to investigate their effects on dendritic cell (DC) calcium signalling and on Th1, Th2 and Th17 responses. DC calcium signalling was determined with a single cell-based confocal assay and IL-33/ST2-TIR Th2-like response with ST2-transduced EL4-6.1 thymoma cells. The Th1/Th17 responses were examined with a LPS/TLR-enhanced antigen presentation assay with OVA-TCRtg CD4 and CD8 spleen cells. Our results revealed a comparable influence of fingolimod and S1P on intracellular calcium level in DC, while an oxy-derivative of fingolimod exhibited an EC50 of 3.3 nm, being 14 times more potent than FTY720-P. The IL-33/ST2-TIR Th2-like response in ST2-EL4 cells was inhibited by fingolimod and analogues at varying degrees. Using the OVA-TCRtg LPS/TLR-enhanced spleen cell assay, we found that fingolimod inhibited both IL-17 and IFN-γ production. In contrast, fingolimod phosphate failed to decrease Th1 cytokines. Interestingly, the effects of the parent compound fingolimod were modulated by the PP2A inhibitor okadaic acid, thus suggesting PP2A as relevant intracellular target. These studies describe detailed immune-modulating properties of fingolimod, including interference with a prototypical Th2 response via IL-33/ST2-TIR. Moreover, differential effects of fingolimod versus its phosphorylated derivative on TLR-activated and antigen-dependent Th1 activation suggest PP2A as an additional target of fingolimod immune therapy. Together with the analogues tested, these data may guide the development of more specific fingolimod derivatives. © 2014 John Wiley & Sons Ltd.

  20. The diagnosis of thymoma and thymic atrophy in patients with myasthenia gravis; Dignostikk av tymom og thymusatrofi hos pasienter med myasthenia gravis

    Energy Technology Data Exchange (ETDEWEB)

    Sund, K.K.; Skeie, G.O.; Gilhus, N.E.; Aarli, J.A.; Varhaug, J.E. [Haukeland Sykehus, Bergen (Norway)

    1997-11-01

    The authors have compared clinical, immunological and radiological data in 20 patients with myasthenia gravis and thymoma and in 21 patients with myasthenia gravis and thymic atrophy. The median age at onset was 54 years in the thymoma group and 63 years in the thymic atrophy group. The severity of the disease was similar in the two groups, and there was no significant difference in the concentration of acetylcholine receptor antibodies. CA antibodies were demonstrated in 17/20 thymoma patients and in 6/21 with thymic atrophy, while 19/20 thymoma patients had antibodies to titin, compared with 9/21 among those with thymic atrophy. The diagnosis and treatment of patients with myasthenia gravis is based upon an evaluation of clinical, immunological and radiological data. 28 refs., 2 tabs.

  1. comparison of clinical features and CT findings between atypical thymoma and thymic carcinoma

    International Nuclear Information System (INIS)

    Wang Xiangyang; Tan Ye; Chen Juan; Wei Jiahu; Pan Jishun; Du Jun; Zhou Cheng

    2011-01-01

    Objective: To investigate the differences and the similarities of clinical presentations and CT features between type B3 thymoma (atypical thymoma) and type C thymoma (thymic carcinoma) in the WHO classification of thymic epithelial tumors. Methods: Complete CT findings of thirty cases of type B3 and seventeen cases of type C thymic epithelial tumors confirmed by histopathology according to WHO 2004 Classification System and clinical features including the prognosis of each case were reviewed retrospectively. Statistical analyses of the data for the age and the long diameter were performed with Independent-Samples t test between the two groups. Statistical analysis for gender, association with myasthenia gravis, method of the operation, contours, shapes, calcification,necrosis, enhancement pattern of the tumors on CT, presence of mediastinal lymphadenopathy, invasion of mediastinal fat, chest wall, pericardium, great vessel, pleural mediastinum, metastasis to the plural, pleural effusion, distant metastasis were performed with Fisher exact test. Kaplan-Meier method was employed for survival analysis. Results: Clinical data: the average age of type B3 group was significantly younger (t=-2.905, P=0.006). 90.0% (27/30) of patients in type B3 group were complicated by myasthenia gravis, while only 5.9% (1/17) of patients in type C group were complicated by myasthenia gravis. The difference between the two groups was statistically significant (P=0.000). The ratio of complete resection of type B3 group (80.0%) was significantly higher than that in type C group (P=0.001), 70.6% (12/17) of patients in type C group died within 2 years after surgical resection, while only 20.0% (6/30) of patients in type B3 group died within one to nine years after surgical resection. Three years' survival ratio of C group was 29.4%, and five years' survival ratio of C group was lower than 14.7%, which was significantly lower than B3 group five years' survival ratio was 94.7%), which was

  2. A three-dimensional mediastinal model created with rapid prototyping in a patient with ectopic thymoma.

    Science.gov (United States)

    Akiba, Tadashi; Nakada, Takeo; Inagaki, Takuya

    2015-01-01

    Preoperative three-dimensional (3D) imaging of a mediastinal tumor using two-dimensional (2D) axial computed tomography is sometimes difficult, and an unexpected appearance of the tumor may be encountered during surgery. In order to evaluate the preoperative feasibility of a 3D mediastinal model that used the rapid prototyping technique, we created a model and report its results. The 2D image showed some of the relationship between the tumor and the pericardium, but the 3D mediastinal model that was created using the rapid prototyping technique showed the 3D lesion in the outer side of the extrapericardium. The patient underwent a thoracoscopic resection of the tumor, and the pathological examination showed a rare middle mediastinal ectopic thymoma. We believe that the construction of mediastinal models is useful for thoracoscopic surgery and other complicated surgeries of the chest diseases.

  3. A case report of radiation-osteomyelitis 9 years after irradiation for thymoma

    International Nuclear Information System (INIS)

    Ohkubo, Ken-ichi; Itoi, Kazumi; Yanagihara, Kazuhiro; Matsuoka, Katsunari; Kuwabara, Masayoshi

    1992-01-01

    Radiation-osteomyelitis of the sternum is rare and usually difficult to cure. A 75-year-old man, who had undergone an exploratory sternotomy for a mediastinal tumor, not resected after all, 9 years earlier and received radiation therapy successively for the histological diagnosis of malignant thymoma, was admitted to our hospital with the chief complaint of fever and pus discharge of the anterior chest wall. He also suffered from diabetes mellitus. The skin around the fistula was dark-red and atrophic due to irradiation dermatitis and the manubrium was fissured in the midline. Open drainage and two-stage operation of direct closure was tried in vain. This case was treated succesfully by resection of necrosed portion of sternum and pectoral muscle flap closure. (author)

  4. Timoma do mediastino médio: relato de caso Middle mediastinal thymoma: case report

    Directory of Open Access Journals (Sweden)

    Elias Kallás

    2005-06-01

    Full Text Available Paciente do sexo feminino, 55 anos, branca, com sinais clínicos sugestivos de miastenia gravis há aproximadamente 3 meses. A prova terapêutica com neostigmina evidenciou melhora da disfagia e ptose palpebral. Na radiografia de tórax observou-se imagem ocupando o mediastino médio com projeção à direita. A tomografia computadorizada de tórax revelou a presença de massa no mediastino médio, sendo indicado o tratamento cirúrgico. Chamou nossa atenção a localização pouco usual, já que, preferencialmente, os timomas localizam-se no mediastino superior e anterior. A evolução pós-operatória foi boa, sem complicações.We report on a case of a 55-year-old female, patient, who presented with clinical signs suggestive of myasthenia gravis over a period of approximately 3 months. The therapeutic option using neostigmine gave an improvement of the dysphagia and palpebral ptosis. A chest radiograph image demonstrated a mass occupying the medium mediastinum with projection to the right. Computed tomography of the thorax revealed the presence of a mass in the medium mediastinum, and thus surgery was inicated. During the operation the was was observed in the medium mediastinum suggesting thymoma. What caught our attention was the unusual location of the tumor as normally thymomas are found in the upper and anterior mediastinum.

  5. Von Hippel-Lindau disease associated with myasthenia gravis not related to thymoma

    Directory of Open Access Journals (Sweden)

    Paolo Pozzato

    2013-04-01

    Full Text Available BACKGROUND Von Hippel-Lindau disease (VHL is a rare autosomal dominant inherited disorder characterized by an increased risk of tumours in a number of locations (eyes, brain, adrenal gland, pancreas, liver, kidneys, or other areas of the body. It is caused by germline mutation in the VHL gene. The VHL gene is a tumour suppressor gene that has been identified on the short arm of chromosome 3. CASE REPORT We report a case of a 60 year-old female with the clinical diagnosis of VHL type 1 (cerebellar haemangioblastoma, pancreatic cysts with subsequent steatorrhoea, and bilateral renal carcinoma who developed weakness and fatigability of skeletal muscles, left lid ptosis, snarling expression and nasal timbre speech. Acetylcholine receptor antibodies were negative in serum, while the electrodiagnostic test demonstrated an alteration of neuromuscolar junction which was consistent with the diagnosis of myasthenia gravis. Contrast-enhanced TC scan of the anterior mediastinum was performed, which excluded thymus enlargement. VHL gene evaluation in this patient identified a new mutation (c279delC9 and polymorphism c291C>G. At present the patient still suffers from ataxia and dysmetria due to cerebellar involvement in VHL, while fatigue and lid ptosis improved after the treatment with oral pyridostigmine 60 mg tid. DISCUSSION AND CONCLUSIONS To our knowledge this is the first report of a case of VHL associated with myasthenia gravis without thymoma. A case of VHL associated with a form of myasthenia gravis related to thymoma has been recently reported. In our case the absence of acetylcholine receptor antibodies may suggest a genetic origin also for the myasthenia gravis.

  6. Onset and Evolution of Clinically Apparent Myasthenia Gravis After Resection of Non-myasthenic Thymomas.

    Science.gov (United States)

    Mineo, Tommaso Claudio; Tamburrini, Alessandro; Schillaci, Orazio; Ambrogi, Vincenzo

    2018-03-06

    Patients with thymoma and without clinical or electromyographical myasthenic signs may occasionally develop myasthenia several years after thymectomy. Hereby, we investigated the predictors and the evolution of this peculiar disease. We performed a retrospective analysis in 104 consecutive patients who underwent thymectomy between 1987 and 2013 for thymoma without clinical or electromyographic signs of myasthenia gravis. Predictors of post-thymectomy onset of myasthenia gravis were investigated with univariate time-to-disease analysis. Evolution of myasthenia was analyzed with time-to-regression analysis. Eight patients developed late myasthenia gravis after a median period of 33 months from thymectomy. No significant correlation was found for age, gender, Masaoka's stage, and World Health Organization histology. Only high preoperative serum acetylcholine-receptor antibodies titer (>0.3 nmol/L) was significantly associated with post-thymectomy myasthenia gravis at univariate time-to-disease (P = 0.003) analysis. Positron emission tomography was always performed in high-titer patients, and increased metabolic activity was detected in 4 of these patients. Surgical treatment through redo-sternotomy or video-assisted thoracoscopy was performed in these last cases with a remission in all patients after 12, 24, 32 and 48 months, respectively. No patient under medical treatment has yet developed a complete remission. In our study the presence of preoperative high-level serum acetylcholine receptor antibodies was the only factor significantly associated with the development of post-thymectomy myasthenia gravis. The persistence of residual islet of ectopic thymic tissue was one of the causes of the onset of myasthenia and its surgical removal was successful. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Postoperative radiotherapy for completely resected Masaoka stage III thymoma: a retrospective study of 65 cases from a single institution

    International Nuclear Information System (INIS)

    Fan, Chengcheng; Hui, Zhouguang; Liang, Jun; Lv, Jima; Mao, Yousheng; Wang, Luhua; He, Jie; Feng, Qinfu; Chen, Yidong; Zhai, Yirui; Zhou, Zongmei; Chen, Dongfu; Xiao, Zefen; Zhang, Hongxing; Li, Jian

    2013-01-01

    The role of adjuvant radiotherapy (RT) for patients with stage III thymoma after complete resection is not definite. Some authors have advocated postoperative RT after complete tumor resection, but some others suggested observation. In this study, we retrospectively evaluated the effect of postoperative RT on survival as well as tumor control in patients with Masaoka stage III thymoma. Between June 1982 and December 2010, 65 patients who underwent complete resection of stage III thymoma entered the study. Fifty-three patients had adjuvant RT after surgery (S + R) and 12 had surgery only (S alone). Of patients who had adjuvant RT, 28 had three-dimensional conformal RT (3D-CRT)/intensity modulated RT (IMRT) and 25 had conventional RT. A median prescribed dose of 56 Gy (range, 28–60 Gy) was given. The median follow-up time was 50 months (range, 5–360 months). Five- and 10-year overall survival (OS) rates were 91.7% and 71.6%, respectively, for S + R and 81.5% and 65.2% for S alone (P = 0.5), respectively. In the subgroup analysis, patients with 3D-CRT/IMRT showed a trend of improved 5-year OS rate compared with conventional RT (100% vs. 86.9%, P =0.12). Compared with S alone, the 5-year OS rate was significantly improved (100% vs. 81.5%, P = 0.049). Relapses occurred in 15 patients (23.1%). There was a trend of lower crude local recurrence rates for S + R (3.8%) compared with S alone (16.7%) (P = 0.09), whereas the crude regional recurrence rates were similar (P = 0.9). No clear dose–response relationship was found according to prescribed doses. Adjuvant 3D-CRT/IMRT showed potential advantages in improving survival and reducing relapse in patients with stage III thymoma after complete resection, whereas adjuvant RT did not significantly improve survival or reduce recurrence for the cohort as a whole. Doses of ≤ 50 Gy may be effective and could be prescribed for adjuvant RT. To confirm the role of adjuvant 3D-CRT/IMRT in patients who undergo a complete

  8. Flux distribution by neutrons semi-conductors detectors during the startup of the EL4 reactor

    International Nuclear Information System (INIS)

    Fuster, S.; Tarabella, A.

    1967-01-01

    The Cea developed neutron semi-conductors detectors which allows a quasi-instantaneous monitoring of neutrons flux distribution, when placed in a reactor during the tests. These detectors have been experimented in the EL4 reactor. The experiment and the results are presented and compared with reference mappings. (A.L.B.)

  9. The regulation of CD5 expression in murine T cells

    Directory of Open Access Journals (Sweden)

    Herzenberg Leonard A

    2001-05-01

    Full Text Available Abstract Background CD5 is a pan-T cell surface marker that is also present on a subset of B cells, B-1a cells.Functional and developmental subsets of T cells express characteristic CD5 levels that vary over roughly a 30-fold range. Previous investigators have cloned a 1.7 Kb fragment containing the CD5 promoter and showed that it can confer similar lymphocyte-specific expression pattern as observed for endogenous CD5 expression. Results We further characterize the CD5 promoter and identify minimal and regulatory regions on the CD5 promoter. Using a luciferase reporter system, we show that a 43 bp region on the CD5 promoter regulates CD5 expression in resting mouse thymoma EL4 T cells and that an Ets binding site within the 43 bp region mediates the CD5 expression. In addition, we show that Ets-1, a member of the Ets family of transcription factors, recognizes the Ets binding site in the electrophoretic mobility shift assay (EMSA. This Ets binding site is directly responsible for the increase in reporter activity when co-transfected with increasing amounts of Ets-1 expression plasmid. We also identify two additional evolutionarily-conserved regions in the CD5 promoter (CD5X and CD5Y and demonstrate the respective roles of the each region in the regulation of CD5 transcription. Conclusion Our studies define a minimal and regulatory promoter for CD5 and show that the CD5 expression level in T cells is at least partially dependent on the level of Ets-1 protein. Based on the findings in this report, we propose a model of CD5 transcriptional regulation in T cells.

  10. Protective specific immunity induced by cyclophosphamide plus tumor necrosis factor alpha combination treatment of EL4-lymphoma-bearing C57BL/6 mice.

    Science.gov (United States)

    Krawczyk, C M; Verstovsek, S; Ujházy, P; Maccubbin, D; Ehrke, M J

    1995-06-01

    A combination treatment protocol initiated 12 days after tumor injection, when the tumor was large, by administering cyclophosphamide (CY, 150 or 250 mg/kg) intraperitoneally followed by intravenous tumor necrosis factor alpha (TNF alpha, 1000 units injection) on days 13, 16, 18, 21, and 23, resulted in about 60% long-term survival (i.e., survival for at least 60 days) in the syngeneic C57BL/6 mouse/EL4 lymphoma model system. The establishment of a specific antitumor immune memory and its possible therapeutic relevance was verified by reinjecting 60-day survivors with EL4 cells; all 60-day survivors that had received the combination treatments rejected the implants and survived for a further 60 days. Thymic cellularity was reduced during treatment and its recovery appeared to correlate with long-term survival and immunity. Thymocytes from mice treated with the combination were found to express significant levels of specific anti-EL4 cytolytic activity following a 4-day stimulation culture with X-irradiated EL4 cells and low concentrations of interleukin-2. This response could not be generated with thymocytes from naive animals. In each case the effect seen with the combination of a moderate CY dose (150 mg/kg) with TNF alpha was better than that seen with either dose of CY alone and equal to or better than that seen with the higher dose of CY combined with TNF alpha. These results indicate that treatment with a single moderate dose of CY in combination with TNF alpha is effective against a large, established tumor in this murine model. Furthermore, all the long-term survivors induced by this treatment developed protective immunity against reimplanted tumor and demonstrated a long-term specific immune memory in the thymus.

  11. Extrusion and drawing of zircaloy 2. Production of pressure tubes for EL-4; Filage et etirage du zircaloy 2. Realisation des tubes de force pour EL-4

    Energy Technology Data Exchange (ETDEWEB)

    Thevenet, J [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires; Buffet, J [Cefilac (France)

    1964-07-01

    The authors give briefly the physical mechanical and chemical properties of zircaloy 2, as far as the transformation of this alloy is concerned. Extrusion: After a few general remarks concerning the extrusion and co-extrusion, including a comparison of the deformation resistance of canning metals and of zircaloy 2, the following points are considered: - the difficulties occurring because of the use of this alloy: - atmosphere protection - adjustment on to the machine tools - low thermal conductivity - economy of the metal (price) - the factors affecting the quality of the extruded products extrusion under a copper can and under lubricant glass - fine grain structure - temperature homogeneity - working temperature The transformation cycle - '550 kg ingot - preliminary shape 'for drawing of EL-4 tubes (112 x 120 L 12 m)' - is described in detail (extrusion or forging of the {phi} = 340 ingot into {phi} = 220 billets, cutting into lengths and hot drilling at {phi} = 125, fixing into a copper can and rough extrusion). Drawing: The main difficulties are due to seizing of the tools and to the necessity of protecting the alloy from the atmosphere during annealings. A brief description is given of drawing out on a short mandrel, on a long mandrel, of laminating on a reducing machine and of the carrying out of an annealing, as well as of the production of EL-4 tubes ({phi} =107 x 113 L 430 m) by drawing out shapes having a size of 112 x 120 on long mandrels. Conclusion: It is possible by extrusion and drawing to produce zircaloy 2 tubes similar to those which may be obtained normally using stainless steel. (authors) [French] Les auteurs donnent un resume succint des proprietes physiques mecaniques et chimiques du zircaloy 2 en ce qui concerne la transformation de cet alliage. Filage: Apres quelques generalites sur le filage et le cofilage, dont une comparaison entre les resistances a la deformation des metaux de gainage et du zircaloy 2, on etudie successivement: - les

  12. Novel Immune Modulating Cellular Vaccine for Prostate Cancer

    Science.gov (United States)

    2014-10-01

    and B16 melanoma cells as control, the C57BL/6 syngeneic thymoma cell line, EL4 , transfected with mRNA encoding either GFP (control) or mPAP-SS were...only DC vaccine. Importantly, vaccine-induced cells also showed effector function against the hormone- 0 25 50 75 10 0 12 5 15 0 EL4 -GFP EL4 -PAP

  13. Advanced inoperable type B3 thymoma: monitoring of a novel therapeutic approach with radio-chemotherapy and sorafenib by FDG-PET and CT

    International Nuclear Information System (INIS)

    Winder, T.; Gasser, K.; Schuster, A.; Becherer, A.; Vries, A. de; Gruber-Moesenbacher, U.; Muendlein, A.; Drexel, H.; Lang, A.

    2010-01-01

    This report highlights the benefit of radio-chemotherapy followed by sorafenib in a 55 years old woman, diagnosed with an inoperable type B3 thymoma and illustrates the potential usefulness of 18 F-FDG in monitoring treatment with sorafenib. (orig.)

  14. Invasive medullary thymoma associated with myasthenia gravis: an unusual case Miastenia gravis em um paciente com timoma medular invasivo: relato de caso

    Directory of Open Access Journals (Sweden)

    JORGE S. REIS FILHO

    2000-12-01

    Full Text Available Thymomas are tumors characterized by a remarkable morphological heterogeneity and variable clinical behavior. This tumor has unique clinical associations, most notably with hematological abnormalities and myasthenia gravis. According with the Müller-Hermelink criteria, there are significant differences between the histological types of thymomas and the association with myasthenia gravis. Among the different histological types, medullary thymoma is the least frequent variant associated with this autoimmune disease. In this report we describe a case of medullary thymoma presenting in a 71-year- old woman with a myasthenic syndrome.Os timomas são tumores caracterizados por grande heterogeneidade morfológica e comportamento clínico variável. Este tumor apresenta associações clínicas singulares, principalmente com doenças hematológicas e com a miastenia gravis. De acordo com a classificação de Müller-Hermelink, existem diferenças significativas entre as variedades histológicas dos timomas e sua associação com a miastenia gravis. Entre os diferentes tipos histológicos, o timoma medular é a variante menos frequentemente associada com esta doença autoimune. Neste relato, nós descrevemos caso de timoma medular em uma paciente de 71 anos de idade com síndrome miastênica.

  15. A case of syndrome involving the inappropriate secretion of antidiuretic hormone developed during radiation therapy in a patient with invasive thymoma complicated with myasthenia gravis

    International Nuclear Information System (INIS)

    Chikuie, Naoki; Ishida, Simon; Sato, Tomohiko; Furutama, Daisuke; Sugino, Shyouichi; Kimura, Humihiro; Hanafusa, Toshiaki

    2007-01-01

    We present the case of a 56-year-old male with a syndrome involving the inappropriate secretion of antidiuretic hormone (SIADH), which developed during radiation therapy for invasive thymoma, complicated with myasthenia gravis (MG). Chest computed tomography revealed a huge mediastinal mass lesion spreading to the pulmonary artery, vena cava and pericardium. He was diagnosed with invasive thymoma, based on the pathological findings of a mediastinal tumor biopsy under computed tomography guidance. He received outpatient radiotherapy for the invasive thymoma, and two weeks after the initiation of radiation at a dose of 22 Gy, was admitted to our hospital because of hypercapnea due to weakness of the diaphragm and disturbance of consciousness. Laboratory examinations of the patient showed hyponatremia, plasma hypoosmolarity in the presence of concentrated urine and inappropriately increased concentration of the plasma antidiuretic hormone. He was also diagnosed as having myasthenia gravis, based on the existence of an anti-acetylcholine receptor antibody. The SIADH was treated by fluid restriction and sodium chloride, and MG was treated with plasma exchange and prednisolone. He recovered from respiratory failure, and his hyponatremia was improved. To our knowledge, this is a rare description of an invasive thymoma associated with SIADH. (author)

  16. Molecular genetic alterations in egfr CA-SSR-1 microsatellite and egfr copy number changes are associated with aggressiveness in thymoma.

    Science.gov (United States)

    Conti, Salvatore; Gallo, Enzo; Sioletic, Stefano; Facciolo, Francesco; Palmieri, Giovannella; Lauriola, Libero; Evoli, Amelia; Martucci, Robert; Di Benedetto, Anna; Novelli, Flavia; Giannarelli, Diana; Deriu, Gloria; Granone, Pierluigi; Ottaviano, Margaret; Muti, Paola; Pescarmona, Edoardo; Marino, Mirella

    2016-03-01

    The key role of egfr in thymoma pathogenesis has been questioned following the failure in identifying recurrent genetic alterations of egfr coding sequences and relevant egfr amplification rate. We investigated the role of the non-coding egfr CA simple sequence repeat 1 (CA-SSR-1) in a thymoma case series. We used sequencing and egfr-fluorescence in situ hybridization (FISH) to genotype 43 thymomas; (I) for polymorphisms and somatic loss of heterozygosity of the non-coding egfr CA-SSR-1 microsatellite and (II) for egfr gene copy number changes. We found two prevalent CA-SSR-1 genotypes: a homozygous 16 CA repeat and a heterozygous genotype, bearing alleles with 16 and 20 CA repeats. The average combined allele length was correlated with tumor subtype: shorter sequences were significantly associated with the more aggressive WHO thymoma subtype group including B2/B3, B3 and B3/C histotypes. Four out of 29 informative cases analysed for somatic CA-SSR-1 loss of heterozygosity showed allelic imbalance (AI), 3/4 with loss of the longer allele. By egfr-FISH analysis, 9 out of 33 cases were FISH positive. Moreover, the two integrated techniques demonstrated that 3 out of 4 CA-SSR-1-AI positive cases with short allele relative prevalence showed significantly low or high chromosome 7 "polysomy"/increased gene copy number by egfr-FISH. Our molecular and genetic and follow up data indicated that CA-SSR-1-allelic imbalance with short allele relative prevalence significantly correlated with EGFR 3+ immunohistochemical score, increased egfr Gene Copy Number, advanced stage and with relapsing/metastatic behaviour in thymomas.

  17. GRANULOCYTE INFILTRATION AND EXPRESSION OF THE PRO-ANGIOGENIC BV8 PROTEIN IN EXPERIMENTAL EL4 AND LEWIS LUNG CARCINOMA TUMORS.

    Science.gov (United States)

    Jiang, Kan; Kwak, Hyeongil; Tosato, Giovanna

    2013-01-18

    Although Vascular Endothelial Growth Factor (VEGF)-targeted therapies have shown efficacy in the treatment of certain advanced cancers, benefits to patients have been modest, which is attributed to tumor resistance to VEGF neutralization. Recent efforts to identify new targets to inhibit tumor angiogenesis have identified Bv8 (prokineticin 2), a myeloid cell-derived protein that promotes endothelial cell growth and tumor angiogenesis, but many mechanistic aspects of the pro-tumorigenic function of Bv8 are unclear. Here we demonstrate that CD11b+, Ly6C+, Ly6G+ granulocytes are the predominant cell source of Bv8 expression in bone marrow, spleen and in tumor tissues. Using granulocyte-deficient Growth factor independence-1 (Gfi1)-null mutant mice and normal littermates, we found that EL4 lymphoma tumors grow significantly larger in the granulocyte and Bv8-deficient mutant mice in comparison to the normal mice that display abundant tumor-associated granulocytes and Bv8 expression. Conversely, Lewis lung carcinoma (LLC-1) tumors grew to a significantly greater size in the normal mice in comparison to the Gfi1-null mice, but normal granulocyte tumor infiltration was modest. Quantitative analysis of tissue vascularization showed that EL4 and LLC-1 tumors from normal and Gfi1-mutant mice are similarly vascularized. These results confirm the critical contribution of the tumor microenvironment in determining the rate of tumor progression independently of tumor angiogenesis, and reveal some of the complexities of granulocyte and Bv8 functions in modulating tumor growth.

  18. Doxorubicin plus tumor necrosis factor alpha combination treatments in EL4-lymphoma-bearing C57BL/6 mice.

    Science.gov (United States)

    Ehrke, M J; Verstovsek, S; Ujházy, P; Meer, J M; Eppolito, C; Maccubbin, D L; Mihich, E

    1998-02-01

    The therapeutic efficacy of a total of 42 single-agent or combination protocols involving doxorubicin (Adriamycin, ADM) and tumor necrosis factor alpha (TNFalpha) were evaluated in the syngeneic murine lymphoma model, C57BL/6-EL4. Combination treatments were the most effective and the therapeutic effects were schedule-dependent; e.g. it was generally advantageous for ADM to precede TNFalpha administration. Two protocols selected for further study were 4 mg/kg ADM i.v. on days 1 and 8 plus TNFalpha, i.v., at either 16000 U (7 microg)/injection, on days 1 and 8 or 4000 U (1.7 microg)/injection, on days 11-15. Survival of mice bearing one of four EL4 sublines having different in vitro drug sensitivities was assessed. These sublines were E10 (ADM-sensitive/TNFalpha-resistant), E16 (sensitive/sensitive), ER2 (ADM-resistant/TNFalpha-sensitive) and ER13 (resistant/resistant). Between 80% and 100% long-term survivors (i.e. tumor free on day 60) were obtained with the two treatments in mice bearing ADM-sensitive sublines, even though one of these sublines, E10, was resistant to TNFalpha in vitro. Induction of long-term survival appeared, therefore, to correlate with in vitro defined sensitivity/resistance to ADM, but not to TNFalpha Treatment-induced modulations of tumoricidal immune effector functions were also examined. Taken together, the results indicated that induction of long-term survival involved complex interactions of: (1) ADM-induced tumor modifications, including, but not limited to, tumor debulking, (2) combination-treatment-induced modifications of splenic cytolytic T cell and macrophage activities, and (3) the restoration of thymus cellularity. Finally, when long-term survivors resulting from treatment of E10- or E16-bearing mice were implanted with ER2 on day 120, the majority survived, indicating that long-term immune memory, capable of recognizing drug resistant variants, had been established.

  19. Myasthenia gravis and thymoma: evaluation of 41 patients Miastenia grave e timoma: avaliação de 41 pacientes

    Directory of Open Access Journals (Sweden)

    JOSÉ LAMARTINE DE ASSIS

    1999-03-01

    Full Text Available We evaluated the epidemiological, clinical, laboratory and therapeutical aspects of 41 patients with thymomatous myasthenia gravis. Thirty five patients (85.36% were submitted to thymectomy. Follow-up ranged from two to 18 years. Diagnosis of thymoma was based upon clinical investigations and CT scan of the anterior mediastinum and in 11 patients supported by immunological tests of anti-striated muscle antibodies with a positive result in more than 80% of cases. Histopathologic examination of all thymomectomized patients confirmed the diagnosis of thymoma. There was a significant predominance of benign over malignant thymoma. Occurred higher prevalence of male patients and of patients over 40 years of age. The therapeutical strategy to control myasthenic clinical findings was the same as that for non-thymomatous myasthenia gravis. The corticosteroids associated to cytotoxic drugs were less often used. Radiotherapy of the anterior mediastinum was more often used in patients having invasive tumors submitted to surgery or not. With regard to survival and control of myasthenia gravis, especially in younger patients and in those submitted to early surgery, results of treatment were surprisingly favorable.Avaliamos 41 pacientes com miastenia grave timomatosa sob os aspectos epidemiológico, clínico e terapêutico. Trinta e cinco pacientes (85,36% foram timectomizados. O seguimento clínico variou de dois meses até 18 anos. O diagnóstico do timoma foi fundamentado no estudo de imagem do mediastino (tomografia axial computadorizada e, em 11 pacientes, complementado com a determinação sérica de anticorpos para músculo estriado com resultado positivo em mais de 80% dos casos e confirmado pelo exame anátomo-patológico do timo realizado em todos os pacientes operados. Ocorreu predomínio significante de timomas benignos sobre timomas malignos, forma clínica generalizada severa, frequente envolvimento do sexo masculino e, em pacientes com mais de

  20. The EL-4 reactor. Changing of a pressure tube on a test loop

    International Nuclear Information System (INIS)

    Foulquier, H.; Clara, P.

    1964-01-01

    Right from the beginning of the EL-4 project, the research convected with the overall design of the reactor was guided by the various technical specifications resulting from a justifiable concern about the reliability. The external and internal tubes of each layer situated in the reactor block had in particular to be interchangeable. The research alone into the dismantling of the external tube, i.e in fact the pressure tube, justified a certain number of full-scale tests on a model. The tests carried out under relevant conditions on a non-irradiated structure made it possible to define a complete ranger of of positioning and un-positioning sequences at a distance for such a pressure tube. (authors) [fr

  1. Extrusion and drawing of zircaloy 2. Production of pressure tubes for EL-4

    International Nuclear Information System (INIS)

    Thevenet, J.

    1964-01-01

    The authors give briefly the physical mechanical and chemical properties of zircaloy 2, as far as the transformation of this alloy is concerned. Extrusion: After a few general remarks concerning the extrusion and co-extrusion, including a comparison of the deformation resistance of canning metals and of zircaloy 2, the following points are considered: - the difficulties occurring because of the use of this alloy: - atmosphere protection - adjustment on to the machine tools - low thermal conductivity - economy of the metal (price) - the factors affecting the quality of the extruded products extrusion under a copper can and under lubricant glass - fine grain structure - temperature homogeneity - working temperature The transformation cycle - '550 kg ingot - preliminary shape 'for drawing of EL-4 tubes (112 x 120 L 12 m)' - is described in detail (extrusion or forging of the φ = 340 ingot into φ = 220 billets, cutting into lengths and hot drilling at φ = 125, fixing into a copper can and rough extrusion). Drawing: The main difficulties are due to seizing of the tools and to the necessity of protecting the alloy from the atmosphere during annealings. A brief description is given of drawing out on a short mandrel, on a long mandrel, of laminating on a reducing machine and of the carrying out of an annealing, as well as of the production of EL-4 tubes (φ =107 x 113 L 430 m) by drawing out shapes having a size of 112 x 120 on long mandrels. Conclusion: It is possible by extrusion and drawing to produce zircaloy 2 tubes similar to those which may be obtained normally using stainless steel. (authors) [fr

  2. Construction of the core of the 'heavy water-gas' reactor EL 4; Structures du coeur du reacteur 'eau- lourde-gaz EL 4'

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, J L; Foulquier, H; Thome, P [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1964-07-01

    The core of this reactor consists of a vessel containing heavy water, through which pass a series of pressure tubes for circulation of the cooling gas under boat pressure. The basic specifications which greatly influenced the design of this construction relate to aspects of safety in operation (fuel loading from both faces of the reactor, replacement of the components on both faces), neutronic demands (minimum absorption of the components lattice parameter, diameter of the pressure tubes) and thermal considerations (output temperature 500 C). These specifications have led to a' horizontal arrangement of the pressure tubes and raised very difficult problems of clearance, which make it impossible (for the dimensions of EL 4) to resort to expansion bellows on the pressure tubes. The result is a semi-rigid vessel in which the pressure tubes contribute to a large extent the mechanical resistance of the system by acting as a brace, whence the high stresses on the joints and pressure tubes (and the choice of zirconium alloys). The construction components include the pressure tube, the joints, the thermal insulation and the liner tube. A brief account is given of the testing methods used and the performances of these various units is particular. The safety factors foreseen for the pressure tube, and the design and manufacture, taking account of tolerances of the thickened ends necessary for fitting the tubes in place and designing the joints. The joints connecting the pressure tubes to the reactor tank, which are only accessible through the inside of the channel prolonging the pressure tube. These joints must not be a weak part in the construction. Two types have been developed: a rolled joint where the ends of the pressure tube are directly flanged onto the tank, and a welded joint using zircaloy-stainless steel transition pieces added to the ends of the pressure tube. All these joints are made by remote control and are removable. Two solutions have been found to the

  3. A case of late-onset, thymoma-associated myasthenia gravis with ryanodine receptor and titin antibodies and concomitant granulomatous myositis.

    Science.gov (United States)

    Stefanou, M I; Komorowski, L; Kade, S; Bornemann, A; Ziemann, U; Synofzik, M

    2016-09-13

    Myasthenia gravis is an autoimmune neuromuscular disorder, which has only rarely been reported to co-manifest with myositis. The diagnosis of concomitant myositis in patients with myasthenia gravis is clinically challenging, and requires targeted investigations for the differential diagnosis, including EMG, autoantibody assays, muscle biopsy and, importantly, imaging of the mediastinum for thymoma screening. This report presents a case-vignette of a 72-year-old woman with progressive proximal muscle weakness and myalgias, diagnosed with thymoma-associated myasthenia and bioptically verified granulomatous myositis, with positive autoantibody status for ryanodine receptor and titin antibodies. The diagnosis of concurrent myositis and myasthenia gravis, especially in the presence of ryanodine receptor and titin antibodies, should lead neurologists to adopt different treatment strategies compared to those applied in myasthenia or myositis alone. Moreover, further evidence is warranted that titin and, particularly, ryanodine receptor antibodies may co-occur or be pathophysiologically involved in myasthenia-myositis cases.

  4. Myasthenia Gravis With Thymoma, Manifesting as AChR-Ab-Positive, Distinct Bulbar Palsy Accompanied by Dysgeusia: A Case Series and Review of Literature

    Directory of Open Access Journals (Sweden)

    Kai Zhu

    2018-04-01

    Full Text Available In this review, we summarized three cases of myasthenia gravis (MG with taste disorder and describe their clinical features in detail. Three MG patients presented with significant bulbar palsy symptoms, high AChR-Ab titers, and negative MuSK-Ab, were diagnosed with thymoma. Furthermore, we observed that dysgeusia could manifest earlier than the occurrence of typical MG symptoms, even predict a MG relapse or a myasthenic crisis in the course of MG. We believe that dysgeusia is a non-motor symptom of MG, which especially exists in MG patients with thymoma and serious bulbar palsy. Therefore, being alert to this symptom may facilitate the early diagnosis of MG and judge the progress of the disease.

  5. Diagnostic imaging and treatment of an invasive thymoma in myasthenia gravis. Bildgebende Diagnostik und Therapie eines invasiven Thymoms mit Myasthenia gravis

    Energy Technology Data Exchange (ETDEWEB)

    Soetje, G.; Brinkmann, G. (Kiel Univ. (Germany, F.R.). Abt. Radiologie); Striepling, E.; Engemann, R. (Kiel Univ. (Germany, F.R.). Abt. Allgemeine Chirurgie)

    1991-05-01

    A 40-year old woman with an invasive thymoma and myasthenia gravis is described in this article. Chest-x-ray, CT and MRI of the mediastinum could not offer definite results on tumour malignancy. Radical surgical removal was the consequence. This revealed a tumour infiltration of the pleura and pericardium; hence an adjuvant irradiation must have been performed. Mestinon-treatment was afterwards gradually reduced. (orig.).

  6. Acute Respiratory Distress due to Thymoma in a Patient Treated with TK Inhibitor: A Case Report and Review of the Current Treatment Options

    Directory of Open Access Journals (Sweden)

    P. Zarogoulidis

    2011-03-01

    Full Text Available Thymic malignancies are rare intrathoracic tumors that may be aggressive and difficult to treat in advanced stage. Surgery is the cornerstone of the management of thymomas: it is significant for the definite histopathological diagnosis and staging, and in most cases, it constitutes the first step of the treatment strategy. For patients with primary unresectable thymomas, the multimodal treatment schedule nowadays includes neoadjuvant chemotherapy, extensive surgery, adjuvant radiotherapy, and in some cases, adjuvant chemotherapy. A patient with a history of stage III COPD and an undiagnosed thoracic mass was admitted to the intensive care unit with acute respiratory distress. A radiologic evaluation by CT scan revealed a mass of 13 cm in diameter at the mediastinum. Fine needle aspiration was performed and revealed a thymoma. Due to poor performance status, the patient was not able to undergo surgery. He refused to be treated with neither chemotherapy nor radiotherapy, but due to EGFR overexpression, treatment with TK inhibitor was suggested. Fine needle aspiration biopsy is commonly used to identify metastasis to the mediastinum. However, it is less often employed as a primary diagnostic tool for tumors, particularly thymic neoplasms. The use of targeted therapies for the treatment of thymic malignancies has been described in the literature. Over the past years, significant efforts have been made to dissect the molecular pathways involved in the carcinogenesis of these tumors. Insights have been obtained following anecdotal clinical responses to targeted therapies, and large-scale genomic analyses have been conducted.

  7. Delayed growth of EL4 lymphoma in SR-A-deficient mice is due to upregulation of nitric oxide and interferon-gamma production by tumor-associated macrophages.

    Science.gov (United States)

    Komohara, Yoshihiro; Takemura, Kenichi; Lei, Xiao Feng; Sakashita, Naomi; Harada, Mamoru; Suzuki, Hiroshi; Kodama, Tatsuhiko; Takeya, Motohiro

    2009-11-01

    Class A scavenger receptors (SR-A, CD204) are highly expressed in tumor-associated macrophages (TAM). To investigate the function of SR-A in TAM, wild-type and SR-A-deficient (SR-A(-/-)) mice were injected with EL4 cells. Although these groups of mice did not differ in the numbers of infiltrating macrophages and lymphocytes and in neovascularization, SR-A(-/-) mice had delayed growth of EL4 tumors. Expression of inducible nitric oxide (NO) synthase and interferon (IFN)-gamma mRNA increased significantly in tumor tissues from SR-A(-/-) mice. Engulfment of necrotic EL4 cells induced upregulation of NO and IFN-gamma production by cultured macrophages, and production of NO and IFN-gamma increased in SR-A(-/-) macrophages in vitro. IFN-beta production by cultured macrophages was also elevated in SR-A(-/-) macrophages in vitro. These results suggested that the antitumor activity of macrophages increased in SR-A(-/-) mice because of upregulation of NO and IFN-gamma production. These data indicate an important role of SR-A in regulating TAM function by inhibiting toll-like receptor (TLR)4-IFN-beta signaling.

  8. Development of Augmented Leukemia/Lymphoma-Specific T-Cell Immunotherapy for Deployment with Haploidentical, Hematompoietic Progenitor-Cell Transplant

    Science.gov (United States)

    2011-05-01

    cells exhibited redirected specific lysis of a genetically modified EL4 target expressing 92% human CD19 (Figure 6a). T cells not genetically modified...but propagated by crosslinking CD3 using g-irradiated aAPC loaded with OKT3 did not appreciably lyse CD19 EL4 cells (Figure 6b). DISCUSSION We and...by genetically modified T cells. Lysis by chromium release assay of CD19+ EL4 tumor cells compared with CD19 parental EL4 cells by (a) T cells

  9. Role of iNOS in Bystander Signaling Between Macrophages and Lymphoma Cells

    International Nuclear Information System (INIS)

    Ghosh, Somnath; Maurya, Dharmendra Kumar; Krishna, Malini

    2008-01-01

    Purpose: The present report describes the bystander effects of radiation between similar and dissimilar cells and the role of iNOS in such communication. Materials and Methods: EL-4 and RAW 264.7 cells were exposed to 5 Gy γ-irradiation. The medium from irradiated cells was transferred to unirradiated cells. Results: Irradiated EL-4 cells as well as those cultured in the presence of medium from γ-irradiated EL-4 cells showed an upregulation of NF-κB, iNOS, p53, and p21/waf1 genes. The directly irradiated and the bystander EL-4 cells showed an increase in DNA damage, apoptosis, and NO production. Bystander signaling was also found to exist between RAW 264.7 (macrophage) and EL-4 (lymphoma) cells. Unstimulated or irradiated RAW 264.7 cells did not induce bystander effect in unirradiated EL-4 cells, but LPS stimulated and irradiated RAW 264.7 cells induced an upregulation of NF-κB and iNOS genes and increased the DNA damage in bystander EL-4 cells. Treatment of EL-4 or RAW 264.7 cells with L-NAME significantly reduced the induction of gene expression and DNA damage in the bystander EL-4 cells, whereas treatment with cPTIO only partially reduced the induction of gene expression and DNA damage in the bystander EL-4 cells. Conclusions: It was concluded that active iNOS in the irradiated cells was essential for bystander response

  10. Introduction of OX40 ligand into lymphoma cells elicits anti-lymphoma immunity in vivo.

    Science.gov (United States)

    Kaneko, Hitomi; Hori, Toshiyuki; Yanagita, Soshi; Kadowaki, Norimitsu; Uchiyama, Takashi

    2005-03-01

    OX40, a member of the TNF receptor superfamily, and its ligand (OX40L) play crucial roles in induction and maintenance of integrated T cell immune response. Engagement of OX40L delivers a costimulatory signal to T cells. In this study, we investigated whether inoculation of OX40L-transfected EL4, a murine T cell lymphoma cell line, could induce anti-lymphoma immunity in mice. Female C57BL/6 mice were inoculated with 1 x 10(5) cells of parental EL4, OX40L-transfected EL4 (EL4-OX40L), or mock control vector-transfected EL4 (EL4-mock), and then the tumor size, overall survival, CTL activity of spleen cells, and the immunohistochemistry were compared. While both parental EL4 and EL4-mock grew rapidly, EL4-OX40L was rejected or grew slower than parental EL4 or EL4-mock. Pretreatment of mice with either anti-CD4 or anti-CD8 mAb accelerated the growth of EL4-OX40L, suggesting that both CD4+ and CD8+ T cells were involved in anti-lymphoma immunity. The immunohistochemical study revealed the infiltration of CD8+ T cells into the tumor of EL4-OX40L. In vitro CTL assay demonstrated that spleen cells of mice that had rejected EL4-OX40L had significant cytotoxic activity against parental EL4. The gene transfer of OX40L into lymphoma cells is an eligible and efficient modality to induce anti-lymphoma immunity.

  11. Anti-Apoptotic Signature in Thymic Squamous Cell Carcinomas - Functional Relevance of Anti-Apoptotic BIRC3 Expression in the Thymic Carcinoma Cell Line 1889c.

    Science.gov (United States)

    Huang, Bei; Belharazem, Djeda; Li, Li; Kneitz, Susanne; Schnabel, Philipp A; Rieker, Ralf J; Körner, Daniel; Nix, Wilfred; Schalke, Berthold; Müller-Hermelink, Hans Konrad; Ott, German; Rosenwald, Andreas; Ströbel, Philipp; Marx, Alexander

    2013-01-01

    The molecular pathogenesis of thymomas and thymic carcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and TCs, suggesting that other oncogenic principles might be important. This made us re-analyze historic expression data obtained in a spectrum of thymomas and thymic squamous cell carcinomas (TSCCs) with a custom-made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC.

  12. Anti-Apoptotic Signature in Thymic Squamous Cell Carcinomas – Functional Relevance of Anti-Apoptotic BIRC3 Expression in the Thymic Carcinoma Cell Line 1889c

    Science.gov (United States)

    Huang, Bei; Belharazem, Djeda; Li, Li; Kneitz, Susanne; Schnabel, Philipp A.; Rieker, Ralf J.; Körner, Daniel; Nix, Wilfred; Schalke, Berthold; Müller-Hermelink, Hans Konrad; Ott, German; Rosenwald, Andreas; Ströbel, Philipp; Marx, Alexander

    2013-01-01

    The molecular pathogenesis of thymomas and thymic carcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and TCs, suggesting that other oncogenic principles might be important. This made us re-analyze historic expression data obtained in a spectrum of thymomas and thymic squamous cell carcinomas (TSCCs) with a custom-made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC. PMID:24427739

  13. Anti-apoptotic signature in thymic squamous cell carcinomas - functional relevance of anti-apoptotic BIRC3 expression in the thymic carcinoma cell line 1889c

    Directory of Open Access Journals (Sweden)

    Bei eHuang

    2013-12-01

    Full Text Available The molecular pathogenesis of thymomas and thymic carcinomas (TCs is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and thymic carcinomas, suggesting that other oncogenic principles might be important. This made us re-analyze historic expression data obtained in a spectrum of thymomas and thymic squamous cell carcinomas (TSCC with a custom made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC.

  14. The fuel element of the first charge for EL 4; presentation, main problems arising in the research, production problems; L'element combustible du 1. jeu de EL 4; presentation, problemes essentiels poses par l'etude, problemes de fabrication

    Energy Technology Data Exchange (ETDEWEB)

    Ringot, C; Bailly, H; Bujas, R [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1964-07-01

    The fuel element making up the first charge for EL-4 is made of slightly enriched uranium oxide canned in stainless steel. This fuel element makes it possible to operate the reactor in the safest conditions awaiting the development of the fuel which will be finally adopted; this will have a low absorption can: beryllium, or a zirconium copper alloy. The 500 mm assembly is made up of 19 small rods placed on 3 rings, inside a graphite jacket. The solution adopted was a solution using completely independent small rods. This report deals with possible problems resulting from their study and production. (authors) [French] L'element combustible du 1er jeu EL-4 est un element combustible a oxyde d'uranium legerement enrichi gaine d'acier inoxydable. C'est un element combustible permettant de faire fonctionner le reacteur EL 4 dans des conditions aussi sures que possible avant de mettre au point le combustible definitif qui sera a gaine peu absorbante: beryllium, ou alliage zirconium-cuivre. L'assemblage de longueur 500 mm est constitue de 19 crayons places sur 3 couronnes, a l'interieur d'une chemise de graphite. La solution adoptee a ete une solution a crayons independants les uns des autres. Ce rapport traite des problemes eventuels poses par leur etude et leur fabrication. (auteurs)

  15. Algoritmo para el 4ap haciendo uso de la metaheuristica sistema hormiga

    Directory of Open Access Journals (Sweden)

    Manuel Vicente Centeno Romero

    2008-07-01

    Full Text Available La metaheurística sistema hormiga consiste en la analogía entre el procedimiento que utilizan las hormigas reales para la búsqueda de alimentos, encontrando la ruta más corta, y los problemas de optimización combinatoria para encontrar la mejor solución. Entre estos problemas se encuentra el de asignación multidimensional (mAP, el cual es un problema NP-difícil para m > 2. En la actualidad no se ha desarrollado trabajo alguno sobre el 4AP (mAP con m=4, tampoco existe publicación sobre la aplicación del sistema hormiga para el mAP. En este trabajo se desarrolló un software que hace uso de la metaheurística sistema hormiga para encontrar la mejor solución o aproximada al 4AP, con problemas generados aleatoriamente. Se implementó una metodología híbrida entre la metodología de Investigación de Operaciones descrita por Taha (1991 y la ingeniería de software (1990. El número de asignaciones tomadas en cuenta para verificar qué tan buenas son las soluciones arrojadas por el software, varía desde n=2 hasta n=25, obteniéndose soluciones exactas para 2 £ n £ 6, ya que al compararse dichas soluciones con las dadas por XPRESS (software de programación lineal que se usa para resolver modelos matemáticos se observa la igualdad en los resultados. Para n _ 7, XPRESS (la versión utilizada no ofrece respuesta alguna, pero el software desarrollado arroja buenos resultados en un tiempo computacional razonable, considerando el número de asignaciones que se procesan en cada n. The metaheuristic ant system consists on the analogy among the procedure used by the real ants for searching food, for finding the shortest route; and the problems of combinatoria optimization to find the best solution. Among these problems we can find the multidimensional assignment problem (mAP, which is a NP-difficult problem for m > 2. At the present time, there isn‘t any work that has been developed, on this topic about the 4AP (mAP with m=4, neither

  16. Blowing loop in the EL-4 reactor: CO{sub 2} flow control analogue study; Boucle de soufflage de la centrale EL-4 - regulation du debit CO{sub 2} - etude analogique

    Energy Technology Data Exchange (ETDEWEB)

    Chazal, G; Merle, J P; Guillemard, B [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires; Leroy, C; Robin, L; Jacquin, J C; Cornudet, A [Societe INDATOM, France (France)

    1966-07-01

    This report describes one study which contributed to the construction of the Monts d'Arree nuclear power station: EL-4. The reactor is cooled by a CO{sub 2} current provided by 3 turbo-blower groups. The priming vapour for the turbines is taken at the exit of the main CO{sub 2} - H{sub 2}O exchangers. The operation of EL 4 is based on a high degree of centralization of the controls which attributes an important role to the general regulation circuits. This general regulation includes in particular an internal blowing loop which controls the CO{sub 2} flow. The study of the control of this CO{sub 2} flow is made up of 3 parts: - analogue representation of the reactors cooling circuit and of the turbo blower unit. - first test campaign using the analogue computer describing the natural behaviour of the system in the absence of control. theoretical determination of the regulation factors; definition of the regulation using an analogue computer and second test campaign for recording the performances of the blowing loop. The 4. part of the report deals with the analogue study: analogue equations - development. (authors) [French] Ce rapport prend place parmi les etudes de realisation de la Centrale des Monts d'Arree EL-4. Le reacteur est refroidi par une circulation de CO{sub 2} assuree par 3 groupes turbosoufflantes. La vapeur d'entrainement des turbines est prelevee a la sortie des echangeurs principaux CO{sub 2} - H{sub 2}O. L'exploitation de EL-4 repose sur une centralisation poussee des moyens de controle-commande qui attribue un role essentiel aux circuits de regulation generale. Cette regulation generale comporte en particulier une boucle interne de soufflage qui realise un asservissement du debit de CO{sub 2}. L'etude de cette regulation du debit CO{sub 2} comprend 3 parties: - representation analogique du circuit de refroidissement du reacteur et de l'ensemble turbine-soufflante. - premiere campagne d'essais sur calculateur analogique decrivant le comportement

  17. [Relationship between sensitivity of tumor cells to chemotherapeutic agent in vivo and in vitro: experiment with mouse lymphoma cells].

    Science.gov (United States)

    Li, Chuan-gang; Li, Mo-lin; Shu, Xiao-hong; Jia, Yu-jie; Liu, Yong-ji; Li, Ming

    2007-06-12

    To study the relationship of the sensitivity of tumor cells to chemotherapeutic agent between in vivo and in vitro. Mouse lymphoma cells of the line E14 were cultured and melphalan resistant EL4 cell line (EL4/melphalan) was established by culturing EL4 cells with continuous low-concentration and intermittent gradually-increasing-concentration of melphalan in vitro. MTT assay was used to evaluate the drug sensitivity and the resistance index of the EL4/melphalan cells to melphalan was calculated. EL4/melphalan and EL4 cells of the concentration of 5 x 10(8)/L were inoculated separately into 20 C57BL/6 mice subcutaneously. 12 days later, the EL4 and EL4/melphalan tumor-bearing mice were randomly divided into 2 groups respectively, 5 mice in each group. Treatment groups were given 7.5 mg/kg melphalan intraperitoneally, and control groups were given the same volume of normal saline. The tumor size was observed every other day. Compared with the EL4 cells, the EL4/melphalan cells had no obvious changes morphologically. They could grow in RPMI 1640 medium containing 5 mg/ml melphalan. The resistance index was 2.87 against melphalan. After the treatment of melphalan of the dose 7.5 mg/kg, the tumor sizes of the treatment groups and control groups inoculated with both EL4 cells and the EL4/melphalan cells gradually decreased at the similar speed, and about one week later all tumors disappeared. However, the tumors of the control groups grew progressively and all the mice died at last. The chemotherapeutic effects of tumors in vivo have nothing to do with the effects of the chemotherapeutic agents on tumor cells in vitro. The tumor cells resistant to melphalan in vitro remain sensitive to the drug in vivo.

  18. MSA Mimic? Rare Occurrence of Anti-Hu Autonomic Failure and Thymoma in a Patient with Parkinsonism: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Vito A. G. Ricigliano

    2018-01-01

    Full Text Available Thymoma is a tumor originating from thymic gland, frequently manifesting with paraneoplastic neurological disorders. Its association with paraneoplastic dysautonomia is relatively uncommon. Here, we describe the challenging case of a 71 year-old female who developed subacute autonomic failure with digestive pseudo-obstruction, dysphagia, urinary tract dysfunction and orthostatic hypotension complicating an underlying extrapyramidal syndrome that had started 3 months before hospital admission. Autonomic symptoms had 2-month course and acutely worsened just before and during hospitalization. Combination of severe dysautonomia and parkinsonism mimicked rapidly progressing multiple system atrophy. However, diagnostic exams showed thymic tumor with positive anti-Hu antibodies on both serum and cerebrospinal fluid. Complete response of dysautonomia to immunoglobulins followed by thymectomy confirmed the diagnosis of anti-Hu-related paraneoplastic neurological syndrome. With regards to extrapyramidal symptoms, despite previous descriptions of paraneoplastic parkinsonism caused by other antineuronal antibodies, in our case no relation between anti-Hu and parkinsonism could be identified. A literature review of published reports describing anti-Hu positivity in thymic neoplasms highlighted that a definite autonomic disease due to anti-Hu antibodies is extremely rare in patients with thymoma but without myasthenia gravis, with only one case published so far.

  19. Impact of Surgical Evaluation of Additional Cine Magnetic Resonance Imaging for Advanced Thymoma with Infiltration of Adjacent Structures: The Thoracic Surgeon's View.

    Science.gov (United States)

    Ried, Michael; Hnevkovsky, Stefanie; Neu, Reiner; von Süßkind-Schwendi, Marietta; Götz, Andrea; Hamer, Okka W; Schalke, Berthold; Hofmann, Hans-Stefan

    2017-04-01

    Background  Preoperative radiological assessment is important for clarification of surgical operability for advanced thymic tumors. Objective was to determine the feasibility of magnetic resonance imaging (MRI) with cine sequences for evaluation of cardiovascular tumor invasion. Patients and Methods  This prospective study included patients with advanced thymoma, who underwent surgical resection. All patients received preoperative computed tomography (CT) scan and cine MRI. Results  Tumor infiltration was surgically confirmed in the pericardium ( n  = 12), myocardium ( n  = 1), superior caval vein (SCV; n  = 3), and aorta ( n  = 2). A macroscopic complete resection was possible in 10 patients, whereas 2 patients with aortic or myocardial tumor invasion had R2 resection. The positive predictive value (PPV) was 50% for cine MRI compared with 0% for CT scan regarding myocardial tumor infiltration. The PPV for tumor infiltration of the aorta was 50%, with a higher sensitivity for the CT scan (100 vs. 50%). Infiltration of the SCV could be detected slightly better with cine MRI (PPV 75 vs. 66.7%). Conclusion  Cine MRI seems to improve the accuracy of preoperative staging of advanced thymoma regarding infiltration of cardiovascular structures and supports the surgical approach. Georg Thieme Verlag KG Stuttgart · New York.

  20. Use of cadmium in solution in the EL 4 reactor moderator irreversible fixing of cadmium on the metallic surfaces; Utilisation du cadmium en solution dans le moderateur du reacteur EL 4 - fixation irreversible du cadmium sur les surfaces metalliques

    Energy Technology Data Exchange (ETDEWEB)

    Croix, O; Paoli, O; Lecomte, J; Dolle, L; Gallic, Y [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1964-07-01

    In the framework of research into the poisoning of the EL-4 reactor by cadmium sulphate, measurements have been made by two different methods of the residual amounts of cadmium liable to be fixed irreversibly on the surfaces in contact with the heavy water. A marked influence of the pH has been noticed. The mechanism of the irreversible fixing is compatible with the hypothesis of an ion-exchange in the surface oxide layer. In a sufficiently wide range of pH the cadmium thus fixed causes very little residual poisoning. The stability of the cadmium sulphate solutions is however rather low in the conditions of poisoning. (authors) [French] Dans le cadre des etudes sur l'empoisonnement du reacteur EL-4 par le sulfate de cadmium, les quantites residuelles de cadmium susceptibles de se fixer irreversiblement sur les parois que mouillerait l'eau lourde, ont ete mesurees experimentalement par deux methodes differentes. On observe une influence nette du pH. Le mecanisme de la fixation irreversible est compatible avec l'hypothese d'un echange d'ions dans la pellicule d'oxyde superficielle. Dans des limites suffisamment larges de pH, la cadmium ainsi fixe n'occasionne pas d'empoisonnement residuel important. La stabilite des solutions de sulfate de cadmium dans les conditions de l'empoisonnement est cependant mediocre. (auteurs)

  1. Methods of Containment Adopted for the EL4 Reactor and Projected Heavy-Water, Gas-Cooled Plants; Mode de Confinement Adopte pour le Reacteur EL4 et les Projets de Centrales Eau Lourde-Gaz

    Energy Technology Data Exchange (ETDEWEB)

    Schulhof, P.; Justin, F. [Commissariat a l' Energie Atomique, Paris (France)

    1967-09-15

    After a brief description of the plant, the paper explains the principles adopted for preventing the release of waste gas, from the EL4 reactor and refers to some of the difficulties associated with this type of containment. From the economic standpoint, the authors present the results of a comparative civil engineering study of pre-stressed concrete and steel shells for a projected 60 MW(e) power station, giving various values for accidental pressures. They demonstrate the influence of the stress values adopted. (author) [French] Les auteurs rappellent les principes adoptes dans le reacteur EL4 pour le confinement des rejets gazeux, apres une description sommaire des installations. Suivent quelques aspects des difficultes introduites par ce type de confinement. Dans le domaine economique, ils presentent le resultat d'une etude comparative de genie civil d'enceintes en beton precontraint et en acier pour un projet de centrale de 600 MW(e), avec diverses valeurs de pression accidentelle. Dans cette etude, ils font ressortir l'influence des valeurs admises pour le taux de travail des materiaux. (author)

  2. Functionalization and cellular uptake of boron carbide nanoparticles

    DEFF Research Database (Denmark)

    Mortensen, M. W.; Björkdahl, O.; Sørensen, P. G.

    2006-01-01

    In this paper we present surface modification strategies of boron carbide nanoparticles, which allow for bioconjugation of the transacting transcriptional activator (TAT) peptide and fluorescent dyes. Coated nanoparticles can be translocated into murine EL4 thymoma cells and B16 F10 malignant...

  3. [Antitumor effect of recombinant Xenopus laevis vascular endothelial growth factor (VEGF) as a vaccine combined with adriamycin on EL4 lymphoma in mice].

    Science.gov (United States)

    Niu, Ting; Liu, Ting; Jia, Yong-Qian; Liu, Ji-Yan; Wu, Yang; Hu, Bing; Tian, Ling; Yang, Li; Kan, Bing; Wei, Yu-Quan

    2005-09-01

    To explore the antitumor effect of immunotherapy with recombinant Xenopus laevis vascular endothelial growth factor (xVEGF) as a vaccine combined with adriamycin on lymphoma model in mice. EL4 lymphoma model was established in C57BL/6 mice. Mice were randomized into four groups: combination therapy, adriamycin alone, xVEGF alone and normal saline (NS) groups, and then were given relevant treatments. The growth of tumor, the survival rate of tumor-bearing mice, and the potential toxicity of regimens above were observed. Anti-VEGF antibody-producing B cells (APBCs) were detected by enzyme-linked immunospot (ELISPOT) assay. In addition, microvessel density (MVD) of tumor was detected by immunohistochemistry, and tumor cell apoptosis was also detected by TUNEL staining. The tumor volumes of mice were significantly smaller in combination group than those in other three groups (P < 0.05). Complete regression of tumor was observed in 3 of 10 mice in combination group. Forty-eight days after inoculation of tumor cells, the survival rate of mice was significantly higher in combination group than in NS group (P < 0.01). The anti-VEGF APBC count in combination group or xVEGF group was significantly higher, compared with that in adriamycin group or NS group (P < 0.01). MVD in tumor tissues was significantly lower in combination group than those in other three groups (P < 0.05). Moreover, tumor cell apoptosis was significantly higher in combination group than those in other three groups (P < 0.05). In this experimental study, the use of xVEGF vaccine and adriamycin as a combination of immunotherapy with chemotherapy has sucessfully produced synergistic antitumor effect on lymphoma in mice.

  4. Timomas malignos: A experiência do IPO do Porto e revisão da literatura Malignant thymomas: The experience of the Portuguese Oncological Institute, Porto, and literature review

    Directory of Open Access Journals (Sweden)

    Berta Sousa

    2007-07-01

    2-IVa, com follow-up variando entre 8 e 144 meses. 10 doentes com ressecção completa receberam tratamento adjuvante, 6 radioterapia (4 doentes B3-II, 2 doentes B3-III, 2 quimioterapia (AB-IVa e 2 radioterapia e quimioterapia (B1-IVa, B2-III. Apenas os 2 doentes que efectuaram quimioterapia adjuvante recidivaram, aos 168 e 46 meses, e morreram aos 168 e 49 meses. Os restantes doentes que efectuaram tratamento adjuvante encontram-se sem evidência de doença. Dos 5 doentes com ressecção incompleta seguido de tratamento complementar (2 doentes AB-III, 2 B1-IVa, 1 B3-III, 3 morreram aos 11 meses (B3-III, aos 12 meses (B1-IVa e aos 241 meses (AB-III, este último por MG. Conclusões: Apesar de se tratar de uma pequena série, os factores preditivos de mau prognóstico foram a ressecção incompleta, estádio avançado e o subtipo histológico B3. É necessário investigar o papel do tratamento adjuvante e neoadjuvante no grupo de doentes com doença avançada e subtipo histológico B3.Introduction: Epithelial thymic tumours (ETT, which comprise the majority of thymomas, are neoplasias developed from the epithelial cells of the thymus and constitute around 30% of anterior mediastinal masses in adults. Thymomas consist of cells with no cytological characteristics of malignity; malignant behaviour is determined by invasion of the capsule and adjacent structures. These tumours present a broad spectrum of clinical and morphological characteristics and the small series of known patients makes establishing a standard treatment difficult. Material and methods: A retrospective study was made into thymoma diagnosed patients admitted to the Portuguese Oncology Institute in Porto (IPOPorto from 1983 to 2004. Clinical characteristics were analysed and a histological classification made in accordance with World Health Organization criteria, Masaoka staging, and their relation to treatment methods. A review of the clinical records of these patients was then made, as well as a

  5. A case of radiation-related pneumonia and bilateral tension pneumothorax after extended thymectomy and adjuvant radiation for thymoma with myasthenia gravis

    International Nuclear Information System (INIS)

    Nakasone, Etsuko; Nakayama, Masayuki; Bando, Masashi; Endo, Shunsuke; Hironaka, Mitsugu; Sugiyama, Yukihiko

    2010-01-01

    A 62-year-old man was admitted to our hospital with a 2-month history of progressive cough and dyspnea. He had undergone thymectomy for thymoma with myasthenia gravis. Adjuvant radiation of 50 Gy had been performed until 6 months before the symptoms developed. Chest computed tomography showed infiltrative findings even outside the irradiated area. We diagnosed radiation-related pneumonia, and 30 mg per day prednisolone was initiated. On the final day, he developed bilateral tension pneumothorax. After chest tube drainage, the right S 5 bulla was resected with video-assisted thoracoscopic surgery (VATS). The right pneumothorax caused the bilateral tension pneumothorax, because the right and left thoracic cavity communicated in the anterior mediastinum after thymectomy. We should be aware of the risk of bilateral tension pneumothorax following radiation-related pneumonia after extended thymectomy and adjuvant radiation in patients with myasthenia gravis. (author)

  6. In vivo imaging of T cell lymphoma infiltration process at the colon.

    Science.gov (United States)

    Ueda, Yoshibumi; Ishiwata, Toshiyuki; Shinji, Seiichi; Arai, Tomio; Matsuda, Yoko; Aida, Junko; Sugimoto, Naotoshi; Okazaki, Toshiro; Kikuta, Junichi; Ishii, Masaru; Sato, Moritoshi

    2018-03-05

    The infiltration and proliferation of cancer cells in the secondary organs are of great interest, since they contribute to cancer metastasis. However, cancer cell dynamics in the secondary organs have not been elucidated at single-cell resolution. In the present study, we established an in vivo model using two-photon microscopy to observe how infiltrating cancer cells form assemblages from single T-cell lymphomas, EL4 cells, in the secondary organs. Using this model, after inoculation of EL4 cells in mice, we discovered that single EL4 cells infiltrated into the colon. In the early stage, sporadic elongated EL4 cells became lodged in small blood vessels. Real-time imaging revealed that, whereas more than 70% of EL4 cells did not move during a 1-hour observation, other EL4 cells irregularly moved even in small vessels and dynamically changed shape upon interacting with other cells. In the late stages, EL4 cells formed small nodules composed of several EL4 cells in blood vessels as well as crypts, suggesting the existence of diverse mechanisms of nodule formation. The present in vivo imaging system is instrumental to dissect cancer cell dynamics during metastasis in other organs at the single-cell level.

  7. Industrial Ultrasonic Inspection of Stainless-Steel Claddings for the EL4 Reactor; Controle Industriel par Ultrasons des Gaines en Acier Inoxydable du Reacteur EL4; Promyshlennyj kontrol' obolochechnykh trub iz nerzhaveyushchej stali reaktora dlya EL4 s pomoshch'yu ul'trazvukovogo metoda; Metodos Ultrasonicos para Control Industrial de las Vainas de Acero Inoxidable del Reactor EL4

    Energy Technology Data Exchange (ETDEWEB)

    Prot, A. C.; Foulquoer, H. E.; Peyrot, J. P. [Centre d' Etudes Nucleaires de Saclay (France)

    1965-09-15

    essentiel de rentabilite du reacteur. Il s'avere que le choix de la methode a utiliser et a mettre au point est delicat; le memoire en donne les elements essentiels. Ce choix etant fait, apres mise au point en laboratoire, deux nouveaux problemes se posent: - la transposition dans le domaine industriel; - la necessite de tenir compte de la qualite permise, a un instant determine, par les procedes de fabrication, en relation avec les normes de reception definies de maniere plus ou moins arbitraire. Ceci se traduit en fait par la necessite d'une etude statistique sur des lots de tubes de diverses provenances, et leur classement par rapport a des seuils plus ou moins severes. On verra que le nombre de tubes a controler est tres superieur a celui prevu initialement. Cela conduit a l'etude d'une machine de controle automatique, capable de satisfaire a la fois les exigences de cadence et celles propres au type de controle choisi: ces dernieres sont generalement d'ordre mecanique et necessitent une construction particulierement soignee. L'ensemble de ces considerations a conduit a concevoir une machine dont la cadence peut des maintenant couvrir sans difficulte les besoins d'une chaihe de fabrication d'elements combustibles. Les possibilites de cette machine sont etroitement liees aux caracteristiques du materiel de controle choisi, en particulier aux performances de l'electronique des appareils de controle par ultrasons et a celles des traducteurs utilises. Il resulte d'ailleurs de cette etude que le materiel standard ne repond que tres imparfaitement au probleme et que l'on doit envisager des maintenant un appareillage particulier pour ce type de controle. (author) [Spanish] Las mayores exigencias a que se someten los reactores obligan a utilizar materiales elaborados y controlados con sumo cuidado. Un aspecto de tal control se refiere a la calidad de las vainas empleadas, cuyas propiedades mecanicas ejercen una influencia decisiva sobre la rentabilidad del reactor. La eleccion

  8. Protective specific immunity induced by doxorubicin plus TNF-alpha combination treatment of EL4 lymphoma-bearing C57BL/6 mice.

    Science.gov (United States)

    Ehrke, M J; Verstovsek, S; Maccubbin, D L; Ujházy, P; Zaleskis, G; Berleth, E; Mihich, E

    2000-07-01

    The therapeutic efficacy of a single (day 8), moderate dose (4 mg/kg, i.v.) of doxorubicin (DOX, Adriamycin) combined with recombinant human TNF-alpha (3 different doses and 5 different schedules, i.v.) was evaluated in C57BL/6 mice bearing an implant (s.c.) of the DOX-sensitive, TNF-alpha-resistant EL4 lymphoma. In parallel to monitoring survival, the levels of several host anti-tumor cytolytic effector functions of splenocytes and thymocytes were evaluated throughout the treatment period and in long-term survivors (LTS). DOX treatment alone resulted in a moderate (approx. 20%) increase in life span but no cures. TNF-alpha alone, at any tested dose or schedule, had little or no positive effect on survival. The combinations of DOX and TNF-alpha were only slightly better than DOX alone with respect to the time to death of mice that died (approx. 29% increase); however, each of the combinations involving 1,000 U TNF-alpha/injection produced a fraction (20% to 80%) of LTS. The host defense activities examined included those of splenic and thymic cytolytic T lymphocytes (CTL) and lymphokine-activated killer cells as well as splenic tumoricidal macrophages. Although most activities were modulated by tumor growth and/or treatment, only CTL responsiveness appeared to correlate with survival. CTL activity in the treated groups with LTS was significantly higher than in control groups late in the treatment period. Finally, ex vivo analyses of splenocytes and thymocytes together with the rejection of implanted tumor at 17 months established that LTS displayed specific long-term immune memory. Copyright 2000 Wiley-Liss, Inc.

  9. Design of the Small Rods Forming the Fuel Element of the First Charge of the EL4 Reactor. Cladding Problems; Etude des crayons constituant l'element combustible du premier jeu d'EL4 - probleme de la gaine; Problema pokrytiya nebol'shikh steeknej, obrazushchikh toplivnyj ehlement pervoj zagruzki reaktora EL.4; Estudio de las barras que constituyen los elementos combustibles de la primera carga del reactor EL4 - el problema de las vainas

    Energy Technology Data Exchange (ETDEWEB)

    Bailly, H.; Ringot, C.; Weisz, M. [Centre d' Etudes Nucleaires de Saclay (France)

    1963-11-15

    The fuel element for the first charge of EL4 makes use of stainless steel cans. The grade of steel chosen and the can thickness depend on the corrosion resistance and mechanical strength required. The operating stresses and temperatures are such that fabrication of a can lasting throughout the life of the fuel element calls for a highly resistant grade of steel, of thickness greater than 0.5 mm. When the can bears on the fuel as a result of creep, deformation in diametrical clearance may lead to ovalization and folding, while deformation in longitudinal clearance may cause buckling of the can. Numerous tests have been carried out on cans of thickness 0.3 and 0.4 mm to determine type of deformation as a function of clearance. To be certain of avoiding ovalization with the thicknesses proposed and to keep the internal temperature of the fuel as low as possible, the clearance must be reduced to zero in fabrication. (author) [French] L'element combustible du premier jeu EL4 utilise des gaines en acier inoxydable. Le choix de la nuance et de l'epaisseur de la gaine est lie a des considerations de tenue a la corrosion et de tenue mecanique. Les contraintes et les temperatures d'utilisation ne permettent pas de concevoir une gaine resistante pendant toute la vie de l'element combustible a moins d'utiliser une nuance tres resistante et d'epaisseur superieure a 0,5 mm. On admet que la gaine s'applique par fluage sur le combustible: la deformation dans les jeux diametraux peut conduire a la formation d'une ovalisation et d'un pli; la deformation dans les jeux longitudinaux peut conduire a des flambages de la gaine. De nombreux essais ont ete realises sur des gaines d'epaisseurs 0,3 et 0,4 mm pour connaitre le mode de deformation en fonction des jeux. Pour etre certain de ne jamais avoir d'ovalisation avec les epaisseurs envisagees, et pour avoir la temperature a coeur du combustible la plus basse possible, on est conduit a reduire a zero le jeu en fabrication. (author

  10. Comparison of CT and chemical-shift MRI for differentiating thymoma from non-thymomatous conditions in myasthenia gravis: value of qualitative and quantitative assessment

    International Nuclear Information System (INIS)

    Priola, A.M.; Priola, S.M.; Gned, D.; Giraudo, M.T.; Fornari, A.; Veltri, A.

    2016-01-01

    Aim: To evaluate the usefulness of computed tomography (CT) and chemical-shift magnetic resonance imaging (MRI) in patients with myasthenia gravis (MG) for differentiating thymoma (THY) from thymic lymphoid hyperplasia (TLH) and normal thymus (NT), and to determine which technique is more accurate. Materials and methods: Eighty-three patients with generalised MG who underwent surgery were divided into the TLH/NT group (A; 65 patients) and THY group (B; 24 patients). Differences in qualitative characteristics and quantitative data (CT: radiodensity in Hounsfield units; MRI: signal intensity index [SII]) between groups were tested using Fisher's exact test and Student's t-test. Logistic regression models were estimated for both qualitative and quantitative analyses. At quantitative analysis, discrimination abilities were determined according to the area under the receiver operating characteristic (ROC) curve (AUROC) with computation of optimal cut-off points. The diagnostic accuracies of CT and MRI were compared using McNemar's test. Results: At qualitative assessment, MRI had higher accuracy than CT (96.4%, 80/83 and 86.7%, 72/83, respectively). At quantitative analysis, both the radiodensity and SII were significantly different between groups (p<0.0001). For CT, at quantitative assessment, the AUROC of the radiodensity in discriminating between groups was 0.904 (optimal cut-off point, 20 HU) with an accuracy of 77.1% (64/83). For MRI, the AUROC of the SII was 0.989 (optimal cut-off point, 7.766%) with an accuracy of 96.4% (80/83), which was significantly higher than CT (p<0.0001). By using optimal cut-off points for cases with an erroneous diagnosis at qualitative assessment, accuracy improved both for CT (89.2%, 74/83) and MRI (97.6%, 81/83). Conclusion: Quantitative analysis is useful in evaluating patients with MG and improves the diagnostic accuracy of CT and MRI based on qualitative assessment. Chemical-shift MRI is more reliable than CT in differentiating

  11. Baicalein induces cell death in murine T cell lymphoma via inhibition of thioredoxin system.

    Science.gov (United States)

    Patwardhan, Raghavendra S; Pal, Debojyoti; Checker, Rahul; Sharma, Deepak; Sandur, Santosh K

    2017-10-01

    We have earlier demonstrated the radioprotective potential of baicalein using murine splenic lymphocytes. Here, we have studied the effect of baicalein on murine T cell lymphoma EL4 cells and investigated the underlying mechanism of action. We observed that baicalein induced a dose dependent cell death in EL4 cells in vitro and significantly reduced the frequency of cancer stem cells. Previously, we have reported that murine and human T cell lymphoma cells have increased oxidative stress tolerance capacity due to active thioredoxin system. Hence, we monitored the effect of baicalein on thioredoxin system in EL4 cells. Docking studies revealed that baicalein could bind to the active site of thioredoxin reductase. Baicalein treatment led to significant reduction in the activity of thioredoxin reductase and nuclear levels of thioredoxin-1 thereby increasing ASK1 levels and caspase-3 activity. Interestingly, CRISPR-Cas9 based knock-out of ASK1 or over-expression of thioredoxin-1 abolished anti-tumor effects of baicalein in EL4 cells. Further, baicalein administration significantly reduced intra-peritoneal tumor burden of EL4 cells in C57BL/6 mice. Thus, our study describes anti-tumor effects of baicalein in EL4 cells via inhibition of thioredoxin system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. A Model for Breast Cancer-Induced Angiogenesis

    Science.gov (United States)

    1997-09-01

    Protein kinase C isozyme expression in phorbol ester- sensitive and -resistant EL4 thymoma cells . J. Biol. Chem. 266:5676-568 1. Jalava A, Akerman K...that exogenous angiogenic factors were unable to stimulate endothelial cell proliferation. Furthermore, under non- stimulated conditions, endothelial... cell proliferation was restricted to the adipose tissue and perilobular connective tissue. The endothelium within the fibrous stroma could almost never

  13. LEW 88180, LEW 87119, and ALH 85119: New EH6, EL7, and EL4 Enstatite Chondrites

    Science.gov (United States)

    Zhang, Y.; Benoit, P. H.; Sears, D. W. G.

    1993-07-01

    The EH and EL chondrites formed in a uniquely reducing environment, containing low-Fe pyroxene, abundant metal, and a number of unusual sulphides and other minerals [1]. An important aspect of their history is that while the EL chondrites consist predominantly of metamorphosed meteorites, the EH consist primarily of little-metamorphosed meteorites (e.g., [2]), and yet EL chondrites have lower equilibrium temperatures than EH chondrite [3,4]. To help understand this observation and its implication for the history of the classes, we have been searching for new enstatite chondrites, looking especially for meteorites of previously unknown chemical-petrologic class. Using our normal INAA methods [5] and sample splits of 100-200 mg, the bulk composition of nine Antarctic enstatite chondrites and one fall were determined. The data were used to assign the meteorites to chemical classes, the Ni/Ir vs. Al/V plot (Fig. 1) being especially useful since it uses the refractory element difference between EH and EL chondrites and is insensitive to metal-silicate heterogeneity. The well-analyzed Qingzhen was included to check our method. ALH84170, ALH84206, and EET87746, which Mason described as E3, E4, and E4 were all found to be EH chondrites [6]. Our data for the three paired EL3 chondrites were discussed earlier (MAC88136, 88180, and 88184) [7,8]. LEW88180, LEW87119, and ALH85119, which Mason described as type E6, E6, and E4 respectively [6], are EH, EL, and EL; thus LEW88180 and ALH85119 appear to be the first EH6 and EL4 chondrites. The compositions of kamacite, phosphide, and niningerite-alabandite (Fig. 2) for ALH84170, ALH84206, EET87746, LEW88180, and ALH85119 are consistent with Mason's petrologic type assignments [6]. The mineral composition of LEW88180 (2.7% Si and 9.4% Ni in the kamacite, 7.8% Ni in the phosphide, and 60% FeS in the niningerite) confirms our classification of this meteorite as EH6. ALH85119 contains kamacite with 0.5% Si and 7% Ni, phosphide with 46

  14. Granzyme B of cytotoxic T cells induces extramitochondrial reactive oxygen species production via caspase-dependent NADPH oxidase activation.

    Science.gov (United States)

    Aguiló, Juan I; Anel, Alberto; Catalán, Elena; Sebastián, Alvaro; Acín-Pérez, Rebeca; Naval, Javier; Wallich, Reinhard; Simon, Markus M; Pardo, Julián

    2010-07-01

    Induction of reactive oxygen species (ROS) is a hallmark of granzyme B (gzmB)-mediated pro-apoptotic processes and target cell death. However, it is unclear to what extent the generated ROS derive from mitochondrial and/or extra-mitochondrial sources. To clarify this point, we have produced a mutant EL4 cell line, termed EL4-rho(0), which lacks mitochondrial DNA, associated with a decreased mitochondrial membrane potential and a defective ROS production through the electron transport chain of oxidative phosphorylation. When incubated with either recombinant gzmB plus streptolysin or ex vivo gzmB(+) cytotoxic T cells, EL4-rho(0) cells showed phosphatydylserine translocation, caspase 3 activation, Bak conformational change, cytochrome c release and apoptotic morphology comparable to EL4 cells. Moreover, EL4-rho(0) cells produced ROS at levels similar to EL4 under these conditions. GzmB-mediated ROS production was almost totally abolished in both cell lines by the pan-caspase inhibitor, Z-VAD-fmk. However, addition of apocynin, a specific inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, led to a significant reduction of ROS production and cell death only in EL4-rho(0) but not EL4 cells. These data suggest that gzmB-induced cell death is accompanied by a caspase-dependent pathway of extra-mitochondrial ROS production, most probably through activation of NADPH oxidase.

  15. Color-Coded Imaging of Syngeneic Orthotopic Malignant Lymphoma Interacting with Host Stromal Cells During Metastasis.

    Science.gov (United States)

    Matsumoto, Takuro; Suetsugu, Atsushi; Hasegawa, Kosuke; Nakamura, Miki; Aoki, Hitomi; Kunisada, Takahiro; Tsurumi, Hisashi; Shimizu, Masahito; Hoffman, Robert M

    2016-04-01

    The EL4 cell line was previously derived from a lymphoma induced in a C57/BL6 mouse by 9,10-dimethyl-1,2-benzanthracene. In a previous study, EL4 lymphoma cells expressing red fluorescent protein (EL4-RFP) were established and injected into the tail vein of C57/BL6 green fluorescent protein (GFP) transgenic mice. Metastasis was observed at multiple sites which were also enriched with host GFP-expressing stromal cells. In the present study, our aim was to establish an orthotopic model of EL4-RFP. In the present study, EL4-RFP lymphoma cells were injected in the spleen of C57/BL6 GFP transgenic mice as an orthotopic model of lymphoma. Resultant primary tumor and metastases were imaged with the Olympus FV1000 scanning laser confocal microscope. EL4-RFP metastasis was observed 21 days later. EL4-RFP tumors in the spleen (primary injection site), liver, supra-mediastinum lymph nodes, abdominal lymph nodes, bone marrow, and lung were visualized by color-coded imaging. EL4-RFP metastases in the liver, lymph nodes, and bone marrow in C57/BL6 GFP mice were rich in GFP stromal cells such as macrophages, fibroblasts, dendritic cells, and normal lymphocytes derived from the host animal. Small tumors were observed in the spleen, which were rich in host stromal cells. In the lung, no mass formation of lymphoma cells occurred, but lymphoma cells circulated in lung peripheral blood vessels. Phagocytosis of EL4-RFP lymphoma cells by macrophages, as well as dendritic cells and fibroblasts, were observed in culture. Color-coded imaging of the lymphoma microenvironment suggests an important role of stromal cells in lymphoma progression and metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Measurement of the in-pile core temperature of an EL-4 pencil element, first charge (can of type-347 stainless steel, 0.4 mm thick, UO{sub 2} fuel, 11 mm diameter). Determination of the apparent thermal conductivity integral of in-pile UO{sub 2}; Mesure de la temperature a coeur en pile d'un crayon EL-4 1er jeu (gaine acier inoxydable, nuance 347 - epaisseur 0,4 mm - combustible UO{sub 2} - diametre 11 mm). Determination de l'integrale de conductibilite thermique apparente de l'UO{sub 2} en pile

    Energy Technology Data Exchange (ETDEWEB)

    Lavaud, B; Ringot, C; Vignesoult, N [Commissariat a l' Energie Atomique, Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France)

    1966-11-01

    'un element combustible EL-4, type premier jeu, a gaine en acier inoxydable. On mesure cette temperature au coeur du crayon en pile a l'aide d'un thermocouple pour haute temperature: tungstene-rhenium a gaine tantale. Le crayon est place dans des conditions de fonctionnement analogues a celles de EL-4, tant en ce qui concerne la puissance specifique et la temperature sur gaine que la pression externe sur la gaine. La puissance specifique est obtenue dans le reacteur EL-3 avec un enrichissement de l'UO{sub 2} legerement superieur a celui normalement prevu pour EL-4. La temperature de gaine et la pression visees sont realisees a l'aide d'un conteneur d'irradiation en zircaloy-2 et a remplissage NaK, adapte, aux conditions du reacteur EL-3. - Les temperatures de l'UO{sub 2} a coeur, et de la surface de la gaine etant mesurees; - La puissance etant calculee a partir des echanges thermiques dans le conteneur etalonne en laboratoire; - La chute de temperature au contact UO{sub 2}-gaine etant deduite de mesures faites en laboratoire dans des conditions de flux calorifique comparables et sous une atmosphere de gaz correspondant au debut de la vie de l'element combustible; on peut tracer la courbe integrale de conductibilite. Les examens micro-graphiques de la structure de l'oxyde permettent de verifier la repartition des temperatures dans l'oxyde, deduite de l'integrale de conductibilite thermique. (auteurs)

  17. A viral long terminal repeat expressed in CD4+CD8+ precursors is downregulated in mature peripheral CD4-CD8+ or CD4+CD8- T cells.

    OpenAIRE

    Paquette, Y; Doyon, L; Laperrière, A; Hanna, Z; Ball, J; Sekaly, R P; Jolicoeur, P

    1992-01-01

    The long terminal repeat from a thymotropic mouse mammary tumor virus variant, DMBA-LV, was used to drive the expression of two reporter genes, murine c-myc and human CD4, in transgenic mice. Expression was observed specifically in thymic immature cells. Expression of c-myc in these cells induced oligoclonal CD4+ CD8+ T-cell thymomas. Expression of human CD4 was restricted to thymic progenitor CD4- CD8- and CD4+ CD8+ T cells and was shut off in mature CD4+ CD8- and CD4- CD8+ T cells, known to...

  18. Cell kinetic studies on radiation induced leukemogenesis

    International Nuclear Information System (INIS)

    Nakao, Isamu; Suzuki, Gen; Imai, Yasufumi; Kawase, Yoshiko; Nose, Masako; Hirashima, Kunitake; Bessho, Masami

    1989-01-01

    The purpose of this study was threefold: (1) to determine the clonal origin of radiation-induced thymic lymphoma in mice with cellular mosaicism for phosphoglycerate kinase; (2) to determine the incidence and latent period of myeloid leukemia and thymic lymphoma induced by whole-body exposure to median doses (3.0 Gy or less) in RFM/MsNrs-2 mice; and (3) to examine the influence of human recombinant interleukin-2 (hrIL-2). Thymic lymphoma was of a single cell origin. The incidence of radiation-induced myeloid leukemia and thymic lymphoma in RFM mice increased in a dose dependent fashion. Mean latent periods of both myeloid leukemia and thymic lymphoma after irradiation became shorter in proportion to radiation doses. When hrIL-2 was injected to RFM mice receiving 3.0 Gy, mean survivals were shorter in thymoma-bearing mice than the control mice. This suggested that hrIL-2 shortens the promotion step of thymoma. Administration of hrIL-2 failed to alter the incidence of myeloid leukemia or the mean survival of mice having myeloid leukemia, indicating that the protocol of hrIL-2 administration was not so sufficient as to alter the myeloid leukemogenesis. (Namekawa, K)

  19. A Color-coded Imageable Syngeneic Mouse Model of Stromal-cell Recruitment by Metastatic Lymphoma.

    Science.gov (United States)

    Matsumoto, Takuro; Suetsugu, Atsushi; Shibata, Yuhei; Nakamura, Nobuhiko; Aoki, Hitomi; Kunisada, Takahiro; Tsurumi, Hisashi; Shimizu, Masahito; Hoffman, Robert M

    2015-09-01

    A syngeneic color-coded imageable lymphoma model has been developed to visualize recruitment of host stromal cells by malignant lymphoma during metastasis. The EL4 cell line was previously derived from a lymphoma induced in a C57/BL6 mouse by 9,10-dimethyl-1,2-benzanthracene. EL4 lymphoma cells expressing red fluorescent protein (EL4-RFP) were initially established. EL4-RFP cells were subsequently injected into the tail vein of C57/BL6-GFP transgenic mice. EL4-RFP metastasis was observed in the lymph nodes of the upper mediastinum and in the liver 28 days after cell injection. Large EL4-RFP liver metastases in C57/BL6-GFP mice contained GFP-expressing stromal cells derived from the host. In addition, EL4-RFP lymphoma metastasis was formed in peri-gastric lymph nodes, which were also enriched in host GFP-expressing cells. Furthermore, EL4-RFP lymphoma cells were also observed in the peripheral blood and bone marrow of C57/BL6-GFP transgenic mice, where they were associated with GFP-expressing host cells. Lymph node, liver and bone marrow metastases were found approximately 4 weeks after transplantation and all RFP-expressing metastases were highly enriched in GFP-expressing host stromal cells. This model of malignant lymphoma can be used to study early tumor development, metastasis, and the role of the stroma, as well as for discovery and evaluation of novel therapeutics for this treatment-resistant disease. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  20. Repair of EL4 leaks

    International Nuclear Information System (INIS)

    1985-03-01

    The reactor shutdown was decided on the 15th of November 1984, because the evolution of the carbon dioxide quantity in the helium blanket of the heavy water. Leaks have been localized on three different channels. Repairs have been made in hard conditions taking into account the reactor state (materials strongly irradiated). The restart has been authorized on the 24th of January 1985 [fr

  1. Involvement of ERK-Nrf-2 signaling in ionizing radiation induced cell death in normal and tumor cells.

    Directory of Open Access Journals (Sweden)

    Raghavendra S Patwardhan

    Full Text Available Prolonged oxidative stress favors tumorigenic environment and inflammation. Oxidative stress may trigger redox adaptation mechanism(s in tumor cells but not normal cells. This may increase levels of intracellular antioxidants and establish a new redox homeostasis. Nrf-2, a master regulator of battery of antioxidant genes is constitutively activated in many tumor cells. Here we show that, murine T cell lymphoma EL-4 cells show constitutive and inducible radioresistance via activation of Nrf-2/ERK pathway. EL-4 cells contained lower levels of ROS than their normal counterpart murine splenic lymphocytes. In response to radiation, the thiol redox circuits, GSH and thioredoxin were modified in EL-4 cells. Pharmacological inhibitors of ERK and Nrf-2 significantly enhanced radiosensitivity and reduced clonogenic potential of EL-4 cells. Unirradiated lymphoma cells showed nuclear accumulation of Nrf-2, upregulation of its dependent genes and protein levels. Interestingly, MEK inhibitor abrogated its nuclear translocation suggesting role of ERK in basal and radiation induced Nrf-2 activation in tumor cells. Double knockdown of ERK and Nrf-2 resulted in higher sensitivity to radiation induced cell death as compared to individual knockdown cells. Importantly, NF-kB which is reported to be constitutively active in many tumors was not present at basal levels in EL-4 cells and its inhibition did not influence radiosensitivity of EL-4 cells. Thus our results reveal that, tumor cells which are subjected to heightened oxidative stress employ master regulator cellular redox homeostasis Nrf-2 for prevention of radiation induced cell death. Our study reveals the molecular basis of tumor radioresistance and highlights role of Nrf-2 and ERK.

  2. Adiponectin deficiency suppresses lymphoma growth in mice by modulating NK cells, CD8 T cells, and myeloid-derived suppressor cells.

    Science.gov (United States)

    Han, Sora; Jeong, Ae Lee; Lee, Sunyi; Park, Jeong Su; Kim, Kwang Dong; Choi, Inpyo; Yoon, Suk Ran; Lee, Myung Sok; Lim, Jong-Seok; Han, Seung Hyun; Yoon, Do Young; Yang, Young

    2013-05-01

    Previously, we found that adiponectin (APN) suppresses IL-2-induced NK cell activation by downregulating the expression of the IFN-γ-inducible TNF-related apoptosis-inducing ligand and Fas ligand. Although the antitumor function of APN has been reported in several types of solid tumors, with few controversial results, no lymphoma studies have been conducted. In this study, we assessed the role of APN in immune cell function, including NK cells, CTLs, and myeloid-derived suppressor cells, in EL4 and B16F10 tumor-bearing APN knockout (KO) mice. We observed attenuated EL4 growth in the APNKO mice. Increased numbers of splenic NK cells and splenic CTLs were identified under naive conditions and EL4-challenged conditions, respectively. In APNKO mice, splenic NK cells showed enhanced cytotoxicity with and without IL-2 stimulation. Additionally, there were decreased levels of myeloid-derived suppressor cell accumulation in the EL4-bearing APNKO mice. Enforced MHC class I expression on B16F10 cells led to attenuated growth of these tumors in APNKO mice. Thus, our results suggest that EL4 regression in APNKO mice is not only due to an enhanced antitumor immune response but also to a high level of MHC class I expression.

  3. Development of Lipid-based Nanoparticles for in vivo Targeted Delivery of Imaging Agents into Breast Cancer Cells

    Science.gov (United States)

    2010-04-01

    Fab to recognize pOV8-K b proteins on the surface of live cells, mouse lym phoma cell line EL4 was pulse d with either cognate (pOV8) or irrelevant...120 0.5 3 M FI Time, hour M FI Figure 11. Binding specificity of Pyro-NP-Fab. EL4 cells sensitized with peptide pOV8 ( ) but not with VSV

  4. An endogenous immune adjuvant released by necrotic cells for enhancement of DNA vaccine potency.

    Science.gov (United States)

    Dorostkar, Rohollah; Bamdad, Taravat; Parsania, Masoud; Pouriayevali, Hassan

    2012-12-01

    Improving vaccine potency in the induction of a strong cell-mediated cytotoxicity can enhance the efficacy of vaccines. Necrotic cells and the supernatant of necrotic tumor cells are attractive adjuvants, on account of their ability to recruit antigen-presenting cells to the site of antigen synthesis as well as its ability to stimulate the maturation of dendritic cells. To evaluate the utility of supernatant of necrotic tumor cells as a DNA vaccine adjuvant in a murine model. The supernatant of EL4 necrotic cells was co-administered with a DNA vaccine expressing the glycoprotein B of Herpes simplex virus-1 as an antigen model under the control of Cytomegalovirus promoter. C57BL/6 mice were vaccinated three times at two weeks intervals with glycoprotein B DNA vaccine and supernatant of necrotic EL4 cells. Five days after the last immunization, cell cytotoxicity, IFN-γ and IL-4 were evaluated. The obtained data showed that the production of IFN-γ from the splenocytes after antigenic stimulation in the presence of the supernatant of necrotic EL4 cells was significantly higher than the other groups (pEL4 cells in the mice immunized with DNA vaccine and supernatant of necrotic EL4 cells comparing to the other groups (p<0.001). The supernatant of necrotic cells contains adjuvant properties that can be considered as a candidate for tumor vaccination.

  5. Diffusion-weighted magnetic resonance imaging of thymoma: ability of the Apparent Diffusion Coefficient in predicting the World Health Organization (WHO) classification and the Masaoka-Koga staging system and its prognostic significance on disease-free survival

    International Nuclear Information System (INIS)

    Priola, Adriano Massimiliano; Priola, Sandro Massimo; Gned, Dario; Ducco, Lorena; Veltri, Andrea; Giraudo, Maria Teresa; Fornari, Alessandro; Ferrero, Bruno

    2016-01-01

    To evaluate the usefulness of diffusion-weighted magnetic resonance for distinguishing thymomas according to WHO and Masaoka-Koga classifications and in predicting disease-free survival (DFS) by using the apparent diffusion coefficient (ADC). Forty-one patients were grouped based on WHO (low-risk vs. high-risk) and Masaoka-Koga (early vs. advanced) classifications. For prognosis, seven patients with recurrence at follow-up were grouped separately from healthy subjects. Differences on ADC levels between groups were tested using Student-t testing. Logistic regression models and areas under the ROC curve (AUROC) were estimated. Mean ADC values were different between groups of WHO (low-risk = 1.58 ± 0.20 x 10 -3 mm 2 /sec; high-risk = 1.21 ± 0.23 x 10 -3 mm 2 /sec; p < 0.0001) and Masaoka-Koga (early = 1.43 ± 0.26 x 10 -3 mm 2 /sec; advanced = 1.31 ± 0.31 x 10 -3 mm 2 /sec; p = 0.016) classifications. Mean ADC of type-B3 (1.05 ± 0.17 x 10 -3 mm 2 /sec) was lower than type-B2 (1.32 ± 0.20 x 10 -3 mm 2 /sec; p = 0.023). AUROC in discriminating groups was 0.864 for WHO classification (cut-point = 1.309 x 10 -3 mm 2 /sec; accuracy = 78.1 %) and 0.730 for Masaoka-Koga classification (cut-point = 1.243 x 10 -3 mm 2 /sec; accuracy = 73.2 %). Logistic regression models and two-way ANOVA were significant for WHO classification (odds ratio[OR] = 0.93, p = 0.007; p < 0.001), but not for Masaoka-Koga classification (OR = 0.98, p = 0.31; p = 0.38). ADC levels were significantly associated with DFS recurrence rate being higher for patients with ADC ≤ 1.299 x 10 -3 mm 2 /sec (p = 0.001; AUROC, 0.834; accuracy = 78.0 %). ADC helps to differentiate high-risk from low-risk thymomas and discriminates the more aggressive type-B3. Primary tumour ADC is a prognostic indicator of recurrence. (orig.)

  6. origin of elements of the Uranium-235 family observed in the Ellez river near the EL-4 experimental nuclear reactor in dismantling (Monts d'Arree- Finistere department)

    International Nuclear Information System (INIS)

    2006-01-01

    In a previous study which concerned the catchment basin of the harbour of Brest, the A.C.R.O. put in evidence a marking by artificial radioelements around the power plant of Brennilis which can be imputed without ambiguities to the nuclear installation. It also put in evidence abnormalities concerning the natural radioactivity which justifies this new study. In the area of the Monts d'Arree, actinium 227 ( 227 Ac), non born by its ascendents which are 235 U and 231 Pa is observed. This phenomenon is characterized by mass activities superior to these ones of 235 U and able to reach these ones of 238 U. Its presence corresponds with the drainage of the Ellez river since the former channel of radioactive effluents releases from the nuclear power plant EL-4 up to the reservoir Saint-Herblot situated 6 km downstream. The strongest values of radioactivity are registered near the disused power plant, at this place a relationship exists between the level of actinium 227 and this one of the artificial radioactivity as it exists a relationship with the decay products of radon exhaled from the subsoil ( 210 Pb). But its presence is not limited to a part of the Ellez river, it is equally observed in terrestrial medium, in places in priori not influenced by the direct liquid effluents of the power plant. This place is situated at more than 4 km and without any connection with the Ellez waters. At this stage of the study, it is not possible to answer with certainty the question of the origin of this phenomenon. A new reorientation is considered indispensable to clarify definitively the origin of this unknown phenomenon in the scientific publications and the environmental monitoring. (N.C.)

  7. The effect of a therapeutic dendritic cell-based cancer vaccination depends on the blockage of CTLA-4 signaling

    DEFF Research Database (Denmark)

    Met, Ozcan; Wang, Mingjun; Pedersen, Anders E

    2006-01-01

    tumor cells, and later on these mice even rejected wild-type EL-4 tumor cells indicating that tumor epitope spreading takes place during the process of vaccination-induced E.G7-OVA rejection. In agreement with these observations, mice having rejected E.G7-OVA tumors showed long lasting CTL memory...... in spleen and bone marrow towards both the SIINFEKL-peptide and other EL-4-derived tumor rejecting epitopes....

  8. [Autologous regulatory T cells can suppress the proliferation of lymphoma cell line in vitro].

    Science.gov (United States)

    Ying, Zhi-Tao; Guo, Jun; Ren, Jun; Kong, Yan; Yuan, Zhi-Hong; Liu, Xi-Juan; Zhang, Chen; Zheng, Wen; Song, Yu-Qin; Zhang, Yun-Tao; Zhu, Jun

    2009-06-01

    This study was aimed to investigate the suppressive effect of regulatory T (Treg) cells on the T cell lymphoma EL4 cell line and to explore its mechanism. C57BL/6 Mouse Treg cells were isolated by MACS (magnetic cell sorting). The purity and the expression of Foxp3 were detected by flow cytometry. The suppressive effect of sorted Treg cells on EL4 cells was detected by MTT assay. The secretion of TGF-beta1 and IL-10 was examined by enzyme-linked immunosorbent assay (ELISA). The results showed that CD4(+)CD25(+) T cells could be successfully isolated by MACS with the purity reaching 91.6% and the expression level of Foxp3 was 78.9%. The ratio of viable cells was more than 95%. Regulatory T cells could suppress the proliferation of EL4 cells effectively in the presence of antigen presenting cells (APCs). And the suppressive effect was most significant at 1:1 ratio. In addition, the suppression still existed without APCs. TGF-beta1 and IL-10 could not be detected by ELISA. It is concluded that the Treg cells can suppress T lymphoma cell in vitro. The suppressive effect of Treg cells works in dose-dependent manner, but not in cytokine-dependent manner. The mechanism of this suppression may take effect through cell-cell contact.

  9. CD44v10, osteopontin and lymphoma growth retardation by a CD44v10-specific antibody.

    Science.gov (United States)

    Megaptche, Amelie Pajip; Erb, Ulrike; Büchler, Markus Wolfgang; Zöller, Margot

    2014-09-01

    Blockade of CD44 is considered a therapeutic option for the elimination of leukemia-initiating cells. However, the application of anti-panCD44 can be burdened by severe side effects. We determined whether these side effects could be avoided by replacing anti-panCD44 with CD44 variant isoform (CD44v)-specific antibodies in CD44v-positive hematological malignancies using the EL4 thymoma and CD44v10-transfected EL4 (EL4-v10) as models. Subcutaneous growth of EL4 and EL4-v10 was equally well inhibited by the anti-panCD44 and anti-CD44v10 antibodies, respectively. Ex vivo analysis indicated that natural killer cytotoxicity and antibody-dependent cellular cytotoxicity were the main effector mechanisms. Under local inflammation, the efficacy of anti-CD44v10 prolonged the survival time twofold compared with untreated, EL4-v10 tumor-bearing mice, and this was due to inflammation-induced expression of osteopontin (OPN). A high level of OPN in EL4-v10 tumors supported leukocyte recruitment and tumor-infiltrating T-cell activation. Taken together, in hematological malignancies expressing CD44v, anti-panCD44 can be replaced by CD44v-specific antibodies without a loss in efficacy. Furthermore, CD44v10-specific antibodies appear particularly advantageous in cutaneous leukemia therapy, as CD44v10 binding of OPN drives leukocyte recruitment and activation.

  10. The Cyrano program. 1 - description and operation of an irradiation device 'Cyrano'. 2 - results of the experiments Cyrano 1 and 2 (study of the EL 4 first-bach pencil); measurement of the thermal conductivity integral for UO{sub 2} sintered up to 2300 deg C; evolution of fission gases at constant power; Programme Cyrano. 1 - description et exploitation d'un dispositif d'irradiation ''cyrano''. 2 - resultats des experiences cyrano 1 et 2 (etude du crayon EL4 1. jeu). Mesure de l'integrale de conductibilite thermique d'UO{sub 2} fritte jusqu'a 2300 deg C. Evolution des gaz de fission a puissance constante

    Energy Technology Data Exchange (ETDEWEB)

    Stora, J P; Chenebault, P [Commissariat a l' Energie Atomique, 91 - Saclay (France). Centre d' Etudes Nucleaires

    1968-07-01

    Two rods of the type 'EL 4 first score' have been irradiated in 'Cyrano' capsules which are suited for continuous measurement of the nuclear power evolved and equipped with thermocouples. The variations of the integral of conductivity of sintered 96 per cent theoretical dense UO{sub 2} has been established until 2300 deg. C; these variations are coherent with those previously measured out-of-pile. The released fission gases have been recovered at different times during the irradiation: the kinetics of release of stable gases is such that, in the experimental conditions (T{sub surface} = 610 deg. C, {integral}{sub T{sub s}}{sup T{sub c}} kdT = 34.7 W cm{sup -1}) the fraction of released gases is still widely increasing after 12 days of irradiation. Numerous observations have been made on concentrations of rare gases locally present in the irradiated fuel. (authors) [French] L'irradiation de deux crayons combustibles type EL 4, 1er jeu, a ete menee a bien dans des capsules 'Cyrano' equipees de dispositifs de mesure continue de la puissance nucleaire et de plusieurs reperes de temperatures; la variation de l'integrale de conductibilite thermique de l'oxyde d'uranium fritte (96 pour cent d. th.) a ete tracee jusqu'a 2300 deg. C; la courbe representative de ces variations est coherente avec celle obtenue precedemment hors pile. Les gaz de fission apparus hors du combustible ont ete extraits du crayon a plusieurs reprises pendant l'experience: la cinetique d'accumulation des gaz stables est telle que dans les conditions etudiees (T{sub surface} = 610 deg. C, {integral}{sub T{sub s}}{sup T{sub c}} kdT = 34.7 W cm{sup -1}) la fraction des gaz degages est encore largement croissante apres 12 jours d'irradiation. De nombreuses observations ont ete recueillies sur la nature et la concentration des gaz rares presents en differents points du combustible irradie. (auteurs)

  11. Genetic Recombination Between Stromal and Cancer Cells Results in Highly Malignant Cells Identified by Color-Coded Imaging in a Mouse Lymphoma Model.

    Science.gov (United States)

    Nakamura, Miki; Suetsugu, Atsushi; Hasegawa, Kousuke; Matsumoto, Takuro; Aoki, Hitomi; Kunisada, Takahiro; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Hoffman, Robert M

    2017-12-01

    The tumor microenvironment (TME) promotes tumor growth and metastasis. We previously established the color-coded EL4 lymphoma TME model with red fluorescent protein (RFP) expressing EL4 implanted in transgenic C57BL/6 green fluorescent protein (GFP) mice. Color-coded imaging of the lymphoma TME suggested an important role of stromal cells in lymphoma progression and metastasis. In the present study, we used color-coded imaging of RFP-lymphoma cells and GFP stromal cells to identify yellow-fluorescent genetically recombinant cells appearing only during metastasis. The EL4-RFP lymphoma cells were injected subcutaneously in C57BL/6-GFP transgenic mice and formed subcutaneous tumors 14 days after cell transplantation. The subcutaneous tumors were harvested and transplanted to the abdominal cavity of nude mice. Metastases to the liver, perigastric lymph node, ascites, bone marrow, and primary tumor were imaged. In addition to EL4-RFP cells and GFP-host cells, genetically recombinant yellow-fluorescent cells, were observed only in the ascites and bone marrow. These results indicate genetic exchange between the stromal and cancer cells. Possible mechanisms of genetic exchange are discussed as well as its ramifications for metastasis. J. Cell. Biochem. 118: 4216-4221, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. Actions needed for RA reactor exploitation - I-IV, Part II, Design project VI-SA 1, Experimental loop for testing the EL-4 reactor fuel elements in the central vertical experimental channel of the RA reactor in Vinca

    International Nuclear Information System (INIS)

    Novakovic, M.

    1961-12-01

    The objective of installing the VISA-1 loop was testing the fuel elements of the EL-4 reactor. The fuel elements planned for testing are natural UO 2 with beryllium cladding, cooled by CO 2 under nominal pressure of 60 at and temperature 600 deg C. central vertical experimental channel of the RA reactor was chosen for installing a test loop cooled by CO 2 . This report contains the detailed design project of the testing loop with the control system and safety analysis of the planned experiment

  13. 'Fluorescent Cell Chip' for immunotoxicity testing: Development of the c-fos expression reporter cell lines

    International Nuclear Information System (INIS)

    Trzaska, Dominika; Zembek, Patrycja; Olszewski, Maciej; Adamczewska, Violetta; Ulleras, Erik; Dastych, JarosIaw

    2005-01-01

    The Fluorescent Cell Chip for in vitro immunotoxicity testing employs cell lines derived from lymphocytes, mast cells, and monocytes-macrophages transfected with various EGFP cytokine reporter gene constructs. While cytokine expression is a valid endpoint for in vitro immunotoxicity screening, additional marker for the immediate-early response gene expression level could be of interest for further development and refinement of the Fluorescent Cell Chip. We have used BW.5147.3 murine thymoma transfected with c-fos reporter constructs to obtain reporter cell lines expressing ECFP under the control of murine c-fos promoter. These cells upon serum withdrawal and readdition and incubation with heavy metal compounds showed paralleled induction of c-Fos expression as evidenced by Real-Time PCR and ECFP fluorescence as evidenced by computer-supported fluorescence microscopy. In conclusion, we developed fluorescent reporter cell lines that could be employed in a simple and time-efficient screening assay for possible action of chemicals on c-Fos expression in lymphocytes. The evaluation of usefulness of these cells for the Fluorescent Cell Chip-based detection of immunotoxicity will require additional testing with a larger number of chemicals

  14. Actions needed for RA reactor exploitation - I-IV, Part II, Design project VI-SA 1, Experimental loop for testing the EL-4 reactor fuel elements in the central vertical experimental channel of the RA reactor in Vinca; Radovi za potrebe eksploatacije reaktora RA - I-IV, II Deo, Predprojekat VI-SA 1, Petlja za ispitivanje gorivnih elemenata reaktora EL-4 u centralnom vertikalnom eksperimentalnom kanalu reaktora RA u Vinci

    Energy Technology Data Exchange (ETDEWEB)

    Novakovic, M [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1961-12-15

    The objective of installing the VISA-1 loop was testing the fuel elements of the EL-4 reactor. The fuel elements planned for testing are natural UO{sub 2} with beryllium cladding, cooled by CO{sub 2} under nominal pressure of 60 at and temperature 600 deg C. central vertical experimental channel of the RA reactor was chosen for installing a test loop cooled by CO{sub 2}. This report contains the detailed design project of the testing loop with the control system and safety analysis of the planned experiment.

  15. Membrane-associated IL 1-like activity on rat dendritic cells

    International Nuclear Information System (INIS)

    Nagelkerken, L.M.; van Breda Vriesman, P.J.C.

    1986-01-01

    The secretion of interleukin 1 (IL 1) by rat dendritic cells (DC) was studied in relation to their ability to induce the production interleukin 2 (IL 2 ) and to induce IL 2 responsiveness. IL 1 (or IL 1-like activity) was measured by its capacity to enhance IL 2 production by EL4 cells. In contrast to peritoneal exudate cells (PEC) or splenic adherent cells, DC from thoracic duct lymph (TD-DC) or from spleen did not secrete detectable amounts of IL 1 on stimulation with LPS/Silica. However, TD-DC and splenic DC were able to enhance IL 2 production by EL4 cells directly, and were only two times less effective than PEC. By preventing cell-to-cell contact between stimulator cells and EL4 cells, it was demonstrated that most of the IL 2-inducing activity of TD-DC and PEC was associated with the cell membrane. Treatment with 1% paraformaldehyde (PFA) to abolish metabolic activity resulted in a 50% decrease (or inactivation) of IL 2-inducing activity of TD-DC in the EL4 assay. Moreover, UVB-irradiation (300 mJ/cm 2 ) of TD-DC, which has been described to inhibit the release of IL 1 by macrophages, caused a 70% decrease in IL 2-inducing activity. These results suggest that membrane-associated structures, that are identical to or mimic Il 1, are involved in the activation of T cells by DC

  16. In vivo targeting of dead tumor cells in a murine tumor model using a monoclonal antibody specific for the La autoantigen.

    Science.gov (United States)

    Al-Ejeh, Fares; Darby, Jocelyn M; Pensa, Katherine; Diener, Kerrilyn R; Hayball, John D; Brown, Michael P

    2007-09-15

    To investigate the potential of the La-specific monoclonal antibody (mAb) 3B9 as an in vivo tumor-targeting agent. The murine EL4 lymphoma cell line was used for in vitro studies and the EL4 model in which apoptosis was induced with cyclophosphamide and etoposide was used for in vivo studies. In vitro studies compared 3B9 binding in the EL4 cell with that in its counterpart primary cell type of the thymocyte. For in vivo studies, 3B9 was intrinsically or extrinsically labeled with carbon-14 or 1,4,7,10-tetra-azacylododecane-N,N',N'',N''''-tetraacetic acid-indium-111, respectively, and biodistribution of the radiotracers was investigated in EL4 tumor-bearing mice, which were treated or not with chemotherapy. La-specific 3B9 mAb bound EL4 cells rather than thymocytes, and binding was detergent resistant. 3B9 binding to dead EL4 cells in vitro was specific, rapid, and saturable. Significantly, more 3B9 bound dead EL4 tumor explant cells after host mice were treated with chemotherapy, which suggested that DNA damage induced 3B9 binding. Tumor binding of 3B9 in vivo was antigen specific and increased significantly after chemotherapy. Tumor accumulation of 3B9 peaked at approximately 50% of the injected dose per gram of tumor 72 h after chemotherapy and correlated with increased tumor cell death. Tumor/organ ratios of 3B9 biodistribution, which included the tumor/blood ratio, exceeded unity 48 or more hours after chemotherapy. La-specific mAb selectively targeted dead tumor cells in vivo, and targeting was augmented by cytotoxic chemotherapy. This novel cell death radioligand may be useful both for radioimmunoscintigraphy and radioimmunotherapy.

  17. Comparison of the Masaoka-Koga and The IASLC/ITMIG Proposal for The TNM 
Staging Systems Based on the Chinese Alliance for Research in Thymomas (ChART
Retrospective Database

    Directory of Open Access Journals (Sweden)

    Guanghui LIANG

    2016-07-01

    Full Text Available Background and objective To compare the predictive effect of the Masaoka-Koga staging system and the International Association for the Study of Lung Cancer (IASLC/the International Thymic Malignancies Interest Group (ITMIG proposal for the new TNM staging on prognosis of thymic malignancies using the Chinese Alliance for Research in Thymomas (ChART retrospective database. Methods From 1992 to 2012, 2,370 patients in ChART database were retrospectively reviewed. Of these, 1,198 patients with complete information on TNM stage, Masaoka-Koga stage, and survival were used for analysis. Cumulative incidence of recurrence (CIR was assessed in R0 patients. Overall survival (OS was evaluated both in an R0 resected cohort, as well as in all patients (any R status. CIR and OS were first analyzed according to the Masaoka-Koga staging system. Then, they were compared using the new TNM staging proposal. Results Based on Masaoka-Koga staging system, significant difference was detected in CIR among all stages. However, No survival difference was revealed between stage I and II, or between stage II and III. Stage IV carried the highest risk of recurrence and worst survival. According to the new TNM staging proposal, CIR in T1a was significantly lower comparing to all other T categories (P<0.05 and there is a significant difference in OS between T1a and T1b (P=0.004. T4 had the worst OS comparing to all other T categories. CIR and OS were significantly worse in N(+ than in N0 patients. Significant difference in CIR and OS was detected between M0 and M1b, but not between M0 and M1a. OS was almost always statistically different when comparison was made between stages I-IIIa and stages IIIb-IVb. However, no statistical difference could be detected among stages IIIb to IVb. Conclusion Compared with Masaoka-Koga staging, the IASLC/ITMIG TNM staging proposal not only describes the extent of tumor invasion but also provides information on lymphatic involvement and tumor

  18. Comparative Analysis of V-Akt Murine Thymoma Viral Oncogene Homolog 3 (AKT3) Gene between Cow and Buffalo Reveals Substantial Differences for Mastitis

    Science.gov (United States)

    Bhattarai, Dinesh; Cheng, Zhangrui; Liang, Xianwei; Deng, Tingxian; Rehman, Zia Ur; Talpur, Hira Sajjad; Worku, Tesfaye; Brohi, Rahim Dad; Safdar, Muhammad; Ahmad, Muhammad Jamil; Salim, Mohammad; Khan, Momen; Ahmad, Hafiz Ishfaq

    2018-01-01

    AKT3 gene is a constituent of the serine/threonine protein kinase family and plays a crucial role in synthesis of milk fats and cholesterol by regulating activity of the sterol regulatory element binding protein (SREBP). AKT3 is highly conserved in mammals and its expression levels during the lactation periods of cattle are markedly increased. AKT3 is highly expressed in the intestine followed by mammary gland and it is also expressed in immune cells. It is involved in the TLR pathways as effectively as proinflammatory cytokines. The aims of this study were to investigate the sequences differences between buffalo and cow. Our results showed that there were substantial differences between buffalo and cow in some exons and noteworthy differences of the gene size in different regions. We also identified the important consensus sequence motifs, variation in 2000 upstream of ATG, substantial difference in the “3′UTR” region, and miRNA association in the buffalo sequences compared with the cow. In addition, genetic analyses, such as gene structure, phylogenetic tree, position of different motifs, and functional domains, were performed to establish their correlation with other species. This may indicate that a buffalo breed has potential resistance to disease, environment changes, and airborne microorganisms and some good production and reproductive traits. PMID:29862252

  19. Comparative Analysis of V-Akt Murine Thymoma Viral Oncogene Homolog 3 (AKT3) Gene between Cow and Buffalo Reveals Substantial Differences for Mastitis.

    Science.gov (United States)

    Ullah, Farman; Bhattarai, Dinesh; Cheng, Zhangrui; Liang, Xianwei; Deng, Tingxian; Rehman, Zia Ur; Talpur, Hira Sajjad; Worku, Tesfaye; Brohi, Rahim Dad; Safdar, Muhammad; Ahmad, Muhammad Jamil; Salim, Mohammad; Khan, Momen; Ahmad, Hafiz Ishfaq; Zhang, Shujun

    2018-01-01

    AKT3 gene is a constituent of the serine/threonine protein kinase family and plays a crucial role in synthesis of milk fats and cholesterol by regulating activity of the sterol regulatory element binding protein (SREBP). AKT3 is highly conserved in mammals and its expression levels during the lactation periods of cattle are markedly increased. AKT3 is highly expressed in the intestine followed by mammary gland and it is also expressed in immune cells. It is involved in the TLR pathways as effectively as proinflammatory cytokines. The aims of this study were to investigate the sequences differences between buffalo and cow. Our results showed that there were substantial differences between buffalo and cow in some exons and noteworthy differences of the gene size in different regions. We also identified the important consensus sequence motifs, variation in 2000 upstream of ATG, substantial difference in the "3'UTR" region, and miRNA association in the buffalo sequences compared with the cow. In addition, genetic analyses, such as gene structure, phylogenetic tree, position of different motifs, and functional domains, were performed to establish their correlation with other species. This may indicate that a buffalo breed has potential resistance to disease, environment changes, and airborne microorganisms and some good production and reproductive traits.

  20. Comparative Analysis of V-Akt Murine Thymoma Viral Oncogene Homolog 3 (AKT3 Gene between Cow and Buffalo Reveals Substantial Differences for Mastitis

    Directory of Open Access Journals (Sweden)

    Farman Ullah

    2018-01-01

    Full Text Available AKT3 gene is a constituent of the serine/threonine protein kinase family and plays a crucial role in synthesis of milk fats and cholesterol by regulating activity of the sterol regulatory element binding protein (SREBP. AKT3 is highly conserved in mammals and its expression levels during the lactation periods of cattle are markedly increased. AKT3 is highly expressed in the intestine followed by mammary gland and it is also expressed in immune cells. It is involved in the TLR pathways as effectively as proinflammatory cytokines. The aims of this study were to investigate the sequences differences between buffalo and cow. Our results showed that there were substantial differences between buffalo and cow in some exons and noteworthy differences of the gene size in different regions. We also identified the important consensus sequence motifs, variation in 2000 upstream of ATG, substantial difference in the “3′UTR” region, and miRNA association in the buffalo sequences compared with the cow. In addition, genetic analyses, such as gene structure, phylogenetic tree, position of different motifs, and functional domains, were performed to establish their correlation with other species. This may indicate that a buffalo breed has potential resistance to disease, environment changes, and airborne microorganisms and some good production and reproductive traits.

  1. Development of a Novel Therapeutic Paradigm Utilizing a Mammary Gland-Targeted, Bin-1 Knockout Mouse Model

    Science.gov (United States)

    2007-03-01

    Thierry-Mieg et al. AceView: identification and functional annotation of cDNA- supported genes in higher organisms— Homo sapiens gene INDO, encoding...stimulating function of RhoB. J Biol Chem 1997; 272:15591–4. 25. Routhier EL , Donover PS, Prendergast GC. hob1+, the homolog of Bin1 in fission yeast, is...tumours on inoculation of EL -4 thymoma or B16 melanoma cells due to an increased tumour-specific CTL response85. TGFβ suppression of tumour-specific

  2. Perioperative echocardiography for invasive thymoma with ...

    African Journals Online (AJOL)

    ... of the mass and haemodynamic changes secondary to compression.3,4 Previous literature has ... The right middle lobe; medial and lateral segmental bronchi; right ... size 35 Fr left double lumen endotracheal tube was sited. Maintenance of ...

  3. Neuropsychiatric symptoms in patients with thymoma- associated ...

    African Journals Online (AJOL)

    1 Department of Psychiatry and Mental Health, Faculty of Health Sciences, University of Cape Town, ... stabilised on immunosuppressive therapy and a thymectomy was ..... Although we enquired about social and occupational function, we.

  4. Iminolactones as Tools for Inversion of the Absolute Configuration of alpha-Amino Acids and as Inhibitors of Cancer Cell Proliferation

    DEFF Research Database (Denmark)

    Jensen, Christina Mernøe; Chow, Hsiao-Qing; Chen, Ming

    2016-01-01

    -proliferative effects toward three cancer cell lines (EL4, MCF7, PC3) with insignificant effect on non-malign cell lines (McCoy, MCF10A, NIH3T3). Thus, iminolactones appear to be potential lead structures for preparation of drugs selectively affecting proliferation of malign cell lines....

  5. Apoptosis in thymocytes and lymphoma cells induced by neutrons and X-rays

    International Nuclear Information System (INIS)

    Ohyama, Harumi; Koike, Sachiko; Ando, Kouichi

    1993-01-01

    Apoptosis is a distinctive mode of programmed cell death with characteristic morphological and biochemical features. The cells undergoing apoptosis display shrinkage, chromatin condensation and internucleosomal breakage of DNA. The cell death is a process through which organisms get rid of unwanted cells. Thymocytes are highly radiosensitive, and undergo typical apoptosis within a few hours after the exposure to X-ray. Also extremely radiosensitive thymic lymphoma cells have been found. The effect of 30 MeV NIRS fast neutrons on the induction of apoptosis in thymocytes and thymoma cells was examined in comparison with that of X-ray. Although apoptotic cells increased gradually with time, the apoptotic process proceeded rapidly in individual cells after the onset. By the measurement of cell size distribution, the appearance of a distinct apoptotic cell peak was observed. In the case of neutron irradiation on SCA1 thymic lymphoma cells, the method for counting apoptotic cells based on chromatin condensation was developed. The cell volume reduction of thymocytes, the dose survival curves and the induction of apoptosis in SCA1 are reported. (K.I.)

  6. Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later-life Notch1-mediated T cell development and leukemogenesis

    International Nuclear Information System (INIS)

    Ahrenhoerster, Lori S.; Leuthner, Tess C.; Tate, Everett R.; Lakatos, Peter A.; Laiosa, Michael D.

    2015-01-01

    Over half of T cell acute lymphoblastic leukemia (T-ALL) patients have activating mutations in the Notch gene. Moreover, the contaminant 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a known carcinogen that mediates its toxicity through the aryl hydrocarbon receptor (AHR), and crosstalk between activated AHR and Notch signaling pathways has previously been observed. Given the importance of Notch signaling in thymocyte development and T-ALL disease progression, we hypothesized that the activated AHR potentiates disease initiation and progression in an in vivo model of Notch1-induced thymoma. This hypothesis was tested utilizing adult and developmental exposure paradigms to TCDD in mice expressing a constitutively active Notch1 transgene (Notch ICN-TG ). Following exposure of adult Notch ICN-TG mice to a single high dose of TCDD, we observed a significant increase in the efficiency of CD8 thymocyte generation. We next exposed pregnant mice to 3 μg/kg of TCDD throughout gestation and lactation to elucidate effects of developmental AHR activation on later-life T cell development and T-ALL-like thymoma susceptibility induced by Notch1. We found that the vehicle-exposed Notch ICN-TG offspring have a peripheral T cell pool heavily biased toward the CD4 lineage, while TCDD-exposed Notch ICN-TG offspring were biased toward the CD8 lineage. Furthermore, while the vehicle-exposed NotchICN-TG mice showed increased splenomegaly and B to T cell ratios indicative of disease, mice developmentally exposed to TCDD were largely protected from disease. These studies support a model where developmental AHR activation attenuates later-life Notch1-dependent impacts on thymocyte development and disease progression. - Highlights: • Adult mice exposed to 30 μg/kg TCDD have higher efficiency of CD8 thymocyte generation. • Mice carrying a constitutively active Notch transgene were exposed to 3 μg/kg TCDD throughout development. • Progression of Notch-induced thymoma was different in

  7. Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later-life Notch1-mediated T cell development and leukemogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ahrenhoerster, Lori S.; Leuthner, Tess C.; Tate, Everett R.; Lakatos, Peter A.; Laiosa, Michael D., E-mail: laiosa@uwm.edu

    2015-03-01

    Over half of T cell acute lymphoblastic leukemia (T-ALL) patients have activating mutations in the Notch gene. Moreover, the contaminant 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a known carcinogen that mediates its toxicity through the aryl hydrocarbon receptor (AHR), and crosstalk between activated AHR and Notch signaling pathways has previously been observed. Given the importance of Notch signaling in thymocyte development and T-ALL disease progression, we hypothesized that the activated AHR potentiates disease initiation and progression in an in vivo model of Notch1-induced thymoma. This hypothesis was tested utilizing adult and developmental exposure paradigms to TCDD in mice expressing a constitutively active Notch1 transgene (Notch{sup ICN-TG}). Following exposure of adult Notch{sup ICN-TG} mice to a single high dose of TCDD, we observed a significant increase in the efficiency of CD8 thymocyte generation. We next exposed pregnant mice to 3 μg/kg of TCDD throughout gestation and lactation to elucidate effects of developmental AHR activation on later-life T cell development and T-ALL-like thymoma susceptibility induced by Notch1. We found that the vehicle-exposed Notch{sup ICN-TG} offspring have a peripheral T cell pool heavily biased toward the CD4 lineage, while TCDD-exposed Notch{sup ICN-TG} offspring were biased toward the CD8 lineage. Furthermore, while the vehicle-exposed NotchICN-TG mice showed increased splenomegaly and B to T cell ratios indicative of disease, mice developmentally exposed to TCDD were largely protected from disease. These studies support a model where developmental AHR activation attenuates later-life Notch1-dependent impacts on thymocyte development and disease progression. - Highlights: • Adult mice exposed to 30 μg/kg TCDD have higher efficiency of CD8 thymocyte generation. • Mice carrying a constitutively active Notch transgene were exposed to 3 μg/kg TCDD throughout development. • Progression of Notch

  8. Elimination of mouse tumor cells from neonate spermatogonial cells utilizing cisplatin-entrapped folic acid-conjugated poly(lactic-co-glycolic acid) nanoparticles in vitro.

    Science.gov (United States)

    Shabani, Ronak; Ashjari, Mohsen; Ashtari, Khadijeh; Izadyar, Fariborz; Behnam, Babak; Khoei, Samideh; Asghari-Jafarabadi, Mohamad; Koruji, Morteza

    2018-01-01

    Some male survivors of childhood cancer are suffering from azoospermia. In addition, spermatogonial stem cells (SSCs) are necessary for the improvement of spermatogenesis subsequent to exposure to cytotoxic agents such as cisplatin. The aim of this study was to evaluate the anticancer activity of cisplatin-loaded folic acid-conjugated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on mouse malignant cell line (EL4) and SSCs in vitro. SSCs were co-cultured with mouse malignant cell line (EL4) cells and divided into four culture groups: 1) control (cells were co-cultured in the culture medium), 2) co-cultured cells were treated with cisplatin (10 μg/mL), 3) co-cultured cells were treated with cisplatin-loaded folic acid-conjugated PLGA NPs, and 4) co-cultures were treated with folic acid-conjugated PLGA for 48 hours. The NPs were prepared, characterized, and targeted with folate. In vitro release characteristics, loading efficiency, and scanning electron microscopy and transmission electron microscopy images were studied. Cancer cells were assayed after treatment using flow cytometry and TUNEL assay. The co-cultures of SSCs and EL4 cells were injected into seminiferous tubules of the testes after treating with cis-diaminedichloroplatinum/PLGA NPs. The mean diameter of PLGA NPs ranged between 150 and 250 nm. The number of TUNEL-positive cells increased, and the expression of Bax and caspase-3 were upregulated in EL4 cells in Group 4 compared with Group 2. There was no pathological tumor in testes after transplantation with treated co-cultured cells. The PLGA NPs appeared to act as a promising carrier for cisplatin administration, which was consistent with a higher activation of apoptosis than free drug.

  9. HPMA copolymer-bound doxorubicin induces immunogenic tumor cell death.

    Science.gov (United States)

    Sirova, M; Kabesova, M; Kovar, L; Etrych, T; Strohalm, J; Ulbrich, K; Rihova, B

    2013-01-01

    Treatment of murine EL4 T cell lymphoma with N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates of doxorubicin (Dox) leads to complete tumor regression and to the development of therapy-dependent longlasting cancer resistance. This phenomenon occurs with two types of Dox conjugates tested, despite differences in the covalent linkage of Dox to the polymer carrier. Such a cancer resistance cannot fully express in conventional treatment with free Dox, due to substantial immunotoxicity of the treatment, which was not observed in the polymer conjugates. In this study, calreticulin (CRT) translocation and high mobility group box-1 protein (HMGB1) release was observed in EL4 cells treated with a conjugate releasing Dox by a pH-dependent manner. As a result, the treated tumor cells were engulfed by dendritic cells (DC) in vitro, and induced their expression of CD80, CD86, and MHC II maturation markers. Conjugates with Dox bound via an amide bond only increased translocation of HSPs to the membrane, which led to an elevated phagocytosis but was not sufficient to induce increase of the maturation markers on DCs in vitro. Both types of conjugates induced engulfment of the target tumor cells in vivo, that was more intense than that seen with free Dox. It means that the induction of anti-tumor immunity documented upon treatment of EL4 lymphoma with HPMA-bound Dox conjugates does not rely solely on CRT-mediated cell death, but involves multiple mechanisms.

  10. Study of the origin of elements of the uranium-235 family observed in excess in the vicinity of the experimental nuclear EL4 reactor under dismantling. Lessons got at this day and conclusions

    International Nuclear Information System (INIS)

    2007-01-01

    This study resumes the discovery of an excess of actinium 227 found around by EL4 nuclear reactor actually in dismantling. The search for the origin of this excess revealed a real inquiry of investigation during three years. Because a nuclear reactor existed in this area a particular attention will have concerned this region. The doubt became the line of conduct to find the answer to the human or natural origin of this excess. Finally and against any evidence, it appears that the origin of this phenomenon was natural, consequence of the particular local geology. The detail of the different investigations is given: search of a possible correlation with the composition of elevations constituent of lanes, search (and underlining) of new sites in the surroundings of the Rusquec pond and the Plouenez station, study of the atmospheric deposits under winds of the nuclear power plant and in the east direction, search of a possible relationship with the gaseous effluents of the nuclear power plant in the past, historical study of radioactive effluents releases in the fifty last years by the analysis of the sedimentary deposits in the Saint-Herbiot reservoir, search of a possible correlation between the excess of actinium 227 and the nuclear power plant activity; search of a possible correlation with a human activity without any relationship with the nuclear activities, search of a correlation with the underground waters, search of a correlation with the geological context, collect of information on the possible transfers in direction of the food chain, determination of the radiological composition of the underground waters ( not perturbed by human activity), search of the cause of an excess of actinium 227 in the old channel of liquid effluents release of the nuclear power plant. The results are given and discussed. And contrary to all expectations the origin of the excess of actinium 227 is completely natural. (N.C.)

  11. In vitro toxicity assay of cisplatin on mouse acute lymphoblastic leukaemia and spermatogonial stem cells.

    Science.gov (United States)

    Shabani, R; Ashtari, K; Behnam, B; Izadyar, F; Asgari, H; Asghari Jafarabadi, M; Ashjari, M; Asadi, E; Koruji, M

    2016-06-01

    Testicular cancer is the most common cancer affecting men in reproductive age, and cisplatin is one of the major helpful chemotherapeutic agents for treatment of this cancer. In addition, exposure of testes cancer cells to cisplatin could potentially eliminate tumour cells from germ cells in patients. The aim of this study was to evaluate the effect of cisplatin on viability of mouse acute lymphoblastic leukaemia cell line (EL-4) and neonatal mouse spermatogonial cells in vitro. In this study, the isolated spermatogonial stem cells (SSC) and EL-4 were divided into six groups including control (received medium), sham (received DMSO in medium) and experimental groups which received different doses of cisplatin (0.5, 5, 10 and 15 μg ml(-1) ). Cells viability was evaluated with MTT assay. The identity of the cultured cells was confirmed by the expression of specific markers. Our finding showed that viability of both SSC and EL-4 cells was reduced with the dose of 15 μg/ml when compared to the control group (P ≤ 0.05). Also, the differences between the IC50 in doses 10 and 15 μg/ml at different time were significant (P ≤ 0.05). The number of TUNEL-positive cells was increased, and the BAX and caspase-3 expressions were upregulated in EL4 cells for group that received an effective dose of cisplatin). In conclusion, despite the dramatic effects of cisplatin on both cells, spermatogonial stem cells could form colony in culture. © 2015 Blackwell Verlag GmbH.

  12. Origin of elements of the Uranium-235 family observed in the Ellez river near the EL-4 experimental nuclear reactor in dismantling (Monts d'Arree- Finistere department); Origine des elements de la famille de l'uranium-235 observes dans la riviere Ellez a proximite du reacteur nucleaire experimental EL4 en cours de demantelement (Mont d'Arree - departement du Finistere). Resultats et premiers constats annee 2006

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-07-01

    In a previous study which concerned the catchment basin of the harbour of Brest, the A.C.R.O. put in evidence a marking by artificial radioelements around the power plant of Brennilis which can be imputed without ambiguities to the nuclear installation. It also put in evidence abnormalities concerning the natural radioactivity which justifies this new study. In the area of the Monts d'Arree, actinium 227 ({sup 227}Ac), non born by its ascendents which are {sup 235}U and {sup 231}Pa is observed. This phenomenon is characterized by mass activities superior to these ones of {sup 235}U and able to reach these ones of {sup 238}U. Its presence corresponds with the drainage of the Ellez river since the former channel of radioactive effluents releases from the nuclear power plant EL-4 up to the reservoir Saint-Herblot situated 6 km downstream. The strongest values of radioactivity are registered near the disused power plant, at this place a relationship exists between the level of actinium 227 and this one of the artificial radioactivity as it exists a relationship with the decay products of radon exhaled from the subsoil ({sup 210}Pb). But its presence is not limited to a part of the Ellez river, it is equally observed in terrestrial medium, in places in priori not influenced by the direct liquid effluents of the power plant. This place is situated at more than 4 km and without any connection with the Ellez waters. At this stage of the study, it is not possible to answer with certainty the question of the origin of this phenomenon. A new reorientation is considered indispensable to clarify definitively the origin of this unknown phenomenon in the scientific publications and the environmental monitoring. (N.C.)

  13. Study of the origin of elements of the uranium-235 family observed in excess in the vicinity of the experimental nuclear EL4 reactor under dismantling. Lessons got at this day and conclusions; Etude de l'origine des elements de la famille de l'uranium-235 observes en exces dans les environs du reacteur nucleaire experimental EL4 en cours de demantelement. Enseignements retires a ce jour et conclusion

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    This study resumes the discovery of an excess of actinium 227 found around by EL4 nuclear reactor actually in dismantling. The search for the origin of this excess revealed a real inquiry of investigation during three years. Because a nuclear reactor existed in this area a particular attention will have concerned this region. The doubt became the line of conduct to find the answer to the human or natural origin of this excess. Finally and against any evidence, it appears that the origin of this phenomenon was natural, consequence of the particular local geology. The detail of the different investigations is given: search of a possible correlation with the composition of elevations constituent of lanes, search (and underlining) of new sites in the surroundings of the Rusquec pond and the Plouenez station, study of the atmospheric deposits under winds of the nuclear power plant and in the east direction, search of a possible relationship with the gaseous effluents of the nuclear power plant in the past, historical study of radioactive effluents releases in the fifty last years by the analysis of the sedimentary deposits in the Saint-Herbiot reservoir, search of a possible correlation between the excess of actinium 227 and the nuclear power plant activity; search of a possible correlation with a human activity without any relationship with the nuclear activities, search of a correlation with the underground waters, search of a correlation with the geological context, collect of information on the possible transfers in direction of the food chain, determination of the radiological composition of the underground waters ( not perturbed by human activity), search of the cause of an excess of actinium 227 in the old channel of liquid effluents release of the nuclear power plant. The results are given and discussed. And contrary to all expectations the origin of the excess of actinium 227 is completely natural. (N.C.)

  14. Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage.

    Directory of Open Access Journals (Sweden)

    Tobias Eggert

    Full Text Available Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL, while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage.

  15. Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage.

    Science.gov (United States)

    Eggert, Tobias; Medina-Echeverz, José; Kapanadze, Tamar; Kruhlak, Michael J; Korangy, Firouzeh; Greten, Tim F

    2014-01-01

    Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC) not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL), while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU) treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage.

  16. Immunomodulatory effect of tea saponin in immune T-cells and T-lymphoma cells via regulation of Th1, Th2 immune response and MAPK/ERK2 signaling pathway.

    Science.gov (United States)

    Bhardwaj, Jyoti; Chaudhary, Narendra; Seo, Hyo-Jin; Kim, Min-Yong; Shin, Tai-Sun; Kim, Jong-Deog

    2014-06-01

    The anti-cancer activity of saponins and phenolic compounds present in green tea was previously reported. However, the immunomodulatory and adjuvanticity activity of tea saponin has never been studied. In this study, we investigated the immunomodulatory effect of tea saponin in T-lymphocytes and EL4 cells via regulation of cytokine response and mitogen-activated protein kinases (MAPK) signaling pathway. Quantitative analysis of mRNA expression level of cytokines were performed by reverse transcription polymerase chain reaction following stimulation with tea saponin, ovalbumin (OVA) alone or tea saponin in combination with OVA. Tea saponin inhibited the proliferation of EL4 cells measured in a dose-dependent manner. No cytotoxicity effect of tea saponin was detected in T-lymphocytes; rather, tea saponin enhanced the proliferation of T-lymphocytes. Tea saponin with OVA increased the expression of interleukin (IL)-1, IL-2, IL-12, interferon-γ and tumor necrosis factor (TNF)-α and decreased the expression level of IL-10 and IL-8 in T-lymphocytes. Furthermore, tea saponin, in the presence of OVA, downregulated the MAPK signaling pathway via inhibition of IL-4, IL-8 and nuclear factor kappaB (NF-κB) in EL4 cells. Th1 cytokines enhancer and Th2 cytokines and NF-κB inhibitor, tea saponin can markedly inhibit the proliferation and invasiveness of T-lymphoma (EL4) cells, possibly due to TNF-α- and NF-κB-mediated regulation of MAPK signaling pathway.

  17. Human adipose tissue-derived mesenchymal stem cells inhibit T-cell lymphoma growth in vitro and in vivo.

    Science.gov (United States)

    Ahn, Jin-Ok; Chae, Ji-Sang; Coh, Ye-Rin; Jung, Woo-Sung; Lee, Hee-Woo; Shin, Il-Seob; Kang, Sung-Keun; Youn, Hwa-Young

    2014-09-01

    Human mesenchymal stem cells (hMSCs) are thought to be one of the most reliable stem cell sources for a variety of cell therapies. This study investigated the anti-tumor effect of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) on EL4 murine T-cell lymphoma in vitro and in vivo. The growth-inhibitory effect of hAT-MSCs on EL4 tumor cells was evaluated using a WST-1 cell proliferation assay. Cell-cycle arrest and apoptosis were investigated by flow cytometry and western blot. To evaluate an anti-tumor effect of hAT-MSCs on T-cell lymphoma in vivo, CM-DiI-labeled hAT-MSCs were circumtumorally injected in tumor-bearing nude mice, and tumor size was measured. hAT-MSCs inhibited T-cell lymphoma growth by altering cell-cycle progression and inducing apoptosis in vitro. hAT-MSCs inhibited tumor growth in tumor-bearing nude mice and prolonged survival time. Immunofluorescence analysis showed that hAT-MSCs migrated to tumor sites. hAT-MSCs suppress the growth of T-cell lymphoma, suggesting a therapeutic option for T-cell lymphoma. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Overexpression of IL-7R alpha provides a competitive advantage during early T-cell development.

    Science.gov (United States)

    Laouar, Yasmina; Crispe, I Nicholas; Flavell, Richard A

    2004-03-15

    Critical checkpoints controlling early thymic T-cell development and homeostasis are set by the proper signaling function of the interleukin 7 receptor (IL-7R) and the pre-T-cell antigen receptor. Although alpha beta T-cell development is observed in IL-7- and IL-7R alpha-deficient mice, the number of thymocytes is significantly reduced, implying a role for the IL-7R in controlling the size of the thymic T-cell compartment. Here, we report the overexpression of IL-7R alpha that occurs in the early T-cell compartment from AKR/J mice, animals that are highly susceptible to the spontaneous development of thymoma. Increased IL-7R alpha was revealed by surface staining, and increased IL-7R alpha mRNA was documented by using reverse transcriptase-polymerase chain reaction (RT-PCR). This resulted in increased survival of AKR/J early thymocytes, shown by the decreased frequency of TUNEL(+) (terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate [dUTP]-fluorescein nick end labeling) cells. In an in vivo thymocyte repopulation model, AKR/J thymocytes had a selective advantage over healthy thymocytes. This advantage occurred at early stages of T-cell development. Our findings support the model that overexpression of growth factor receptors can contribute to proliferation and malignancy.

  19. Photodynamic Therapy for Cancer Cells Using a Flash Wave Light Xenon Lamp

    Science.gov (United States)

    Kimura, Makoto; Kashikura, Kasumi; Yokoi, Satomi; Koiwa, Yumiko; Tokuoka, Yoshikazu; Kawashima, Norimichi

    We determined photodynamic therapy (PDT) efficacy using a flash wave (FW) and a continuous wave (CW) light, of which the fluence rate was 70 W/cm2, for murine thymic lymphoma cells (EL-4) cultivated in vitro. The irradiation frequency and the pulse width of the FW light were in the range of 1-32 Hz and less than one millisecond, respectively. 5-Aminolevulinic acid-induced protoporphyrin IX (ALA-PpIX) was used as a photosensitizer. When EL-4 with ALA administration was irradiated by the light for 4 h (irradiation fluence: 1.0J/cm2), the survival rate of EL-4 by the FW light was lower than that by the CW light, except for the FW light with irradiation frequency of 32 Hz, and decreased gradually with decreasing irradiation frequency. Moreover, the FW light, especially at lower irradiation frequency, was superior to the CW light for the generation of singlet oxygen in an aqueous PpIX solution. Therefore, thehigher PDT efficacy for EL-4 of the FW light would be caused by the greater generation of singlet oxygen in the cells.

  20. Immune cells from SR/CR mice induce the regression of established tumors in BALB/c and C57BL/6 mice

    DEFF Research Database (Denmark)

    Koch, Janne; Hau, Jann; Pravsgaard Christensen, Jan

    2013-01-01

    of resistance to EL-4 lymphoma cells and J774A.1 monocyte-macrophage cancer cells. The cancer resistance against S180 sarcoma cells could be transferred to susceptible non-resistant BALB/c mice as well as C57BL/6 mice after depletion of both CD4+/CD8+ leukocytes and B-cells from SR/CR mice. In the responding...

  1. In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor.

    Science.gov (United States)

    Boissonnas, Alexandre; Fetler, Luc; Zeelenberg, Ingrid S; Hugues, Stéphanie; Amigorena, Sebastian

    2007-02-19

    Although the immune system evolved to fight infections, it may also attack and destroy solid tumors. In most cases, tumor rejection is initiated by CD8(+) cytotoxic T lymphocytes (CTLs), which infiltrate solid tumors, recognize tumor antigens, and kill tumor cells. We use a combination of two-photon intravital microscopy and immunofluorescence on ordered sequential sections to analyze the infiltration and destruction of solid tumors by CTLs. We show that in the periphery of a thymoma growing subcutaneously, activated CTLs migrate with high instantaneous velocities. The CTLs arrest in close contact to tumor cells expressing their cognate antigen. In regions where most tumor cells are dead, CTLs resume migration, sometimes following collagen fibers or blood vessels. CTLs migrating along blood vessels preferentially adopt an elongated morphology. CTLs also infiltrate tumors in depth, but only when the tumor cells express the cognate CTL antigen. In tumors that do not express the cognate antigen, CTL infiltration is restricted to peripheral regions, and lymphocytes neither stop moving nor kill tumor cells. Antigen expression by tumor cells therefore determines both CTL motility within the tumor and profound tumor infiltration.

  2. STAT3/5-dependent IL9 overexpression contributes to neoplastic cell survival in mycosis fungoides

    DEFF Research Database (Denmark)

    Vieyra-Garcia, Pablo A.; Wei, Tianling; Naym, David Gram

    2016-01-01

    preparations. To explore the mechanism of IL9 secretion, we knocked down STAT3/5 and IRF4 by siRNA transfection in CTCL cell lines receiving psoralen+UVA (PUVA) ± anti-IL9 antibody. To further examine the role of IL9 in tumor development, the EL-4 T-cell lymphoma model was used in C57BL/6 mice.  Results...

  3. Anti-apoptotic signature in thymic squamous cell carcinomas – functional relevance of anti-apoptotic BIRC3 expression in the thymic carcinoma cell line 1889c

    OpenAIRE

    Huang, Bei; Belharazem, Djeda; Li, Li; Kneitz, Susanne; Schnabel, Philipp A.; Rieker, Ralf J.; Körner, Daniel; Nix, Wilfried; Schalke, Berthold; Müller-Hermelink, Hans Konrad; Ott, German; Rosenwald, Andreas; Ströbel, Philipp; Marx, Alexander

    2016-01-01

    The molecular pathogenesis of thymomas and thymic carcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and thymic carcinomas, suggesting that other oncogenic principles might ...

  4. Antigen-specific primed cytotoxic T cells eliminate tumour cells in vivo and prevent tumour development, regardless of the presence of anti-apoptotic mutations conferring drug resistance.

    Science.gov (United States)

    Jaime-Sánchez, Paula; Catalán, Elena; Uranga-Murillo, Iratxe; Aguiló, Nacho; Santiago, Llipsy; M Lanuza, Pilar; de Miguel, Diego; A Arias, Maykel; Pardo, Julián

    2018-05-09

    Cytotoxic CD8 + T (Tc) cells are the main executors of transformed and cancer cells during cancer immunotherapy. The latest clinical results evidence a high efficacy of novel immunotherapy agents that modulate Tc cell activity against bad prognosis cancers. However, it has not been determined yet whether the efficacy of these treatments can be affected by selection of tumoural cells with mutations in the cell death machinery, known to promote drug resistance and cancer recurrence. Here, using a model of prophylactic tumour vaccination based on the LCMV-gp33 antigen and the mouse EL4 T lymphoma, we analysed the molecular mechanism employed by Tc cells to eliminate cancer cells in vivo and the impact of mutations in the apoptotic machinery on tumour development. First of all, we found that Tc cells, and perf and gzmB are required to efficiently eliminate EL4.gp33 cells after LCMV immunisation during short-term assays (1-4 h), and to prevent tumour development in the long term. Furthermore, we show that antigen-pulsed chemoresistant EL4 cells overexpressing Bcl-X L or a dominant negative form of caspase-3 are specifically eliminated from the peritoneum of infected animals, as fast as parental EL4 cells. Notably, antigen-specific Tc cells control the tumour growth of the mutated cells, as efficiently as in the case of parental cells. Altogether, expression of the anti-apoptotic mutations does not confer any advantage for tumour cells neither in the short-term survival nor in long-term tumour formation. Although the mechanism involved in the elimination of the apoptosis-resistant tumour cells is not completely elucidated, neither necroptosis nor pyroptosis seem to be involved. Our results provide the first experimental proof that chemoresistant cancer cells with mutations in the main cell death pathways are efficiently eliminated by Ag-specific Tc cells in vivo during immunotherapy and, thus, provide the molecular basis to treat chemoresistant cancer cells with CD8 Tc

  5. Radiation leukemia virus and x-irradiation induce in C57BL/6 mice two distinct T-cell neoplasms: a growth factor-dependent lymphoma and a growth factor-independent lymphoma

    International Nuclear Information System (INIS)

    Haas, Martin; Rothenberg, Ellen; Bogart, M.H.; Jones, O.W.

    1987-01-01

    Two different classes of neoplastic T cells were isolated from radiation leukemia virus (RadLV)-inoculated and from X-ray-treated C57BL/6 mice. One consisted of growth factor-dependent T-cell lymphoma (FD-TCL) lines which were established from the spleens and thymuses of treated mice within a day of lymphoma detection. Non-thymic, factor-dependent TCL cells produced interleukin-2 upon lectin stimulation, and were autostimulatory because they secreted growth factor(s) constitutively. In vivo, FD-TCL cells that were injected intraperitoneally or intravenously homed to the spleen, proliferated in it and killed the injected mice. The isolation and study of FD-TCL cells was facilitated by their cultivation on stromal hematopoietic monolayers in supplemented ''lymphocyte medium'', until an autostimulating, self-sustaining concentration of FD-TCL cells was obtained. FD-TCL cells could not be grown from lymphoid tissue of normal, control mice. In contrast, T-cell lymphoma (TCL) lines, which were established from virus-induced thymomas which had been kept in situ for 4-6 weeks after detection, consisted of factor-independent cells that possessed an aneuploid karyotype. The phenotypic markers of TCL cells differed from those of FD-TCL cells, suggesting heterogeneity in the stages of differentiation at which cells can give rise to growth factor-independent (TCL) and to growth factor-dependent (FD-TCL) lines. (author)

  6. Thymus cells in myasthenia gravis selectively enhance production of anti-acetylcholine-receptor antibody by autologous blood lymphocytes

    International Nuclear Information System (INIS)

    Newsom-Davis, J.; Willcox, N.; Calder, L.

    1981-01-01

    We investigated the role of the thymus in 16 patients with myasthenia gravis without thymoma by studying the production of anti-acetylcholine-receptor antibody by thymic and blood lymphocytes cultured alone or together. In 10 responders (with the highest receptor-antibody titers in their plasma), cultured thymic cells spontaneously produced measurable receptor antibody. Receptor-antibody production by autologous blood lymphocytes was enhanced by the addition of responder's thymic cells, irradiated to abrogate antibody production and suppression (P<0.01). This enhancement was greater and more consistent than that by pokeweed mitogen; it depended on viable thymic cells, appeared to be selective for receptor antibody, and correlated with the ratio of thymic helper (OKT4-positive or OKT4+) to suppressor (OKT8+) T cells (P<0.01). These results suggest that myasthenic thymus contains cell-bound acetylcholine-receptor-like material or specific T cells (or both) that can aid receptor-antibody production. This may be relevant to the benefits of thymectomy in myasthenia and to the breakdown in self-tolerance in this and other autoimmune diseases

  7. Thymus cells in myasthenia gravis selectively enhance production of anti-acetylcholine-receptor antibody by autologous blood lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Newsom-Davis, J.; Willcox, N.; Calder, L.

    1981-11-26

    We investigated the role of the thymus in 16 patients with myasthenia gravis without thymoma by studying the production of anti-acetylcholine-receptor antibody by thymic and blood lymphocytes cultured alone or together. In 10 responders (with the highest receptor-antibody titers in their plasma), cultured thymic cells spontaneously produced measurable receptor antibody. Receptor-antibody production by autologous blood lymphocytes was enhanced by the addition of responder's thymic cells, irradiated to abrogate antibody production and suppression (P<0.01). This enhancement was greater and more consistent than that by pokeweed mitogen; it depended on viable thymic cells, appeared to be selective for receptor antibody, and correlated with the ratio of thymic helper (OKT4-positive or OKT4+) to suppressor (OKT8+) T cells (P<0.01). These results suggest that myasthenic thymus contains cell-bound acetylcholine-receptor-like material or specific T cells (or both) that can aid receptor-antibody production. This may be relevant to the benefits of thymectomy in myasthenia and to the breakdown in self-tolerance in this and other autoimmune diseases.

  8. Radiosensitization effect by combination with paclitaxel in vivo, including the effect on intratumor quiescent cells

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Ono, Koji; Suzuki, Minoru; Nishimura, Yasumasa; Kinashi, Yuko; Takagaki, Masao; Hori, Hitoshi; Nagasawa, Hideko; Uto, Yoshihiro; Tsuchiya, Izumi; Sadahiro, Sotaro; Murayama, Chieko

    2001-01-01

    Purpose: To evaluate the radiosensitization effect on solid tumors upon combination treatment with paclitaxel (TXL), including the effect on intratumor quiescent (Q) cells. Methods and Materials: Mice bearing SCC VII or EL4 solid tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days to label all proliferating (P) cells. The mice then received γ-irradiation with or without tirapazamine (TPZ) at various time points after TXL administration. Another group of mice received a series of test doses of γ-rays while alive or after tumor clamping to obtain hypoxic fractions (HFs) in the tumors at various time points after TXL administration. Immediately after irradiation, the tumor cells were isolated and incubated with a cytokinesis blocker. The micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, 6 h after irradiation, the tumor cells were isolated from the solid tumors in another group of mice, and the apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequency in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. For the measurement of the HFs, the MN or apoptosis frequency of Q cells was then used to calculate the surviving fraction of Q cells from the regression line for the relationship between the MN or apoptosis frequency and the surviving fraction of total tumor cells. Results: In both SCC VII and EL4 tumors, maximum values of mitotic index (MI) and apoptosis frequency were observed 9 and 24 h after TXL administration, respectively. However, on the whole, the apoptosis frequency for SCC VII was very low. γ-Irradiation 9 h after TXL administration induced significant radiosensitization effects on the total cells of both tumors. Irradiation at 60 h had a more significant effect on total cells of EL4 tumor, but no significant effect on total cells of SCC VII

  9. Radiobiologic significance of apoptosis and micronucleation in quiescent cells within solid tumors following γ-ray irradiation

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Ono, Koji; Suzuki, Minoru; Kinashi, Yuko; Takagaki, Masao

    2001-01-01

    Purpose: To determine the frequency of apoptosis in quiescent (Q) cells within solid tumors following γ-ray irradiation, using four different tumor cell lines. In addition, to assess the significance of detecting apoptosis in these cell lines. Methods and Materials: C3H/He mice bearing SCC VII or FM3A tumors, Balb/c mice bearing EMT6/KU tumors, and C57BL mice bearing EL4 tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received γ-ray irradiation at a dose of 4-25 Gy while alive or after tumor clamping. Immediately after irradiation, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (=Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, 6 hours after irradiation, tumor cell suspensions obtained in the same manner were fixed. The apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequency in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Results: In total cells, SCC VII, FM3A, and EMT6/KU cells showed reasonable relationships between MN frequency and surviving fraction (SF). However, fewer micronuclei were induced in EL4 cells than the other cell lines. In contrast, a comparatively close relationship between apoptosis frequency and SF was found in total cells of EL4 cell line. Less apoptosis was observed in the other cell lines. Quiescent tumor cells exhibited significantly lower values of MN and apoptosis frequency probably due to their large hypoxic fraction, similar to total tumor cells on clamped irradiation. Conclusion: γ-ray irradiation induced MN formation in SCC VII, FM3A, and EMT6/KU tumor cells, and the apoptosis was marked in EL4 cells compared with

  10. Suppressive activities and mechanisms of ugonin J on vascular smooth muscle cells and balloon angioplasty-induced neointimal hyperplasia.

    Science.gov (United States)

    Pan, Chun-Hsu; Li, Pei-Chuan; Chien, Yi-Chung; Yeh, Wan-Ting; Liaw, Chih-Chuang; Sheu, Ming-Jyh; Wu, Chieh-Hsi

    2018-02-01

    Neointimal hyperplasia (or restenosis) is primarily attributed to excessive proliferation and migration of vascular smooth muscle cells (VSMCs). In this study, we investigated the inhibitory effects and mechanisms of ugonin J on VSMC proliferation and migration as well as neointimal formation. Cell viability and the cell-cycle distribution were, respectively, analyzed using an MTT assay and flow cytometry. Cell migration was examined using a wound-healing analysis and a transwell assay. Protein expressions and gelatinase activities were, respectively, measured using Western blot and gelatin zymography. Balloon angioplasty-induced neointimal formation was induced in a rat carotid artery model and then examined using immunohistochemical staining. Ugonin J induced cell-cycle arrest at the G 0 /G 1 phase and apoptosis to inhibit VSMC growth. Ugonin J also exhibited marked suppressive activity on VSMC migration. Ugonin J significantly reduced activations of focal adhesion kinase, phosphoinositide 3-kinase, v-akt murine thymoma viral oncogene homolog 1, and extracellular signal-regulated kinase 1/2 proteins. Moreover, ugonin J obviously reduced expressions and activity levels of matrix metalloproteinase-2 and matrix metalloproteinase-9. In vivo data indicated that ugonin J prevented balloon angioplasty-induced neointimal hyperplasia. Our study suggested that ugonin J has the potential for application in the prevention of balloon injury-induced neointimal formation. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Establishment of imageable model of T-cell lymphoma growing in syngenic mice

    Czech Academy of Sciences Publication Activity Database

    Větvička, David; Hovorka, Ondřej; Kovář, Lubomír; Říhová, Blanka

    2009-01-01

    Roč. 29, č. 11 (2009), s. 4513-4518 ISSN 0250-7005 R&D Projects: GA AV ČR IAA400200702; GA AV ČR KAN200200651; GA ČR GD310/08/H077 Institutional research plan: CEZ:AV0Z50200510 Keywords : Imageable model * EL-4 T- cell lymphoma * whole body imaging Subject RIV: EC - Immunology Impact factor: 1.428, year: 2009

  12. Ascorbyl stearate and ionizing radiation potentiate apoptosis through intracellular thiols and oxidative stress in murine T lymphoma cells.

    Science.gov (United States)

    Mane, Shirish D; Kamatham, Akhilender Naidu

    2018-02-01

    Ascorbyl stearate (Asc-s) is a derivative of ascorbic acid with better anti-tumour efficacy compared to its parent compound ascorbic acid. In this study, we have examined radio-sensitizing effect of Asc-s in murine T cell lymphoma (EL4) cells at 4 Gy. Asc-s and radiation treatment reduced cell proliferation, induced apoptosis in a dose dependent manner by arresting the cells at S/G2-M phase of cell cycle. It also decreased the frequency of cancer stem cells per se, with significantly higher decrease in combination with radiation treatment./Further, Asc-s and radiation treatment increased the level of reactive oxygen species (ROS), drop in mitochondrial membrane potential (MMP) and increased caspase-3 activity resulting in apoptosis of EL4 cells. Further it also significantly decreased GSH/GSSG ratio due to binding of Asc-s with thiols. The increase in oxidative stress induced by Asc-s and radiation treatment was abrogated by thiol antioxidants in EL4 cells. Interestingly, this redox modulation triggered significant increase in protein glutathionylation in a time dependent manner. Asc-s treatment resulted in glutathionylation of IKK, p50-NF-kB and mutated p53, thereby inhibiting cancer progression during oxidative stress. Asc-s quenches GSH ensuing Asc-s + GSH adduct thereby further modulating GSH/GSSG ratio as evident from HPLC and docking studies. The anti-tumour effect of Asc-s along with radiation was studied by injecting EL4 cells in synegenicC57/BL6 male mice. Intraperitoneal injection of Asc-s followed by radiation exposure at 4 Gy to the tumour bearing mice resulted in radio-sensitization which is evident from significant regression of tumour as evident from tumour burden index. The survival study supports the data that Asc-s pre-treatment enhances radio-sensitization in murine lymphoma. Our data, suggest that Asc-s and ionizing radiation induced cell cycle arrest and apoptosis by perturbing redox balance through irreversible complexes of thiols with Asc

  13. 5-Lipoxygenase contributes to PPARγ activation in macrophages in response to apoptotic cells.

    Science.gov (United States)

    von Knethen, Andreas; Sha, Lisa K; Kuchler, Laura; Heeg, Annika K; Fuhrmann, Dominik; Heide, Heinrich; Wittig, Ilka; Maier, Thorsten J; Steinhilber, Dieter; Brüne, Bernhard

    2013-12-01

    Macrophage polarization to an anti-inflammatory phenotype upon contact with apoptotic cells is a contributing hallmark to immune suppression during the late phase of sepsis. Although the peroxisome proliferator-activated receptor γ (PPARγ) supports this macrophage phenotype switch, it remains elusive how apoptotic cells activate PPARγ. Assuming that a molecule causing PPARγ activation in macrophages originates in the cell membrane of apoptotic cells we analyzed lipid rafts from apoptotic, necrotic, and living human Jurkat T cells which showed the presence of 5-lipoxygenase (5-LO) in lipid rafts of apoptotic cells only. Incubating macrophages with lipid rafts of apoptotic, but not necrotic or living cells, induced PPAR responsive element (PPRE)-driven mRuby reporter gene expression in RAW 264.7 macrophages stably transduced with a 4xPPRE containing vector. Experiments with lipid rafts of apoptotic murine EL4 T cells revealed similar results. To verify the involvement of 5-LO in activating PPARγ in macrophages, Jurkat T cells were incubated with the 5-LO inhibitor MK-866 prior to induction of apoptosis, which failed to induce mRuby expression. Similar results were obtained with lipid rafts of apoptotic EL4 T cells preexposed to the 5-LO inhibitors zileuton and CJ-13610. Interestingly, Jurkat T cells overexpressing 5-LO failed to activate PPARγ in macrophages, while their 5-LO overexpressing apoptotic counterparts did. Our results suggest that during apoptosis 5-LO gets associated with lipid rafts and synthesizes ligands that in turn stimulate PPARγ in macrophages. © 2013.

  14. A hotspot in the glucocorticoid receptor DNA-binding domain susceptible to loss of function mutation

    Science.gov (United States)

    Banuelos, Jesus; Shin, Soon Cheon; Lu, Nick Z.

    2015-01-01

    Glucocorticoids (GCs) are used to treat a variety of inflammatory disorders and certain cancers. However, GC resistance occurs in subsets of patients. We found that EL4 cells, a GC-resistant mouse thymoma cell line, harbored a point mutation in their GC receptor (GR) gene, resulting in the substitution of arginine 493 by a cysteine in the second zinc finger of the DNA-binding domain. Allelic discrimination analyses revealed that the R493C mutation occurred on both alleles. In the absence of GCs, the GR in EL4 cells localized predominantly in the cytoplasm and upon dexamethasone treatment underwent nuclear translocation, suggesting the ligand binding ability of the GR in EL4 cells was intact. In transient transfection assays, the R493C mutant could not transactivate the MMTV-luciferase reporter. Site-directed mutagenesis to revert the R493C mutation restored the transactivation activity. Cotransfection experiments showed that the R493C mutant did not inhibit the transcriptional activities of the wild-type GR. In addition, the R493C mutant did not repress either the AP-1 or NF-κB reporters as effectively as WT GR. Furthermore, stable expression of the WT GR in the EL4 cells enabled GC-mediated gene regulation, specifically upregulation of IκBα and downregulation of interferon γ and interleukin 17A. Arginine 493 is conserved among multiple species and all human nuclear receptors and its mutation has also been found in the human GR, androgen receptor, and mineralocorticoid receptor. Thus, R493 is necessary for the transcriptional activity of the GR and a hotspot for mutations that result in GC resistance. PMID:25676786

  15. J.O. no. 10 of the 13 january 2004, page 991, text no. 14. Decrees, orders. General texts. Decree no. 2004-47 of the 12 january 2004 modifying the decree no. 96-978 of the 31 october 1996 relative to the creation of the nuclear installation no. 162 named EL4-D, installation of storage for the Monts d'Arree power plants materials; J.O. no. 10 du 13 janvier 2004, page 991, texte no. 14. Decrets, arretes, circulaires. Textes generaux. Decret no. 2004-47 du 12 janvier 2004 modifiant le decret no. 96-978 du 31 octobre 1996 relatif a la creation de l'installation nucleaire de base no. 162 denommee EL4-D, installation d'entreposage de materiels de la centrale nucleaire des monts d'Arree

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-06-01

    The reactor EL4, implemented in december 1966, has definitely shutdown on the 31 july 1985. This reactor was an industrial prototype, built and exploited by Cea and EDF. In the framework of the partial dismantling of the installation, the decree 96-978 of the 31 october 1996 agreed the Cea to modify the installation to become a storage installation. (A.L.B.)

  16. The Cyrano program. 1 - description and operation of an irradiation device 'Cyrano'. 2 - results of the experiments Cyrano 1 and 2 (study of the EL 4 first-bach pencil); measurement of the thermal conductivity integral for UO2 sintered up to 2300 deg C; evolution of fission gases at constant power

    International Nuclear Information System (INIS)

    Stora, J.P.; Chenebault, P.

    1968-01-01

    Two rods of the type 'EL 4 first score' have been irradiated in 'Cyrano' capsules which are suited for continuous measurement of the nuclear power evolved and equipped with thermocouples. The variations of the integral of conductivity of sintered 96 per cent theoretical dense UO 2 has been established until 2300 deg. C; these variations are coherent with those previously measured out-of-pile. The released fission gases have been recovered at different times during the irradiation: the kinetics of release of stable gases is such that, in the experimental conditions (T surface = 610 deg. C, ∫ T s T c kdT = 34.7 W cm -1 ) the fraction of released gases is still widely increasing after 12 days of irradiation. Numerous observations have been made on concentrations of rare gases locally present in the irradiated fuel. (authors) [fr

  17. Up-regulation of interleukin-4 production via NF-AT/AP-1 activation in T cells by biochanin A, a phytoestrogen and its metabolites

    International Nuclear Information System (INIS)

    Park, Jin; Chung, Su Wol; Kim, Seung Hyun; Kim, Tae Sung

    2006-01-01

    Phytoestrogens are naturally occurring compounds derived from plants. Although phytoestrogens exhibit many biological functions including estrogen agonist/antagonist properties, the effect on allergic responses remains unclear. In this study, we investigated whether biochanin A, a phytoestrogen and its metabolites, genistein, p-ethylphenol and phenolic acid, affect production of IL-4, a pro-inflammatory cytokine closely associated with allergic immune responses, in primary CD4 + T cells and EL4 T lymphoma cells. Biochanin A, genistein and p-ethylphenol significantly enhanced IL-4 production from both CD4 + T cells and EL4 cells in a dose-dependent manner, while phenolic acid did not. Biochanin A, genistein and p-ethylphenol also enhanced IL-4 gene promoter activity in EL4 cells transiently transfected with IL-4 promoter constructs, but this effect was impaired in EL4 cells transfected with an IL-4 promoter construct deleted of a P4 site carrying NF-AT and AP-1 binding sites. In addition, biochanin A, genistein and p-ethylphenol increased both NF-AT and AP-1 DNA binding activities, indicating that they might enhance IL-4 production via NF-AT/AP-1 activation. Furthermore, biochanin A, genistein and p-ethylphenol increased p38 MAPK phosphorylation and PKC activity, while they did not affect ERK phosphorylation. The enhanced NF-AT DNA binding activities were suppressed by inhibitors for PI3-K and PKC, but not by p38 MAPK inhibitors. In contrast, the enhanced AP-1 DNA binding activities and p38 MAPK phosphorylation were significantly suppressed by specific inhibitors for PKC and p38 MAPK, but not by PI3-K inhibitors. These results demonstrate, for the first time, that biochanin A, genistein and p-ethylphenol enhance IL-4 production in activated T cells by two independent pathways, PI3-K/PKC/NF-AT and PKC/p38 MAPK/AP-1

  18. J.O. no. 10 of the 13 january 2004, page 991, text no. 14. Decrees, orders. General texts. Decree no. 2004-47 of the 12 january 2004 modifying the decree no. 96-978 of the 31 october 1996 relative to the creation of the nuclear installation no. 162 named EL4-D, installation of storage for the Monts d'Arree power plants materials

    International Nuclear Information System (INIS)

    2004-06-01

    The reactor EL4, implemented in december 1966, has definitely shutdown on the 31 july 1985. This reactor was an industrial prototype, built and exploited by Cea and EDF. In the framework of the partial dismantling of the installation, the decree 96-978 of the 31 october 1996 agreed the Cea to modify the installation to become a storage installation. (A.L.B.)

  19. CpG oligodeoxynucleotide induces apoptosis and cell cycle arrest in A20 lymphoma cells via TLR9-mediated pathways.

    Science.gov (United States)

    Qi, Xu-Feng; Zheng, Li; Kim, Cheol-Su; Lee, Kyu-Jae; Kim, Dong-Heui; Cai, Dong-Qing; Qin, Jun-Wen; Yu, Yan-Hong; Wu, Zheng; Kim, Soo-Ki

    2013-07-01

    Recent studies have suggested that the anti-cancer activity of CpG-oligodeoxynucleotides (CpG-ODNs) is owing to their immunomodulatory effects in tumor-bearing host. The purpose of this study is to investigate the directly cytotoxic activity of KSK-CpG, a novel CpG-ODN with an alternative CpG motif, against A20 and EL4 lymphoma cells in comparison with previously used murine CpG motif (1826-CpG). To evaluate the potential cytotoxic effects of KSK-CpG on lymphoma cells, cell viability assay, confocal microscopy, flow cytometry, DNA fragmentation, Western blotting, and reverse transcription-polymerase chain reaction (RT-PCR) analysis were used. We found that KSK-CpG induced direct cytotoxicity in A20 lymphoma cells, but not in EL4 lymphoma cells, at least in part via TLR9-mediated pathways. Apoptotic cell death was demonstrated to play an important role in CpG-ODNs-induced cytotoxicity. In addition, both mitochondrial membrane potential decrease and G1-phase arrest were involved in KSK-CpG-induced apoptosis in A20 cells. The activities of apoptotic molecules such as caspase-3, PARP, and Bax were increased, but the activation of p27 Kip1 and ERK were decreased in KSK-CpG-treated A20 cells. Furthermore, autocrine IFN-γ partially contributed to apoptotic cell death in KSK-CpG-treated A20 cells. Collectively, our findings suggest that KSK-CpG induces apoptotic cell death in A20 lymphoma cells at least in part by inducing G1-phase arrest and autocrine IFN-γ via increasing TLR9 expression, without the need for immune system of tumor-bearing host. This new understanding supports the development of TLR9-targeted therapy with CpG-ODN as a direct therapeutic agent for treating B lymphoma. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Detection of immunotoxicity using T-cell based cytokine reporter cell lines ('Cell Chip')

    International Nuclear Information System (INIS)

    Ringerike, Tove; Ulleraas, Erik; Voelker, Rene; Verlaan, Bert; Eikeset, Aase; Trzaska, Dominika; Adamczewska, Violetta; Olszewski, Maciej; Walczak-Drzewiecka, Aurelia; Arkusz, Joanna; Loveren, Henk van; Nilsson, Gunnar; Lovik, Martinus; Dastych, Jaroslaw; Vandebriel, Rob J.

    2005-01-01

    Safety assessment of chemicals and drugs is an important regulatory issue. The evaluation of potential adverse effects of compounds on the immune system depends today on animal experiments. An increasing demand, however, exists for in vitro alternatives. Cytokine measurement is a promising tool to evaluate chemical exposure effects on the immune system. Fortunately, this type of measurement can be performed in conjunction with in vitro exposure models. We have taken these considerations as the starting point to develop an in vitro method to efficiently screen compounds for potential immunotoxicity. The T-cell lymphoma cell line EL-4 was transfected with the regulatory sequences of interleukin (IL)-2, IL-4, IL-10, interferon (IFN)-γ or actin fused to the gene for enhanced green fluorescent protein (EGFP) in either a stabile or a destabilised form. Consequently, changes in fluorescence intensity represent changes in cytokine expression with one cell line per cytokine. We used this prototype 'Cell Chip' to test, by means of flow cytometry, the immunomodulatory potential of 13 substances and were able to detect changes in cytokine expression in 12 cases (successful for cyclosporine, rapamycin, pentamidine, thalidomide, bis(tri-n-butyltin)oxide, house dust mite allergen (Der p I), 1-chloro-2,4-dinitrobenzene, benzocaine, tolylene 2,4-diisocyanate, potassium tetrachloroplatinate, sodium dodecyl sulphate and mercuric chloride; unsuccessful for penicillin G). In conclusion, this approach seems promising for in vitro screening for potential immunotoxicity, especially when additional cell lines besides T-cells are included

  1. G2M arrest and apoptosis in murine T lymphoma cells following exposure to 212Bi alpha particle irradiation

    International Nuclear Information System (INIS)

    Palayoor, S.T.; Humm, J.L.; Macklis, R.M.

    1993-01-01

    Asynchronous exponentially growing EL4 murine T lymphoma cells were exposed either to high LET α-radiation from 212 Bi-DTPA or to γ-radiation from a 137 Cs source. Radiation-induced cell cycle perturbation was studied by flow cytometry. Alpha irradiation, like γ, transiently arrested cells in the G2M phase in a dose-dependent manner. The maximum percentages of cells accumulated in G2M 18 h after α- and γ-irradiation were comparable, though the dose-response relationships differed. The ''RBE'' value for G2M block for α- versus γ-radiation was approx. 4. (author)

  2. 89Zr-Oxine Complex PET Cell Imaging in Monitoring Cell-based Therapies

    Science.gov (United States)

    Wu, Haitao; Asiedu, Kingsley O.; Szajek, Lawrence P.; Griffiths, Gary L.; Choyke, Peter L.

    2015-01-01

    Purpose To develop a clinically translatable method of cell labeling with zirconium 89 (89Zr) and oxine to track cells with positron emission tomography (PET) in mouse models of cell-based therapy. Materials and Methods This study was approved by the institutional animal care committee. 89Zr-oxine complex was synthesized in an aqueous solution. Cell labeling conditions were optimized by using EL4 mouse lymphoma cells, and labeling efficiency was examined by using dendritic cells (DCs) (n = 4), naïve (n = 3) and activated (n = 3) cytotoxic T cells (CTLs), and natural killer (NK) (n = 4), bone marrow (n = 4), and EL4 (n = 4) cells. The effect of 89Zr labeling on cell survival, proliferation, and function were evaluated by using DCs (n = 3) and CTLs (n = 3). Labeled DCs (444–555 kBq/[5 × 106] cells, n = 5) and CTLs (185 kBq/[5 × 106] cells, n = 3) transferred to mice were tracked with microPET/CT. In a melanoma immunotherapy model, tumor targeting and cytotoxic function of labeled CTLs were evaluated with imaging (248.5 kBq/[7.7 × 106] cells, n = 4) and by measuring the tumor size (n = 6). Two-way analysis of variance was used to compare labeling conditions, the Wilcoxon test was used to assess cell survival and proliferation, and Holm-Sidak multiple tests were used to assess tumor growth and perform biodistribution analyses. Results 89Zr-oxine complex was synthesized at a mean yield of 97.3% ± 2.8 (standard deviation). It readily labeled cells at room temperature or 4°C in phosphate-buffered saline (labeling efficiency range, 13.0%–43.9%) and was stably retained (83.5% ± 1.8 retention on day 5 in DCs). Labeling did not affect the viability of DCs and CTLs when compared with nonlabeled control mice (P > .05), nor did it affect functionality. 89Zr-oxine complex enabled extended cell tracking for 7 days. Labeled tumor-specific CTLs accumulated in the tumor (4.6% on day 7) and induced tumor regression (P cell tracking technique for use with PET that is

  3. (89)Zr-Oxine Complex PET Cell Imaging in Monitoring Cell-based Therapies.

    Science.gov (United States)

    Sato, Noriko; Wu, Haitao; Asiedu, Kingsley O; Szajek, Lawrence P; Griffiths, Gary L; Choyke, Peter L

    2015-05-01

    To develop a clinically translatable method of cell labeling with zirconium 89 ((89)Zr) and oxine to track cells with positron emission tomography (PET) in mouse models of cell-based therapy. This study was approved by the institutional animal care committee. (89)Zr-oxine complex was synthesized in an aqueous solution. Cell labeling conditions were optimized by using EL4 mouse lymphoma cells, and labeling efficiency was examined by using dendritic cells (DCs) (n = 4), naïve (n = 3) and activated (n = 3) cytotoxic T cells (CTLs), and natural killer (NK) (n = 4), bone marrow (n = 4), and EL4 (n = 4) cells. The effect of (89)Zr labeling on cell survival, proliferation, and function were evaluated by using DCs (n = 3) and CTLs (n = 3). Labeled DCs (444-555 kBq/[5 × 10(6)] cells, n = 5) and CTLs (185 kBq/[5 × 10(6)] cells, n = 3) transferred to mice were tracked with microPET/CT. In a melanoma immunotherapy model, tumor targeting and cytotoxic function of labeled CTLs were evaluated with imaging (248.5 kBq/[7.7 × 10(6)] cells, n = 4) and by measuring the tumor size (n = 6). Two-way analysis of variance was used to compare labeling conditions, the Wilcoxon test was used to assess cell survival and proliferation, and Holm-Sidak multiple tests were used to assess tumor growth and perform biodistribution analyses. (89)Zr-oxine complex was synthesized at a mean yield of 97.3% ± 2.8 (standard deviation). It readily labeled cells at room temperature or 4°C in phosphate-buffered saline (labeling efficiency range, 13.0%-43.9%) and was stably retained (83.5% ± 1.8 retention on day 5 in DCs). Labeling did not affect the viability of DCs and CTLs when compared with nonlabeled control mice (P > .05), nor did it affect functionality. (89)Zr-oxine complex enabled extended cell tracking for 7 days. Labeled tumor-specific CTLs accumulated in the tumor (4.6% on day 7) and induced tumor regression (P cell tracking technique for use with PET that is applicable to a broad range of

  4. Management ofinvasive thymoma at Groote Schuur Hospital, Cape ...

    African Journals Online (AJOL)

    1991-03-02

    Mar 2, 1991 ... type, pleomorphism and mitotic count. Chemotherapy has a role in patients with metastatic disease and reponses may be seen.1S,17. This series supports the need for a multidisciplinary approach in treatment of patients with invasive thymic tumours. The support of the National Cancer Association of South ...

  5. High Molecular Weight Isoforms of Growth Hormone In Cells of the Immune System

    Science.gov (United States)

    Weigent, Douglas A.

    2013-01-01

    A substantial body of research exists to support the idea that cells of the immune system produce growth hormone (GH). However, the structure and mechanism of action of lymphocyte-derived GH continues to remain largely unknown. Here we present the results of Western analysis of whole cell extracts showing that different molecular weight isoforms of GH of approximately 100 kDa, 65 kDa, and 48 kDa can be detected in primary mouse cells of the immune system and in the mouse EL4 cell line. The identity of the 65 kDa and 48 kDa isoforms of GH were confirmed by mass spectrometry. The various isoforms were detected in both enriched T and B spleen cell populations. The large molecular weight isoform appears to reside primarily in the cytoplasm whereas the lower molecular weight 65 kDa and 48 kDa isoforms were detected primarily in the nucleus. These results also suggest that GH isoforms are induced by oxidative stress. In EL4 cells overexpressing GH, the expression of luciferase controlled by a promoter containing the antioxidant response element is increased almost three-fold above control. The data suggest that the induction of isoforms of the GH molecule in cells of the immune system may be an important mechanism of adaptation and/or protection of lymphoid cells under conditions of oxidative stress. PMID:21741628

  6. Cyclooxygenase inhibitors potentiate receptor tyrosine kinase therapies in bladder cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    Bourn J

    2018-06-01

    Full Text Available Jennifer Bourn,1,2 Maria Cekanova1,2 1Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA; 2UT-ORNL Graduate School of Genome Science and Technology, The University of Tennessee, Knoxville, TN, USA Purpose: Receptor tyrosine kinase inhibitors (RTKIs are used as targeted therapies for patients diagnosed with cancer with highly expressed receptor tyrosine kinases (RTKs, including the platelet-derived growth factor receptor (PDGFR and c-Kit receptor. Resistance to targeted therapies is partially due to the activation of alternative pro-survival signaling pathways, including cyclooxygenase (COX-2. In this study, we validated the effects of two RTKIs, axitinib and AB1010, in combination with COX inhibitors on the V-akt murine thymoma oncogene homolog 1 (Akt and COX-2 signaling pathways in bladder cancer cells.Methods: The expression of several RTKs and their downstream signaling targets was analyzed by Western blot (WB analysis in human and canine bladder transitional cell carcinoma (TCC cell lines. The effects of RTKIs and COX inhibitors in bladder TCC cells were assessed by MTS for cell viability, by Caspase-3/7 and Annexin V assay for apoptosis, by WB analysis for detection of COX-2 and Akt signaling pathways, and by enzyme-linked immunosorbent assay for detection of prostaglandin E2 (PGE2 levels.Results: All tested TCC cells expressed the c-Kit and PDGFRα receptors, except human 5637 cells that had low RTKs expression. In addition, all tested cells expressed COX-1, COX-2, Akt, extracellular signal regulated kinases 1/2, and nuclear factor kappa-light-chain-enhance of activated B cells proteins, except human UM-UC-3 cells, where no COX-2 expression was detected by WB analysis. Both RTKIs inhibited cell viability and increased apoptosis in a dose-dependent manner in tested bladder TCC cells, which positively correlated with their expression levels of the PDGFRα and c

  7. Postoperative Radiation Therapy for Non-Small Cell Lung Cancer and Thymic Malignancies

    International Nuclear Information System (INIS)

    Gomez, Daniel R.; Komaki, Ritsuko

    2012-01-01

    For many thoracic malignancies, surgery, when feasible, is the preferred upfront modality for local control. However, adjuvant radiation plays an important role in minimizing the risk of locoregional recurrence. Tumors in the thoracic category include certain subgroups of non-small cell lung cancer (NSCLC) as well as thymic malignancies. The indications, radiation doses, and treatment fields vary amongst subtypes of thoracic tumors, as does the level of data supporting the use of radiation. For example, in the setting of NSCLC, postoperative radiation is typically reserved for close/positive margins or N2/N3 disease, although such diseases as superior sulcus tumors present unique cases in which the role of neoadjuvant vs. adjuvant treatment is still being elucidated. In contrast, for thymic malignancies, postoperative radiation therapy is often used for initially resected Masaoka stage III or higher disease, with its use for stage II disease remaining controversial. This review provides an overview of postoperative radiation therapy for thoracic tumors, with a separate focus on superior sulcus tumors and thymoma, including a discussion of acceptable radiation approaches and an assessment of the current controversies involved in its use

  8. iNKT cell cytotoxic responses control T-lymphoma growth in vitro and in vivo

    Science.gov (United States)

    Bassiri, Hamid; Das, Rupali; Guan, Peng; Barrett, David M.; Brennan, Patrick J.; Banerjee, Pinaki P.; Wiener, Susan J.; Orange, Jordan S.; Brenner, Michael B.; Grupp, Stephan A.; Nichols, Kim E.

    2013-01-01

    Invariant natural killer T (iNKT) cells comprise a lineage of CD1d-restricted glycolipid-reactive T lymphocytes with important roles in host immunity to cancer. iNKT cells indirectly participate in antitumor responses by inducing dendritic cell maturation and producing cytokines that promote tumor clearance by CD8+ T and NK cells. Although iNKT cells thereby act as potent cellular adjuvants, it is less clear whether they directly control the growth of tumors. To gain insights into the direct contribution of iNKT cells to tumor immune surveillance, we developed in vitro and in vivo systems to selectively examine the antitumor activity of iNKT cells in the absence of other cytolytic effectors. Using the EL4 T-lymphoma cell line as a model, we find that iNKT cells exert robust and specific lysis of tumor cells in vitro in a manner that is differentially-induced by iNKT cell agonists of varying TCR affinities, such as OCH, α-galactosyl ceramide and PBS44. In vitro blockade of CD1d-mediated lipid antigen presentation, disruption of T cell receptor (TCR) signaling, or loss of perforin expression significantly reduce iNKT cell killing. Consistent with these findings, iNKT cell reconstitution of T, B, and NK cell-deficient mice slows EL4 growth in vivo via TCR-CD1d and perforin-dependent mechanisms. Together, these observations establish that iNKT cells are sufficient to control the growth of T-lymphoma in vitro and in vivo. They also suggest that the induction of iNKT cell cytotoxic responses in situ might serve as a more effective strategy to prevent and/or treat CD1d+ cancers, such as T-lymphoma. PMID:24563871

  9. Control of E.L.4. dismantling products

    International Nuclear Information System (INIS)

    Rotelle, O.; Dionisio Gomes, A.; Pinaux, M.

    1998-01-01

    Te Brennilis power plant ( a 70 MW heavy water moderated reactor, cooled with Co2) was shut down in July 1985, after 18 years of service. The fuel elements and the heavy water were transferred to facilities for treatment and temporary storage. The second phase of the Brennilis power plant de-construction began in September 1997. Except for the reactor building, the concrete structures will be drained and demolished after inspection and declassification. In the reactor building, only the heavy water circuits will be disassembled. Once this operation has been carried out, new work will be started to provide reactor containment and monitoring. Two types of wastes are produced by the de-construction operations (concrete, steel, nonferrous metals, electrical wiring, insulation, filters, technological wastes): low activity:medium activity wastes, i;e; stored on the surface after being treated and packaged; for very low activity wastes, two possibilities are under consideration: creation of a dedicated surface storage facility and recycling through approved channels. (N.C.)

  10. Reduction of Myeloid-derived Suppressor Cells and Lymphoma Growth by a Natural Triterpenoid

    Science.gov (United States)

    Radwan, Faisal F. Y.; Hossain, Azim; God, Jason M.; Leaphart, Nathan; Elvington, Michelle; Nagarkatti, Mitzi; Tomlinson, Stephen; Haque, Azizul

    2016-01-01

    Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A’s anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen presentation and CD4+ T cell recognition of lymphoma in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma. PMID:25142864

  11. iNKT cell cytotoxic responses control T-lymphoma growth in vitro and in vivo .

    Science.gov (United States)

    Bassiri, Hamid; Das, Rupali; Guan, Peng; Barrett, David M; Brennan, Patrick J; Banerjee, Pinaki P; Wiener, Susan J; Orange, Jordan S; Brenner, Michael B; Grupp, Stephan A; Nichols, Kim E

    2014-01-01

    Invariant natural killer T (iNKT) cells comprise a lineage of CD1d-restricted glycolipid-reactive T lymphocytes with important roles in host immunity to cancer. iNKT cells indirectly participate in antitumor responses by inducing dendritic cell maturation and producing cytokines that promote tumor clearance by CD8+ T and NK cells. Although iNKT cells thereby act as potent cellular adjuvants, it is less clear whether they directly control the growth of tumors. To gain insights into the direct contribution of iNKT cells to tumor immune surveillance, we developed in vitro and in vivo systems to selectively examine the antitumor activity of iNKT cells in the absence of other cytolytic effectors. Using the EL4 T-lymphoma cell line as a model, we found that iNKT cells exert robust and specific lysis of tumor cells in vitro in a manner that is differentially induced by iNKT cell agonists of varying T-cell receptor (TCR) affinities, such as OCH, α-galactosyl ceramide, and PBS44. In vitro blockade of CD1d-mediated lipid antigen presentation, disruption of TCR signaling, or loss of perforin expression significantly reduce iNKT cell killing. Consistent with these findings, iNKT cell reconstitution of T, B, and NK cell–deficient mice slows EL4 growth in vivo via TCR-CD1d and perforin-dependent mechanisms. Together, these observations establish that iNKT cells are sufficient to control the growth of T lymphoma in vitro and in vivo. They also suggest that the induction of iNKT cell cytotoxic responses in situ might serve as a more effective strategy to prevent and/or treat CD1d+ cancers, such as T lymphoma. ©2013 AACR.

  12. Low dose decitabine treatment induces CD80 expression in cancer cells and stimulates tumor specific cytotoxic T lymphocyte responses.

    Directory of Open Access Journals (Sweden)

    Li-Xin Wang

    Full Text Available Lack of immunogenicity of cancer cells has been considered a major reason for their failure in induction of a tumor specific T cell response. In this paper, we present evidence that decitabine (DAC, a DNA methylation inhibitor that is currently used for the treatment of myelodysplastic syndrome (MDS, acute myeloid leukemia (AML and other malignant neoplasms, is capable of eliciting an anti-tumor cytotoxic T lymphocyte (CTL response in mouse EL4 tumor model. C57BL/6 mice with established EL4 tumors were treated with DAC (1.0 mg/kg body weight once daily for 5 days. We found that DAC treatment resulted in infiltration of IFN-γ producing T lymphocytes into tumors and caused tumor rejection. Depletion of CD8(+, but not CD4(+ T cells resumed tumor growth. DAC-induced CTL response appeared to be elicited by the induction of CD80 expression on tumor cells. Epigenetic evidence suggests that DAC induces CD80 expression in EL4 cells via demethylation of CpG dinucleotide sites in the promoter of CD80 gene. In addition, we also showed that a transient, low-dose DAC treatment can induce CD80 gene expression in a variety of human cancer cells. This study provides the first evidence that epigenetic modulation can induce the expression of a major T cell co-stimulatory molecule on cancer cells, which can overcome immune tolerance, and induce an efficient anti-tumor CTL response. The results have important implications in designing DAC-based cancer immunotherapy.

  13. Low Dose Decitabine Treatment Induces CD80 Expression in Cancer Cells and Stimulates Tumor Specific Cytotoxic T Lymphocyte Responses

    Science.gov (United States)

    Zhou, Ji-Hao; Yao, Yu-Shi; Li, Yong-Hui; Xu, Yi-Han; Li, Jing-Xin; Gao, Xiao-Ning; Zhou, Min-Hang; Jiang, Meng-Meng; Gao, Li; Ding, Yi; Lu, Xue-Chun; Shi, Jin-Long; Luo, Xu-Feng; Wang, Jia; Wang, Li-Li; Qu, Chunfeng; Bai, Xue-Feng; Yu, Li

    2013-01-01

    Lack of immunogenicity of cancer cells has been considered a major reason for their failure in induction of a tumor specific T cell response. In this paper, we present evidence that decitabine (DAC), a DNA methylation inhibitor that is currently used for the treatment of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and other malignant neoplasms, is capable of eliciting an anti-tumor cytotoxic T lymphocyte (CTL) response in mouse EL4 tumor model. C57BL/6 mice with established EL4 tumors were treated with DAC (1.0 mg/kg body weight) once daily for 5 days. We found that DAC treatment resulted in infiltration of IFN-γ producing T lymphocytes into tumors and caused tumor rejection. Depletion of CD8+, but not CD4+ T cells resumed tumor growth. DAC-induced CTL response appeared to be elicited by the induction of CD80 expression on tumor cells. Epigenetic evidence suggests that DAC induces CD80 expression in EL4 cells via demethylation of CpG dinucleotide sites in the promoter of CD80 gene. In addition, we also showed that a transient, low-dose DAC treatment can induce CD80 gene expression in a variety of human cancer cells. This study provides the first evidence that epigenetic modulation can induce the expression of a major T cell co-stimulatory molecule on cancer cells, which can overcome immune tolerance, and induce an efficient anti-tumor CTL response. The results have important implications in designing DAC-based cancer immunotherapy. PMID:23671644

  14. Low dose decitabine treatment induces CD80 expression in cancer cells and stimulates tumor specific cytotoxic T lymphocyte responses.

    Science.gov (United States)

    Wang, Li-Xin; Mei, Zhen-Yang; Zhou, Ji-Hao; Yao, Yu-Shi; Li, Yong-Hui; Xu, Yi-Han; Li, Jing-Xin; Gao, Xiao-Ning; Zhou, Min-Hang; Jiang, Meng-Meng; Gao, Li; Ding, Yi; Lu, Xue-Chun; Shi, Jin-Long; Luo, Xu-Feng; Wang, Jia; Wang, Li-Li; Qu, Chunfeng; Bai, Xue-Feng; Yu, Li

    2013-01-01

    Lack of immunogenicity of cancer cells has been considered a major reason for their failure in induction of a tumor specific T cell response. In this paper, we present evidence that decitabine (DAC), a DNA methylation inhibitor that is currently used for the treatment of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and other malignant neoplasms, is capable of eliciting an anti-tumor cytotoxic T lymphocyte (CTL) response in mouse EL4 tumor model. C57BL/6 mice with established EL4 tumors were treated with DAC (1.0 mg/kg body weight) once daily for 5 days. We found that DAC treatment resulted in infiltration of IFN-γ producing T lymphocytes into tumors and caused tumor rejection. Depletion of CD8(+), but not CD4(+) T cells resumed tumor growth. DAC-induced CTL response appeared to be elicited by the induction of CD80 expression on tumor cells. Epigenetic evidence suggests that DAC induces CD80 expression in EL4 cells via demethylation of CpG dinucleotide sites in the promoter of CD80 gene. In addition, we also showed that a transient, low-dose DAC treatment can induce CD80 gene expression in a variety of human cancer cells. This study provides the first evidence that epigenetic modulation can induce the expression of a major T cell co-stimulatory molecule on cancer cells, which can overcome immune tolerance, and induce an efficient anti-tumor CTL response. The results have important implications in designing DAC-based cancer immunotherapy.

  15. Decree no. 96-978 from October 31, 1996 giving permission to the French atomic energy Commission (CEA) to create a basic nuclear installation intended to maintain under supervision and in an intermediate dismantling state the old basic nuclear installation no. 28, named Monts d'Arree-EL 4 nuclear power plant (a decommissioned reactor), in the Monts d'Arree site of the Loqueffret town (Finistere, Brittany)

    International Nuclear Information System (INIS)

    Borotra, F.; Lepage, C.

    1996-01-01

    This decree from the French ministry of industry and postal services gives permission to the CEA to create a new basic nuclear installation, named EL 4D, which is devoted to the storage of materials from the partially dismantled Monts d'Arree EL 4 reactor. Thus, the CEA is allowed to carry out confining works on the reactor building with the closure of all apertures with the exception of the personnel entry sieve, on the circuits and equipments of the reactor vessel with the plugging of fuel channels, heavy water, helium and demineralized water pipes and of the heads of control rod drive mechanisms and other channels, and on the primary coolant circuit outside the reactor vessel and the steam generators with the installation of welded hatches. The irradiated fuels building, the solid wastes repository, the ventilation building, the heavy water and helium circuits, the fuel handling systems and the effluents treatment plant will be completely dismantled. The other buildings will be pulled down. The rest of the decree enumerates the general technical and safety prescriptions which have to be followed in order to ensure the protection of the personnel against ionizing radiations and of the environment against radioactive pollution. (J.S.)

  16. Effect of API-1 and FR180204 on cell proliferation and apoptosis in human DLD-1 and LoVo colorectal cancer cells.

    Science.gov (United States)

    Saglam, Atiye Seda Yar; Alp, Ebru; Elmazoglu, Zubeyir; Menevse, Emine Sevda

    2016-10-01

    The activation of the phosphatidylinositol-3 kinase/v-akt murine thymoma viral oncogene homolog (Akt) and mitogen activated protein kinase kinase/extracellular signal-regulated kinase (ERK) pathways are implicated in the majority of cancers. Selective inhibition of Akt and ERK represents a potential approach for cancer therapy. Therefore, the present study aimed to investigate the apoptotic and anti-proliferative effects of the novel and selective Akt inhibitor 4-amino-5,8-dihydro-5-oxo-8-β-D-ribofuranosyl-pyrido[2,3-d]pyrimidine-6-carboxamide (API-1) and selective ERK1/2 inhibitor FR180204 (FR) alone and in combination on colorectal cancer (CRC) cells (DLD-1 and LoVo). In addition, the effects of API-1 and FR on Akt and ERK signaling pathways were also investigated. The effects of the agents on DLD-1 and LoVo cells were evaluated in terms of cell viability, cytotoxicity, DNA synthesis rate, DNA fragmentation and caspase-3 activity levels. In addition, quantitative reverse transcription-polymerase chain reaction and western blot analysis were performed to examine relevant mRNA and protein levels. The present study observed that the combination of FR with API-1 resulted in significant apoptosis and cytotoxicity compared with any single agent alone in a time-dependent manner in these cells. Also, treatment with FR and API-1 in combination decreased the expression levels of B-cell lymphoma-2 (BCL2), Bcl-2-like1, cyclin D1 and cMYC, and increased the expression levels of BCL2-associated X protein and BCL2 antagonist/killer via phosphorylated Akt and phosphorylated ERK1/2 downregulation. The combination of Akt and ERK1/2 inhibitors resulted in enhanced apoptotic and anti-proliferative effects against CRC cells. The present study hypothesizes that the combination of FR and API-1 in CRC cells may contribute toward potential anti-carcinogenic effects. Additional analyses using other cancer cell lines and animal models are required to confirm these findings in vitro and in

  17. Semi-allogeneic dendritic cells can induce antigen-specific T-cell activation, which is not enhanced by concurrent alloreactivity.

    Science.gov (United States)

    Wells, James W; Cowled, Chris J; Darling, David; Guinn, Barbara-Ann; Farzaneh, Farzin; Noble, Alistair; Galea-Lauri, Joanna

    2007-12-01

    Alloreactive T-cell responses are known to result in the production of large amounts of proinflammatory cytokines capable of activating and maturing dendritic cells (DC). However, it is unclear whether these allogeneic responses could also act as an adjuvant for concurrent antigen-specific responses. To examine effects of simultaneous alloreactive and antigen-specific T-cell responses induced by semi-allogeneic DC. Semi-allogeneic DC were generated from the F(1) progeny of inbred strains of mice (C57BL/6 and C3H, or C57BL/6 and DBA). We directly primed antigen-specific CD8(+) and CD4(+) T-cells from OT-I and OT-II mice, respectively, in the absence of allogeneic responses, in vitro, and in the presence or absence of alloreactivity in vivo. In vitro, semi-allogeneic DC cross-presented ovalbumin (OVA) to naïve CD8(+) OT-I transgenic T-cells, primed naïve CD4(+) OT-II transgenic T-cells and could stimulate strong alloreactive T-cell proliferation in a primary mixed lymphocyte reaction (MLR). In vivo, semi-allogeneic DC migrated efficiently to regional lymph nodes but did not survive there as long as autologous DC. In addition, they were not able to induce cytotoxic T-lymphocyte (CTL) activity to a target peptide, and only weakly stimulated adoptively transferred OT-II cells. The CD4(+) response was unchanged in allo-tolerized mice, indicating that alloreactive T-cell responses could not provide help for concurrently activated antigen-specific responses. In an EL4 tumour-treatment model, vaccination with semi-allogeneic DC/EL4 fusion hybrids, but not allogeneic DC/EL4 hybrids, significantly increased mouse survival. Expression of self-Major histocompatibility complex (MHC) by semi-allogeneic DC can cause the induction of antigen-specific immunity, however, concurrently activated allogeneic bystander responses do not provide helper or adjuvant effects.

  18. Role of G3BP1 in glucocorticoid receptor-mediated microRNA-15b and microRNA-23a biogenesis in endothelial cells

    KAUST Repository

    Kwok, Hoi-Hin

    2017-05-18

    MicroRNAs (miRNAs) are a family of non-coding RNAs that play crucial roles in regulating various normal cellular responses. Recent studies revealed that the canonical miRNA biogenesis pathway is subject to sophisticated regulation. Hormonal control of miRNA biogenesis by androgen and estrogen has been demonstrated, but the direct effects of the glucocorticoid receptor (GR) on miRNA biogenesis are unknown. This study revealed the role of GR in miRNA maturation. We showed that two GR agonists, dexamethasone and ginsenoside-Rg1 rapidly suppressed the expression of mature miR-15b, miR-23a, and miR-214 in human endothelial cells. RNA pulldown coupled with proteomic analysis identified GTPase-activating protein (SH3 domain) binding protein 1 (G3BP1) as one of the RNA-binding proteins mediating GR-regulated miRNA maturation. Activated GR induced phosphorylation of v-AKT Murine Thymoma Viral Oncogene Homologue (AKT) kinase, which in turn phosphorylated and promoted nuclear translocation of G3BP1. The nuclear G3BP1 bound to the G3BP1 consensus sequence located on primary miR-15b~16-2 and miR-23a~27a~24-2 to inhibit their maturation. The findings from this study have advanced our understanding of the non-genomic effects of GR in the vascular system.

  19. Human trophoblast-derived hydrogen sulfide stimulates placental artery endothelial cell angiogenesis.

    Science.gov (United States)

    Chen, Dong-Bao; Feng, Lin; Hodges, Jennifer K; Lechuga, Thomas J; Zhang, Honghai

    2017-09-01

    Endogenous hydrogen sulfide (H2S), mainly synthesized by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH), has been implicated in regulating placental angiogenesis; however, the underlying mechanisms are unknown. This study was to test a hypothesis that trophoblasts synthesize H2S to promote placental angiogenesis. Human choriocarcinoma-derived BeWo cells expressed both CBS and CTH proteins, while the first trimester villous trophoblast-originated HTR-8/SVneo cells expressed CTH protein only. The H2S producing ability of BeWo cells was significantly inhibited by either inhibitors of CBS (carboxymethyl hydroxylamine hemihydrochloride, CHH) or CTH (β-cyano-L-alanine, BCA) and that in HTR-8/SVneo cells was inhibited by CHH only. H2S donors stimulated cell proliferation, migration, and tube formation in ovine placental artery endothelial cells (oFPAECs) as effectively as vascular endothelial growth factor. Co-culture with BeWo and HTR-8/SVneo cells stimulated oFPAEC migration, which was inhibited by CHH or BCA in BeWo but CHH only in HTR-8/SVneo cells. Primary human villous trophoblasts (HVT) were more potent than trophoblast cell lines in stimulating oFPAEC migration that was inhibited by CHH and CHH/BCA combination in accordance with its H2S synthesizing activity linked to CBS and CTH expression patterns. H2S donors activated endothelial nitric oxide synthase (NOS3), v-AKT murine thymoma viral oncogene homolog 1 (AKT1), and extracellular signal-activated kinase 1/2 (mitogen-activated protein kinase 3/1, MAPK3/1) in oFPAECs. H2S donor-induced NOS3 activation was blocked by AKT1 but not MAPK3/1 inhibition. In keeping with our previous studies showing a crucial role of AKT1, MAPK3/1, and NOS3/NO in placental angiogenesis, these data show that trophoblast-derived endogenous H2S stimulates placental angiogenesis, involving activation of AKT1, NOS3/NO, and MAPK3/1. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study

  20. MHC-I modulation due to changes in tumor cell metabolism regulates tumor sensitivity to CTL and NK cells

    Science.gov (United States)

    Catalán, Elena; Charni, Seyma; Jaime, Paula; Aguiló, Juan Ignacio; Enríquez, José Antonio; Naval, Javier; Pardo, Julián; Villalba, Martín; Anel, Alberto

    2015-01-01

    Tumor cells have a tendency to use glucose fermentation to obtain energy instead of mitochondrial oxidative phosphorylation (OXPHOS). We demonstrated that this phenotype correlated with loss of ERK5 expression and with reduced MHC class I expression. Consequently, tumor cells could evade cytotoxic T lymphocyte (CTL)-mediated immune surveillance, but also increase their sensitivity to natural killer (NK) cells. These outcomes were evaluated using two cellular models: leukemic EL4 cells and L929 transformed fibroblasts and their derived ρ° cell lines, which lack mitochondrial DNA. We have also used a L929 cell sub-line that spontaneously lost matrix attachment (L929dt), reminiscent of metastasis generation, that also downregulated MHC-I and ERK5 expression. MHC-I expression is lower in ρ° cells than in the parental cell lines, but they were equally sensitive to CTL. On the contrary, ρ° cells were more sensitive to activated NK cells than parental cells. On the other hand, L929dt cells were resistant to CTL and NK cells, showed reduced viability when forced to perform OXPHOS, and surviving cells increased MHC-I expression and became sensitive to CTL. The present results suggest that when the reduction in MHC-I levels in tumor cells due to glycolytic metabolism is partial, the increase in sensitivity to NK cells seems to predominate. However, when tumor cells completely lose MHC-I expression, the combination of treatments that increase OXPHOS with CTL-mediated immunotherapy could be a promising therapeutic approach. PMID:25949869

  1. MHC-I modulation due to changes in tumor cell metabolism regulates tumor sensitivity to CTL and NK cells.

    Science.gov (United States)

    Catalán, Elena; Charni, Seyma; Jaime, Paula; Aguiló, Juan Ignacio; Enríquez, José Antonio; Naval, Javier; Pardo, Julián; Villalba, Martín; Anel, Alberto

    2015-01-01

    Tumor cells have a tendency to use glucose fermentation to obtain energy instead of mitochondrial oxidative phosphorylation (OXPHOS). We demonstrated that this phenotype correlated with loss of ERK5 expression and with reduced MHC class I expression. Consequently, tumor cells could evade cytotoxic T lymphocyte (CTL)-mediated immune surveillance, but also increase their sensitivity to natural killer (NK) cells. These outcomes were evaluated using two cellular models: leukemic EL4 cells and L929 transformed fibroblasts and their derived ρ° cell lines, which lack mitochondrial DNA. We have also used a L929 cell sub-line that spontaneously lost matrix attachment (L929dt), reminiscent of metastasis generation, that also downregulated MHC-I and ERK5 expression. MHC-I expression is lower in ρ° cells than in the parental cell lines, but they were equally sensitive to CTL. On the contrary, ρ° cells were more sensitive to activated NK cells than parental cells. On the other hand, L929dt cells were resistant to CTL and NK cells, showed reduced viability when forced to perform OXPHOS, and surviving cells increased MHC-I expression and became sensitive to CTL. The present results suggest that when the reduction in MHC-I levels in tumor cells due to glycolytic metabolism is partial, the increase in sensitivity to NK cells seems to predominate. However, when tumor cells completely lose MHC-I expression, the combination of treatments that increase OXPHOS with CTL-mediated immunotherapy could be a promising therapeutic approach.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-03-01

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

  3. Modulation of radiation-induced apoptosis and G2/M block in murine T-lymphoma cells

    International Nuclear Information System (INIS)

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

    1995-01-01

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

  4. Cooperativity of CD44 and CD49d in leukemia cell homing, migration, and survival offers a means for therapeutic attack.

    Science.gov (United States)

    Singh, Vibuthi; Erb, Ulrike; Zöller, Margot

    2013-11-15

    A CD44 blockade drives leukemic cells into differentiation and apoptosis by dislodging from the osteogenic niche. Because anti-CD49d also supports hematopoietic stem cell mobilization, we sought to determine the therapeutic efficacy of a joint CD49d/CD44 blockade. To unravel the underlying mechanism, the CD49d(-) EL4 lymphoma was transfected with CD49d or point-mutated CD49d, prohibiting phosphorylation and FAK binding; additionally, a CD44(-) Jurkat subline was transfected with murine CD44, CD44 with a point mutation in the ezrin binding site, or with cytoplasmic tail-truncated CD44. Parental and transfected EL4 and Jurkat cells were evaluated for adhesion, migration, and apoptosis susceptibility in vitro and in vivo. Ligand-binding and Ab-blocking studies revealed CD44-CD49d cooperation in vitro and in vivo in adhesion, migration, and apoptosis resistance. The cooperation depends on ligand-induced proximity such that both CD44 and CD49d get access to src, FAK, and paxillin and via lck to the MAPK pathway, with the latter also supporting antiapoptotic molecule liberation. Accordingly, synergisms were only seen in leukemia cells expressing wild-type CD44 and CD49d. Anti-CD44 together with anti-CD49d efficiently dislodged EL4-CD49d/Jurkat-CD44 in bone marrow and spleen. Dislodging was accompanied by increased apoptosis susceptibility that strengthened low-dose chemotherapy, the combined treatment most strongly interfering with metastatic settlement and being partly curative. Ab treatment also promoted NK and Ab-dependent cellular cytotoxicity activation, which affected leukemia cells independent of CD44/CD49d tail mutations. Thus, mostly owing to a blockade of joint signaling, anti-CD44 and anti-CD49d hamper leukemic cell settlement and break apoptosis resistance, which strongly supports low-dose chemotherapy.

  5. Characterization of the myeloid-derived suppressor cell subset regulated by NK cells in malignant lymphoma.

    Science.gov (United States)

    Sato, Yusuke; Shimizu, Kanako; Shinga, Jun; Hidaka, Michihiro; Kawano, Fumio; Kakimi, Kazuhiro; Yamasaki, Satoru; Asakura, Miki; Fujii, Shin-Ichiro

    2015-03-01

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population with the ability to suppress immune responses and are currently classified into three distinct MDSC subsets: monocytic, granulocytic and non-monocytic, and non-granulocytic MDSCs. Although NK cells provide an important first-line defense against newly transformed cancer cells, it is unknown whether NK cells can regulate MDSC populations in the context of cancer. In this study, we initially found that the frequency of MDSCs in non-Hodgkin lymphoma (NHL) patients was increased and inversely correlated with that of NK cells, but not that of T cells. To investigate the regulation of MDSC subsets by NK cells, we used an EL4 murine lymphoma model and found the non-monocytic and non-granulocytic MDSC subset, i.e., Gr1 + CD11b + Ly6G med Ly6C med MDSC, is increased after NK cell depletion. The MDSC population that expresses MHC class II, CD80, CD124, and CCR2 is regulated mainly by CD27 + CD11b + NK cells. In addition, this MDSC subset produces some immunosuppressive cytokines, including IL-10 but not nitric oxide (NO) or arginase. We also examined two subsets of MDSCs (CD14 + HLA-DR - and CD14 - HLA-DR - MDSC) in NHL patients and found that higher IL-10-producing CD14 + HLA-DR - MDSC subset can be seen in lymphoma patients with reduced NK cell frequency in peripheral blood. Our analyses of MDSCs in this study may enable a better understanding of how MDSCs manipulate the tumor microenvironment and are regulated by NK cells in patients with lymphoma.

  6. IL-2 and GM-CSF are regulated by DNA demethylation during activation of T cells, B cells and macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yan [College of Animal Science and Technology, Northwest A and F University, Yangling, Shaanxi 712100 (China); Department of Genome Biology, John Curtin School of Medical Research, The Australian National University, ACT 2601 (Australia); Ohms, Stephen J. [ACRF Biomolecular Resource Facility, John Curtin School of Medical Research, The Australian National University, ACT 2601 (Australia); Shannon, Frances M. [Department of Genome Biology, John Curtin School of Medical Research, The Australian National University, ACT 2601 (Australia); The University of Canberra, ACT 2602 (Australia); Sun, Chao, E-mail: sunchao2775@163.com [College of Animal Science and Technology, Northwest A and F University, Yangling, Shaanxi 712100 (China); Fan, Jun Y., E-mail: jun.fan@anu.edu.au [Department of Genome Biology, John Curtin School of Medical Research, The Australian National University, ACT 2601 (Australia)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer DNA methylation is dynamic and flexible and changes rapidly upon cell activation. Black-Right-Pointing-Pointer DNA methylation controls the inducible gene expression in a given cell type. Black-Right-Pointing-Pointer Some enzymes are involved in maintaining the methylation profile of immune cells. -- Abstract: DNA demethylation has been found to occur at the promoters of a number of actively expressed cytokines and is believed to play a critical role in transcriptional regulation. While many DNA demethylation studies have focused on T cell activation, proliferation and differentiation, changes in DNA methylation in other types of immune cells are less well studied. We found that the expression of two cytokines (IL-2 and GM-CSF) responded differently to activation in three types of immune cells: EL4, A20 and RAW264.7 cells. Using the McrBC and MeDIP approaches, we observed decreases in DNA methylation at a genome-wide level and at the promoters of the genes of these cytokines. The expression of several potential enzymes/co-enzymes involved in the DNA demethylation pathways seemed to be associated with immune cell activation.

  7. IL-2 and GM-CSF are regulated by DNA demethylation during activation of T cells, B cells and macrophages

    International Nuclear Information System (INIS)

    Li, Yan; Ohms, Stephen J.; Shannon, Frances M.; Sun, Chao; Fan, Jun Y.

    2012-01-01

    Highlights: ► DNA methylation is dynamic and flexible and changes rapidly upon cell activation. ► DNA methylation controls the inducible gene expression in a given cell type. ► Some enzymes are involved in maintaining the methylation profile of immune cells. -- Abstract: DNA demethylation has been found to occur at the promoters of a number of actively expressed cytokines and is believed to play a critical role in transcriptional regulation. While many DNA demethylation studies have focused on T cell activation, proliferation and differentiation, changes in DNA methylation in other types of immune cells are less well studied. We found that the expression of two cytokines (IL-2 and GM-CSF) responded differently to activation in three types of immune cells: EL4, A20 and RAW264.7 cells. Using the McrBC and MeDIP approaches, we observed decreases in DNA methylation at a genome-wide level and at the promoters of the genes of these cytokines. The expression of several potential enzymes/co-enzymes involved in the DNA demethylation pathways seemed to be associated with immune cell activation.

  8. Reduction of myeloid-derived suppressor cells and lymphoma growth by a natural triterpenoid.

    Science.gov (United States)

    Radwan, Faisal F Y; Hossain, Azim; God, Jason M; Leaphart, Nathan; Elvington, Michelle; Nagarkatti, Mitzi; Tomlinson, Stephen; Haque, Azizul

    2015-01-01

    Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A's anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen (Ag) presentation and CD4+ T cell recognition of lymphoma cells in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma. © 2014 Wiley Periodicals, Inc.

  9. Ubiquitinated proteins enriched from tumor cells by a ubiquitin binding protein Vx3(A7) as a potent cancer vaccine.

    Science.gov (United States)

    Aldarouish, Mohanad; Wang, Huzhan; Zhou, Meng; Hu, Hong-Ming; Wang, Li-Xin

    2015-04-16

    Our previous studies have demonstrated that autophagosome-enriched vaccine (named DRibbles: DRiPs-containing blebs) induce a potent anti-tumor efficacy in different murine tumor models, in which DRibble-containing ubiquitinated proteins are efficient tumor-specific antigen source for the cross-presentation after being loaded onto dendritic cells. In this study, we sought to detect whether ubiquitinated proteins enriched from tumor cells could be used directly as a novel cancer vaccine. The ubiquitin binding protein Vx3(A7) was used to isolate ubiquitinated proteins from EL4 and B16-F10 tumor cells after blocking their proteasomal degradation pathway. C57BL/6 mice were vaccinated with different doses of Ub-enriched proteins via inguinal lymph nodes or subcutaneous injection and with DRibbles, Ub-depleted proteins and whole cell lysate as comparison groups, respectively. The lymphocytes from the vaccinated mice were re-stimulated with inactivated tumor cells and the levels of IFN-γ in the supernatant were detected by ELISA. Anti-tumor efficacy of Ub-enriched proteins vaccine was evaluated by monitoring tumor growth in established tumor mice models. Graphpad Prism 5.0 was used for all statistical analysis. We found that after stimulation with inactivated tumor cells, the lymphocytes from the Ub-enriched proteins-vaccinated mice secreted high level of IFN-γ in dose dependent manner, in which the priming vaccination via inguinal lymph nodes injection induced higher IFN-γ level than that via subcutaneous injection. Moreover, the level of secreted IFN-γ in the Ub-enriched proteins group was markedly higher than that in the whole cell lysate and Ub-depleted proteins. Interestingly, the lymphocytes from mice vaccinated with Ub-enriched proteins, but not Ub-depleted proteins and whole cell lysates, isolated from EL4 or B16-F10 tumor cells also produced an obvious level of IFN-γ when stimulated alternately with inactivated B16-F10 or EL4 tumor cells. Furthermore, Ub

  10. Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment

    International Nuclear Information System (INIS)

    Bathe, Oliver F; Dalyot-Herman, Nava; Malek, Thomas R

    2003-01-01

    Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro-generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor transgenic mouse persisted long after adoptive transfer as memory T cells. When recipient mice were challenged with the OVA-expressing E.G7 thymoma, tumor growth was delayed and sometimes prevented. The reasons for therapeutic failures were not clear. OT-I CTL were adoptively transferred to C57BL/6 mice 21 – 28 days prior to tumor challenge. At this time, the donor cells had the phenotypical and functional characteristics of memory CD8+ T cells. Recipients which developed tumor despite adoptive immunotherapy were analyzed to evaluate the reason(s) for therapeutic failure. Dose-response studies demonstrated that the degree of tumor protection was directly proportional to the number of OT-I CTL adoptively transferred. At a low dose of OT-I CTL, therapeutic failure was attributed to insufficient numbers of OT-I T cells that persisted in vivo, rather than mechanisms that actively suppressed or anergized the OT-I T cells. In recipients of high numbers of OT-I CTL, the E.G7 tumor that developed was shown to be resistant to fresh OT-I CTL when examined ex vivo. Furthermore, these same tumor cells no longer secreted a detectable level of OVA. In this case, resistance to immunotherapy was secondary to selection of clones of E.G7 that expressed a lower level of tumor antigen. Memory engraftment with tumor-specific CTL provides long-term protection against tumor. However, there are several limitations to this immunotherapeutic strategy, especially when targeting a single antigen. This study illustrates the importance of administering large numbers of effectors to engraft sufficiently efficacious immunologic memory. It also demonstrates the importance of targeting several

  11. 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)

  12. Stem Cells

    Science.gov (United States)

    Stem cells are cells with the potential to develop into many different types of cells in the body. ... the body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  13. Automated profiling of individual cell-cell interactions from high-throughput time-lapse imaging microscopy in nanowell grids (TIMING).

    Science.gov (United States)

    Merouane, Amine; Rey-Villamizar, Nicolas; Lu, Yanbin; Liadi, Ivan; Romain, Gabrielle; Lu, Jennifer; Singh, Harjeet; Cooper, Laurence J N; Varadarajan, Navin; Roysam, Badrinath

    2015-10-01

    There is a need for effective automated methods for profiling dynamic cell-cell interactions with single-cell resolution from high-throughput time-lapse imaging data, especially, the interactions between immune effector cells and tumor cells in adoptive immunotherapy. Fluorescently labeled human T cells, natural killer cells (NK), and various target cells (NALM6, K562, EL4) were co-incubated on polydimethylsiloxane arrays of sub-nanoliter wells (nanowells), and imaged using multi-channel time-lapse microscopy. The proposed cell segmentation and tracking algorithms account for cell variability and exploit the nanowell confinement property to increase the yield of correctly analyzed nanowells from 45% (existing algorithms) to 98% for wells containing one effector and a single target, enabling automated quantification of cell locations, morphologies, movements, interactions, and deaths without the need for manual proofreading. Automated analysis of recordings from 12 different experiments demonstrated automated nanowell delineation accuracy >99%, automated cell segmentation accuracy >95%, and automated cell tracking accuracy of 90%, with default parameters, despite variations in illumination, staining, imaging noise, cell morphology, and cell clustering. An example analysis revealed that NK cells efficiently discriminate between live and dead targets by altering the duration of conjugation. The data also demonstrated that cytotoxic cells display higher motility than non-killers, both before and during contact. broysam@central.uh.edu or nvaradar@central.uh.edu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Wortmannin efficiently suppresses the recovery from radiation-induced damage in pimonidazole-unlabeled quiescent tumor cell population

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Suzuki, Minoru; Kondo, Natsuko; Narabayashi, Masaru; Ono, Koji; Sakurai, Yoshinori; Tanaka, Hiroki; Maruhashi, Akira

    2013-01-01

    Labeling of proliferating (P) cells in mice bearing EL4 tumors was achieved by continuous administration of 5-bromo-2'-deoxyuridine (BrdU). Tumors were irradiated with γ-rays at 1 h after pimonidazole administration followed by caffeine or wortmannin treatment. Twenty-four hours later, assessment of the responses of quiescent (Q) and total (=P+Q) cell populations were based on the frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of the pimonidazole-unlabeled tumor cell fractions was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. The pimonidazole-unlabeled cell fraction showed significantly enhanced radio-sensitivity compared with the whole cell fraction more remarkably in Q cells than total cells. However, a significantly greater decrease in radio-sensitivity in the pimonidazole-unlabeled than the whole cell fraction, evaluated using an assay performed 24 hours after irradiation, was more clearly observed in Q cells than total cells. In both the pimonidazole-unlabeled and the whole cell fractions, wortmannin efficiently suppressed the reduction in sensitivity due to delayed assay. Wortmannin combined with γ-ray irradiation is useful for suppressing the recovery from radiation-induced damage especially in the pimonidazole-unlabeled cell fraction within the total and Q tumor cell populations. (author)

  15. Characterization of cell-surface receptors for monoclonal-nonspecific suppressor factor (MNSF)

    International Nuclear Information System (INIS)

    Nakamura, M.; Ogawa, H.; Tsunematsu, T.

    1990-01-01

    Monoclonal-nonspecific suppressor factor (MNSF) is a lymphokine derived from murine T cell hybridoma. The target tissues are both LPS-stimulated B cells and Con A-stimulated T cells. Since the action of MNSF may be mediated by its binding to specific cell surface receptors, we characterized the mode of this binding. The purified MNSF was labeled with 125 I, using the Bolton-Hunter reagent. The labeled MNSF bound specifically to a single class of receptor (300 receptors per cell) on mitogen-stimulated murine B cells or T cells with an affinity of 16 pM at 24 degrees C, in the presence of sodium azide. Competitive experiments showed that MNSF bound to the specific receptor and that the binding was not shared with IL2, IFN-gamma, and TNF. Various cell types were surveyed for the capacity to specifically bind 125 I-MNSF. 125 I-MNSF bound to MOPC-31C (a murine plasmacytoma line) and to EL4 (a murine T lymphoma line). The presence of specific binding correlates with the capacity of the cells to respond to MNSF. These data support the view that like other polypeptide hormones, the action of MNSF is mediated by specific cell surface membrane receptor protein. Identification of these receptors will provide insight into the apparently diverse activities of MNSF

  16. Increased cFLIP expression in thymic epithelial tumors blocks autophagy via NF-κB signalling.

    Science.gov (United States)

    Belharazem, Djeda; Grass, Albert; Paul, Cornelia; Vitacolonna, Mario; Schalke, Berthold; Rieker, Ralf J; Körner, Daniel; Jungebluth, Philipp; Simon-Keller, Katja; Hohenberger, Peter; Roessner, Eric M; Wiebe, Karsten; Gräter, Thomas; Kyriss, Thomas; Ott, German; Geserick, Peter; Leverkus, Martin; Ströbel, Philipp; Marx, Alexander

    2017-10-27

    The anti-apoptotic cellular FLICE-like inhibitory protein cFLIP plays a pivotal role in normal tissues homoeostasis and the development of many tumors, but its role in normal thymus (NT), thymomas and thymic carcinomas (TC) is largely unknown. Expression, regulation and function of cFLIP were analyzed in biopsies of NT, thymomas, thymic squamous cell carcinomas (TSCC), thymic epithelial cells (TECs) derived thereof and in the TC line 1889c by qRT-PCR, western blot, shRNA techniques, and functional assays addressing survival, senescence and autophagy. More than 90% of thymomas and TSCCs showed increased cFLIP expression compared to NT. cFLIP expression declined with age in NTs but not in thymomas. During short term culture cFLIP expression levels declined significantly slower in neoplastic than non-neoplastic primary TECs. Down-regulation of cFLIP by shRNA or NF-κB inhibition accelerated senescence and induced autophagy and cell death in neoplastic TECs. The results suggest a role of cFLIP in the involution of normal thymus and the development of thymomas and TSCC. Since increased expression of cFLIP is a known tumor escape mechanism, it may serve as tissue-based biomarker in future clinical trials, including immune checkpoint inhibitor trials in the commonly PD-L1 high thymomas and TCs.

  17. Identification of cysteine-644 as the covalent site of attachment of dexamethasone 21-mesylate to murine glucocorticoid receptors in WEHI-7 cells

    International Nuclear Information System (INIS)

    Smith, L.I.; Bodwell, J.E.; Mendel, D.B.; Ciardelli, T.; North, W.G.; Munck, A.

    1988-01-01

    Dexamethasone 21-mesylate is a highly specific synthetic glucocorticoid derivative that binds covalently to glucocorticoid receptors via sulfhydryl groups. The authors have identified the amino acid that reacts with the dexamethasone 21-mesylate by using enzymatic digestion and microsequencing for radiolabel. Nonactivated glucocorticoid receptors obtained from labeling intact WEHI-7 mouse thymoma cells with [ 3 H]dexamethasone 21-mesylate were immunopurified and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Trypsin digestion followed by reversed-phase high-performance liquid chromatography (reversed-phase HPLC) produced a single [ 3 H]dexamethasone 21-mesylate labeled peptide. Automated Edman degradation of this peptide revealed that the [ 3 H]dexamethasone 21-mesylate was located at position 5 from the amino terminus. Dual-isotope labeling studies with [ 3 H]dexamethasone 21-mesylate and [ 35 S]methionine demonstrated that this peptide contained methionine. Staphylococcus aureus V8 protease digestion of [ 3 H]dexamethasone 21-mesylate labeled steroid-binding subunits generated a different radiolabeled peptide containing label at position 7 from the amino terminus. On the basis of the published amino acid sequence of the murine glucocorticoid receptor, their data clearly identify cysteine-644 as the single residue in the steroid-binding domain that covalently binds dexamethasone 21-mesylate. They have confirmed this finding by demonstrating that a synthetic peptide representing the amino acid sequence 640-650 of the murine glucocorticoid receptor behaves in an identical manner on reversed-phase HPLC as the trypsin-generated peptide from intact cells

  18. A T-cell specific transcriptional enhancer element 3' of Cα in the human T-cell receptor α locus

    International Nuclear Information System (INIS)

    Ho, Icheng; Yang, Lihsuan; Morle, G.; Leiden, J.M.

    1989-01-01

    A transcriptional enhancer element has been identified 4.5 kilobases 3' of C α (constant region α chain) in the human T-cell receptor (TCR) α-chain locus. This enhancer is active on both a TCR V α (variable region α chain) promoter and the minimal simian virus 40 promoter in TCR α/β Jurkat and EL4 cells but is inactive on a V α promoter TCR γ/δ PEER and Molt-13 cells, clone 13 B cells, and HeLa fibroblasts. The enhancer has been localized to a 116-base-pair BstXI/Dra I restriction enzyme fragment, which lacks immunoglobulin octamer and κB enhancer motifs but does contain a consensus cAMP-response element (CRE). DNase I footprint analyses demonstrated that the minimal enhancer contains two binding sites for Jurkat nuclear proteins. One of these sites corresponds to the CRE, while the other does not correspond to a known transcriptional enhancer motif. These data support a model in which TCR α gene transcription is regulated by a unique set of cis-acting sequences and trans-acting factors, which are differentially active in cells of the TCR α/β lineage. In addition, the TCR α enhancer may play a role in activating oncogene expression in T-lymphoblastoid tumors that have previously been shown to display chromosomal translocations into the human TCR α locus

  19. Ephrinb1 and Ephrinb2 Are Associated with Interleukin-7 Receptor α and Retard Its Internalization from the Cell Surface*

    Science.gov (United States)

    Luo, Hongyu; Wu, Zenghui; Qi, Shijie; Jin, Wei; Han, Bing; Wu, Jiangping

    2011-01-01

    IL-7 plays vital roles in thymocyte development, T cell homeostasis, and the survival of these cells. IL-7 receptor α (IL-7Rα) on thymocytes and T cells is rapidly internalized upon IL-7 ligation. Ephrins (Efns) are cell surface molecules and ligands of the largest receptor kinase family, Eph kinases. We discovered that T cell-specific double gene knock-out (dKO) of Efnb1 and Efnb2 in mice led to reduced IL-7Rα expression in thymocytes and T cells, and that IL-7Rα down-regulation was accelerated in dKO CD4 cells upon IL-7 treatment. On the other hand, Efnb1 and Efnb2 overexpression on T cell lymphoma EL4 cells retarded IL-7Rα down-regulation. dKO T cells manifested compromised STAT5 activation and homeostatic proliferation, an IL-7-dependent process. Fluorescence resonance energy transfer and immunoprecipitation demonstrated that Efnb1 and Efnb2 interacted physically with IL-7Rα. Such interaction likely retarded IL-7Rα internalization, as Efnb1 and Efnb2 were not internalized. Therefore, we revealed a novel function of Efnb1 and Efnb2 in stabilizing IL-7Rα expression at the post-translational level, and a previously unknown modus operandi of Efnbs in the regulation of expression of other vital cell surface receptors. PMID:22069310

  20. Ultrasonic testing of canning tubes in stainless steel of the EL 4 reactor; Controle par ultrasons des tubes de gaine en acier inoxydable du reacteur EL 4

    Energy Technology Data Exchange (ETDEWEB)

    Prot, A; Monnier, P [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1964-07-01

    From all the methods possible for controlling thin cans the one chosen, for numerous reasons, vas that making use of ultrasonic techniques. A method has been developed which should make it possible to carry out a rapid and efficient industrial control of canning tubes, The reasons for the choice of the ultrasonic method are given in detail, together with the principles of the method and the actual control parameters. In the present state of our research, it should be possible to control at least 50 000 tubes a year. Improvements brought about in the details of the control technique itself should make it possible to increase this rate considerably. (authors) [French] Parmi toutes les methodes possibles de controle des gaines minces, le procede retenu pour de multiples raisons a ete celui faisant appel a la technique des ultrasons. Une methode a ete mise au point qui doit permettre un controle industriel rapide et efficace des tubes de gaine. Sont exposes en detail, les raisons du choix de la methode par ultrasons, les principes de cette methode et les parametres du controle proprement dit. Dans l'etat actuel de nos etudes la cadence devrait permettre le controle de 50000 tubes par an au minimum. Des ameliorations de detail portant sur la technique de controle elle-meme, doivent permettre d'accelerer tres notablement cette cadence. (auteurs)

  1. Analog study of the power control, temperature and flow of the reactor EL4; Etude analogique de la regulation de puissance, temperature et debit du reacteur EL4

    Energy Technology Data Exchange (ETDEWEB)

    Boulven, J; Chazal, G

    1966-07-01

    This study concerns the implementing and the exact determination of the gains of the plant control loops and the knowledge of the system response during possible solicitations under normal conditions. (A.L.B.)

  2. Altered AKT1 and MAPK1 Gene Expression on Peripheral Blood Mononuclear Cells and Correlation with T-Helper-Transcription Factors in Systemic Lupus Erythematosus Patients

    Directory of Open Access Journals (Sweden)

    Sonia Garcia-Rodriguez

    2012-01-01

    Full Text Available Kinases have been implicated in the immunopathological mechanisms of Systemic Lupus Erythematosus (SLE. v-akt murine-thymoma viral-oncogene-homolog 1 (AKT1 and mitogen-activated-protein-kinase 1 (MAPK1 gene expressions in peripheral mononuclear cells from thirteen SLE patients with inactive or mild disease were evaluated using quantitative real-time reverse-transcription polymerase-chain-reaction and analyzed whether there was any correlation with T-helper (Th transcription factors (TF gene expression, cytokines, and S100A8/S100A9-(Calprotectin. Age- and gender-matched thirteen healthy controls were examined. AKT1 and MAPK1 expressions were upregulated in SLE patients and correlated with Th17-(Retinoic acid-related orphan receptor (ROR-C, T-regulatory-(Treg-(Transforming Growth Factor Beta (TGFB-2, and Th2-(interleukin (IL-5-related genes. MAPK1 expression correlated with Th1-(IL-12A, T-box TF-(T-bet, Th2-(GATA binding protein-(GATA-3, and IL-10 expressions. IL-10 expression was increased and correlated with plasma Tumor Necrosis Factor (TNF-α and Th0-(IL-2, Th1-(IL-12A, T-bet, GATA3, Treg-(Forkhead/winged-helix transcription factor- (FOXP-3, and IL-6 expressions. FOXP3 expression, FOXP3/RORC, and FOXP3/GATA3 expression ratios were increased. Plasma IL-1β, IL-12(p70, Interferon-(IFN-γ, and IL-6 cytokines were augmented. Plasma IL-1β, IL-6, IL-2, IFN-γ, TNF-α, IL-10, and IL-13 correlated with C-reactive protein, respectively. Increased Calprotectin correlated with neutrophils. Conclusion, SLE patients presented a systemic immunoinflammatory activity, augmented AKT1 and MAPK1 expressions, proinflammatory cytokines, and Calprotectin, together with increased expression of Treg-related genes, suggesting a regulatory feedback opposing the inflammatory activity.

  3. Cells and cell biochemistry.

    Science.gov (United States)

    Farley, Alistair; Hendry, Charles; McLafferty, Ella

    This article, which forms part of the life sciences series, aims to promote understanding of the basic structure and function of cells. It assists healthcare professionals to appreciate the complex anatomy and physiology underpinning the functioning of the human body. Several introductory chemical concepts and terms are outlined. The basic building blocks of all matter, atoms, are examined and the way in which they may interact to form new compounds within the body is discussed. The basic structures and components that make up a typical cell are considered.

  4. Induction of apoptosis by Fe(salen)Cl through caspase-dependent pathway specifically in tumor cells.

    Science.gov (United States)

    Pradhan, Nitika; Pratheek, B M; Garai, Antara; Kumar, Ashutosh; Meena, Vikram S; Ghosh, Shyamasree; Singh, Sujay; Kumari, Shikha; Chandrashekar, T K; Goswami, Chandan; Chattopadhyay, Subhasis; Kar, Sanjib; Maiti, Prasanta K

    2014-10-01

    Iron-based compounds possess the capability of inducing cell death due to their reactivity with oxidant molecules, but their specificity towards cancer cells and the mechanism of action are hitherto less investigated. A Fe(salen)Cl derivative has been synthesized that remains active in monomer form. The efficacy of this compound as an anti-tumor agent has been investigated in mouse and human leukemia cell lines. Fe(salen)Cl induces cell death specifically in tumor cells and not in primary cells. Mouse and human T-cell leukemia cell lines, EL4 and Jurkat cells are found to be susceptible to Fe(salen)Cl and undergo apoptosis, but normal mouse spleen cells and human peripheral blood mononuclear cells (PBMC) remain largely unaffected by Fe(salen)Cl. Fe(salen)Cl treated tumor cells show significantly higher expression level of cytochrome c that might have triggered the cascade of reactions leading to apoptosis in cancer cells. A significant loss of mitochondrial membrane potential upon Fe(salen)Cl treatment suggests that Fe(salen)Cl induces apoptosis by disrupting mitochondrial membrane potential and homeostasis, leading to cytotoxity. We also established that apoptosis in the Fe(salen)Cl-treated tumor cells is mediated through caspase-dependent pathway. This is the first report demonstrating that Fe(salen)Cl can specifically target the tumor cells, leaving the primary cells least affected, indicating an excellent potential for this compound to emerge as a next-generation anti-tumor drug. © 2014 International Federation for Cell Biology.

  5. Repletion of zinc in zinc-deficient cells strongly up-regulates IL-1β-induced IL-2 production in T-cells.

    Science.gov (United States)

    Daaboul, Doha; Rosenkranz, Eva; Uciechowski, Peter; Rink, Lothar

    2012-10-01

    Mild zinc deficiency in humans negatively affects IL-2 production resulting in declined percentages of cytolytic T cells and decreased NK cell lytic activity, which enhances the susceptibility to infections and malignancies. T-cell activation is critically regulated by zinc and the normal physiological zinc level in T-cells slightly lies below the optimal concentration for T-cell functions. A further reduction in zinc level leads to T-cell dysfunction and autoreactivity, whereas high zinc concentrations (100 μM) were shown to inhibit interleukin-1 (IL-1)-induced IL-1 receptor kinase (IRAK) activation. In this study, we investigated the molecular mechanism by which zinc regulates the IL-1β-induced IL-2 expression in T-cells. Zinc supplementation to zinc-deficient T-cells increased intracellular zinc levels by altering the expression of zinc transporters, particularly Zip10 and Zip12. A zinc signal was observed in the murine T-cell line EL-4 6.1 after 1 h of stimulation with IL-1β, measured by specific zinc sensors FluoZin-3 and ZinPyr-1. This signal is required for the phosphorylation of MAPK p38 and NF-κB subunit p65, which triggers the transcription of IL-2 and strongly increases its production. These results indicate that short-term zinc supplementation to zinc-deficient T-cells leads to a fast rise in zinc levels which subsequently enhance cytokine production. In conclusion, low and excessive zinc levels might be equally problematic for zinc-deficient subjects, and stabilized zinc levels seem to be essential to avoid negative concentration-dependent zinc effects on T-cell activation.

  6. Micronodular thymic neoplasms: case series and literature review with emphasis on the spectrum of differentiation.

    Science.gov (United States)

    Mneimneh, Wadad S; Gökmen-Polar, Yesim; Kesler, Kenneth A; Loehrer, Patrick J; Badve, Sunil

    2015-11-01

    We report nine cases of micronodular thymoma with lymphoid B-cell hyperplasia and one case of micronodular thymic carcinoma with lymphoid hyperplasia from our institution. For a better understanding of these rare tumors, clinical records, and histological features of these cases were reviewed, with detailed review of additional 64 literature cases of micronodular thymic neoplasms. The joint analysis identified 64 cases of micronodular thymoma with lymphoid B-cell hyperplasia and 9 cases of micronodular thymic carcinoma with lymphoid hyperplasia. Both groups revealed slight male predilection, with male:female ratio of 1.3:1 and 5:4, and occurred at >40 years of age, with a mean of 64 (41-83) and 62 (42-78) years, respectively. Myasthenia gravis was noted in 3/64 (5%) and 1/9 (11%) patients, respectively. Other systemic, disimmune, or hematologic disorders were noted in 6/64 (9%) and 1/9 (11%) patients, respectively. Components of conventional thymoma were reported in 11/64 (17%) micronodular thymomas with lymphoid B-cell hyperplasia, with transitional morphology between the two components in most of them. Cellular morphology was predominantly spindle in micronodular thymoma with lymphoid B-cell hyperplasia when specified (30/43), and epithelioid in micronodular thymic carcinoma with lymphoid hyperplasia (6/9), and cytological atypia was more encountered in the latter. Dedifferentiation/transformation from micronodular thymoma with lymphoid B-cell hyperplasia to micronodular thymic carcinoma with lymphoid hyperplasia seems to occur in a small subset of cases. Three cases of micronodular thymomas with lymphoid B-cell hyperplasia were described with co-existent low-grade B-cell lymphomas. Follow-up data were available for 30 micronodular thymomas with lymphoid B-cell hyperplasia and 6 micronodular thymic carcinomas with lymphoid hyperplasia, with a mean of 47 (0.2-180) months and 23 (3-39) months, respectively. Patients were alive without disease, except for five

  7. TGF-β of lung cancer microenvironment upregulates B7H1 and GITRL expression in dendritic cells and is associated with regulatory T cell generation.

    Science.gov (United States)

    Ni, Xiao Yan; Sui, Hua Xiu; Liu, Yao; Ke, Shi Zhong; Wang, Yi Nan; Gao, Feng Guang

    2012-08-01

    The effects of TGF-β on dendritic cells (DCs) on the tumor microenvironment are not well understood. We report, here, the establishment of an in vitro lung cancer microenvironment by co-incubation of seminaphtharhodafluor (SNARF) labeled Lewis lung cancer (LLC) cells, carboxyfluorescein succinimidyl ester (CFSE) labeled fibroblasts and 4-chloromethyl-7-hydroxycoumarin (CMHC) labeled DCs. Raw 264.7, EL4 and NCI-H446 cells were able to synthesize TGF-β which was determined by flow cyto-metry and western blotting, respectively. Furthermore, TGF-β efficiently increased regulatory T-cell (Treg) expansion and upregulated DC B7H1 and GITRL expression. TGF-β and the co-incubation of LLC cells, fibroblasts with DCs could augment the expression of B7H1 and GITRL molecules of DCs. The data presented here indicate that the B7H1 and GITRL molecules may play an important role in TGF-β-induced Treg expansion of lung cancer microenvironment.

  8. Induction of apoptosis by Fe(salenCl through caspase-dependent pathway specifically in tumor cells

    Directory of Open Access Journals (Sweden)

    Nitika Pradhan

    2017-10-01

    Full Text Available Iron-based compounds possess the capability of inducing cell death due to their reactivity with oxidant molecules, but their specificity towards cancer cells and the mechanism of action are hitherto less investigated. A Fe(salenCl derivative has been synthesized that remains active in monomer form. The efficacy of this compound as an anti-tumor agent has been investigated in mouse and human leukemia cell lines. Fe(salenCl induces cell death specifically in tumor cells and not in primary cells. Mouse and human T-cell leukemia cell lines, EL4 and Jurkat cells are found to be susceptible to Fe(salenCl and undergo apoptosis, but normal mouse spleen cells and human peripheral blood mononuclear cells (PBMC remain largely unaffected by Fe(salenCl. Fe(salenCl treated tumor cells show significantly higher expression level of cytochrome c that might have triggered the cascade of reactions leading to apoptosis in cancer cells. A significant loss of mitochondrial membrane potential upon Fe(salenCl treatment suggests that Fe(salenCl induces apoptosis by disrupting mitochondrial membrane potential and homeostasis, leading to cytotoxity. We also established that apoptosis in the Fe(salenCl-treated tumor cells is mediated through caspase-dependent pathway. This is the first report demonstrating that Fe(salenCl can specifically target the tumor cells, leaving the primary cells least affected, indicating an excellent potential for this compound to emerge as a next-generation anti-tumor drug.

  9. Stem cells

    NARCIS (Netherlands)

    Jukes, Jojanneke; Both, Sanne; Post, Janine; van Blitterswijk, Clemens; Karperien, Marcel; de Boer, Jan; van Blitterswijk, Clemens A.

    2008-01-01

    This chapter defines stem cells and their properties. It identifies the major differences between embryonic and adult stem cells. Stem cells can be defined by two properties: the ability to make identical copies of themselves and the ability to form other cell types of the body. These properties are

  10. Cell Biochips

    Science.gov (United States)

    Pioufle, B. Le; Picollet-D'Hahan, N.

    A cell biochip is a microsystem, equipped with electronic and microfluidic functions, designed to manipulate or analyse living cells. The first publications in this emerging area of research appeared toward the end of the 1980s. In 1989 Washizu described a biochip designed to fuse two cells by electropermeabilisation of the cytoplasmic membrane [1]. Research centers have devised a whole range of cell chip structures, for simultaneous or sequential analysis of single cells, cell groups, or cell tissues reconstituted on the chip. The cells are arranged in a square array on a parallel cell chip for parallel analysis, while they are examined and processed one by one in a microchannel in the case of a series cell chip. In contrast to these biochips for high-throughput analysis of a large number of cells, single-cell chips focus on the analysis of a single isolated cell. As in DNA microarrays, where a large number of oligonucleotides are ordered in a matrix array, parallel cell chips order living cells in a similar way. At each point of the array, the cells can be isolated, provided that the cell type allows this, e.g., blood cells, or cultivated in groups (most adhesion cells can only survive in groups). The aim is to allow massively parallel analysis or processing. Le Pioufle et al. describe a microdevice for the culture of single cells or small groups of cells in a micropit array [2]. Each pit is equipped to stimulate the cell or group of cells either electrically or fluidically. Among the applications envisaged are gene transfer, cell sorting, and screening in pharmacology. A complementary approach, combining the DNA microarray and cell biochip ideas, has been put forward by Bailey et al. [3]. Genes previously arrayed on the chip transfect the cultured cells on the substrate depending on their position in the array (see Fig. 19.1). This way of achieving differential lipofection on a chip was then taken up again by Yoshikawa et al. [4] with primary cells, more

  11. Rationale and early outcomes for the management of thymoma with proton therapy.

    Science.gov (United States)

    Zhu, He J; Hoppe, Bradford S; Flampouri, Stella; Louis, Debbie; Pirris, John; Nichols, R Charles; Henderson, Randal H; Mercado, Catherine E

    2018-04-01

    Radiotherapy for thymic malignancies is technically challenging due to their close proximity to the heart, lungs, esophagus, and breasts, raising concerns about significant acute and late toxicities from conventional photon radiotherapy. Proton therapy (PT) may reduce the radiation dose to these vital organs, leading to less toxicity. We reviewed the dosimetry and outcomes among patients treated with PT for thymic malignancies at our institution. From January 2008 to March 2017, six patients with de novo Masaoka stages II-III thymic malignancies were treated with PT on an IRB-approved outcomes tracking protocol. Patients were evaluated weekly during treatment, then every 3 months for 2 years, then every 6 months for 3 more years, and then annually for CTCAE vs. four toxicities and disease recurrence. Comparison intensity-modulated radiotherapy (IMRT) plans were developed for each patient. Mean doses to the heart, esophagus, bilateral breasts, lungs, and V20 of bilateral lungs were evaluated for the two treatment plans. At last follow-up (median follow-up, 2.6 years), there were two patients with recurrences, including metastatic disease in the patient treated definitively with chemotherapy and PT without surgery and a local-regional recurrence in the lung outside the proton field in one of the post-operative cases. No patients with de novo disease experienced grade ≥3 toxicities after PT. The mean dose to the heart, lung, and esophagus was reduced on average by 36.5%, 33.5%, and 60%, respectively, using PT compared with IMRT (P<0.05 for each dose parameter). PT achieved superior dose sparing to the heart, lung, and esophagus compared to IMRT for thymic malignancies. Patients treated with PT had few radiation-induced toxicities and similar survival compared to historic proton data.

  12. Anesthetic management of a patient with stiff-person syndrome and thymoma: a case report

    Institute of Scientific and Technical Information of China (English)

    QIN Xiang; WANG Dong-xin; WU Xin-min

    2006-01-01

    @@ Stiff-person syndrome (SPS, also called stiff-man syndrome) is a rare neurological disease with autoimmune features. It is characterized by fluctuating and progressive muscle rigidity, and episodic spasm that prominently involve axial and limb musculature.1,2 Herein we report a case of anesthetic management of a patient with SPS for thymectomy and review several other cases.

  13. Profiling of glycan receptors for minute virus of mice in permissive cell lines towards understanding the mechanism of cell recognition.

    Directory of Open Access Journals (Sweden)

    Sujata Halder

    Full Text Available The recognition of sialic acids by two strains of minute virus of mice (MVM, MVMp (prototype and MVMi (immunosuppressive, is an essential requirement for successful infection. To understand the potential for recognition of different modifications of sialic acid by MVM, three types of capsids, virus-like particles, wild type empty (no DNA capsids, and DNA packaged virions, were screened on a sialylated glycan microarray (SGM. Both viruses demonstrated a preference for binding to 9-O-methylated sialic acid derivatives, while MVMp showed additional binding to 9-O-acetylated and 9-O-lactoylated sialic acid derivatives, indicating recognition differences. The glycans recognized contained a type-2 Galβ1-4GlcNAc motif (Neu5Acα2-3Galβ1-4GlcNAc or 3'SIA-LN and were biantennary complex-type N-glycans with the exception of one. To correlate the recognition of the 3'SIA-LN glycan motif as well as the biantennary structures to their natural expression in cell lines permissive for MVMp, MVMi, or both strains, the N- and O-glycans, and polar glycolipids present in three cell lines used for in vitro studies, A9 fibroblasts, EL4 T lymphocytes, and the SV40 transformed NB324K cells, were analyzed by MALDI-TOF/TOF mass spectrometry. The cells showed an abundance of the sialylated glycan motifs recognized by the viruses in the SGM and previous glycan microarrays supporting their role in cellular recognition by MVM. Significantly, the NB324K showed fucosylation at the non-reducing end of their biantennary glycans, suggesting that recognition of these cells is possibly mediated by the Lewis X motif as in 3'SIA-Le(X identified in a previous glycan microarray screen.

  14. Cell Motility

    CERN Document Server

    Lenz, Peter

    2008-01-01

    Cell motility is a fascinating example of cell behavior which is fundamentally important to a number of biological and pathological processes. It is based on a complex self-organized mechano-chemical machine consisting of cytoskeletal filaments and molecular motors. In general, the cytoskeleton is responsible for the movement of the entire cell and for movements within the cell. The main challenge in the field of cell motility is to develop a complete physical description on how and why cells move. For this purpose new ways of modeling the properties of biological cells have to be found. This long term goal can only be achieved if new experimental techniques are developed to extract physical information from these living systems and if theoretical models are found which bridge the gap between molecular and mesoscopic length scales. Cell Motility gives an authoritative overview of the fundamental biological facts, theoretical models, and current experimental developments in this fascinating area.

  15. Cell Phones

    Science.gov (United States)

    ... Radiation-Emitting Products and Procedures Home, Business, and Entertainment Products Cell Phones Cell Phones Share Tweet Linkedin ... Follow FDA on Facebook View FDA videos on YouTube View FDA photos on Flickr FDA Archive Combination ...

  16. Photovoltaic Cells

    OpenAIRE

    Karolis Kiela

    2012-01-01

    The article deals with an overview of photovoltaic cells that are currently manufactured and those being developed, including one or several p-n junction, organic and dye-sensitized cells using quantum dots. The paper describes the advantages and disadvantages of various photovoltaic cells, identifies the main parameters, explains the main reasons for the losses that may occur in photovoltaic cells and looks at the ways to minimize them.Article in Lithuanian

  17. Electrochemical Cell

    DEFF Research Database (Denmark)

    1999-01-01

    The invention relates to a rechargeable electrochemical cell comprising a negative electrode, an electrolyte and a positive electrode in which the positive electrode structure comprises a lithium cobalt manganese oxide of the composition Li¿2?Co¿y?Mn¿2-y?O¿4? where 0 ... for capacity losses in lithium ion cells and lithium-alloy cells....

  18. Cell Nutrition

    NARCIS (Netherlands)

    Malda, J.; Radisic, M.; Levenberg, S.; Woodfield, T.; Oomens, C.W.J.; Baaijens, F.P.T.; Svalander, P.; Vunjak-Novakovic, G.; Blitterswijk, C.; Thomsen, P.; Lindahl, A.; Hubbel, J.A.

    2008-01-01

    This chapter summarizes the role of mass transport in providing nutrients to the cells. It describes how mathematical modeling can enhance the understanding of nutrient limitation in tissue engineering. The nutrient requirements of the cells are explained and the components of the cell culture

  19. Ultrasonic testing of canning tubes in stainless steel of the EL 4 reactor

    International Nuclear Information System (INIS)

    Prot, A.; Monnier, P.

    1964-01-01

    From all the methods possible for controlling thin cans the one chosen, for numerous reasons, vas that making use of ultrasonic techniques. A method has been developed which should make it possible to carry out a rapid and efficient industrial control of canning tubes, The reasons for the choice of the ultrasonic method are given in detail, together with the principles of the method and the actual control parameters. In the present state of our research, it should be possible to control at least 50 000 tubes a year. Improvements brought about in the details of the control technique itself should make it possible to increase this rate considerably. (authors) [fr

  20. Impact of MR-guided boiling histotripsy in distinct murine tumor models.

    Science.gov (United States)

    Hoogenboom, Martijn; Eikelenboom, Dylan C; van den Bijgaart, Renske J E; Heerschap, Arend; Wesseling, Pieter; den Brok, Martijn H; Fütterer, Jurgen J; Adema, Gosse J

    2017-09-01

    Interest in mechanical high intensity focused ultrasound (HIFU) ablation is rapidly growing. Boiling histotripsy (BH) is applied for mechanical fragmentation of soft tissue into submicron fragments with limited temperature increase using the shock wave and cavitation effects of HIFU. Research on BH has been largely limited to ex vivo experiments. As a consequence, the in vivo pathology after BH treatment and the relation to preexistent tissue characteristics are not well understood. This study reports on in vivo MR guided BH treatment, either with 100 or 200 pulses per focal spot, in three different subcutaneous mouse tumor models: a soft-tissue melanoma (B16OVA), a compact growing thymoma (EL4), and a highly vascularized neuroblastoma (9464D). Extensive treatment evaluation was performed using MR imaging followed by histopathology 2h after treatment. T2 weighted MRI allowed direct in vivo visualization of the BH lesions in all tumor models. The 100-pulse treated area in the B16OVA tumors was larger than the predicted treatment volume (500±10%). For the more compact growing EL4 and 9464D tumors this was 95±13% and 55±33%, respectively. Histopathology after the 100-pulse treatment revealed completely disintegrated lesions in the treated area with sharp borders in the compact EL4 and 9464D tumors, while for B16OVA tumors the lesion contained a mixture of discohesive (partly viable) clusters of cells, micro-vessel remainings, and tumor cell debris. The treatment of B16OVA with 200 pulses increased the fragmentation of tumor tissue. In all tumor types only micro-hemorrhages were detected after ablation (slightly higher after 200-pulse treatment for the highly vascularized 9464D tumors). Collagen staining revealed that the collagen fibers were to a greater or lesser extent still intact and partly clotted together near the lesion border in all tumor models. In conclusion, this study reveals effective mechanical fragmentation of different tumor types using BH without

  1. Regulation of S100A8/A9 (calprotectin) binding to tumor cells by zinc ion and its implication for apoptosis-inducing activity.

    Science.gov (United States)

    Nakatani, Yuichi; Yamazaki, Masatoshi; Chazin, Walter J; Yui, Satoru

    2005-10-24

    S100A8/A9 (calprotectin), which is released by neutrophils under inflammatory conditions, has the capacity to induce apoptosis in various cells. We previously reported that S100A8/A9 induces apoptosis of EL-4 lymphoma cells via the uptake of extracellular zinc in a manner similar to DTPA, a membrane-impermeable zinc chelator. In this study, S100A8/A9-induced apoptosis was examined in several cell lines that are weakly sensitive to DTPA, suggesting S100A8/A9 is directly responsible for apoptosis in these cells. Since zinc inhibits apoptosis of MM46, one of these cells, the regulation by zinc of the capacity of S100A8/A9 to bind MM46 cells was studied. When MM46 cells were incubated with S100A8/A9 in standard or zinc-depleted medium, the amounts of S100A8/A9 bound to cells was markedly lower at 3 h than at 1 h. In contrast, when MM46 cells were incubated with S100A8/A9 in the presence of high levels of zinc, binding to cells was the same at 1 and 3 h. When the cells were permeabilized with saponin prior to analysis, a larger amount of cell-associated S100A8/A9 was detected at 3 h. The amount was further increased in cells treated with chloroquine, suggesting that S100A8/A9 was internalized and degraded in lysosomes. Although it has been reported that S100A8/A9 binds to heparan sulfate on cell membranes, the amount of S100A8/A9 bound to MM46 cells was not reduced by heparinase treatment, but was reduced by trypsin treatment. These results suggest that S100A8/A9 induces apoptosis by direct binding to MM46 cells, and that this activity is regulated by zinc.

  2. Types of Stem Cells

    Science.gov (United States)

    ... Stem Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... Learn About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

  3. Fuel Cells

    DEFF Research Database (Denmark)

    Smith, Anders; Pedersen, Allan Schrøder

    2014-01-01

    Fuel cells have been the subject of intense research and development efforts for the past decades. Even so, the technology has not had its commercial breakthrough yet. This entry gives an overview of the technological challenges and status of fuel cells and discusses the most promising applications...... of the different types of fuel cells. Finally, their role in a future energy supply with a large share of fluctuating sustainable power sources, e.g., solar or wind, is surveyed....

  4. Cell suicide

    International Nuclear Information System (INIS)

    May, E.; Coffigny, H.

    2000-01-01

    In the fight of the cell against the damages caused to its DNA by genotoxic agents and specially by ionizing radiations, the p53 protein plays a central part. It intervenes in the proliferation control and the differentiation but also in the keeping of genome integrity. It can direct the damages cells toward suicide, or apoptosis, to avoid the risk of tumor appearance that would be fatal to the whole organism. That is by the disordered state of cells suicide programs that the tumor cells are going to develop. The knowledge of apoptosis mechanisms, to eventually start them on demand, rises up broad hopes in the cancer therapy. (N.C.)

  5. Two distinct affinity binding sites for IL-1 on human cell lines

    International Nuclear Information System (INIS)

    Bensimon, C.; Wakasugi, N.; Tagaya, Y.; Takakura, K.; Yodoi, J.; Tursz, T.; Wakasugi, H.

    1989-01-01

    We used two human cell lines, NK-like YT-C3 and an EBV-containing B cell line, 3B6, as models to study the receptor(s) for IL-1. Two distinct types of saturable binding sites were found on both cell lines at 37 degrees C. Between 1 pM and 100 pM of 125I-IL-1-alpha concentration, saturable binding sites were detected on the YT-C3 cells with a K of 4 x 10(-11) M. The K found for the IL-1-alpha binding sites on 3B6 cells was 7.5 x 10(-11) M. An additional binding curve was detected above 100 pM on YT-C3 cells with a K of 7 x 10(-9) M and on 3B6 cells with a K of 5 x 10(-9) M. Scatchard plot analysis revealed 600 sites/cell with high affinity binding and 7000 sites/cell with low affinity for YT-C3 cells and 300 sites/cell with high affinity binding and 6000 sites/cell with low affinity for 3B6 cells. At 37 degrees C, the internalization of 125I-labeled IL-1 occurred via both high and low affinity IL-1R on both YT-C3 and 3B6 cells, whereas the rates of internalization for high affinity binding sites on YT-C3 cells were predominant in comparison to that of low affinity binding sites. In chemical cross-linking studies of 125 I-IL-1-alpha to 3B6 and YT-C3 cells, two protein bands were immunoprecipitated with Mr around 85 to 90 kDa leading to an estimation of the Mr of the IL-1R around 68 to 72 kDa. In similar experiments, the Mr found for the IL-1R expressed on the murine T cell line EL4 was slightly higher (around 80 kDa). Whether these distinct affinity binding sites are shared by a single molecule or by various chains remains to be elucidated

  6. Murine interleukin 1 receptor. Direct identification by ligand blotting and purification to homogeneity of an interleukin 1-binding glycoprotein

    International Nuclear Information System (INIS)

    Bird, T.A.; Gearing, A.J.; Saklatvala, J.

    1988-01-01

    Functional receptors (IL1-R) for the proinflammatory cytokine interleukin 1 (IL1) were solubilized from plasma membranes of the NOB-1 subclone of murine EL4 6.1 thymoma cells using the zwitterionic detergent 3[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). Membrane extracts were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose membranes, and ligand blotted with 125 I-labeled recombinant human IL1 alpha in order to reveal proteins capable of specifically binding IL1. A single polydisperse polypeptide of Mr approximately equal to 80,000 was identified in this way, which bound IL1 alpha and IL1 beta with the same affinity as the IL1-R on intact NOB-1 cells (approximately equal to 10(-10) M). The IL1-binding polypeptide was only seen in membranes from IL1-R-bearing cells and did not react with interleukin 2, tumor necrosis factor alpha, or interferon. IL1-R was purified to apparent homogeneity from solubilized NOB-1 membranes by affinity chromatography on wheat germ agglutinin-Sepharose and IL1 alpha-Sepharose. Gel electrophoresis and silver staining of purified preparations revealed a single protein of Mr approximately equal to 80,000 which reacted positively in the ligand-blotting procedure and which we identify as the ligand-binding moiety of the murine IL1-R. Purified IL1-R exhibited the same affinity and specificity as the receptor on intact cells. The relationship of this protein to proteins identified by covalent cross-linking studies is discussed

  7. Fuel cells

    NARCIS (Netherlands)

    Veen, van J.A.R.; Janssen, F.J.J.G.; Santen, van R.A.

    1999-01-01

    The principles and present-day embodiments of fuel cells are discussed. Nearly all cells are hydrogen/oxygen ones, where the hydrogen fuel is usually obtained on-site from the reforming of methane or methanol. There exists a tension between the promise of high efficiency in the conversion of

  8. 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

  9. Learn About Stem Cells

    Science.gov (United States)

    ... Patient Handbook Stem Cell Glossary Search Toggle Nav Stem Cell Basics Stem cells are the foundation from which ... original cell’s DNA, cytoplasm and cell membrane. About stem cells Stem cells are the foundation of development in ...

  10. Implication of extracellular zinc exclusion by recombinant human calprotectin (MRP8 and MRP14) from target cells in its apoptosis-inducing activity.

    Science.gov (United States)

    Yui, Satoru; Nakatani, Yuichi; Hunter, Michael J; Chazin, Walter J; Yamazaki, Masatoshi

    2002-06-01

    Calprotectin is a calcium-binding and zinc-binding protein complex that is abundant in the cytosol of neutrophils. This factor is composed of 8 and 14 kDa subunits, which have also been termed migration inhibitory factor-related proteins MRP8 and MRP14. We previously reported that rat calprotectin purified from inflammatory neutrophils induces apoptosis of various tumor cells or normal fibroblasts in a zinc-reversible manner. The present study was undertaken to elucidate which subunit is responsible for the apoptosis-inducing activity, and to explore the mechanism of zinc-reversible apoptosis induction. The apoptosis-inducing activity of recombinant human MRP8 (rhMRP8) and recombinant human MRP14 (rhMRP14) was examined against EL-4 lymphoma cells in vitro. To determine whether zinc deprivation by calprotectin was essential for the cytotoxicity, the activity of calprotectin was tested under conditions where physical contact between the factor and the cells was precluded by a low molecular weight cut-off dialysis membrane. The cytotoxicity of rhMRP14 against EL-4 cells was first detected at 10 microM in a standard medium, whereas rhMRP8 caused only marginal cytotoxicity at 40 microM. A mixture of both proteins showed higher specific activity (onset of cytotoxicity at 5 microM). When the cells were cultured in divalent cation-depleted medium, each dose-response curve was shifted to about a four-fold lower concentration range. Calprotectin was found to induce cell death even when the complex and the target cells were separated by dialysis membrane. A membrane-impermeable zinc chelator, diethylenetriamine pentaacetic acid (DTPA), also induced target cell apoptosis in a similar time-course as calprotectin. Moreover, the activities of calprotectin and DTPA were completely inhibited by the presence of zinc ions. These data indicate that calprotectin has higher specific activity to induce apoptosis than the Individual subunits, and that the mechanism is exclusion of zinc

  11. Role of Mitochondrial DNA Copy Number Alteration in Human Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Chen-Sung Lin

    2016-05-01

    Full Text Available We investigated the role of mitochondrial DNA (mtDNA copy number alteration in human renal cell carcinoma (RCC. The mtDNA copy numbers of paired cancer and non-cancer parts from five resected RCC kidneys after radical nephrectomy were determined by quantitative polymerase chain reaction (Q-PCR. An RCC cell line, 786-O, was infected by lentiviral particles to knock down mitochondrial transcriptional factor A (TFAM. Null target (NT and TFAM-knockdown (TFAM-KD represented the control and knockdown 786-O clones, respectively. Protein or mRNA expression levels of TFAM; mtDNA-encoded NADH dehydrogenase subunit 1 (ND1, ND6 and cytochrome c oxidase subunit 2 (COX-2; nuclear DNA (nDNA-encoded succinate dehydrogenase subunit A (SDHA; v-akt murine thymoma viral oncogene homolog 1 gene (AKT-encoded AKT and v-myc myelocytomatosis viral oncogene homolog gene (c-MYC-encoded MYC; glycolytic enzymes including hexokinase II (HK-II, glucose 6-phosphate isomerase (GPI, phosphofructokinase (PFK, and lactate dehydrogenase subunit A (LDHA; and hypoxia-inducible factors the HIF-1α and HIF-2α, pyruvate dehydrogenase kinase 1 (PDK1, and pyruvate dehydrogenase E1 component α subunit (PDHA1 were analyzed by Western blot or Q-PCR. Bioenergetic parameters of cellular metabolism, basal mitochondrial oxygen consumption rate (mOCRB and basal extracellular acidification rate (ECARB, were measured by a Seahorse XFe-24 analyzer. Cell invasiveness was evaluated by a trans-well migration assay and vimentin expression. Doxorubicin was used as a chemotherapeutic agent. The results showed a decrease of mtDNA copy numbers in resected RCC tissues (p = 0.043. The TFAM-KD clone expressed lower mtDNA copy number (p = 0.034, lower mRNA levels of TFAM (p = 0.008, ND1 (p = 0.007, and ND6 (p = 0.017, and lower protein levels of TFAM and COX-2 than did the NT clone. By contrast, the protein levels of HIF-2α, HK-II, PFK, LDHA, AKT, MYC and vimentin; trans-well migration activity (p = 0

  12. Fuel cells

    International Nuclear Information System (INIS)

    Niederdoeckl, J.

    2001-01-01

    Europe has at present big hopes on the fuel cells technology, in comparison with other energy conversion technologies, this technology has important advantages, for example: high efficiency, very low pollution and parallel use of electric and thermal energy. Preliminary works for fuel cells developing and its commercial exploitation are at full speed; until now the European Union has invested approx. 1.7 billion Schillings, 60 relevant projects are being executed. The Austrian industry is interested in applying this technique to drives, thermal power stations and the miniature fuel cells as replacement of batteries in electronic products (Notebooks, mobile telephones, etc.). A general description of the historic development of fuel cells including the main types is given as well as what is the situation in Austria. (nevyjel)

  13. Dry cell battery poisoning

    Science.gov (United States)

    Batteries - dry cell ... Acidic dry cell batteries contain: Manganese dioxide Ammonium chloride Alkaline dry cell batteries contain: Sodium hydroxide Potassium hydroxide Lithium dioxide dry cell batteries ...

  14. Evaluation of apoptosis and micronucleation induced by reactor neutron beams with two different cadmium ratios in total and quiescent cell populations within solid tumors

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Ono, Koji; Sakurai, Yoshinori; Takagaki, Masao; Kobayashi, Tooru; Kinashi, Yuko; Suzuki, Minoru

    2001-01-01

    Purpose: Response of quiescent (Q) and total tumor cells in solid tumors to reactor neutron beam irradiation with two different cadmium (Cd) ratios was examined in terms of micronucleus (MN) frequency and apoptosis frequency, using four different tumor cell lines. Methods and Materials: C57BL mice bearing EL4 tumors, C3H/He mice bearing SCC VII or FM3A tumors, and Balb/c mice bearing EMT6/KU tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty min after i.p. injection of sodium borocaptate- 10 B (BSH), or 3 h after oral administration of p-boronophenylalanine- 10 B (BPA), the tumors were irradiated with neutron beams. The tumors without 10 B-compound administration were irradiated with neutron beams or γ-rays. This neutron beam irradiation was performed using neutrons with two different Cd ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the MN frequency in cells without BrdU labeling (=Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, for apoptosis assay, 6 h after irradiation, tumor cell suspensions obtained in the same manner were fixed, and the apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequencies in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Results: Without 10 B-compounds, the sensitivity difference between total and Q cells was reduced by neutron beam irradiation. Under our particular neutron beam irradiation condition, relative biological effectiveness (RBE) of neutrons was larger in Q cells than in total cells, and the RBE values were larger for low Cd-ratio than high Cd-ratio neutrons. With 10 B-compounds, both frequencies were increased for each cell population, especially for total cells. BPA

  15. Solar cells

    International Nuclear Information System (INIS)

    1980-01-01

    A method of producing solar cells is described which consists of producing a substantially monocrystalline tubular body of silicon or other suitable semiconductor material, treating this body to form an annular rectifying junction and then cutting it longitudinally to form a number of nearly flat ribbons from which the solar cells are fabricated. The P=N rectifying junction produced by the formation of silicon dioxide on the layers at the inner and outer surfaces of the body can be formed by ion-implantation or diffusion. (U.K.)

  16. Electrochemical cell

    Science.gov (United States)

    Kaun, T.D.

    An improved secondary electrochemical cell is disclosed having a negative electrode of lithium aluminum, a positive electrode of iron sulfide, a molten electrolyte of lithium chloride and potassium chloride, and the combination that the fully charged theoretical capacity of the negative electrode is in the range of 0.5 to 1.0 that of the positive electrode. The cell thus is negative electrode limiting during discharge cycling. Preferably, the negative electrode contains therein, in the approximate range of 1 to 10 volume % of the electrode, an additive from the materials of graphitized carbon, aluminum-iron alloy, and/or magnesium oxide.

  17. Stem Cells

    DEFF Research Database (Denmark)

    Sommerlund, Julie

    2004-01-01

    In his influential essay on markets, An essay on framing and overflowing (1998), Michel Callon writes that `the growing complexity of industrialized societies [is] due in large part to the movements of the technosciences, which are causing connections and interdependencies to proliferate'. This p...... and tantalizing than stem cells, in research, in medicine, or as products.......'. This paper is about tech-noscience, and about the proliferation of connections and interdependencies created by it.More specifically, the paper is about stem cells. Biotechnology in general has the power to capture the imagination. Within the field of biotechnology nothing seems more provocative...

  18. Fuel cells:

    DEFF Research Database (Denmark)

    Sørensen, Bent

    2013-01-01

    A brief overview of the progress in fuel cell applications and basic technology development is presented, as a backdrop for discussing readiness for penetration into the marketplace as a solution to problems of depletion, safety, climate or environmental impact from currently used fossil and nucl......A brief overview of the progress in fuel cell applications and basic technology development is presented, as a backdrop for discussing readiness for penetration into the marketplace as a solution to problems of depletion, safety, climate or environmental impact from currently used fossil...... and nuclear fuel-based energy technologies....

  19. Squamous Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Squamous cell carcinoma Overview Squamous cell carcinoma: This man's skin ... a squamous cell carcinoma on his face. Squamous cell carcinoma: Overview Squamous cell carcinoma (SCC) is a ...

  20. Photovoltaic cell

    Science.gov (United States)

    Gordon, Roy G.; Kurtz, Sarah

    1984-11-27

    In a photovoltaic cell structure containing a visibly transparent, electrically conductive first layer of metal oxide, and a light-absorbing semiconductive photovoltaic second layer, the improvement comprising a thin layer of transition metal nitride, carbide or boride interposed between said first and second layers.

  1. Potent Cells

    Science.gov (United States)

    Liu, Dennis

    2007-01-01

    It seems hard to believe that Dolly the cloned sheep was born 10 years ago, kindling furious arguments over the prospects and ethics of cloning a human. Today, the controversy over cloning is entwined, often confused, with concerns over the use of human embryonic stem cells. Most people are unclear what cloning is, and they know even less when it…

  2. H-2 restriction of the T cell response to chemically induced tumors: evidence from F1 → parent chimeras

    International Nuclear Information System (INIS)

    Lannin, D.R.; Yu, S.; McKhann, C.F.

    1982-01-01

    It has been well established that T cells that react to tumor antigen on virus-induced tumors must share H-2D or H-2K specificities with the tumor. It has been impossible to perform similar studies with chemically induced tumors because each chemically induced tumor expresses a unique tumor antigen that cannot be studied in association with other H-2 types. This study provies evidence that H-2 recognition is also necessary for recognition of chemically induced tumors. We have found that F 1 → parent chimeras preferentially recognize chemically induced tumors of parental H-2 type. C3H/HeJ and C57BL/6 mice were lethally irradiated and restored with (C3H x C57BL/6) F 1 hybrid bone marrow. The F 1 → C3H chimera but not the F 1 → C57BL/6 chimera was able to respond to a C3H fibrosarcoma in mixed lymphocyte-tumor cell culture and also to neutralize the tumor in an in vivo tumor neutralization assay. On the other hand, the F 1 → C57BL/6 chimera but not the F 1 → C3H chimera was able to kill the C57BL/6 lymphoma EL4 in an in vitro cytotoxicity assay. Both chimeras were tolerant to C3H and C57BL/6 alloantigens but could respond normally to Con A and to BALB/c spleen cells in mixed lymphocyte cultures and cytotoxicity assay

  3. Ultrasound guided electrochemotherapy for the treatment of a clear ...

    African Journals Online (AJOL)

    Ultrasound guided biopsy yielded a diagnosis of clear cell thymoma upon histopathology. After complete staging procedures, the owner elected to treat the cat with electrochemotherapy (ECT) using systemic bleomycin. Two sessions of ultrasound guided ECT were performed at two week intervals with trains of biphasic ...

  4. Diseases of the thorax

    International Nuclear Information System (INIS)

    Kido, C.; Tanaka, H.

    1983-01-01

    This paper covers the following topics: right-sided aortic arch; pneumonia; thoracic dissecting aneurysum; right subclavian aneurysm; pericardial cyst; thymoma; thymic cyst; mediastinal neurinoma; pulmonary abscess; old pneumothorax; pulmonary tuberculosis; squamous cell carcinoma of the right lung; adenocarcinoma of the left lung; vasculomyosarcoma of the right lung; pulmonary bulla; and tumor of the thoracic wall

  5. Properties of Na+/K+ ATPase and alkaline phosphatase alter during spontaneous and radiation-induced leukemogenesis in mice

    International Nuclear Information System (INIS)

    Gonta-Grabiec, K.; Rossowski, W.

    1986-01-01

    Properties are characterized of Na + /K + ATPase and alkaline phosphatase in thymocytes or thymoblasts from mice of two strains: AKR in which thymoma developed spontaneously, and C57Bl in which the development was induced by X-irradiation (total dose: 5.4 Gy in 3 fractions). It was found that before thymoma could be discerned morphologically the properties of the two enzymes changed. There was a decrease in 86 Rb uptake and in the rate of ATP hydrolysis per cell (both strains) as well as an increase in alkaline phosphatase activity per cell (C57Bl mice). In both spontaneous and radiation-induced thymomas 86 Rb uptake, ATP hydrolysis and 3 H-ouabain binding per cell were higher than in normal thymuses. Likewise, alkaline phosphatase activity per cell was higher in the thymomas than in the thymuses; this increase was accompanied by the appearance of additional isoenzyme(s) (1 in AKR, 2 in C57Bl). These changes were compared with cAMP content and 3 H-thymidine incorporation, taken as indicators of the proliferative activity, and their high correlation in both AKR and C57Bl mice allowed to distinguish a pre-leukemic period. In that period thymoblasts clearly differed from the normal ones in Na + /K + ATPase and alkaline phosphatase properties as well as proliferation, although the morphology of the thymus was still unchanged. (author)

  6. Restoration of lymphocyte proliferation and CTL generation by murine rIL-2 after treatment of allogeneic stimulator cells by ultraviolet B irradiation, heat, or paraformaldehyde

    International Nuclear Information System (INIS)

    Flye, M.W.; Yu, S.

    1991-01-01

    Following a 5-day mixed lymphocyte culture (MLC), C3H/HeJ (H-2k) splenocytes stimulated with DBA/2 (H-2d) gamma-irradiated splenocytes (2000 rads) are specifically cytotoxic in a 4-hr 51 Cr-release assay to P815 (H-2d) target cells (62 +/- 2% cytolysis) but not to third-party EL4 (H-2b). However, when the DBA/2 stimulator cells were treated with heat inactivation (45 degree C for 1 hr), fixed with 1% paraformaldehyde (15 min), or irradiated with ultraviolet-B light (10(4) J/M2), no cell proliferation or cytolytic activity developed in the MLCs. The levels of IL-1, IL-2, and IL-6 from the supernatants of MLC using stimulators undergoing either of the three treatments were markedly decreased compared with that from gamma-irradiated stimulators. Both cell proliferation and specific cytolysis were restored in a dose-dependent fashion by the addition of murine rIL-2 to the MLCs. If the stimulator cells were first activated with 5 micrograms/ml pokeweed mitogen or lipopolysaccharide for 2 days, the subsequent treatment with heat, paraformaldehyde, or UV-B did not significantly affect the development of cytolysis (54-70% cytolysis). Suppressor cells were not detected when cells from the nonresponsive MLCs (2.5 x 10(6) cells) were added to an MLC freshly prepared with gamma-irradiated stimulator cells, or were injected intraperitoneally (50 x 10(6) cells) into naive mice 2 days before recovery and in vitro sensitization of splenocytes. Therefore, modification of the stimulating alloantigen can prevent the release of cytokines that function as an essential second signal in the development of the proliferative response and subsequent cytolysis. The cytokine found to be essential for restoration of this response is IL-2

  7. Ghost cell lesions

    Directory of Open Access Journals (Sweden)

    E Rajesh

    2015-01-01

    Full Text Available Ghost cells have been a controversy for a long time. Ghost cell is a swollen/enlarged epithelial cell with eosnophilic cytoplasm, but without a nucleus. In routine H and E staining these cells give a shadowy appearance. Hence these cells are also called as shadow cells or translucent cells. The appearance of these cells varies from lesion to lesion involving odontogenic and nonodontogenic lesions. This article review about the origin, nature and significance of ghost cells in different neoplasms.

  8. 13-methyltetradecanoic acid exhibits anti-tumor activity on T-cell lymphomas in vitro and in vivo by down-regulating p-AKT and activating caspase-3.

    Directory of Open Access Journals (Sweden)

    Qingqing Cai

    Full Text Available 13-Methyltetradecanoic acid (13-MTD, a saturated branched-chain fatty acid purified from soy fermentation products, induces apoptosis in human cancer cells. We investigated the inhibitory effects and mechanism of action of 13-MTD on T-cell non-Hodgkin's lymphoma (T-NHL cell lines both in vitro and in vivo. Growth inhibition in response to 13-MTD was evaluated by the cell counting kit-8 (CCK-8 assay in three T-NHL cell lines (Jurkat, Hut78, EL4 cells. Flow cytometry analyses were used to monitor the cell cycle and apoptosis. Proteins involved in 13-MTD-induced apoptosis were examined in Jurkat cells by western blotting. We found that 13-MTD inhibited proliferation and induced the apoptosis of T-NHL cell lines. 13-MTD treatment also induced a concentration-dependent arrest of Jurkat cells in the G1-phase. During 13-MTD-induced apoptosis in Jurkat cells, the cleavage of caspase-3 and poly ADP-ribose polymerase (PARP, a caspase enzymolysis product were detected after incubation for 2 h, and increased after extending the incubation time. However, there was no change in the expression of Bcl-2 or c-myc proteins. The appearance of apoptotic Jurkat cells was accompanied by the inhibition of AKT and nuclear factor-kappa B (NF-κB phosphorylation. In addition, 13-MTD could also effectively inhibit the growth of T-NHL tumors in vivo in a xenograft model. The tumor inhibition rate in the experimental group was 40%. These data indicate that 13-MTD inhibits proliferation and induces apoptosis through the down-regulation of AKT phosphorylation followed by caspase activation, which may provide a new approach for treating T-cell lymphomas.

  9. Double-stranded RNA promotes CTL-independent tumor cytolysis mediated by CD11b+Ly6G+ intratumor myeloid cells through the TICAM-1 signaling pathway

    Science.gov (United States)

    Shime, Hiroaki; Matsumoto, Misako; Seya, Tsukasa

    2017-01-01

    PolyI:C, a synthetic double-stranded RNA analog, acts as an immune-enhancing adjuvant that regresses tumors in cytotoxic T lymphocyte (CTL)-dependent and CTL-independent manner, the latter of which remains largely unknown. Tumors contain CD11b+Ly6G+ cells, known as granulocytic myeloid-derived suppressor cells (G-MDSCs) or tumor-associated neutrophils (TANs) that play a critical role in tumor progression and development. Here, we demonstrate that CD11b+Ly6G+ cells respond to polyI:C and exhibit tumoricidal activity in an EL4 tumor implant model. PolyI:C-induced inhibition of tumor growth was attributed to caspase-8/3 cascade activation in tumor cells that occurred independently of CD8α+/CD103+ dendritic cells (DCs) and CTLs. CD11b+Ly6G+ cells was essential for the antitumor effect because depletion of CD11b+Ly6G+ cells totally abrogated tumor regression and caspase activation after polyI:C treatment. CD11b+Ly6G+ cells that had been activated with polyI:C showed cytotoxicity and inhibited tumor growth through the production of reactive oxygen species (ROS)/reactive nitrogen species (RNS). These responses were abolished in either Toll/interleukin-1 receptor domain-containing adaptor molecule-1 (TICAM-1)−/− or interferon (IFN)-αβ receptor 1 (IFNAR1)−/− mice. Thus, our results suggest that polyI:C activates the TLR3/TICAM-1 and IFNAR signaling pathways in CD11b+Ly6G+ cells in tumors, thereby eliciting their antitumor activity, independent of those in CD8α+/CD103+ DCs that prime CTLs. PMID:27834952

  10. Antiparietal cell antibody test

    Science.gov (United States)

    APCA; Anti-gastric parietal cell antibody; Atrophic gastritis - anti-gastric parietal cell antibody; Gastric ulcer - anti-gastric parietal cell antibody; Pernicious anemia - anti-gastric parietal cell antibody; ...

  11. Stem Cell Basics

    Science.gov (United States)

    ... Tips Info Center Research Topics Federal Policy Glossary Stem Cell Information General Information Clinical Trials Funding Information Current ... Basics » Stem Cell Basics I. Back to top Stem Cell Basics I. Introduction: What are stem cells, and ...

  12. Basal Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

  13. Merkel Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Merkel cell carcinoma Overview Merkel cell carcinoma: This rare skin ... hard patch (1) or firm bump (2). Merkel cell carcinoma: Overview What is Merkel cell carcinoma? Merkel ...

  14. Electrorefining cell evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Bronson, M.C.; Thomas, R.L. (ed.)

    1989-04-14

    Operational characteristics of the LANL electrorefining cell, a modified LANL electrorefining cell, and an advanced electrorefining cell (known as the CRAC cell) were determined. Average process yields achieved were: 75% for the LANL cell, 82% for the modified LANL cell, and 86% for the CRAC cell. All product metal from the LANL and modified LANL cells was within foundry specifications. Metal from one run in the CRAC cell exceeded foundry specifications for tantalum. The LANL and modified LANL cells were simple in design and operation, but product separation was more labor intensive than with the CRAC cell. The CRAC cell was more complicated in design but remained relatively simple in operation. A decision analysis concluded that the modified LANL cell was the preferred cell. It was recommended that the modified LANL cell be implemented by the Plutonium Recovery Project at Rocky Flats and that development of the CRAC cell continue. 8 refs., 22 figs., 12 tabs.

  15. Sickle cell anemia

    Science.gov (United States)

    Anemia - sickle cell; Hemoglobin SS disease (Hb SS); Sickle cell disease ... Sickle cell anemia is caused by an abnormal type of hemoglobin called hemoglobin S. Hemoglobin is a protein inside red blood cells ...

  16. The nature of tolerance in adult recipient mice made tolerant of alloantigens with supralethal irradiation followed by syngeneic bone marrow cell transplantation plus injection of F1 spleen cells

    International Nuclear Information System (INIS)

    Tomita, Y.; Himeno, K.; Mayumi, H.; Tokuda, N.; Nomoto, K.

    1989-01-01

    The length of time after syngeneic bone marrow reconstitution when tolerance to alloantigens can be induced in adult mice during T cell differentiation from bone marrow cells was studied by exposing those T cells to (recipient x donor)F1 spleen cells. Supralethally irradiated C3H/He Slc(C3H; H-2k) mice were reconstituted with 1 x 10(7) syngeneic T cell-depleted bone marrow cells and then injected intravenously with 5 x 10(7) (C3H x C57BL/6[B6])F1 (B6C3F1; H-2bxk) or (C3H x AKR/J[AKR])F1 (AKC3F1; H-2kxk) spleen cells at various intervals. In the fully allogeneic combination of B6C3F1----C3H, EL-4 tumor originating from B6 was accepted, and survival of grafted B6 skin was significantly prolonged in the tolerant C3H mice treated with irradiation on day -1 followed by injection of syngeneic bone marrow cells on day 0 plus B6C3F1 spleen cells on days 0, 5, or 10, in a tolerogen-specific manner. In the multiminor histocompatibility antigen-disparate combination of AKC3F1----C3H, AKR skin grafts were permanently accepted in the tolerant C3H mice treated with AKC3F1 spleen cells on days 0, 5, 10, or 15. Immunological parameters, including cytotoxic T lymphocyte activity and delayed foot-pad reaction (DFR), were almost completely suppressed in C3H mice made tolerant of B6 or AKR antigens. A chimeric assay using a direct immunofluorescence method revealed that the tolerant C3H mice given B6C3F1 spleen cells on day 0 were mixed-chimeric for at least 8 weeks after syngeneic bone marrow reconstitution, but not definitely chimeric thereafter. The C3H mice given AKC3F1 spleen cells on day 0 were chimeric even 43 weeks after syngeneic bone marrow reconstitution, but the C3H mice given AKC3F1 spleen cells on day 15 showed temporal chimerism that disappeared within 43 weeks. The untolerant mice were never detectably chimeric

  17. Potency of Stem Cells

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Potency of Stem Cells. Totipotent Stem Cells (Zygote + first 2 divisions). -Can form placenta, embryo, and any cell of the body. Pluripotent (Embryonic Stem Cells). -Can form any cell of the body but can not form placenta, hence no embryo. Multipotent (Adult stem cells).

  18. DNA-cell conjugates

    Science.gov (United States)

    Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn; Mathies, Richard; Chandra, Ravi; Douglas, Erik; Twite, Amy; Toriello, Nicholas; Onoe, Hiroaki

    2018-05-15

    The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.

  19. DNA-cell conjugates

    Science.gov (United States)

    Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn; Mathies, Richard; Chandra, Ravi; Douglas, Erik; Twite, Amy; Toriello, Nicholas; Onoe, Hiroaki

    2016-05-03

    The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.

  20. Skin Stem Cells in Skin Cell Therapy

    Directory of Open Access Journals (Sweden)

    Mollapour Sisakht

    2015-12-01

    Full Text Available Context Preclinical and clinical research has shown that stem cell therapy is a promising therapeutic option for many diseases. This article describes skin stem cells sources and their therapeutic applications. Evidence Acquisition Compared with conventional methods, cell therapy reduces the surgical burden for patients because it is simple and less time-consuming. Skin cell therapy has been developed for variety of diseases. By isolation of the skin stem cell from the niche, in vitro expansion and transplantation of cells offers a surprising healing capacity profile. Results Stem cells located in skin cells have shown interesting properties such as plasticity, transdifferentiation, and specificity. Mesenchymal cells of the dermis, hypodermis, and other sources are currently being investigated to promote regeneration. Conclusions Because skin stem cells are highly accessible from autologous sources and their immunological profile is unique, they are ideal for therapeutic approaches. Optimization of administrative routes requires more investigation own to the lack of a standard protocol.

  1. NKT Cell Responses to B Cell Lymphoma.

    Science.gov (United States)

    Li, Junxin; Sun, Wenji; Subrahmanyam, Priyanka B; Page, Carly; Younger, Kenisha M; Tiper, Irina V; Frieman, Matthew; Kimball, Amy S; Webb, Tonya J

    2014-06-01

    Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally impaired. In a mouse model of blastoid variant mantle cell lymphoma, treatment of tumor-bearing mice with a potent NKT cell agonist, α-galactosylceramide (α-GalCer), resulted in a significant decrease in disease pathology. Ex vivo studies demonstrated that NKT cells from α-GalCer treated mice produced IFN-γ following α-GalCer restimulation, unlike NKT cells from vehicle-control treated mice. These data demonstrate an important role for NKT cells in the immune response to an aggressive hematologic malignancy like mantle cell lymphoma.

  2. Integrated circuit cell library

    Science.gov (United States)

    Whitaker, Sterling R. (Inventor); Miles, Lowell H. (Inventor)

    2005-01-01

    According to the invention, an ASIC cell library for use in creation of custom integrated circuits is disclosed. The ASIC cell library includes some first cells and some second cells. Each of the second cells includes two or more kernel cells. The ASIC cell library is at least 5% comprised of second cells. In various embodiments, the ASIC cell library could be 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, or 95% or more comprised of second cells.

  3. Modeling cell-in-cell structure into its biological significance

    OpenAIRE

    He, M-f; Wang, S; Wang, Y; Wang, X-n

    2013-01-01

    Although cell-in-cell structure was noted 100 years ago, the molecular mechanisms of ?entering' and the destination of cell-in-cell remain largely unclear. It takes place among the same type of cells (homotypic cell-in-cell) or different types of cells (heterotypic cell-in-cell). Cell-in-cell formation affects both effector cells and their host cells in multiple aspects, while cell-in-cell death is under more intensive investigation. Given that cell-in-cell has an important role in maintainin...

  4. nduced pluripotent stem cells and cell therapy

    Directory of Open Access Journals (Sweden)

    Banu İskender

    2013-12-01

    Full Text Available Human embryonic stem cells are derived from the inner cell mass of a blastocyst-stage embryo. They hold a huge promise for cell therapy with their self-renewing ability and pluripotency, which is known as the potential to differentiate into all cell types originating from three embryonic germ layers. However, their unique pluripotent feature could not be utilised for therapeutic purposes due to the ethical and legal problems during derivation. Recently, it was shown that the cells from adult tissues could be reverted into embryonic state, thereby restoring their pluripotent feature. This has strenghtened the possiblity of directed differentition of the reprogrammed somatic cells into the desired cell types in vitro and their use in regenerative medicine. Although these cells were termed as induced pluripotent cells, the mechanism of pluripotency has yet to be understood. Still, induced pluripotent stem cell technology is considered to be significant by proposing novel approaches in disease modelling, drug screening and cell therapy. Besides their self-renewing ability and their potential to differentiate into all cell types in a human body, they arouse a great interest in scientific world by being far from the ethical concerns regarding their embryonic counterparts and their unique feature of being patient-specific in prospective cell therapies. In this review, induced pluripotent stem cell technology and its role in cell-based therapies from past to present will be discussed. J Clin Exp Invest 2013; 4 (4: 550-561

  5. Automated Cell-Cutting for Cell Cloning

    Science.gov (United States)

    Ichikawa, Akihiko; Tanikawa, Tamio; Matsukawa, Kazutsugu; Takahashi, Seiya; Ohba, Kohtaro

    We develop an automated cell-cutting technique for cell cloning. Animal cells softened by the cytochalasin treatment are injected into a microfluidic chip. The microfluidic chip contains two orthogonal channels: one microchannel is wide, used to transport cells, and generates the cutting flow; the other is thin and used for aspiration, fixing, and stretching of the cell. The injected cell is aspirated and stretched in the thin microchannel. Simultaneously, the volumes of the cell before and after aspiration are calculated; the volumes are used to calculate the fluid flow required to aspirate half the volume of the cell into the thin microchannel. Finally, we apply a high-speed flow in the orthogonal microchannel to bisect the cell. This paper reports the cutting process, the cutting system, and the results of the experiment.

  6. Stem cell biobanks.

    Science.gov (United States)

    Bardelli, Silvana

    2010-04-01

    Stem cells contribute to innate healing and harbor a promising role for regenerative medicine. Stem cell banking through long-term storage of different stem cell platforms represents a fundamental source to preserve original features of stem cells for patient-specific clinical applications. Stem cell research and clinical translation constitute fundamental and indivisible modules catalyzed through biobanking activity, generating a return of investment.

  7. Regulation of cell cycle progression by cell-cell and cell-matrix forces

    NARCIS (Netherlands)

    Uroz, Marina; Wistorf, Sabrina; Serra-Picamal, Xavier; Conte, Vito; Sales-Pardo, Marta; Roca-Cusachs, Pere; Guimerà, Roger; Trepat, Xavier

    2018-01-01

    It has long been proposed that the cell cycle is regulated by physical forces at the cell-cell and cell-extracellular matrix (ECM) interfaces 1-12 . However, the evolution of these forces during the cycle has never been measured in a tissue, and whether this evolution affects cell cycle progression

  8. Sickle cell test

    Science.gov (United States)

    ... cell anemia Sickle cell trait Iron deficiency or blood transfusions within the past 3 months can cause a " ... slight risk any time the skin is broken) Alternative Names Sickledex; Hgb S test Images Red blood cells, sickle cell Red blood cells, multiple sickle ...

  9. Host cell reactivation in mammalian cells

    International Nuclear Information System (INIS)

    Lytle, C.D.; Benane, S.G.; Stafford, J.E.

    1976-01-01

    The survival of UV-irradiated herpes simplex virus was determined in cultured Potoroo (a marsupial) and human cells under lighting conditions which promoted photereactivation. Photoreactivation was readily demonstrated for herpes virus in two lines of Potoroo cells with dose reduction factors of 0.7 to 0.8 for ovary cells and 0.5 to 0.7 for kidney cells. Light from Blacklite (near UV) lamps was more effective than from Daylight (mostly visible) lamps, suggesting that near UV radiation was more effecient for photoreactivation in Potoroo cells. The quantitative and qualitative aspects of this photoreactivation were similar to those reported for a similar virus infecting chick embryo cells. UV-survival curves of herpes virus in Potoroo cells indicated a high level of 'dark' host cell reactivation. No photoreactivation was found for UV-irradiated vaccinia virus in Potoroo cells. A similar photoreactivation study was done using special control lighting (lambda>600 nm) and human cells with normal repair and with cells deficient in excision repair (XP). No photoreactivation was found for UV-irradiated herpes virus in either human cell with either Blacklite or Daylight lamps as the sources of photoreactivating light. This result contrasts with a report of photoreactivation for a herpes virus in the same XP cells using incandescent lamps. (author)

  10. In silico characterization of cell-cell interactions using a cellular automata model of cell culture.

    Science.gov (United States)

    Kihara, Takanori; Kashitani, Kosuke; Miyake, Jun

    2017-07-14

    Cell proliferation is a key characteristic of eukaryotic cells. During cell proliferation, cells interact with each other. In this study, we developed a cellular automata model to estimate cell-cell interactions using experimentally obtained images of cultured cells. We used four types of cells; HeLa cells, human osteosarcoma (HOS) cells, rat mesenchymal stem cells (MSCs), and rat smooth muscle A7r5 cells. These cells were cultured and stained daily. The obtained cell images were binarized and clipped into squares containing about 10 4 cells. These cells showed characteristic cell proliferation patterns. The growth curves of these cells were generated from the cell proliferation images and we determined the doubling time of these cells from the growth curves. We developed a simple cellular automata system with an easily accessible graphical user interface. This system has five variable parameters, namely, initial cell number, doubling time, motility, cell-cell adhesion, and cell-cell contact inhibition (of proliferation). Within these parameters, we obtained initial cell numbers and doubling times experimentally. We set the motility at a constant value because the effect of the parameter for our simulation was restricted. Therefore, we simulated cell proliferation behavior with cell-cell adhesion and cell-cell contact inhibition as variables. By comparing growth curves and proliferation cell images, we succeeded in determining the cell-cell interaction properties of each cell. Simulated HeLa and HOS cells exhibited low cell-cell adhesion and weak cell-cell contact inhibition. Simulated MSCs exhibited high cell-cell adhesion and positive cell-cell contact inhibition. Simulated A7r5 cells exhibited low cell-cell adhesion and strong cell-cell contact inhibition. These simulated results correlated with the experimental growth curves and proliferation images. Our simulation approach is an easy method for evaluating the cell-cell interaction properties of cells.

  11. Galvanic cells: setting up the Daniell cell.

    OpenAIRE

    Milla González, Miguel

    2008-01-01

    With the reagents (0.05M copper nitrate solution, 0.05M zinc nitrate solution) and material (glassware, potentiometer, electric wire) availabe in the laboratory, the user must set up the Daniell cell. Different configurations can be possible if the half cells are filled with either electrolyte solution. The cell connections to the measuring device can also be changed. In all instances, an explanation of the set up cell is obtained as well as of the measured potential difference.

  12. Lung cancer - small cell

    Science.gov (United States)

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  13. Stem Cell Information: Glossary

    Science.gov (United States)

    ... Tips Info Center Research Topics Federal Policy Glossary Stem Cell Information General Information Clinical Trials Funding Information Current ... here Home » Glossary Back to top Glossary Adult stem cell Astrocyte Blastocoel Blastocyst Bone marrow stromal cells Bone ...

  14. Squamous cell cancer (image)

    Science.gov (United States)

    Squamous cell cancer involves cancerous changes to the cells of the middle portion of the epidermal skin layer. It is ... malignant tumor, and is more aggressive than basal cell cancer, but still may be relatively slow-growing. It ...

  15. Pancreatic islet cell tumor

    Science.gov (United States)

    ... cell tumors; Islet of Langerhans tumor; Neuroendocrine tumors; Peptic ulcer - islet cell tumor; Hypoglycemia - islet cell tumor ... stomach acid. Symptoms may include: Abdominal pain Diarrhea ... and small bowel Vomiting blood (occasionally) Glucagonomas make ...

  16. NK cells and T cells: mirror images?

    NARCIS (Netherlands)

    Versteeg, R.

    1992-01-01

    The expression of MHC class I molecules protects cells against lysis by natural killer (NK) cells. It is possible that NK cells are 'educated' to recognize self MHC class I molecules and that the combination of self peptide and MHC class I molecule blocks NK-mediated lysis. Here, Rogier Versteeg

  17. Snail modulates cell metabolism in MDCK cells

    Energy Technology Data Exchange (ETDEWEB)

    Haraguchi, Misako, E-mail: haraguci@m3.kufm.kagoshima-u.ac.jp [Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Indo, Hiroko P. [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Iwasaki, Yasumasa [Health Care Center, Kochi University, Kochi 780-8520 (Japan); Iwashita, Yoichiro [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Fukushige, Tomoko [Department of Dermatology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Majima, Hideyuki J. [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Izumo, Kimiko; Horiuchi, Masahisa [Department of Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Kanekura, Takuro [Department of Dermatology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Furukawa, Tatsuhiko [Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Ozawa, Masayuki [Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan)

    2013-03-22

    Highlights: ► MDCK/snail cells were more sensitive to glucose deprivation than MDCK/neo cells. ► MDCK/snail cells had decreased oxidative phosphorylation, O{sub 2} consumption and ATP content. ► TCA cycle enzyme activity, but not expression, was lower in MDCK/snail cells. ► MDCK/snail cells showed reduced PDH activity and increased PDK1 expression. ► MDCK/snail cells showed reduced expression of GLS2 and ACLY. -- Abstract: Snail, a repressor of E-cadherin gene transcription, induces epithelial-to-mesenchymal transition and is involved in tumor progression. Snail also mediates resistance to cell death induced by serum depletion. By contrast, we observed that snail-expressing MDCK (MDCK/snail) cells undergo cell death at a higher rate than control (MDCK/neo) cells in low-glucose medium. Therefore, we investigated whether snail expression influences cell metabolism in MDCK cells. Although gylcolysis was not affected in MDCK/snail cells, they did exhibit reduced pyruvate dehydrogenase (PDH) activity, which controls pyruvate entry into the tricarboxylic acid (TCA) cycle. Indeed, the activity of multiple enzymes involved in the TCA cycle was decreased in MDCK/snail cells, including that of mitochondrial NADP{sup +}-dependent isocitrate dehydrogenase (IDH2), succinate dehydrogenase (SDH), and electron transport Complex II and Complex IV. Consequently, lower ATP content, lower oxygen consumption and increased survival under hypoxic conditions was also observed in MDCK/snail cells compared to MDCK/neo cells. In addition, the expression and promoter activity of pyruvate dehydrogenase kinase 1 (PDK1), which phosphorylates and inhibits the activity of PDH, was increased in MDCK/snail cells, while expression levels of glutaminase 2 (GLS2) and ATP-citrate lyase (ACLY), which are involved in glutaminolysis and fatty acid synthesis, were decreased in MDCK/snail cells. These results suggest that snail modulates cell metabolism by altering the expression and activity of

  18. Cell control report

    CERN Document Server

    2013-01-01

    Please note this is a Short Discount publication. This extensive report provides an essential overview of cells and their use as factory automation building blocks. The following issues are discussed in depth: Cell integration Cell software and standards Future technologies applied to cells Plus Cell control applications including: - rotary parts manufacturing - diesel engine component development - general cell control development at the General Electric Corporation - a vendor list.

  19. GSPEL - Fuel Cell Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Fuel Cell Lab (FCL)Established to investigate, integrate, testand verifyperformance and technology readiness offuel cell systems and fuel reformers for use with...

  20. Squamous cell skin cancer

    Science.gov (United States)

    ... that reflect light more, such as water, sand, concrete, and areas that are painted white. The higher ... - skin - squamous cell; Skin cancer - squamous cell; Nonmelanoma skin cancer - squamous ...

  1. Transplantational and specific antitumor immunity in retrospective view: new models based on transgenesis of individual chains of T-cell receptor

    Directory of Open Access Journals (Sweden)

    D. B. Kazanskiy

    2016-01-01

    Full Text Available Findings in experimental oncology in beginning of last century and subsequent achievements of genetics of tissue compatibility resulted in divergence of transplantational immunology and oncoimmunology. However, central achievements of both scientific fields are based on unified phenomenon of interaction between T-cell receptor (TCR and histocompatibility molecules. In this review we describe the history of ideas, achievements and unique experience of the team of the Laboratory of Regulatory Mechanisms in Immunity at Scientific Research Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center for all time of existence. This experience shows that efficiency of immunological defense including immunological surveillance are critically influenced by T-cell receptor repertoire. Transgenesis of individual chains of TCR is one of possible means to manage T-cell repertoire. Functional outcomes of transgenesis may be different due to diverse extent of dependence of α- and β-chains expression on the rules of allelic exclusion. Expression of transgenic β-chains results in the expansion of TCR repertoire diversity. Expression of β-chains is under strong control by allelic exclusion, resulting in formation of repertoire bearing mainly invariant transgenic β-chain pared with different α-chains and overall narrowing of repertoire. Earlier, we cloned genes encoding α- and β-chains of TCR of CD8+ memory cells specific to histocompatibility molecule H-2Kb . After introduction them in zigotes we have obtained transgenic mouse strains, which could be used for modeling of interactions between tumor cells and immune system of recipient. Normally, B10. D2 (R101 mice reject lymphoma EL4 cells in 12–14 days after transplantation, in spite of the fact, that allogeneic difference between B10. D2 (R101 (Kd Id Db mice and lymphoma EL4 (H-2b cells is only in one product of MHC, the H-2Kb molecule. Transgenics carrying β-chains of TCR displayed

  2. Epithelial cell polarity, stem cells and cancer

    DEFF Research Database (Denmark)

    Martin-Belmonte, Fernando; Perez-Moreno, Mirna

    2011-01-01

    , deregulation of adhesion and polarity proteins can cause misoriented cell divisions and increased self-renewal of adult epithelial stem cells. In this Review, we highlight some advances in the understanding of how loss of epithelial cell polarity contributes to tumorigenesis.......After years of extensive scientific discovery much has been learned about the networks that regulate epithelial homeostasis. Loss of expression or functional activity of cell adhesion and cell polarity proteins (including the PAR, crumbs (CRB) and scribble (SCRIB) complexes) is intricately related...

  3. Stem cell plasticity.

    Science.gov (United States)

    Lakshmipathy, Uma; Verfaillie, Catherine

    2005-01-01

    The central dogma in stem cell biology has been that cells isolated from a particular tissue can renew and differentiate into lineages of the tissue it resides in. Several studies have challenged this idea by demonstrating that tissue specific cell have considerable plasticity and can cross-lineage restriction boundary and give rise to cell types of other lineages. However, the lack of a clear definition for plasticity has led to confusion with several reports failing to demonstrate that a single cell can indeed differentiate into multiple lineages at significant levels. Further, differences between results obtained in different labs has cast doubt on some results and several studies still await independent confirmation. In this review, we critically evaluate studies that report stem cell plasticity using three rigid criteria to define stem cell plasticity; differentiation of a single cell into multiple cell lineages, functionality of differentiated cells in vitro and in vivo, robust and persistent engraft of transplanted cells.

  4. [Exosomes and Immune Cells].

    Science.gov (United States)

    Seo, Naohiro

    2017-05-01

    In addition to the cytokines and cytotoxic granules, exosomes have been known as the intercellular communicator and cytotoxic missile of immune cells for the past decade. It has been well known that mature dendritic cell(DC)-derived exosomes participate in the T cell and natural killer(NK)cell activation, while immature DCs secrete tolerogenic exosomes for regulatory T(Treg)cell generation. Treg cell-derived EVs act as a suppressor against pathogenic type-1 T helper(Th1)cell responses. CD8+ T cells produce tumoricidal exosomes for preventing tumor invasion and metastasis transiently after T cell receptor(TCR)-mediated stimulation. Thus, immune cells produce functional exosomes in the activation state- and/or differentiation stage-dependent manner. In this review, the role of immune cell-derived exosomes will be introduced, focusing mainly on immune reaction against tumor.

  5. Exposure to 4-tert-octylphenol, an environmentally persistent alkylphenol, enhances interleukin-4 production in T cells via NF-AT activation

    International Nuclear Information System (INIS)

    Lee, Mi H.; Kim, Eugene; Kim, Tae S.

    2004-01-01

    4-tert-Octylphenol (OP) is a representative endocrine disruptor that may have adverse effects on human health. The influence of this compound on allergic immune responses remains unclear. In this study, we have examined the effects of OP on production of interleukin-4 (IL-4), a pro-inflammatory cytokine closely associated