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Sample records for cells iii role

  1. Role of phosphorylated histone H3 serine 10 in DEN-induced deregulation of Pol III genes and cell proliferation and transformation

    OpenAIRE

    Zhong, Qian; Shi, Ganggang; Zhang, Qingsong; Zhang, Yanmei; Levy, Daniel; Zhong, Shuping

    2013-01-01

    The products of Pol III genes (RNA polymerase III-dependent genes), such as tRNAs and 5S rRNA, are elevated in both transformed and tumor cells suggesting that they play a crucial role in tumorigenesis. An increase in Brf1 (TFIIIB-related factor 1), a subunit of TFIIIB, augments Pol III gene transcription and is sufficient for cell transformation and tumor formation. We have demonstrated that enhancement of Brf1 and Pol III gene expression is associated with the occurrences of hepatocellular ...

  2. Helicobacter pylori antigens, acetylsalicylic acid, LDL and 7-ketocholesterol - their potential role in destabilizing the gastric epithelial cell barrier. An in vitro model of Kato III cells.

    Science.gov (United States)

    Gajewski, Adrian; Mnich, Eliza; Szymański, Karol; Hinc, Krzysztof; Obuchowski, Michał; Moran, Anthony P; Chmiela, Magdalena

    2016-01-01

    Colonization of gastric tissue in humans by H. pylori Gram-negative bacteria initiates gastric and duodenal ulcers and even gastric cancers. Infections promote inflammation and damage to gastric epithelium which might be followed by the impairment of its barrier function. The role of H. pylori components in these processes has not been specified. H. pylori cytotoxicity may potentially increase in the milieu of anti-inflammatory drugs including acetylsalicylic acid (ASA). The lipid transport-associated molecule such as low density lipoprotein (LDL), which is a classic risk factor of coronary heart disease (CHD) and 7-ketocholesterol (7-kCh) a product of cholesterol oxidation, which may occur during the oxidative stress in LDL could also be considered as pro-inflammatory. The aim of this study was to evaluate the cytotoxicity of H. pylori antigens, ASA, LDL and 7-kCh towards Kato III gastric epithelial cells, on the basis of the cell ability to reduce tetrazolium salt (MTT) and morphology of cell nuclei assessed by 4',6-diamidino-2-phenylindole (DAPI) staining. Kato III cells were stimulated for 24 h, at 37°C and 5% CO2, with H. pylori antigens: cytotoxin associated gene A (CagA) protein, the urease A subunit (UreA), lipopolysaccharide (LPS) and ASA, LDL or 7-kCh. H. pylori LPS, ASA, LDL and 7-kCh, but not H. pylori glycine acid extract (GE), demonstrated cytotoxicity against Kato III cells, which was related to a diminished percentage of MTT reducing cells and to an increased cell population with the signs of DNA damage. The results suggest that damage to gastric epithelial cells can be induced independently by H. pylori antigens, ASA and endogenous lipid transport-associated molecules. During H. pylori infection in vivo, especially in CHD patients, synergistic or antagonistic interactions between these factors might possibly influence the disease course. Further study is necessary to explain these potential effects. PMID:26619253

  3. Giant cell arteritis. Part III. New trends in its treatment (role of genetically engineered drugs

    Directory of Open Access Journals (Sweden)

    Azamat Makhmudovich Satybaldyev

    2013-01-01

    Full Text Available Giant cell arteritis (GCA is a well-known vasculitis sensitive to glucocorticoid (GC immuno-suppression. However, during long-term treatment there may be many adverse reactions that remain a serious problem so far. Since GCA encompasses a broad spectrum of clinical subtypes, ranging from severe visual loss and neurological deficits to isolated systemic signs, its treatment must be adjusted specially to each case. The literature contains contradicting recommendations for the therapy for GCA. The paper considers different treatment options for GCA, including that with neuro-ophthalmic and neurological complications, as well as the evidence for their possible adjuvant therapies. Although there is no randomized controlled clinical trial in GCA with ocular and neurological complications, the data available in the literature suggest that these patients are recommended to be admitted for high-dose intravenous methylprednisolone, monitoring, and prevention of GC-induced complications. It is expedient to use aspirin in these cases. The evidence supporting the use of methotrexate, as well as genetically engineered agents (GEAs, infliximab, etanercept as steroid-sparing agents is discussed. Cases of using individual GEAs (adalimumab, tocilizumab and rituximab as an alternative to GC monotherapy are described. It is concluded that there is a need for extended clinical trials evaluating the most effective and safe GC-sparing drugs.

  4. Giant cell arteritis. Part III. New trends in its treatment (role of genetically engineered drugs

    Directory of Open Access Journals (Sweden)

    Azamat Makhmudovich Satybaldyev

    2013-03-01

    Full Text Available Giant cell arteritis (GCA is a well-known vasculitis sensitive to glucocorticoid (GC immuno-suppression. However, during long-term treatment there may be many adverse reactions that remain a serious problem so far. Since GCA encompasses a broad spectrum of clinical subtypes, ranging from severe visual loss and neurological deficits to isolated systemic signs, its treatment must be adjusted specially to each case. The literature contains contradicting recommendations for the therapy for GCA. The paper considers different treatment options for GCA, including that with neuro-ophthalmic and neurological complications, as well as the evidence for their possible adjuvant therapies. Although there is no randomized controlled clinical trial in GCA with ocular and neurological complications, the data available in the literature suggest that these patients are recommended to be admitted for high-dose intravenous methylprednisolone, monitoring, and prevention of GC-induced complications. It is expedient to use aspirin in these cases. The evidence supporting the use of methotrexate, as well as genetically engineered agents (GEAs, infliximab, etanercept as steroid-sparing agents is discussed. Cases of using individual GEAs (adalimumab, tocilizumab and rituximab as an alternative to GC monotherapy are described. It is concluded that there is a need for extended clinical trials evaluating the most effective and safe GC-sparing drugs.

  5. The role of sphingosine kinase-1 in EGFRvIII-regulated growth and survival of glioblastoma cells

    OpenAIRE

    Estrada-Bernal, Adriana; Lawler, Sean E; Nowicki, Michal O.; Chaudhury, Abhik Ray; Van Brocklyn, James R.

    2010-01-01

    We have previously shown that high expression levels of the lipid kinase sphingosine kinase-1 (SphK1) correlate with poor survival of glioblastoma (GBM) patients. In this study we examined the regulation of SphK1 expression by epidermal growth factor receptor (EGFR) signaling in GBM cells. As the EGFR gene is often overexpressed and mutated in GBM, and EGFR has been shown to regulate SphK1 in some cell types, we examined the effect of EGF signaling and the constitutively active EGFRvIII mutan...

  6. Role of survival post-progression in phase III trials of systemic chemotherapy in advanced non-small-cell lung cancer: a systematic review.

    Directory of Open Access Journals (Sweden)

    Katsuyuki Hotta

    Full Text Available BACKGROUND: In advanced non-small-cell lung cancer (NSCLC, with the increasing number of active compounds available in salvage settings, survival after progression to first-line chemotherapy seems to have improved. A literature survey was conducted to examine whether survival post-progression (SPP has improved over the years and to what degree SPP correlates with overall survival (OS. METHODS AND FINDINGS: Median progression-free survival (MPFS time and median survival time (MST were extracted in phase III trials of first-line chemotherapy for advanced NSCLC. SPP was pragmatically defined as the time interval of MST minus MPFS. The relationship between MPFS and MST was modeled in a linear function. We used the coefficient of determination (r(2 to assess the correlation between them. Seventy trials with 145 chemotherapy arms were identified. Overall, median SPP was 4.7 months, and a steady improvement in SPP was observed over the 20 years (9.414-day increase per year; p<0.001 in parallel to the increase in MST (11.253-day increase per year; p<0.001; MPFS improved little (1.863-day increase per year. Overall, a stronger association was observed between MST and SPP (r(2 = 0.8917 than MST and MPFS time (r(2 = 0.2563, suggesting SPP and MPFS could account for 89% and 25% of the variation in MST, respectively. The association between MST and SPP became closer over the years (r(2 = 0.4428, 0.7242, and 0.9081 in 1988-1994, 1995-2001, and 2002-2007, respectively. CONCLUSIONS: SPP has become more closely associated with OS, potentially because of intensive post-study treatments. Even in advanced NSCLC, a PFS advantage is unlikely to be associated with an OS advantage any longer due to this increasing impact of SPP on OS, and that the prolongation of SPP might limit the original role of OS for assessing true efficacy derived from early-line chemotherapy in future clinical trials.

  7. Root growth restraint can be an acclimatory response to low pH and is associated with reduced cell mortality: a possible role of class III peroxidases and NADPH oxidases.

    Science.gov (United States)

    Graças, J P; Ruiz-Romero, R; Figueiredo, L D; Mattiello, L; Peres, L E P; Vitorello, V A

    2016-07-01

    Low pH (Solanum lycopersicum cv Micro-Tom) roots were exposed directly or gradually to low pH through step-wise changes in pH over periods ranging from 4 to 24 h. Roots exposed gradually to pH 4.5 grew even less than those exposed directly, indicating a plant-coordinated response. Direct exposure to pH 4.0 suppressed root growth and caused high cell mortality, in contrast to roots exposed gradually, in which growth remained inhibited but cell viability was maintained. Total class III peroxidase activity increased significantly in all low pH treatments, but was not correlated with the observed differential responses. Use of the enzyme inhibitors salicylhydroxamic acid (SHAM) or diphenyleneiodonium chloride (DPI) suggest that peroxidase and, to a lesser extent, NADPH oxidase were required to prevent or reduce injury in all low pH treatments. However, a role for other enzymes, such as the alternative oxidase is also possible. The results with SHAM, but not DPI, were confirmed in tobacco BY-2 cells. Our results indicate that root growth inhibition from low pH can be part of an active plant response, and suggest that peroxidases may have a critical early role in reducing loss of cell viability and in the observed root growth constraint. PMID:26891589

  8. Effect of type III group B streptococcal capsular polysaccharide on invasion of respiratory epithelial cells.

    OpenAIRE

    Hulse, M L; Smith, S; Chi, E Y; Pham, A; Rubens, C E

    1993-01-01

    Group B streptococcal (GBS) capsular polysaccharide is an important virulence factor, and its role in invasion of cultured respiratory epithelial cells was investigated. A type III GBS clinical isolate, COH1, and asialo and unencapsulated isogenic transposon capsule mutants of it were compared in an in vitro invasion assay. The results demonstrated that capsule attenuated the invasion process. Invasion was not affected when the A549 epithelial cells were preincubated with purified type III GB...

  9. Sorption behavior of europium(III) and curium(III) on the cell surfaces of microorganisms

    Energy Technology Data Exchange (ETDEWEB)

    Ozaki, T.; Kimura, T.; Ohnuki, T.; Yoshida, Z. [Advanced Science Research Center, Japan Atomic Energy Research Inst., Ibaraki (Japan); Gillow, J.B.; Francis, A.J. [Environmental Sciences Dept., Brookhaven National Lab., Upton, NY (United States)

    2004-07-01

    We investigated the association of europium(III) and curium(III) with the microorganisms Chlorella vulgaris, Bacillus subtilis, Pseudomonas fluorescens, Halomonas sp., Halobacterium salinarum, and Halobacterium halobium. We determined the kinetics and distribution coefficients (K{sub d}) for Eu(III) and Cm(III) sorption at pH 3-5 by batch experiments, and evaluated the number of water molecules in the inner-sphere (N{sub H{sub 2}O}) and the degree of strength of ligand field (R{sub E/M}) for Eu(III) by time-resolved laser-induced fluorescence spectroscopy (TRLFS). Exudates from C. vulgaris, Halomonas sp., and H. halobium had an affinity for Eu(III) and Cm(III). The log K{sub d} of Eu(III) and Cm(III) showed that their sorption was not fully due to the exchange with three protons on the functional groups on cell surfaces. The halophilic microorganisms (Halomonas sp., Halobacterium salinarum, H. halobium) showed almost no pH dependence in log K{sub d}, indicating that an exchange with Na{sup +} on the functional groups was involved in their sorption. The {delta}N{sub H{sub 2}O} (= 9 - N{sub H{sub 2}O}) for Eu(III) on C. vulgaris was 1-3, while that for the other microorganisms was over 3, demonstrating that the coordination of Eu(III) with C. vulgaris was predominantly an outer-spherical process. The R{sub E/M} for Eu(III) on halophilic microorganisms was 2.5-5, while that for non-halophilic ones was 1-2.5. This finding suggests that the coordination environment of Eu(III) on the halophilic microorganisms is more complicated than that on the other three non-halophilic ones. (orig.)

  10. Global gene expression profiling of Yersinia pestis replicating inside macrophages reveals the roles of a putative stress-induced operon in regulating type III secretion and intracellular cell division.

    Science.gov (United States)

    Fukuto, Hana S; Svetlanov, Anton; Palmer, Lance E; Karzai, A Wali; Bliska, James B

    2010-09-01

    Yersinia pestis, the causative agent of plague, is a facultative intracellular pathogen. Previous studies have indicated that the ability of Y. pestis to survive inside macrophages may be critical during the early stages of plague pathogenesis. To gain insights into the biology of intracellular Y. pestis and its environment following phagocytosis, we determined the genome-wide transcriptional profile of Y. pestis KIM5 replicating inside J774.1 macrophage-like cells using DNA microarrays. At 1.5, 4, and 8 h postinfection, a total of 801, 464, and 416 Y. pestis genes were differentially regulated, respectively, compared to the level of gene expression of control bacteria grown in tissue culture medium. A number of stress-response genes, including those involved in detoxification of reactive oxygen species, as well as several metabolic genes involved in macromolecule synthesis, were significantly induced in intracellular Y. pestis, consistent with the presence of oxidative stress and nutrient starvation inside Yersinia-containing vacuoles. A putative stress-induced operon consisting of y2313, y2315, and y2316 (y2313-y2316), and a previously unidentified open reading frame, orfX, was studied further on the basis of its high level of intracellular expression. Mutant strains harboring either deletion, Deltay2313-y2316 or DeltaorfX, exhibited diverse phenotypes, including reduced effector secretion by the type III secretion system, increased intracellular replication, and filamentous morphology of the bacteria growing inside macrophages. The results suggest a possible role for these genes in regulating cell envelope characteristics in the intracellular environment. PMID:20566693

  11. Comparative study of antithrombin III. Protease complex metabolism by fibroblasts and vascular endothelial cells

    International Nuclear Information System (INIS)

    125I-labeled human antithrombin III (125I-AT III).protease complexes are specifically bound to both cultured human skin fibroblast (HSF) cells and adult bovine aortic endothelial (ABAE) cells; however, there is a significant difference in the rate and degree of metabolism of the complexes by these two cell types. HSF cells appear to internalize the complexes at a rate of about 2.5 pmole/1 X 10(6) cells/h and subsequently degrade them at a rate of 0.6 pmole/1 X 10(6) cells/h. ABAE cells internalize and degrade the complexes at rates approximately 100 and 30 times lower, respectively. Neither cell type interacts with free 125I-AT III but only with its combined form with either thrombin or trypsin. These data indicate the major role of HSF cells in the removal of AT III.protease complexes from extravascular spaces in the body, in contrast to the inert vascular surface with regard to AT III.protease complexes provided by the vascular endothelium

  12. Peroxiredoxin III protects pancreatic ß cells from apoptosis.

    Science.gov (United States)

    Wolf, Gabriele; Aumann, Nicole; Michalska, Marta; Bast, Antje; Sonnemann, Jürgen; Beck, James F; Lendeckel, Uwe; Newsholme, Philip; Walther, Reinhard

    2010-11-01

    Type 1 diabetes mellitus is characterized by a progressive autoimmune destruction of insulin-producing β cells. Macrophages and T lymphocytes release cytokines, which induce the synthesis of oxygen and nitrogen radicals in the pancreatic islets. The resulting cellular and mitochondrial damage promotes β cell death. β cells are very sensitive to the autoimmune free radical-dependent attack due to their low content of antioxidant enzymes such as glutathione peroxidase and catalase. A focal point of β cell protection should be the control of the mitochondrial redox status, which will result in the preservation of metabolic stimulus-secretion coupling. For this reason, there is a considerable interest in the mitochondrial peroxiredoxin III (PRX III), a thioredoxin-dependent peroxide reductase, which was shown to be able to protect against both oxidative and nitrosative stress. Using the Tet-On-system, we generated stably transfected rat insulinoma cells over- or under-expressing PRX III in a doxycyclin-dependent manner to analyze the effect of increased or decreased amounts of cellular PRX III, following treatment with several stressors. We provide evidence that PRX III protects pancreatic β cells from cell stress induced by accumulation of hydrogen peroxide, or the induction of inducible nitric oxide synthase or caspase-9 and -3 by pro-inflammatory cytokines or streptozotocin. Basal insulin secretion was markedly decreased in cells expressing lower levels of PRX III. We suggest PRX III may be a suitable target for promoting deceleration or even prevention of stress-associated apoptosis in pancreatic β cells and the manifestation of insulin-dependent diabetes mellitus. PMID:20807727

  13. Interaction of Eu(III) with mammalian cells: Cytotoxicity, uptake, and speciation as a function of Eu(III) concentration and nutrient composition.

    Science.gov (United States)

    Sachs, Susanne; Heller, Anne; Weiss, Stephan; Bok, Frank; Bernhard, Gert

    2015-10-01

    In case of the release of lanthanides and actinides into the environment, knowledge about their behavior in biological systems is necessary to assess and prevent adverse health effects for humans. We investigated the interaction of europium with FaDu cells (human squamous cell carcinoma cell line) combining analytical methods, spectroscopy, and thermodynamic modeling with in-vitro cell experiments under defined conditions. Both the cytotoxicity of Eu(III) onto FaDu cells and its cellular uptake are mainly concentration-dependent. Moreover, they are governed by its chemical speciation in the nutrient medium. In complete cell culture medium, i.e., in the presence of fetal bovine serum, Eu(III) is stabilized in solution in a wide concentration range by complexation with serum proteins resulting in low cytotoxicity and cellular Eu(III) uptake. In serum-free medium, Eu(III) precipitates as hardly soluble phosphate species, exhibiting a significantly higher cytotoxicity and slightly higher cellular uptake. The presence of a tenfold excess of citrate in serum-free medium causes the formation of Eu(HCit)2(3-) complexes in addition to the dominating Eu(III) phosphate species, resulting in a decreased Eu(III) cytotoxicity and cellular uptake. The results of this study underline the crucial role of a metal ion's speciation for its toxicity and bioavailability. PMID:26055652

  14. The role of In in III-nitride ternary semiconductors

    CERN Multimedia

    Redondo cubero, A

    This proposal aims to study the role of In in the outstanding efficiency of luminescent devices based on group III-nitride ternary semiconductors. To study the microscopic environments of In in GaInN and AlInN, Perturbed Angular Correlation (PAC) experiments will be performed using the PAC-probes $^{111m}$Cd($^{111}$Cd), $^{115}$Cd($^{115}$In) and $^{117}$Cd($^{117}$In). Temperature dependent PAC measurements using the $^{111}$In($^{111}$Cd) probe indicated that In in GaN and AlN forms a complex with a defect, possibly a nitrogen vacancy (V$_{N}$), which is stable up to high temperatures and might be involved in the luminescence mechanisms. Analysing these results two questions arose: \\\\ \\\\1. Does the fact that the actual measurement is performed with the daughter nucleus $^{111}$Cd (being an acceptor) influence the probe-defect interaction? This question can be answered by performing measurements with the complementary probe $^{117}$Cd($^{117}$In). \\\\ \\\\ 2. What is the significance of $\\textit{a...

  15. Shoot meristem function and leaf polarity: the role of class III HD-ZIP genes.

    Directory of Open Access Journals (Sweden)

    Mary E Byrne

    2006-06-01

    Full Text Available The shoot apical meristem comprises an organized cluster of cells with a central region population of self-maintaining stem cells providing peripheral region cells that are recruited to form differentiated lateral organs. Leaves, the principal lateral organ of the shoot, develop as polar structures typically with distinct dorsoventrality. Interdependent interactions between the meristem and developing leaf provide essential cues that serve both to maintain the meristem and to pattern dorsoventrality in the initiating leaf. A key component of both processes are the class III HD-ZIP genes. Current findings are defining the developmental role of members of this family and are identifying multiple mechanisms controlling expression of these genes.

  16. Proton Beam Therapy of Stage II and III Non-Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Hidetsugu, E-mail: hnakayam@tokyo-med.ac.jp [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan); Satoh, Hiroaki [Department of Respiratory Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Sugahara, Shinji [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan); Kurishima, Koichi [Department of Respiratory Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Tsuboi, Koji; Sakurai, Hideyuki [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Ishikawa, Shigemi [Department of Thoracic Surgery, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Tokuuye, Koichi [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan)

    2011-11-15

    Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non-small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4-85.4). The median proton dose given was 78.3 Gy (range, 67.1-91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non-small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non-small-cell lung cancer who are unsuitable for surgery or chemotherapy.

  17. Proton Beam Therapy of Stage II and III Non–Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non–small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4–85.4). The median proton dose given was 78.3 Gy (range, 67.1–91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non–small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non–small-cell lung cancer who are unsuitable for surgery or chemotherapy.

  18. File list: Pol.ALL.20.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.ALL.20.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III All cel...l types ERX204069 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.ALL.20.RNA_Polymerase_III.AllCell.bed ...

  19. File list: Pol.PSC.05.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.PSC.05.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Plurip...otent stem cell http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.PSC.05.RNA_polymerase_III.AllCell.bed ...

  20. File list: Pol.ALL.50.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Pol.PSC.20.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. File list: Pol.PSC.05.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: Pol.PSC.10.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.PSC.10.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Plurip...otent stem cell http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.PSC.10.RNA_polymerase_III.AllCell.bed ...

  4. Role of Peroxiredoxin III in the Pathogenesis of Pre-eclampsia as Evidenced in Mice

    Directory of Open Access Journals (Sweden)

    Lianqin Li

    2010-01-01

    Full Text Available As a member of peroxiredoxin (Prx family, PrxIII has been demonstrated to play an important role in scavenging intracellular reactive oxygen species (ROS. Since PrxIII knockout mice exhibited oxidative stress in placentas resembling pathophysiologic changes in placentas of human pre-eclampsia, we measured blood pressure through the carotid artery and detected oxidative status by western blotting in pregnant mice. We did not notice hypertension in pregnant PrxIII knockout mice as compared with wild-type littermates, although endothelin-1 was overexpressed in PrxIII-deficient placentas. Our results indicate that PrxIII is not involved in pre-eclamptic development. Instead, PrxIII is an indispensable antioxidant in placentas where oxidative stress exists.

  5. Organic / IV, III-V Semiconductor Hybrid Solar Cells

    Directory of Open Access Journals (Sweden)

    Pang-Leen Ong

    2010-03-01

    Full Text Available We present a review of the emerging class of hybrid solar cells based on organic-semiconductor (Group IV, III-V, nanocomposites, which states separately from dye synthesized, polymer-metal oxides and organic-inorganic (Group II-VI nanocomposite photovoltaics. The structure of such hybrid cell comprises of an organic active material (p-type deposited by coating, printing or spraying technique on the surface of bulk or nanostructured semiconductor (n-type forming a heterojunction between the two materials. Organic components include various photosensitive monomers (e.g., phtalocyanines or porphyrines, conjugated polymers, and carbon nanotubes. Mechanisms of the charge separation at the interface and their transport are discussed. Also, perspectives on the future development of such hybrid cells and comparative analysis with other classes of photovoltaics of third generation are presented.

  6. File list: Pol.Bon.50.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: Pol.Emb.10.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: Pol.Adl.05.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: Pol.Bld.20.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: Pol.Unc.10.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.10.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Unclass...ified http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Unc.10.RNA_Polymerase_III.AllCell.bed ...

  11. File list: Pol.Bon.05.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: Pol.Dig.50.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Dig.50.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Digesti...ve tract http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Dig.50.RNA_Polymerase_III.AllCell.bed ...

  13. File list: Pol.Adp.20.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adp.20.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Adipoc...yte http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Adp.20.RNA_polymerase_III.AllCell.bed ...

  14. File list: Pol.Pan.20.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Pan.20.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Pancrea...s http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Pan.20.RNA_Polymerase_III.AllCell.bed ...

  15. File list: Pol.Plc.20.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Plc.20.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Placen...ta http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Plc.20.RNA_polymerase_III.AllCell.bed ...

  16. File list: Pol.Neu.05.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: Pol.CDV.20.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.CDV.20.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Cardiov...ascular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.CDV.20.RNA_Polymerase_III.AllCell.bed ...

  18. File list: Pol.Utr.05.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: Pol.Pan.05.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: Pol.Lng.05.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lng.05.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Lung S...RX016555,SRX150101,SRX150102 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Lng.05.RNA_polymerase_III.AllCell.bed ...

  1. File list: Pol.Brs.05.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. File list: Pol.Oth.05.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: Pol.Gon.10.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: Pol.Oth.20.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: Pol.Myo.10.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: Pol.Bon.20.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: Pol.Utr.20.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: Pol.Myo.10.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: Pol.Myo.50.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: Pol.Utr.10.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: Pol.Emb.50.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: Pol.CDV.10.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.CDV.10.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Cardio...vascular http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.CDV.10.RNA_polymerase_III.AllCell.bed ...

  13. File list: Pol.Adp.10.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adp.10.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Adipocy...te http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Adp.10.RNA_Polymerase_III.AllCell.bed ...

  14. File list: Pol.Lar.50.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lar.50.RNA_polymerase_III.AllCell ce10 RNA polymerase RNA polymerase III Larvae... http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Lar.50.RNA_polymerase_III.AllCell.bed ...

  15. File list: Pol.Spl.10.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Spl.10.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Spleen ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Spl.10.RNA_Polymerase_III.AllCell.bed ...

  16. File list: Pol.Prs.10.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Prs.10.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Prosta...te http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Prs.10.RNA_polymerase_III.AllCell.bed ...

  17. File list: Pol.Pan.10.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Pan.10.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Pancrea...s http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Pan.10.RNA_Polymerase_III.AllCell.bed ...

  18. File list: Pol.Oth.50.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.50.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Others... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Oth.50.RNA_polymerase_III.AllCell.bed ...

  19. File list: Pol.Unc.50.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.50.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Unclass...ified http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Unc.50.RNA_Polymerase_III.AllCell.bed ...

  20. File list: Pol.Neu.50.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.50.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Neural ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.50.RNA_Polymerase_III.AllCell.bed ...

  1. File list: Pol.Myo.05.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Myo.05.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Muscle ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Myo.05.RNA_Polymerase_III.AllCell.bed ...

  2. File list: Pol.Epd.10.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Epd.10.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Epider...mis SRX016997 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Epd.10.RNA_polymerase_III.AllCell.bed ...

  3. File list: Pol.Plc.10.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Plc.10.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Placent...a http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Plc.10.RNA_Polymerase_III.AllCell.bed ...

  4. File list: Pol.Emb.05.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.05.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Embryo ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.05.RNA_Polymerase_III.AllCell.bed ...

  5. File list: Pol.Emb.20.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.20.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Embryo ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.20.RNA_Polymerase_III.AllCell.bed ...

  6. File list: Pol.Gon.05.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Gon.05.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Gonad h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Gon.05.RNA_Polymerase_III.AllCell.bed ...

  7. File list: Pol.Spl.20.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Spl.20.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Spleen ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Spl.20.RNA_Polymerase_III.AllCell.bed ...

  8. File list: Pol.Epd.50.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Epd.50.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Epiderm...is http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Epd.50.RNA_Polymerase_III.AllCell.bed ...

  9. File list: Pol.Pan.50.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Pan.50.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Pancrea...s http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Pan.50.RNA_Polymerase_III.AllCell.bed ...

  10. File list: Pol.Plc.05.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Plc.05.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Placent...a http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Plc.05.RNA_Polymerase_III.AllCell.bed ...

  11. File list: Pol.Lar.20.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lar.20.RNA_polymerase_III.AllCell ce10 RNA polymerase RNA polymerase III Larvae... http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Lar.20.RNA_polymerase_III.AllCell.bed ...

  12. File list: Pol.Unc.50.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.50.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Unclas...sified http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Unc.50.RNA_polymerase_III.AllCell.bed ...

  13. File list: Pol.Bon.50.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bon.50.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Bone h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bon.50.RNA_polymerase_III.AllCell.bed ...

  14. File list: Pol.Oth.05.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.05.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Others... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Oth.05.RNA_polymerase_III.AllCell.bed ...

  15. File list: Pol.ALL.05.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.ALL.05.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III All ce...,SRX150396,SRX015144,SRX150101,SRX150102 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.ALL.05.RNA_polymerase_III.AllCell.bed ...

  16. File list: Pol.Unc.20.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.20.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Unclas...sified http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Unc.20.RNA_polymerase_III.AllCell.bed ...

  17. File list: Pol.Adl.10.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adl.10.RNA_polymerase_III.AllCell ce10 RNA polymerase RNA polymerase III Adult ...SRX395531,SRX331268,SRX331270,SRX395532 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Adl.10.RNA_polymerase_III.AllCell.bed ...

  18. File list: Pol.Kid.05.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Kid.05.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Kidney... SRX016996 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Kid.05.RNA_polymerase_III.AllCell.bed ...

  19. File list: Pol.ALL.50.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.ALL.50.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III All ce...,SRX017001,SRX018606,SRX150396,SRX015144 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.ALL.50.RNA_polymerase_III.AllCell.bed ...

  20. File list: Pol.Kid.20.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Kid.20.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Kidney... SRX016996 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Kid.20.RNA_polymerase_III.AllCell.bed ...

  1. File list: Pol.Emb.05.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.05.RNA_polymerase_III.AllCell ce10 RNA polymerase RNA polymerase III Embryo... http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Emb.05.RNA_polymerase_III.AllCell.bed ...

  2. File list: Pol.Neu.05.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.05.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Neural... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Neu.05.RNA_polymerase_III.AllCell.bed ...

  3. File list: Pol.Unc.50.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.50.RNA_polymerase_III.AllCell ce10 RNA polymerase RNA polymerase III Unclas...sified http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Unc.50.RNA_polymerase_III.AllCell.bed ...

  4. File list: Pol.Neu.50.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: Pol.Bld.50.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.50.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Blood ...SRX150560,SRX018610,SRX015143,SRX017006,SRX150396,SRX015144 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.50.RNA_polymerase_III.AllCell.bed ...

  6. File list: Pol.Plc.50.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Plc.50.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Placen...ta http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Plc.50.RNA_polymerase_III.AllCell.bed ...

  7. File list: Pol.Gon.20.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Gon.20.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Gonad ...http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Gon.20.RNA_polymerase_III.AllCell.bed ...

  8. File list: Pol.Pan.10.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Pan.10.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Pancre...as http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Pan.10.RNA_polymerase_III.AllCell.bed ...

  9. File list: Pol.Emb.50.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: Pol.Pan.20.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Pan.20.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Pancre...as http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Pan.20.RNA_polymerase_III.AllCell.bed ...

  11. File list: Pol.Emb.20.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.20.RNA_polymerase_III.AllCell ce10 RNA polymerase RNA polymerase III Embryo... http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Emb.20.RNA_polymerase_III.AllCell.bed ...

  12. File list: Pol.Gon.50.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Gon.50.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Gonad ...http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Gon.50.RNA_polymerase_III.AllCell.bed ...

  13. File list: Pol.Epd.50.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Epd.50.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III Epider...mis SRX016997 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Epd.50.RNA_polymerase_III.AllCell.bed ...

  14. Global impact of Salmonella type III secretion effector SteA on host cells

    International Nuclear Information System (INIS)

    Highlights: • We analyzed HeLa cells transcriptome in response to Salmonella SteA. • Significant differential expression was detected for 58 human genes. • They are involved in ECM organization and regulation of some signaling pathways. • Cell death, cell adhesion and cell migration were decreased in SteA-expressing cells. • These results contribute to understand the role of SteA during infections. - Abstract: Salmonella enterica is a Gram-negative bacterium that causes gastroenteritis, bacteremia and typhoid fever in several animal species including humans. Its virulence is greatly dependent on two type III secretion systems, encoded in pathogenicity islands 1 and 2. These systems translocate proteins called effectors into eukaryotic host cell. Effectors interfere with host signal transduction pathways to allow the internalization of pathogens and their survival and proliferation inside vacuoles. SteA is one of the few Salmonella effectors that are substrates of both type III secretion systems. Here, we used gene arrays and bioinformatics analysis to study the genetic response of human epithelial cells to SteA. We found that constitutive synthesis of SteA in HeLa cells leads to induction of genes related to extracellular matrix organization and regulation of cell proliferation and serine/threonine kinase signaling pathways. SteA also causes repression of genes related to immune processes and regulation of purine nucleotide synthesis and pathway-restricted SMAD protein phosphorylation. In addition, a cell biology approach revealed that epithelial cells expressing steA show altered cell morphology, and decreased cytotoxicity, cell–cell adhesion and migration

  15. Global impact of Salmonella type III secretion effector SteA on host cells

    Energy Technology Data Exchange (ETDEWEB)

    Cardenal-Muñoz, Elena, E-mail: e_cardenal@us.es; Gutiérrez, Gabriel, E-mail: ggpozo@us.es; Ramos-Morales, Francisco, E-mail: framos@us.es

    2014-07-11

    Highlights: • We analyzed HeLa cells transcriptome in response to Salmonella SteA. • Significant differential expression was detected for 58 human genes. • They are involved in ECM organization and regulation of some signaling pathways. • Cell death, cell adhesion and cell migration were decreased in SteA-expressing cells. • These results contribute to understand the role of SteA during infections. - Abstract: Salmonella enterica is a Gram-negative bacterium that causes gastroenteritis, bacteremia and typhoid fever in several animal species including humans. Its virulence is greatly dependent on two type III secretion systems, encoded in pathogenicity islands 1 and 2. These systems translocate proteins called effectors into eukaryotic host cell. Effectors interfere with host signal transduction pathways to allow the internalization of pathogens and their survival and proliferation inside vacuoles. SteA is one of the few Salmonella effectors that are substrates of both type III secretion systems. Here, we used gene arrays and bioinformatics analysis to study the genetic response of human epithelial cells to SteA. We found that constitutive synthesis of SteA in HeLa cells leads to induction of genes related to extracellular matrix organization and regulation of cell proliferation and serine/threonine kinase signaling pathways. SteA also causes repression of genes related to immune processes and regulation of purine nucleotide synthesis and pathway-restricted SMAD protein phosphorylation. In addition, a cell biology approach revealed that epithelial cells expressing steA show altered cell morphology, and decreased cytotoxicity, cell–cell adhesion and migration.

  16. Methods for fabricating thin film III-V compound solar cell

    Science.gov (United States)

    Pan, Noren; Hillier, Glen; Vu, Duy Phach; Tatavarti, Rao; Youtsey, Christopher; McCallum, David; Martin, Genevieve

    2011-08-09

    The present invention utilizes epitaxial lift-off in which a sacrificial layer is included in the epitaxial growth between the substrate and a thin film III-V compound solar cell. To provide support for the thin film III-V compound solar cell in absence of the substrate, a backing layer is applied to a surface of the thin film III-V compound solar cell before it is separated from the substrate. To separate the thin film III-V compound solar cell from the substrate, the sacrificial layer is removed as part of the epitaxial lift-off. Once the substrate is separated from the thin film III-V compound solar cell, the substrate may then be reused in the formation of another thin film III-V compound solar cell.

  17. [The Malady of Emperor Frederick III. and Virchow's diagnostic role].

    Science.gov (United States)

    Sedivy, Roland

    2015-04-01

    Crownprince Frederick Wilhelm of Prussia was once the hope of the liberal movement in Germany. He embodied and lived a humanistic ideal based on the spirit of the enlightenment. Starting in January 1887 the passionate pipe smoker suffered on an unusual long hoarseness. A polyp of the vocal cord was diagnosed. Although this diagnosis seemed harmless, an odyssee was launched that made history. Rudolf Virchow-the foremost pathologist of that time-was involved in the following histological diagnosis. His role and that of the sprouting histopathology will be presented in this essay. PMID:25925224

  18. Interleukin-8 (IL-8) over-production and autocrine cell activation are key factors in monomethylarsonous acid [MMA(III)]-induced malignant transformation of urothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Escudero-Lourdes, C., E-mail: cescuder@uaslp.mx [Centro de Investigación y Estudios de Posgrado (CIEP), Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí (Mexico); Wu, T.; Camarillo, J.M.; Gandolfi, A.J. [Department of Pharmacology and Toxicology College of Pharmacy, University of Arizona. Tucson, AZ (United States)

    2012-01-01

    The association between chronic human exposure to arsenicals and bladder cancer development is well recognized; however, the underlying molecular mechanisms have not been fully determined. We propose that inflammatory responses can play a pathogenic role in arsenic-related bladder carcinogenesis. In previous studies, it was demonstrated that chronic exposure to 50 nM monomethylarsenous acid [MMA(III)] leads to malignant transformation of an immortalized model of urothelial cells (UROtsa), with only 3 mo of exposure necessary to trigger the transformation-related changes. In the three-month window of exposure, the cells over-expressed pro-inflammatory cytokines (IL-1β, IL-6 and IL-8), consistent with the sustained activation of NFKβ and AP1/c-jun, ERK2, and STAT3. IL-8 was over-expressed within hours after exposure to MMA(III), and sustained over-expression was observed during chronic exposure. In this study, we profiled IL-8 expression in UROtsa cells exposed to 50 nM MMA(III) for 1 to 5 mo. IL-8 expression was increased mainly in cells after 3 mo MMA(III) exposure, and its production was also found increased in tumors derived from these cells after heterotransplantation in SCID mice. UROtsa cells do express both receptors, CXCR1 and CXCR2, suggesting that autocrine cell activation could be important in cell transformation. Supporting this observation and consistent with IL-8 over-expression, CXCR1 internalization was significantly increased after three months of exposure to MMA(III). The expression of MMP-9, cyclin D1, bcl-2, and VGEF was significantly increased in cells exposed to MMA(III) for 3 mo, but these mitogen-activated kinases were significantly decreased after IL-8 gene silencing, together with a decrease in cell proliferation rate and in anchorage-independent colony formation. These results suggest a relevant role of IL-8 in MMA(III)-induced UROtsa cell transformation. -- Highlights: ► IL-8 is over-expressed in human MMA(III)-exposed urothelial

  19. Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Stage III Ovarian Cancer

    Science.gov (United States)

    2016-03-17

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  20. III-nitride core–shell nanowire arrayed solar cells

    International Nuclear Information System (INIS)

    A solar cell based on a hybrid nanowire–film architecture consisting of a vertically aligned array of InGaN/GaN multi-quantum well core–shell nanowires which are electrically connected by a coalesced p-InGaN canopy layer is demonstrated. This unique hybrid structure allows for standard planar device processing, solving a key challenge with nanowire device integration, while enabling various advantages by the nanowire absorbing region such as higher indium composition InGaN layers by elastic strain relief, more efficient carrier collection in thinner layers, and enhanced light trapping from nano-scale optical index changes. This hybrid structure is fabricated into working solar cells exhibiting photoresponse out to 2.1 eV and short-circuit current densities of ∼1 mA cm−2 under 1 sun AM1.5G. This proof-of-concept nanowire-based device demonstrates a route forward for high-efficiency III-nitride solar cells. (paper)

  1. Erlotinib Hydrochloride and Radiation Therapy in Stage III-IV Squamous Cell Cancer of the Head and Neck

    Science.gov (United States)

    2012-10-30

    Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity

  2. Cre Reporter System To Monitor the Translocation of Type III Secreted Proteins into Host Cells

    OpenAIRE

    Briones, Gabriel; Hofreuter, Dirk; Galán, Jorge E.

    2006-01-01

    Central to the study of type III secretion systems is the availability of reporter systems to monitor bacterial protein translocation into host cells. We report here the development of a bacteriophage P1 Cre recombinase-based system to monitor the translocation of bacterial proteins into mammalian cells. Bacteriophage P1 Cre recombinase fused to the secretion and translocation signals of Salmonella enterica serovar Typhimurium of the type III secreted protein SopE was secreted in a type III s...

  3. Histidine-rich glycoprotein does not interfere with interactions between antithrombin III and heparin-like compounds on vascular endothelial cells

    International Nuclear Information System (INIS)

    The role of histidine-rich glycoprotein in controlling heparin-like compounds on the endothelial cell surface is still unclear. The effects of this heparin-neutralizing protein on the interaction between antithrombin III and cultured porcine aortic endothelial cells were examined. Displacement of 125I-labeled antithrombin III specifically bound to endothelial cells by unlabeled histidine-rich glycoprotein was much less potent than that by unlabeled antithrombin III. One hundred-fold molar excess of histidine-rich glycoprotein displaced specific 125I-antithrombin III binding only by 20%. Furthermore, the endothelial cell-mediated acceleration of thrombin inactivation by antithrombin III was diminished by protamine sulfate, but was not affected by histidine-rich glycoprotein even at a histidine-rich glycoprotein/antithrombin III molar ratio of approximately 7:1. These data indicate that histidine-rich glycoprotein does not interfere with the interaction of endothelial cell heparin-like compounds with antithrombin III. Thus, it may not play an important role in the modulation of anticoagulant activity of endothelial cells in vivo, suggesting that the commonly accepted view of the probable function of this protein is erroneous

  4. The role of Ia molecules in the activation of T lymphocytes. III. Antigen-specific, Ia-restricted, interleukin 2-producing T cell hybridomas with detectable affinity for the restricting I-A molecule

    OpenAIRE

    1983-01-01

    Antigen-specific I region-restricted, interleukin 2-producing T cell hybridomas were produced by fusing GAT-specific T cell blasts with BW5147. Two antigen-specific phenotypes were identified, one autoreactive and one nonautoreactive. All of the antigen-specific and autoreactive clones were H-2 restricted, mapping to the IA subregion by genetic analysis and monoclonal antibody inhibition. Both the antigen- specific and autoreactive stimulation are the property of a single cell and required no...

  5. Role of cytochrome B in the processing of the subunits of complex III in the yeast mitochondria

    International Nuclear Information System (INIS)

    The work described in this dissertation deals with the effect of cytochrome b on the biogenesis and assembly of the subunits of complex III in the mitochondrial membrane of the yeast Saccharomyces cerevisiae. The cytochrome b-mutants (Box mutants of S. cerevisiae form an excellent system to study such a role of cytochome B. The amounts of cytochrome c1 in the mitochrondria, as determined both spectroscopically and immunologically, were not affected by the absence of cytochrome b. Pulse labelling of the cells with (35S) methionine in the presence of CCCP showed the accumulation of the precursors to the core protein I and the iron-sulfur protein in similar amounts in the mutant Box 6-2 and the wild type cells. Synthesis of the iron sulfur protein and the cytochrome c1 by in vitro translation of mRNA isolated from wild type and mutant Box 6-2 in a rabbit reticulocyte lysate system, also confirmed that the synthesis of the nuclear encoded subunits was not affected in the mutants. Pulse labeling of the cells in the absence of CCCP and subsequent chase with cold methionine, however, showed much less of the mature subunits of core protein I and the iron-sulfur protein in the mitochrondria of the mutant cells relative to the wild type. These results indicate that cytochrome b is necessary for the proper processing of certain subunits of complex III

  6. Role of cytochrome B in the processing of the subunits of complex III in the yeast mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Sen, K.G.

    1986-01-01

    The work described in this dissertation deals with the effect of cytochrome b on the biogenesis and assembly of the subunits of complex III in the mitochondrial membrane of the yeast Saccharomyces cerevisiae. The cytochrome b-mutants (Box mutants of S. cerevisiae form an excellent system to study such a role of cytochome B. The amounts of cytochrome c/sub 1/ in the mitochrondria, as determined both spectroscopically and immunologically, were not affected by the absence of cytochrome b. Pulse labelling of the cells with (/sup 35/S) methionine in the presence of CCCP showed the accumulation of the precursors to the core protein I and the iron-sulfur protein in similar amounts in the mutant Box 6-2 and the wild type cells. Synthesis of the iron sulfur protein and the cytochrome c/sub 1/ by in vitro translation of mRNA isolated from wild type and mutant Box 6-2 in a rabbit reticulocyte lysate system, also confirmed that the synthesis of the nuclear encoded subunits was not affected in the mutants. Pulse labeling of the cells in the absence of CCCP and subsequent chase with cold methionine, however, showed much less of the mature subunits of core protein I and the iron-sulfur protein in the mitochrondria of the mutant cells relative to the wild type. These results indicate that cytochrome b is necessary for the proper processing of certain subunits of complex III.

  7. A Possible Anticancer Agent, Type III Interferon, Activates Cell Death Pathways and Produces Antitumor Effects

    Directory of Open Access Journals (Sweden)

    Masatoshi Tagawa

    2011-01-01

    Full Text Available Recently identified interleukin-28 and -29 belong to a novel type III interferon (IFN family, which could have distinct biological properties from type I and II IFNs. Type I IFNs, IFN-α/β, have been clinically applied for treating a certain kind of malignancies for over 30 years, but a wide range of the adverse effects hampered the further clinical applications. Type III IFNs, IFN-λs, have similar signaling pathways as IFN-α/β and inhibits proliferation of tumor cells through cell cycle arrest or apoptosis. Restricted patterns of type III IFN receptor expression in contrast to ubiquitously expressed IFN-α/β receptors suggest that type III IFNs have limited cytotoxicity to normal cells and can be a possible anticancer agent. In this paper, we summarize the current knowledge on the IFN-λs-mediated tumor cell death and discuss the functional difference between type I and III IFNs.

  8. Impact of Neoadjuvant Radiation on Survival in Stage III Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: The role of surgery in Stage III non-small-cell lung cancer (NSCLC) is controversial. This study was undertaken to assess the impact of neoadjuvant radiation therapy for Stage III NSCLC. Methods and Materials: This was a retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database that included patients who were 18 years and older with NSCLC classified as Stage III and who underwent definitive therapy from 1988 to 2004. Patients were characterized by type of treatment received. Survival functions were estimated by the Kaplan-Meier method, and Cox regression model was used to analyze trends in overall (OS) and cause-specific survival (CSS). Results: A total of 48,131 patients were selected, with a median follow-up of 10 months (range, 0-203 months). By type of treatment, the 3-year OS was 10% with radiation therapy (RT), 37% with surgery (S), 34% with surgery and postoperative radiation (S-RT), and 45% with neoadjuvant radiation followed by surgery (Neo-RT) (p = 0.0001). Multivariable Cox model identified sex, race, laterality, T stage, N stage, and type of treatment as factors affecting survival. Estimated hazard ratios (HR) adjusted for other variables in regression model showed the types of treatment: S (HR, 1.3; 95% confidence interval [CI], 1.2-1.4), S-RT (HR, 1.2; 95% CI, 1.1-1.3), and RT (HR, 2.3; 95% CI, 2.15-2.53) were associated with significantly worse overall survival when compared with Neo-RT (p = 0.0001). Conclusion: This population based study demonstrates that patients with Stage III NSCLC receiving Neo-RT had significantly improved overall survival when compared with other treatment groups.

  9. An important role for type III interferon (IFN-lambda/IL-28) in TLR-induced antiviral activity

    DEFF Research Database (Denmark)

    Ank, Nina; Iversen, Marie B; Bartholdy, Christina;

    2008-01-01

    Type III IFNs (IFN-lambda/IL-28/29) are cytokines with type I IFN-like antiviral activities, which remain poorly characterized. We herein show that most cell types expressed both types I and III IFNs after TLR stimulation or virus infection, whereas the ability of cells to respond to IFN-lambda w...

  10. ERα mediates alcohol-induced deregulation of Pol III genes in breast cancer cells

    OpenAIRE

    Zhang, Qingsong; Jin, Jian; Zhong, Qian; Yu, Xiaoli; Levy, Daniel; Zhong, Shuping

    2012-01-01

    The association of alcohol consumption and breast cancer is more pronounced in cases that are positive for estrogen receptor (ER+) than in cases that are negative (ER−). Its mechanism remains to be determined. Deregulation of RNA polymerase III (Pol III) transcription enhances cellular tRNAs and 5S rRNA production, increasing translational capacity to promote cell transformation and tumor formation. Here, we report that alcohol increases Pol III gene transcription in both normal and cancer br...

  11. Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma

    Science.gov (United States)

    2016-05-02

    Advanced Pleural Malignant Mesothelioma; HLA-A*0201 Positive Cells Present; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pleural Malignant Mesothelioma; Stage III Pleural Mesothelioma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pleural Mesothelioma

  12. TGF-{beta}-stimulated aberrant expression of class III {beta}-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Eun Jee [Department of Ophthalmology, National Health Insurance Corporation Ilsan Hospital, Gyeonggi-do (Korea, Republic of); Chun, Ji Na; Jung, Sun-Ah [Konyang University Myunggok Medical Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of); Cho, Jin Won [Department of Biology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Lee, Joon H., E-mail: joonhlee@konyang.ac.kr [Konyang University Myunggok Medical Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer TGF-{beta} induces aberrant expression of {beta}III in RPE cells via the ERK pathway. Black-Right-Pointing-Pointer TGF-{beta} increases O-GlcNAc modification of {beta}III in RPE cells. Black-Right-Pointing-Pointer Mature RPE cells have the capacity to express a neuron-associated gene by TGF-{beta}. -- Abstract: The class III {beta}-tubulin isotype ({beta}{sub III}) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III {beta}-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology in pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-{beta} (TGF-{beta}) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-{beta} on the aberrant expression of class III {beta}-tubulin and the intracellular signaling pathway mediating these changes. TGF-{beta}-induced aberrant expression and O-linked-{beta}-N-acetylglucosamine (O-GlcNac) modification of class III {beta}-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-{beta} also stimulated phosphorylation of ERK. TGF-{beta}-induced aberrant expression of class III {beta}-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-{beta} stimulated aberrant expression of class III {beta}-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-{beta} stimulation and provide useful information

  13. TGF-β-stimulated aberrant expression of class III β-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells

    International Nuclear Information System (INIS)

    Highlights: ► TGF-β induces aberrant expression of βIII in RPE cells via the ERK pathway. ► TGF-β increases O-GlcNAc modification of βIII in RPE cells. ► Mature RPE cells have the capacity to express a neuron-associated gene by TGF-β. -- Abstract: The class III β-tubulin isotype (βIII) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III β-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology in pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-β (TGF-β) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-β on the aberrant expression of class III β-tubulin and the intracellular signaling pathway mediating these changes. TGF-β-induced aberrant expression and O-linked-β-N-acetylglucosamine (O-GlcNac) modification of class III β-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-β also stimulated phosphorylation of ERK. TGF-β-induced aberrant expression of class III β-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-β stimulated aberrant expression of class III β-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-β stimulation and provide useful information towards understanding the pathogenesis of proliferative vitreoretinal diseases.

  14. Activation of type III interferon genes by pathogenic bacteria in infected epithelial cells and mouse placenta.

    Directory of Open Access Journals (Sweden)

    Hélène Bierne

    Full Text Available Bacterial infections trigger the expression of type I and II interferon genes but little is known about their effect on type III interferon (IFN-λ genes, whose products play important roles in epithelial innate immunity against viruses. Here, we studied the expression of IFN-λ genes in cultured human epithelial cells infected with different pathogenic bacteria and in the mouse placenta infected with Listeria monocytogenes. We first showed that in intestinal LoVo cells, induction of IFN-λ genes by L. monocytogenes required bacterial entry and increased further during the bacterial intracellular phase of infection. Other Gram-positive bacteria, Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis, also induced IFN-λ genes when internalized by LoVo cells. In contrast, Gram-negative bacteria Salmonella enterica serovar Typhimurium, Shigella flexneri and Chlamydia trachomatis did not substantially induce IFN-λ. We also found that IFN-λ genes were up-regulated in A549 lung epithelial cells infected with Mycobacterium tuberculosis and in HepG2 hepatocytes and BeWo trophoblastic cells infected with L. monocytogenes. In a humanized mouse line permissive to fetoplacental listeriosis, IFN-λ2/λ3 mRNA levels were enhanced in placentas infected with L. monocytogenes. In addition, the feto-placental tissue was responsive to IFN-λ2. Together, these results suggest that IFN-λ may be an important modulator of the immune response to Gram-positive intracellular bacteria in epithelial tissues.

  15. Induction of polyclonal B cell activation and differentiation by the AIDS retrovirus (HTLV-III/LAV)

    International Nuclear Information System (INIS)

    The immune systems of individuals infected with HTLV-III/LAV are characterized by a profound defect in cellular immunity together with paradoxical polyclonal B cell activation. The present study examined the direct effects of HTLV-III/LAV on B lymphocytes. Peripheral blood B cells from healthy donors were incubated with a variety of HTLV-III/LAV isolates for 1 h and 3H-thymidine incorporation was measured at multiple time points. Responses ranged from 9000-28,000 cpm and peaked on day 4. This B cell activation was not enhanced by the addition of interleukin-2 to culture, was not synergistic with Staphylococcus aureus Cowan I, was not modulated by the addition of T lymphocytes to culture, and was not associated with B cell transformation. Supernatant Ig could first be detected in virus-activated cultures at day 4, plateaued by day 8, and yielded a mean of 12,500 ng IgG+IgM/ml/50,000 B cells. Thus, HTLV-III/LAV is a potent T cell independent B cell mitogen capable of inducing B cell activation, proliferation, and differentiation comparable in magnitude to that of the most potent B cell activators. This biological property of HTLV-III/LAV may help explain the profound polyclonal B cell activation observed in patients with AIDS and may provide investigators with another probe for investigating the mechanisms of B cell activation

  16. EGFR and its mutant EGFRvIII as modulators of tumor cell radiosensitivity

    International Nuclear Information System (INIS)

    Purpose: Exposure of human carcinoma and malignant glioma cells to ionizing radiation (IR)activates EGFR,which as a consequence mediates a cytoprotective response. We have demonstrated that expression of a dominant negative mutant, EGFR-CD533 disrupts this cytoprotective response, resulting in significant radiosensitization. During studies of in vivo radiosensitization with intratumoral delivery of the Adenovirus (Ad) vector, Ad-EGFR-CD533, it became apparent that xenografts from human carcinoma and malignant glioma cells invariably expressed the constitutively active EGFR mutant, EGFRvIII. This mutant EGFRvIII is frequently found in vivo in glioblastoma, breast, prostate, lung and ovarian carcinoma, but does not appear to be expressed in tumor cells under in vitro conditions. The functional consequences of EGFRvIII expression on tumor cell radiation responses are currently unknown. We have therefore investigated in a transient transfection cell system the responses of EGFRvIII and downstream signal transduction pathways to IR. In addition, the capacity of EGFR-CD533 to disrupt the function of EGFRvIII was tested. Materials and Methods: The MDA-MB-231, U-87 MG and U-373 MG cell lines were established as tumors and then intratumorally transduced with Ad-EGFR-CD533 or Ad-LacZ (control vector). The transduction efficiency was > 40% in MDA-MB-231 tumors and reached > 70% in the glioma xenografts. Radiosensitivity was measured by ex vivo colony formation and growth delay assays. The functional consequences of EGFRvIII expression on cellular IR responses were studied in transiently transfected Chinese hamster ovary (CHO) cells because tumor cells do not express EGFRvIII in vitro. Transfection with null vectors and vectors encoding either EGFRvIII or EGFR were performed and similar protein expression levels were verified by Western blot analyses. Results: The radiosensitivity of Ad-EGFR-CD533 transduced tumors was significantly increased compared with Ad-LacZ transduced

  17. High Efficiency Quantum Dot III-V Multijunction Solar Cell for Space Power Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We are proposing to utilize quantum dots to develop a super high-efficiency multijunction III-V solar cell for space. In metamorphic triple junction space solar...

  18. Cell-internal structure of hexagonal polytypes in III-V semiconductors

    International Nuclear Information System (INIS)

    Semiconductor nanowires (NW) play a key role in future nanotechnology. Despite of the zinc-blende (3C) bulk structure III-V nanowires exhibit a mixture of wurtzite (2H) and zinc-blende (3C) layers. With better control over the crystal structure it became possible to grow not only pure 3C or 2H layers but also small segments of the hexagonal 4H polytype. This offers a new degree of freedom for NW device design, like polytypic superlattices. Therefore, we investigate the structural properties of the different polytypes (3C,2H,4H,6H). We perform ab-initio calculations within the density functional theory for different III-V compounds (GaAs, InAs, InP, InSb). The structural properties are calculated versus the hexagonality of the polytypes using the LDA exchange-correlation functional. Experiment (XRD) and theory show that hexagonal bilayers tends to increase the layer thickness along the c-axis, while simultaneously reduce the in-plane distances. Thereby, the change of the lattice parameters scales linearly with the hexagonality of the polytype. Overall an increase in the relative aspect ratio of the 2H structure by 0.6% compared to the ideal structure is observed. It turns out that only a careful treatment of the cell-internal parameters could guarantee a correct description of the structural properties.

  19. Impact of Eu(III) on mammalian cells as a function of its speciation

    Energy Technology Data Exchange (ETDEWEB)

    Sachs, Susanne; Heller, Anne; Geipel, Gerhard; Bernhard, Gert [Helmholtz-Zentrum Dresden-Rossendorf, Institute of Resource Ecology, Bautzner Landstr. 400, 01328 Dresden (Germany)

    2014-07-01

    In the case of the accidental release of long-lived radionuclides, e.g., actinides, into the environment, knowledge of their behavior in bio-systems is necessary to asses and to prevent radiological and chemical induced adverse health effects. This includes knowledge of the bioavailability and chemo-/radio-toxicity of these elements for/onto cells, which are governed to a large extent by their speciation [1,2]. In order to gain a better process understanding, we study the interaction of trivalent actinides/lanthanides with mammalian cells on a cellular level combining biochemical and analytical methods. Results of these studies can contribute to the estimation of low dose effects and the development of new decontamination strategies. The cellular tolerance of FaDu cells (human squamous cell carcinoma cell line) toward Eu(III) as an analog for trivalent actinides as well as its uptake into the cells has been studied as a function of the Eu(III) concentration and nutrient composition. To differentiate between chemo-toxic and radio-toxic effects of Eu(III), {sup 152}Eu (β{sup -}, ε) was applied as radioactive tracer besides europium with natural isotope composition. The Eu(III) speciation in the cell culture media has been investigated by time-resolved laser-induced fluorescence spectroscopy as well as by solubility studies in combination with ultrafiltration, ultracentrifugation, cation and anion analysis. These results are used to correlate cytotoxicity and uptake of Eu(III) on/into the cells with its chemical speciation in the nutrient. Presently, we are studying the interaction of Eu(III) with NRK-52E cells (rat kidney epithelial-like cells). The results of these studies will be discussed and compared to those obtained with FaDu cells. From the studies with FaDu cells it was concluded that the Eu(III) cytotoxicity onto these cells depends on the Eu(III) concentration and is influenced by its chemical speciation. This was also reported, for instance, for the

  20. File list: Pol.NoD.50.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.NoD.50.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III No desc...ription http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.NoD.50.RNA_Polymerase_III.AllCell.bed ...

  1. File list: Pol.NoD.50.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.NoD.50.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III No des...cription http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.NoD.50.RNA_polymerase_III.AllCell.bed ...

  2. File list: Pol.NoD.20.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.NoD.20.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III No des...cription http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.NoD.20.RNA_polymerase_III.AllCell.bed ...

  3. File list: Pol.NoD.05.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.NoD.05.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III No des...cription http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.NoD.05.RNA_polymerase_III.AllCell.bed ...

  4. File list: Pol.NoD.10.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.NoD.10.RNA_polymerase_III.AllCell hg19 RNA polymerase RNA polymerase III No des...cription http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.NoD.10.RNA_polymerase_III.AllCell.bed ...

  5. Cytotoxic and genotoxic potential of Cr(VI), Cr(III)-nitrate and Cr(III)-EDTA complex in human hepatoma (HepG2) cells.

    Science.gov (United States)

    Novotnik, Breda; Ščančar, Janez; Milačič, Radmila; Filipič, Metka; Žegura, Bojana

    2016-07-01

    Chromium (Cr) and ethylenediaminetetraacetate (EDTA) are common environmental pollutants and can be present in high concentrations in surface waters at the same time. Therefore, chelation of Cr with EDTA can occur and thereby stable Cr(III)-EDTA complex is formed. Since there are no literature data on Cr(III)-EDTA toxicity, the aim of our work was to evaluate and compare Cr(III)-EDTA cytotoxic and genotoxic activity with those of Cr(VI) and Cr(III)-nitrate in human hepatoma (HepG2) cell line. First the effect of Cr(VI), Cr(III)-nitrate and Cr(III)-EDTA on cell viability was studied in the concentration range from 0.04 μg mL(-1) to 25 μg mL(-1) after 24 h exposure. Further the influence of non-cytotoxic concentrations of Cr(VI), Cr(III)-nitrate and Cr(III)-EDTA on DNA damage and genomic stability was determined with the comet assay and cytokinesis block micronucleus cytome assay, respectively. Cell viability was decreased only by Cr(VI) at concentrations above 1.0 μg mL(-1). Cr(VI) at ≥0.2 μg mL(-1) and Cr(III) at ≥1.0 μg mL(-1) induced DNA damage, while after Cr(III)-EDTA exposure no formation DNA strand breaks was determined. Statistically significant formation of micronuclei was induced only by Cr(VI) at ≥0.2 μg mL(-1), while no influence on the frequency of nuclear buds nor nucleoplasmic bridges was observed at any exposure. This study provides the first evidence that Cr(III)-EDTA did not induce DNA damage and had no influence on the genomic stability of HepG2 cells. PMID:27043378

  6. Role of cancer stem cells in hepatocarcinogenesis

    OpenAIRE

    Wang, Bo; Jacob, Samson T.

    2011-01-01

    There has been considerable interest in cancer stem cells (CSCs) among cancer biologists and clinicians, most likely because of their role in the heterogeneity of cancer and their potential application in cancer therapeutics. Recent studies suggest that CSCs play a key role in liver carcinogenesis. A small subpopulation of cancer cells with CSC properties has been identified and characterized from hepatocellular carcinoma (HCC) cell lines, animal models and human primary HCCs. Considering the...

  7. The role of the enzyme alpha-amylase in binding of An(III)/Ln(III) by oral ingestion

    International Nuclear Information System (INIS)

    In case of incorporation, radionuclides represent a serious health risk to humans due to their (radio-)toxicity. Thus, the determination of their speciation and transport on a molecular level is crucial for the understanding of the transport, metabolism, deposition and elimination in the human organisms. In case of oral ingestion of contaminated food or radioactive substances the first contact medium in the mouth is the aqueous bio-fluid saliva which contains inorganic ions (mainly Na+, K+, Ca2+, Cl-, CO32-, PO43-) and numerous biomolecules, mainly proteins. One of the major proteins in saliva is the digestive enzyme α-amylase which catalyzes the hydrolysis of the α-1,4 glycosidic linkages of polysaccharides like starch or glycogen. [1] In this study the speciation of curium(III) and europium(III) in saliva as the first contact medium at oral incorporation was investigated with time-resolved laser-induced fluorescence spectroscopy (TRLFS). For TRLFS measurements, fresh saliva samples from human sources have been spiked in vitro with Eu(III) or Cm(III). The identification of the dominant species was achieved by a comparison of the spectroscopic data with reference spectra obtained from synthetic saliva and the main single components of the bio-fluid. In the pH range from 6.8 to 7.4 similar spectra were obtained. With respect to reference data, the spectra indicate the formation of a ternary metal complex containing phosphate and carbonate anions and, in addition, a coordination of organic matter, namely α-amylase, to the central metal cation is suggested. To get more information about the binding behavior of α-amylase various investigations with Eu(III) as inactive analog for An(III) were carried out with porcine pancreatic α-amylase (PPA) which serves as model system for various α-amylase species. Sorption experiments showed a high affinity of Eu(III) to α-amylase in a wide pH range, namely between pH 4 and 8. The analysis of binding isotherms demonstrated

  8. Analysis of novel silicon and III-V solar cells by simulation and experiment; Analyse neuartiger Silizium- und III-V-Solarzellen mittels Simulation und Experiment

    Energy Technology Data Exchange (ETDEWEB)

    Hermle, Martin

    2008-11-27

    This work presents various simulation studies of silicon and III-V solar cells. For standard silicon solar cells, one of the critical parameters to obtain good performance, is the rear side recombination velocity. The optical and electrical differences of the different cell structures were determined. The optical differences and the effective recombination velocity Sback of the different rear side structures for 1 Ohmcm material were extracted. Beside standard silicon solar cells, back junction silicon solar cells were investigated. Especially the influence of the front surface field and the electrical shading due to the rear side, was investigated. In the last two chapters, III-V solar cells were analysed. For the simulation of III-V multi-junction solar cells, the simulation of the tunneldiode is the basic prerequisite. In this work, the numerical calibration of an GaAs tunneldiode was achieved by using an non-local tunnel model. Using this model, it was possible to successfully simulate a III-V tandem solar cell. The last chapter deals with an optimization of the III-V 3-junction cell for space applications. Especially the influence of the GaAs middle cell was investigated. Due to structural changes, the end-of-life efficiency was drastically increased.

  9. Improved Antileishmanial Activity of Dppz through Complexation with Antimony(III and Bismuth(III: Investigation of the Role of the Metal

    Directory of Open Access Journals (Sweden)

    Cynthia Demicheli

    2012-10-01

    Full Text Available Two novel trivalent antimony(III and bismuth(III complexes with the nitrogen-donor heterocyclic ligand dipyrido[3,2-a:2',3'-c]phenazine (dppz were synthesized and characterized as [Sb(dppzCl3]∙H2O∙CH3OH and [Bi(dppzCl3]. The crystal structure of Sb(III complex was determined by X-ray crystallography. These complexes were evaluated for their activity against the promastigote form of Sb(III-sensitive and –resistant Leishmania infantum chagasi and Leishmania amazonensis strains. Both complexes were more effective than dppz alone in inhibiting the growth of Leishmania promastigotes and were at least 77 and 2,400 times more active than potassium antimonyl tartrate in Sb(III-sensitive and -resistant Leishmania, respectively. The cytotoxicity of dppz and its complexes against mouse peritoneal macrophages occurred at dppz concentrations at least 6-fold greater than those found to be active against Leishmania promastigotes.To investigate the role of the metal in the improved antileishmanial activity of dppz, the activity of the Sb(III complex was compared between the Sb-resistant mutants and their respective parental sensitive strains. The lack of cross-resistance to the Sb(III-dppz complex together with the much lower activity of antimonyl tartrate, SbCl3 and BiCl3 strongly support the model that the metal is not active by itself but improves the activity of dppz through complexation.

  10. Head and Neck Squamous Cell Carcinomas Do Not Express EGFRvIII

    International Nuclear Information System (INIS)

    Purpose: To assess the prevalence of EGFRvIII, a specific variant of EGFR (epidermal growth factor receptor), in 3 well-defined cohorts of head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Immunohistochemistry for the specific detection of EGFRvIII using the L8A4 antibody was optimized on formalin-fixed, paraffin-embedded tissue using glioblastoma tissue. It was compared with EGFR and EGFRvIII RNA expression using a specific reverse transcription–polymerase chain reaction also optimized for formalin-fixed, paraffin-embedded tissue. Tissue microarrays including 531 HNSCCs of various stages with complete clinicopathologic and follow-up data were tested for the presence of EGFRvIII. Results: None of the 531 cases showed EGFRvIII protein expression. Using an immunohistochemistry protocol reported by others revealed cytoplasmic staining in 8% of cases. Reverse transcription–polymerase chain reaction for the EGFRvIII transcript of the 28 highest cytoplasmic staining cases, as well as 69 negative cases, did not show expression in any of the tested cases, suggesting aspecific staining by a nonoptimal protocol. Conclusions: The EGFRvIII mutation is not present in HNSCC. Therefore, EGFRvIII does not influence treatment response in HNSCC and is not a usable clinical prognostic marker

  11. Head and Neck Squamous Cell Carcinomas Do Not Express EGFRvIII

    Energy Technology Data Exchange (ETDEWEB)

    Melchers, Lieuwe J., E-mail: l.j.melchers@umcg.nl [Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Clausen, Martijn J.A.M. [Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Mastik, Mirjam F. [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Slagter-Menkema, Lorian [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Laan, Bernard F.A.M. van der [Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Wal, Jacqueline E. van der; Vegt, Bert van der [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Roodenburg, Jan L.N. [Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Schuuring, Ed [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands)

    2014-10-01

    Purpose: To assess the prevalence of EGFRvIII, a specific variant of EGFR (epidermal growth factor receptor), in 3 well-defined cohorts of head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Immunohistochemistry for the specific detection of EGFRvIII using the L8A4 antibody was optimized on formalin-fixed, paraffin-embedded tissue using glioblastoma tissue. It was compared with EGFR and EGFRvIII RNA expression using a specific reverse transcription–polymerase chain reaction also optimized for formalin-fixed, paraffin-embedded tissue. Tissue microarrays including 531 HNSCCs of various stages with complete clinicopathologic and follow-up data were tested for the presence of EGFRvIII. Results: None of the 531 cases showed EGFRvIII protein expression. Using an immunohistochemistry protocol reported by others revealed cytoplasmic staining in 8% of cases. Reverse transcription–polymerase chain reaction for the EGFRvIII transcript of the 28 highest cytoplasmic staining cases, as well as 69 negative cases, did not show expression in any of the tested cases, suggesting aspecific staining by a nonoptimal protocol. Conclusions: The EGFRvIII mutation is not present in HNSCC. Therefore, EGFRvIII does not influence treatment response in HNSCC and is not a usable clinical prognostic marker.

  12. Isotherm kinetics of Cr(III) removal by non-viable cells of Acinetobacter haemolyticus.

    Science.gov (United States)

    Yahya, Siti Khairunnisa; Zakaria, Zainul Akmar; Samin, Jefri; Raj, A S Santhana; Ahmad, Wan Azlina

    2012-06-01

    The potential use of non-viable biomass of a Gram negative bacterium i.e. Acinetobacter haemolyticus to remove Cr(III) species from aqueous environment was investigated. Highest Cr(III) removal of 198.80 mg g(-1) was obtained at pH 5, biomass dosage of 15 mg cell dry weight, initial Cr(III) of 100 mg L(-1) and 30 min of contact time. The Langmuir and Freundlich models fit the experimental data (R(2)>0.95) while the kinetic data was best described using the pseudo second-order kinetic model (R(2)>0.99). Cr(III) was successfully recovered from the bacterial biomass using either 1M of CH(3)COOH, HNO(3) or H(2)SO(4) with 90% recovery. TEM and FTIR suggested the involvement of amine, carboxyl, hydroxyl and phosphate groups during the biosorption of Cr(III) onto the cell surface of A. haemolyticus. A. haemolyticus was also capable to remove 79.87 mg g(-1) Cr(III) (around 22.75%) from raw leather tanning wastewater. This study demonstrates the potential of using A. haemolyticus as biosorbent to remove Cr(III) from both synthetic and industrial wastewater. PMID:22398363

  13. Indium Zinc Oxide Mediated Wafer Bonding for III-V/Si Tandem Solar Cells

    Energy Technology Data Exchange (ETDEWEB)

    Tamboli, Adele C.; Essig, Stephanie; Horowitz, Kelsey A. W.; Woodhouse, Michael; van Hest, Maikel F. A. M.; Norman, Andrew G.; Steiner, Myles A.; Stradins, Paul

    2015-06-14

    Silicon-based tandem solar cells are desirable as a high efficiency, economically viable approach to one sun or low concentration photovoltaics. We present an approach to wafer bonded III-V/Si solar cells using amorphous indium zinc oxide (IZO) as an interlayer. We investigate the impact of a heavily doped III-V contact layer on the electrical and optical properties of bonded test samples, including the predicted impact on tandem cell performance. We present economic modeling which indicates that the path to commercial viability for bonded cells includes developing low-cost III-V growth and reducing constraints on material smoothness. If these challenges can be surmounted, bonded tandems on Si can be cost-competitive with incumbent PV technologies, especially in low concentration, single axis tracking systems.

  14. Self-assembled Targeting of Cancer Cells by Iron(III)-doped, Silica Nanoparticles

    OpenAIRE

    Mitchell, K.K. Pohaku; Sandoval, S.; Cortes-Mateos, M. J.; Alfaro, J.G.; Kummel, A. C.; Trogler, W.C.

    2014-01-01

    Iron(III)-doped silica nanoshells are shown to possess an in vitro cell-receptor mediated targeting functionality for endocytosis. Compared to plain silica nanoparticles, iron enriched ones are shown to be target-specific, a property that makes them potentially better vehicles for applications, such as drug delivery and tumor imaging, by making them more selective and thereby reducing the nanoparticle dose. Iron(III) in the nanoshells can interact with endogenous transferrin, a serum protein ...

  15. Self-assembled targeting of cancer cells by iron(iii)-doped, silica nanoparticles

    OpenAIRE

    Mitchell, KKP; Sandoval, S.; Cortes-Mateos, MJ; Alfaro, JG; Kummel, AC; Trogler, WC

    2014-01-01

    © the Partner Organisations 2014. Iron(iii)-doped silica nanoshells are shown to possess an in vitro cell-receptor mediated targeting functionality for endocytosis. Compared to plain silica nanoparticles, iron enriched ones are shown to be target-specific, a property that makes them potentially better vehicles for applications, such as drug delivery and tumor imaging, by making them more selective and thereby reducing the nanoparticle dose. Iron(iii) in the nanoshells can interact with endoge...

  16. The role of molecular oxygen in the iron(III)-promoted oxidative dehydrogenation of amines.

    Science.gov (United States)

    Saucedo-Vázquez, Juan Pablo; Kroneck, Peter M H; Sosa-Torres, Martha Elena

    2015-03-28

    A mechanistic study is presented of the oxidative dehydrogenation of the iron(III) complex [Fe(III)L(3)](3+), 1, (L(3) = 1,9-bis(2'-pyridyl)-5-[(ethoxy-2''-pyridyl)methyl]-2,5,8-triazanonane) in ethanol in the presence of molecular oxygen. The product of the reaction was identified by NMR spectroscopy and X-ray crystallography as the identical monoimine complex [Fe(II)L(4)](2+), 2, (L(4) = 1,9-bis(2'-pyridyl)-5-[(ethoxy-2''-pyridyl)methyl]-2,5,8-triazanon-1-ene) also formed under an inert nitrogen atmosphere. Molecular oxygen is an active player in the oxidative dehydrogenation of iron(III) complex 1. Reduced oxygen species, e.g., superoxide, (O2˙(-)) and peroxide (O2(2-)), are formed and undergo single electron transfer reactions with ligand-based radical intermediates. The experimental rate law can be described by the third order rate equation, -d[(Fe(III)L(3))(3+)]/dt = kOD[(Fe(III)L(3))(3+)][EtO(-)][O2], with kOD = 3.80 ± 0.09 × 10(7) M(-2) s(-1) (60 °C, μ = 0.01 M). The reduction O2 → O2˙(-) represents the rate determining step, with superoxide becoming further reduced to peroxide as shown by a coupled heme catalase assay. In an independent study, with H2O2, replacing O2 as the oxidant, the experimental rate law depended on [H2O2]: -d[(Fe(III)L(3))(3+)]/dt = kH2O2[(Fe(III)L(3))(3+)][H2O2]), with kH2O2 = 6.25 ± 0.02 × 10(-3) M(-1) s(-1). In contrast to the reaction performed under N2, no kinetic isotope effect (KIE) or general base catalysis was found for the reaction of iron(III) complex 1 with O2. Under N2, two consecutive one-electron oxidation steps of the ligand coupled to proton removal produced the iron(II)-monoimine complex [Fe(II)L(4)](2+) and the iron(II)-amine complex [Fe(II)L(3)](2+) in a 1 : 1 ratio (disproportionation), with the amine deprotonation being the rate determining step. Notably, the reaction is almost one order of magnitude faster in the presence of O2, with kEtO(-) = 3.02 ± 0.09 × 10(5) M(-1) s(-1) (O2) compared to k

  17. The role of the enzyme alpha-amylase in binding of An(III)/Ln(III) by oral ingestion

    Energy Technology Data Exchange (ETDEWEB)

    Barkleit, A.; Bernhard, G. [Institute of Resource Ecology, Helmholtz-Zentrum Dresden-Rossendorf, P.O. Box 510119, 01314 Dresden (Germany); Division of Radiochemistry and Resource Ecology, Technische Universitaet Dresden, 01062 Dresden (Germany); Heller, A. [Institute of Resource Ecology, Helmholtz-Zentrum Dresden-Rossendorf, P.O. Box 510119, 01314 Dresden (Germany)

    2014-07-01

    In case of incorporation, radionuclides represent a serious health risk to humans due to their (radio-)toxicity. Thus, the determination of their speciation and transport on a molecular level is crucial for the understanding of the transport, metabolism, deposition and elimination in the human organisms. In case of oral ingestion of contaminated food or radioactive substances the first contact medium in the mouth is the aqueous bio-fluid saliva which contains inorganic ions (mainly Na{sup +}, K{sup +}, Ca{sup 2+}, Cl{sup -}, CO{sub 3}{sup 2-}, PO{sub 4}{sup 3-}) and numerous biomolecules, mainly proteins. One of the major proteins in saliva is the digestive enzyme α-amylase which catalyzes the hydrolysis of the α-1,4 glycosidic linkages of polysaccharides like starch or glycogen. [1] In this study the speciation of curium(III) and europium(III) in saliva as the first contact medium at oral incorporation was investigated with time-resolved laser-induced fluorescence spectroscopy (TRLFS). For TRLFS measurements, fresh saliva samples from human sources have been spiked in vitro with Eu(III) or Cm(III). The identification of the dominant species was achieved by a comparison of the spectroscopic data with reference spectra obtained from synthetic saliva and the main single components of the bio-fluid. In the pH range from 6.8 to 7.4 similar spectra were obtained. With respect to reference data, the spectra indicate the formation of a ternary metal complex containing phosphate and carbonate anions and, in addition, a coordination of organic matter, namely α-amylase, to the central metal cation is suggested. To get more information about the binding behavior of α-amylase various investigations with Eu(III) as inactive analog for An(III) were carried out with porcine pancreatic α-amylase (PPA) which serves as model system for various α-amylase species. Sorption experiments showed a high affinity of Eu(III) to α-amylase in a wide pH range, namely between pH 4 and 8

  18. Toxic variability and radiation potentiation by Rh(III) complexes in Salmonella typhimurium cells

    International Nuclear Information System (INIS)

    Stationary-phase cells of Salmonella typhimurium were irradiated in phosphate-buffered saline in the presence of rhodium complexes to test for the potentiation of radiation-induced cell killing. Eleven Rh complexes, two Rh(I) and nine Rh(III), were tested. Seven Rh(III) complexes were found to be radiation potentiators; six potentiate only under hypoxic conditions, and one potentiates under both hypoxic and oxic conditions. Four of these seven Rh(III) complexes demonstrate potentiation that is 2 to 13 times greater than the sensitization caused by oxygen. Irradiating cells in Ham's F-12 culture medium rather than in phosphate-buffered saline eliminates this latter hypoxic radiation potentiation. None of the seven Rh(III) radiation potentiators are directly toxic to cells. However, four complexes were tested for hypoxic radiation-induced cytocidal toxicity, and three were found to be toxic after irradiation. The efficiency of this toxicity is not sufficient to account for the observed radiation potentiation. It is suggested that both reductive and oxidative free radical events are involved in the spectrum of Rh(III) potentiation observed

  19. Probing chromium(III) from chromium(VI) in cells by a fluorescent sensor

    Science.gov (United States)

    Hu, Xiangquan; Chai, Jie; Liu, Yanfei; Liu, Bin; Yang, Binsheng

    2016-01-01

    Cellular uptake of Cr(VI), followed by its reduction to Cr(III) with the formation of kinetically inert Cr(III) complexes, is a complex process. To better understand its physiological and pathological functions, efficient methods for the monitoring of Cr(VI) are desired. In this paper a selective fluorescent probe L, rhodamine hydrazide bearing a benzo[b]furan-2-carboxaldehyde group, was demonstrated as a red chemosensor for Cr(III) at about 586 nm. This probe has been used to probe Cr(III) which is reduced from Cr(VI) by reductants such as glutathione (GSH), vitamin C, cysteine (Cys), H2O2 and Dithiothreitol (DTT) by fluorescence spectra. Cr(VI) metabolism in vivo is primarily driven by Vc and GSH. Vc could reduce CrO42 - to Cr(III) in a faster rate than GSH. The indirectly detection limit for Cr(VI) by L + GSH system was determined to be 0.06 μM at pH = 6.2. Moreover, the confocal microscopy image experiments indicated that Cr(VI) can be reduced to Cr(III) inside cells rapidly and the resulted Cr(III) can be captured and imaged timely by L.

  20. The role of antiferromagnetic exchange interactions in dinuclear Cr(III) dithiocarbamates and a stepwise behavior of magnetic moment

    Science.gov (United States)

    Aytekin, O.; Bayri, A.

    2012-12-01

    In this study the role of the antiferromagnetic interactions in recently synthesized dinuclear Cr(III) complex has been investigated. Since there was not enough structural information for the characterization of the synthesis, we claim that there should be antiferromagnetic interactions between the dinuclear Fe(III) ions, if the proposed structure is the real structure. A new experiment is proposed to test the predictions of this theoretical investigation.

  1. The ruthenium complex cis-(dichloro)tetrammineruthenium(III) chloride induces apoptosis and damages DNA in murine sarcoma 180 cells

    Indian Academy of Sciences (India)

    Aliny Pereira De Lima; Flávia De Castro Pereira; Cesar Augusto Sam Tiago Vilanova-Costa; Alessandra De Santana Braga Barbosa Ribeiro; Luiz Alfredo Pavanin; Wagner Batista Dos Santos; Elisângela De Paula Silveira-Lacerda

    2010-09-01

    Ruthenium(III) complexes are increasingly attracting the interest of researchers due to their promising pharmacological properties. Recently, we reported that the cis-(dichloro)tetrammineruthenium(III) chloride compound has cytotoxic effects on murine sarcoma 180 (S-180) cells. In an effort to understand the mechanism responsible for their cytotoxicity, study we investigated the genotoxicity, cell cycle distribution and induction of apoptosis caused by cis-(dichloro)tetrammineruthenium(III) chloride in S-180 tumour cells. cis-(dichloro)tetrammineruthenium(III) chloride treatment induced significant DNA damage in S-180 cells, as detected by the alkaline comet assay. In the cell cycle analysis, cis-(dichloro)tetrammineruthenium(III) chloride caused an increase in the number of cells in G1 phase, accompanied by a decrease in the S and G2 phases after 24 h of treatment. In contrast, the cell cycle distribution of S-180 cells treated with cis-(dichloro)tetrammineruthenium(III) chloride for 48 h showed a concentration-dependent increase in the sub-G1 phase (indicating apoptosis), with a corresponding decrease in cells in the G1, S and G2 phases. In addition, cis-(dichloro)tetrammineruthenium(III) chloride treatment induced apoptosis in a time-dependent manner, as observed by the increased numbers of annexin V-positive cells. Taken together, these findings strongly demonstrate that DNA damage, cell cycle changes and apoptosis may correlate with the cytotoxic effects of cis-(dichloro)tetrammineruthenium(III) chloride on S-180 cells.

  2. Fusarium graminearum produces different xylanases causing host cell death that is prevented by the xylanase inhibitors XIP-I and TAXI-III in wheat.

    Science.gov (United States)

    Tundo, Silvio; Moscetti, Ilaria; Faoro, Franco; Lafond, Mickaël; Giardina, Thierry; Favaron, Francesco; Sella, Luca; D'Ovidio, Renato

    2015-11-01

    To shed light on the role of Xylanase Inhibitors (XIs) during Fusarium graminearum infection, we first demonstrated that three out of four F. graminearum xylanases, in addition to their xylan degrading activity, have also the capacity to cause host cell death both in cell suspensions and wheat spike tissue. Subsequently, we demonstrated that TAXI-III and XIP-I prevented both the enzyme and host cell death activities of F. graminearum xylanases. In particular, we showed that the enzymatic inhibition by TAXI-III and XIP-I was competitive and only FGSG_11487 escaped inhibition. The finding that TAXI-III and XIP-I prevented cell death activity of heat inactivated xylanases and that XIP-I precluded the cell death activity of FGSG_11487 - even if XIP-I does not inhibit its enzyme activity - suggests that the catalytic and the cell death activities are separated features of these xylanases. Finally, the efficacy of TAXI-III or XIP-I to prevent host cell death caused by xylanases was confirmed in transgenic plants expressing separately these inhibitors, suggesting that the XIs could limit F. graminearum infection via direct inhibition of xylanase activity and/or by preventing host cell death. PMID:26475196

  3. Binding of cetuximab to the EGFRvIII deletion mutant and its biological consequences in malignant glioma cells

    International Nuclear Information System (INIS)

    Background and purpose: Despite the clinical use of cetuximab, a chimeric antibody against EGFR, little is known regarding its interaction with EGFRvIII, a frequently expressed deletion mutant of EGFR. Therefore, we investigated the interaction and the functional consequences of cetuximab treatment on glioma cells stably expressing EGFRvIII. Materials and methods: The human glioma cell line U373 genetically modified to express EGFRvIII was used to measure the binding of cetuximab and its internalization using flow cytometry and confocal microscopy. Proliferation and cell survival were analyzed by cell growth and clonogenic survival assays. Results: Cetuximab is able to bind to EGFRvIII and causes an internalization of the receptor and decreases its expression levels. Furthermore, in contrast to EGF, cetuximab was able to activate EGFRvIII which was evidenced by multiple phosphorylation sites and its downstream signaling targets. Despite this activation, the growth rate and the radiosensitivity of the EGFRvIII-expressing glioma cells were not modulated. Conclusions: Cetuximab binds to EGFRvIII and leads to the initial activation, internalization and subsequent downregulation of EGFRvIII, but it does not seem to modulate the proliferation or radiosensitivity of EGFRvIII-expressing glioma cells. Thus, approaches to treat EGFRvIII-expressing glioma cells should be evaluated more carefully.

  4. Functional redundancy between DNA ligases I and III in DNA replication in vertebrate cells

    Science.gov (United States)

    Arakawa, Hiroshi; Bednar, Theresa; Wang, Minli; Paul, Katja; Mladenov, Emil; Bencsik-Theilen, Alena A.; Iliakis, George

    2012-01-01

    In eukaryotes, the three families of ATP-dependent DNA ligases are associated with specific functions in DNA metabolism. DNA ligase I (LigI) catalyzes Okazaki-fragment ligation at the replication fork and nucleotide excision repair (NER). DNA ligase IV (LigIV) mediates repair of DNA double strand breaks (DSB) via the canonical non-homologous end-joining (NHEJ) pathway. The evolutionary younger DNA ligase III (LigIII) is restricted to higher eukaryotes and has been associated with base excision (BER) and single strand break repair (SSBR). Here, using conditional knockout strategies for LIG3 and concomitant inactivation of the LIG1 and LIG4 genes, we show that in DT40 cells LigIII efficiently supports semi-conservative DNA replication. Our observations demonstrate a high functional versatility for the evolutionary new LigIII in DNA replication and mitochondrial metabolism, and suggest the presence of an alternative pathway for Okazaki fragment ligation. PMID:22127868

  5. New III-V cell design approaches for very high efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Lundstrom, M.S.; Melloch, M.R.; Lush, G.B.; Patkar, M.P.; Young, M.P. (Purdue Univ., Lafayette, IN (United States))

    1993-04-01

    This report describes to examine new solar cell desip approaches for achieving very high conversion efficiencies. The program consists of two elements. The first centers on exploring new thin-film approaches specifically designed for M-III semiconductors. Substantial efficiency gains may be possible by employing light trapping techniques to confine the incident photons, as well as the photons emitted by radiative recombination. The thin-film approach is a promising route for achieving substantial performance improvements in the already high-efficiency, single-junction, III-V cell. The second element of the research involves exploring desip approaches for achieving high conversion efficiencies without requiring extremely high-quality material. This work has applications to multiple-junction cells, for which the selection of a component cell often involves a compromise between optimum band pp and optimum material quality. It could also be a benefit manufacturing environment by making the cell's efficiency less dependent on materialquality.

  6. Isolation of III-V/Ge Multijunction Solar Cells by Wet Etching

    Directory of Open Access Journals (Sweden)

    A. Turala

    2013-01-01

    Full Text Available Microfabrication cycles of III-V multijunction solar cells include several technological steps and end with a wafer dicing step to separate individual cells. This step introduces damage at lateral facets of the junctions that act as charge trapping centers, potentially causing performance and reliability issues, which become even more important with today’s trend of cell size reduction. In this paper we propose a process of wet etching of microtrenches that allows electrical isolation of individual solar cells with no damage to the sidewalls. Etching with bromine-methanol, the solution that is typically used for nonselective etching of III-V compounds, results in the formation of unwanted holes on the semiconductor surfaces. We investigate the origin of holes formation and discuss methods to overcome this effect. We present an implementation of the isolation step into a solar cell fabrication process flow. This improved fabrication process opens the way for improved die strength, yield, and reliability.

  7. Regulation of the antibody response to type III pneumococcal polysaccharide by contrasuppressor T cells

    OpenAIRE

    1984-01-01

    A soluble membrane component of type III pneumococcal polysaccharide- coupled spleen cells (S3-SCSM) induces S3-specific suppressor T cells (Ts) in mice. These Ts can be detected only if mice are pretreated with cyclophosphamide (Cy) or if cells adherent to the lectin Vicia villosa are removed from the spleen cell population prior to transfer. The V. villosa-adherent spleen cells from mice injected with S3-SCSM could abrogate suppression mediated by Ts induced by S3-SCSM in Cy-treated mice. T...

  8. Interaction of lasioglossin III with CCRF-CEM cells

    Czech Academy of Sciences Publication Activity Database

    Slaninová, Jiřina; Mlsová, V.; Günterová, Jana; Borovičková, Lenka; Čeřovský, Václav

    Praha : Institute of Organic Chemistry and Biochemistry AS CR, v. v. i, 2011 - (Slaninová, J.), s. 136-138 ISBN 978-80-86241-44-9. - (Collection Symposium Series. 13). [Biologically Active Peptides /12./. Praha (CZ), 27.04.2011-29.04.2011] R&D Projects: GA ČR GA203/08/0536 Institutional research plan: CEZ:AV0Z40550506 Keywords : lasioglossin * antimicrobial peptides * cancer cells * flow cytometry Subject RIV: CC - Organic Chemistry

  9. Rare Lung Diseases III: Pulmonary Langerhans’ Cell Histiocytosis

    OpenAIRE

    Juvet, Stephen C; David Hwang; Downey, Gregory P.

    2010-01-01

    Pulmonary Langerhans’ cell histiocytosis (PLCH) is an unusual cystic lung disease that is also characterized by extrapulmonary manifestations. The current review discusses the presenting features and relevant diagnostic testing and treatment options for PLCH in the context of a clinical case. While the focus of the present article is adult PLCH and its pulmonary manifestations, it is important for clinicians to distinguish the adult and pediatric forms of the disease, as well as to be alert f...

  10. Human erythrocytes and neuroblastoma cells are affected in vitro by Au(III) ions

    International Nuclear Information System (INIS)

    Gold compounds are well known for their neurological and nephrotoxic implications. However, haematological toxicity is one of the most serious toxic and less studied effects. The lack of information on these aspects of Au(III) prompted us to study the structural effects induced on cell membranes, particularly that of human erythrocytes. AuCl3 was incubated with intact erythrocytes, isolated unsealed human erythrocyte membranes (IUM) and molecular models of the erythrocyte membrane. The latter consisted of multibilayers of dimyristoylphosphatidylcholine and dimyristoylphosphatidylethanolamine, phospholipids classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. This report presents evidence that Au(III) interacts with red cell membranes as follows: (a) in scanning electron microscopy studies on human erythrocytes it was observed that Au(III) induced shape changes at a concentration as low as 0.01 μM; (b) in isolated unsealed human erythrocyte membranes Au(III) induced a decrease in the molecular dynamics and/or water content at the glycerol backbone level of the lipid bilayer polar groups in a 5-50 μM concentration range, and (c) X-ray diffraction studies showed that Au(III) in the 10 μm-1 mM range induced increasing structural perturbation only to dimyristoylphosphatidylcholine bilayers. Additional experiments were performed in human neuroblastoma cells SH-SY5Y. A statistically significant decrease of cell viability was observed with Au(III) ranging from 0.1 μM to 100 μM.

  11. A novel alcohol/iron (III) fuel cell

    Science.gov (United States)

    Yi, Qingfeng; Zou, Tao; Zhang, Yuanyuan; Liu, Xiaoping; Xu, Guorong; Nie, Huidong; Zhou, Xiulin

    2016-07-01

    A novel alcohol fuel cell is constructed by using Fe3+ as the oxidation agent instead of the conventional O2. Various alcohols as the fuels are tested, including methanol, ethanol, n-propanol and iso-propanol. In this fuel cell, the anode catalysts tested are PdSn/β-cd-CNT, PdSn/CNT, Pd/β-cd-CNT, Pd/CNT and Pd/β-cd-C, prepared by using multi-walled carbon nanotube (CNT) and carbon powder (C), as well as β-cyclodexdrin (β-cd) modified CNT (β-cd-CNT) and β-cd modified C (β-cd-C), as the substrates to immobilize PdSn and Pd nanoparticles in glycol solvent. The as-synthesized PdSn/β-cd-CNT catalyst presents significantly higher electroactivity for alcohol oxidation than the conventional Pd/C catalyst. Fe3+ reduction reaction is carried out on the cathode made of carbon powder. The anolyte (alcohols in 1 mol L-1 NaOH) and catholyte (Fe3+ in 0.5 mol L-1 NaCl) are separated with a Nafion 117 membrane. Open circuit voltage (OCV) of the cell with the anode PdSn/β-cd-CNT is 1.14-1.22 V, depending upon the used alcohol. The maximum power densities with methanol, ethanol, n-propanol and iso-propanol fuels are 15.2, 16.1, 19.9 and 12.2 mW cm-2, respectively.

  12. Role of paramagnetic chromium in chromium(VI)-induced damage in cultured mammalian cells.

    OpenAIRE

    Sugiyama, M

    1994-01-01

    Chromium(VI) compounds are known to be potent toxic and carcinogenic agents. Because chromium(VI) is easily taken up by cells and is subsequently reduced to chromium(III), the formation of paramagnetic chromium such as chromium(V) and chromium(III) is believed to play a role in the adverse biological effects of chromium(VI) compounds. The present report, uses electron spin resonance (ESR) spectroscopy; the importance of the role of paramagnetic chromium in chromium(VI)-induced damage in intac...

  13. A bacterial type III effector family uses the papain-like hydrolytic activity to arrest the host cell cycle

    OpenAIRE

    Yao, Qing; Cui, Jixin; Zhu, Yongqun; Wang, Guolun; Hu, Liyan; Long, Chengzu; Cao, Ran; Liu, Xinqi; Huang, Niu; Chen, She; Liu, LiPing; Shao, Feng

    2009-01-01

    Pathogenic bacteria deliver effector proteins into host cells through the type III secretion apparatus to modulate the host function. We identify a family of proteins, homologous to the type III effector Cif from enteropathogenic Escherichia coli, in pathogens including Yersinia, Photorhabdus, and Burkholderia that contain functional type III secretion systems. Like Cif, this family of proteins is capable of arresting the host cell cycle at G2/M. Structure of one of the family members, Cif ho...

  14. Visible light photodegradation of phenanthrene catalyzed by Fe(III)-smectite: Role of soil organic matter

    International Nuclear Information System (INIS)

    Highlights: • Soil organic matter (SOM) has significant influence on the transformation of PAHs. • Photodegradation rate is strongly dependent on the SOM fractions and their content. • Photolysis is determined by the interaction between phenanthrene, clay and SOM. -- Abstract: In the present study, phenanthrene is employed as a model to explore the roles played by three soil organic matter (SOM) fractions, i.e., dissolved organic matter (DOM), humic acid (HA), and fulvic acid (FA), in its photodegradation with assistance of Fe(III)-smectite under visible-light. Slight decrease in phenanthrene photodegradation rate was observed in the presence of DOM, which is explained in terms of oxidative-radical competition between DOM and target phenanthrene molecules due to the high electron–donor capacity of phenolic moieties in DOM. On the other hand, a critic content is observed with FA (0.70 mg/g) and HA (0.65 mg/g). Before reaching the critic content, the removal of phenanthrene is accelerated; while after that, the photodegradation rate is suppressed. The acceleration of phenanthrene degradation can be attributed to the photosensitization of FA and HA. Due to the strong interaction between phenanthrene and the phenyl rings, however, the retention of phenanthrene on SOM–Fe(III)-smectite in the presence of high content of HA or FA is enhanced, thus slowing down its photodegradation. Those observations provide valuable insights into the transformation and fate of PAHs in the natural soil environment and open a window for using clay–humic substances complexes for remediation of contaminated soil

  15. Sequestration and speciation of Eu(iii) on gamma alumina: role of temperature and contact order.

    Science.gov (United States)

    Cai, Yawen; Ren, Xuemei; Lang, Yue; Liu, Zhiyong; Zong, Pengfei; Wang, Xiangke; Yang, Shitong

    2015-11-01

    The speciation, migration and transport of radionuclides in the environment are significantly influenced by their interactions with the natural minerals and humic substances therein. In view of this, the effect of temperature and contact order on the sorption behaviors of trivalent Eu(iii) in the γ-Al2O3/Eu(iii) and γ-Al2O3/HA/Eu(iii) systems was studied using batch experiments and the extended X-ray absorption fine structure spectroscopy (EXAFS) technique. The endothermic sorption behavior of Eu(iii) in the γ-Al2O3/Eu(iii) systems was induced by the hydrolysis reaction of Eu(iii) in solution and the complexation of Eu(iii) with the γ-Al2O3 surface sites. The endothermic sorption of Eu(iii) in the γ-Al2O3/HA/Eu(iii) systems was attributed to the endothermic binding of HA on γ-Al2O3 and the endothermic complexation between Eu(iii) and HA. EXAFS analysis suggested the formation of type B ternary complexes and their thermodynamic stability improves with rising temperature. The different sorption percentages under various contact orders were closely related to the binding mode of Eu(iii) on the exposed γ-Al2O3 surfaces or the γ-Al2O3/HA colloids. The findings obtained herein are important to evaluate the security of the radioactive waste repository and predict the fate of trivalent actinides (e.g., Am(iii), Cm(iii), Pu(iii), etc.) near the geological repository. PMID:26428412

  16. Effect of the Salmonella Pathogenicity Island 2 Type III Secretion System on Salmonella Survival in Activated Chicken Macrophage-Like HD11 Cells

    OpenAIRE

    Wisner, Amanda L. S.; Potter, Andrew A.; Köster, Wolfgang

    2011-01-01

    In order to better identify the role of the Salmonella pathogenicity island 2 (SPI-2) type III secretion system (T3SS) in chickens, we used the well-known gentamicin protection assay with activated HD11 cells. HD11 cells are a macrophage-like chicken cell line that can be stimulated with phorbol 12-myristate 13-acetate (PMA) to exhibit more macrophage-like morphology and greater production of reactive oxygen species (ROS). Activated HD11 cells were infected with a wild-type Salmonella enteric...

  17. The role of Coproporphyrinogen III oxidase and Ferrochelatase genes in heme biosynthesis and regulation in Aspergillus niger

    NARCIS (Netherlands)

    Punt, P.J.; Weert, S. de; Ram, A.F.J.; Hondel, C.A.M.J.J. van den; Lokman, Christien; Haas, H.; Werner, E.R.; Franken, A.C.W.

    2013-01-01

    Heme is a suggested limiting factor in peroxidase production by Aspergillus spp., which are well-known suitable hosts for heterologous protein production. In this study, the role of genes coding for coproporphyrinogen III oxidase (hemF) and ferrochelatase (hemH) was analyzed by means of deletion and

  18. The role of coproporphyrinogen III oxidase and ferrochelatase genes in heme biosynthesis and regulation in Aspergillus niger

    NARCIS (Netherlands)

    Franken, A.C.W.; Werner, E.R.; Haas, H.; Lokman, B.C.; Hondel, C.A.M.J.J. van den; Ram, A.F.J.; Weert, S. de; Punt, P.J.

    2013-01-01

    Heme is a suggested limiting factor in peroxidase production by Aspergillus spp., which are well-known suitable hosts for heterologous protein production. In this study, the role of genes coding for coproporphyrinogen III oxidase (hemF) and ferrochelatase (hemH) was analyzed by means of deletion and

  19. SPSP Phase III Recruiting, Selecting, and Developing Secure Power Systems Professionals: Behavioral Interview Guidelines by Job Roles

    Energy Technology Data Exchange (ETDEWEB)

    O' Neil, Lori Ross [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Conway, T. J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Tobey, D. H. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Greitzer, Frank L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Dalton, Angela C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Pusey, Portia K. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-03-01

    The Secure Power Systems Professional Phase III final report was released last year which an appendix of Behavioral Interview Guidelines by Job Roles. This new report is that appendix broken out as a standalone document to assist utilities in recruiting and developing Secure Power Systems Professionals at their site.

  20. Broadband and omnidirectional anti-reflection layer for III/V multi-junction solar cells

    CERN Document Server

    Diedenhofen, Silke L; Haverkamp, Erik; Bauhuis, Gerard; Schermer, John; Rivas, Jaime Gómez; 10.1016/j.solmat.2012.02.022

    2012-01-01

    We report a novel graded refractive index antireflection coating for III/V quadruple solar cells based on bottom-up grown tapered GaP nanowires. We have calculated the photocurrent density of an InGaP-GaAs-InGaAsP-InGaAs solar cell with a MgF2/ZnS double layer antireflection coating and with a graded refractive index coating. The photocurrent density can be increased by 5.9 % when the solar cell is coated with a graded refractive index layer with a thickness of 1\\mu m. We propose to realize such a graded refractive index layer by growing tapered GaP nanowires on III/V solar cells. For a first demonstration of the feasibility of the growth of tapered nanowires on III/V solar cells, we have grown tapered GaP nanowires on AlInP/GaAs substrates. We show experimentally that the reflection from the nanowire coated substrate is reduced and that the transmission into the substrate is increased for a broad spectral and angular range.

  1. Reliability Analysis of III-V Solar Cells Grown on Recycled GaAs Substrates and an Electroplated Nickel Substrate

    Directory of Open Access Journals (Sweden)

    Ray-Hua Horng

    2013-01-01

    Full Text Available This study involved analyzing the reliability of two types of III-V solar cells: (1 III-V solar cells grown on new and recycled gallium arsenide (GaAs substrates and (2 the III-V solar cells transferred onto an electroplated nickel (Ni substrate as III-V thin-film solar cells by using a cross-shaped pattern epitaxial lift-off (CPELO process. The III-V solar cells were grown on new and recycled GaAs substrates to evaluate the reliability of the substrate. The recycled GaAs substrate was fabricated by using the CPELO process. The performance of the solar cells grown on the recycled GaAs substrate was affected by the uneven surface morphology of the recycled GaAs substrate, which caused the propagation of these dislocations into the subsequently grown active layer of the solar cell. The III-V solar cells were transferred onto an electroplated Ni substrate, which was also fabricated by using CPELO technology. The degradation of the III-V thin-film solar cell after conducting a thermal shock test could have been caused by microcracks or microvoids in the active layer or interface of the heterojunction, which resulted in the reduction of the external quantum efficiency response and the increase of recombination loss.

  2. Impact of flavonoids on matrix metalloproteinase secretion and invadopodia formation in highly invasive A431-III cancer cells.

    Directory of Open Access Journals (Sweden)

    Yo-Chuen Lin

    Full Text Available Metastasis is a major cause of mortality in cancer patients. Invadopodia are considered to be crucial structures that allow cancer cells to penetrate across the extracellular matrix (ECM by using matrix metalloproteinases (MMPs. Previously, we isolated a highly invasive A431-III subline from parental A431 cells by Boyden chamber assay. The A431-III cells possess higher invasive and migratory abilities, elevated levels of MMP-9 and an enhanced epithelial-mesenchymal transition (EMT phenotype. In this study, we discovered that A431-III cells had an increased potential to form invadopodia and an improved capacity to degrade ECM compared with the original A431 cells. We also observed enhanced phosphorylation levels of cortactin and Src in A431-III cells; these phosphorylated proteins have been reported to be the main regulators of invadopodia formation. Flavonoids, almost ubiquitously distributed in food plants and plant food products, have been documented to exhibit anti-tumor properties. Therefore, it was of much interest to explore the effects of flavonoid antioxidants on the metastatic activity of A431-III cells. Exposure of A431-III cells to two potent dietary flavonoids, namely luteolin (Lu and quercetin (Qu, caused inhibition of invadopodia formation and decrement in ECM degradation. We conclude that Lu and Qu attenuate the phosphorylation of cortactin and Src in A431-III cells. As a consequence, there ensues a disruption of invadopodia generation and the suppression of MMP secretion. These changes, in concert, bring about a reduction in metastasis.

  3. Chemotherapy for advanced non-small-cell lung cancer: Role of paclitaxel and gemcitabine

    OpenAIRE

    Lam, WK; Tsang, KWT; Ip, MSM

    1999-01-01

    Objective. To review the role of chemotherapy in advanced non-small-cell lung cancer, focusing on cisplatin-based regimens and two new drugs: paclitaxel and gemcitabine. Data sources. Medline search of the relevant English literature. Study selection. Open and randomised comparative (phases II and III) studies, and meta-analyses of cytotoxic drugs/regimens used to treat advanced non-small-cell lung cancer. Data extraction. The following factors were studied and compared: symptomatic response ...

  4. The Vibrio parahaemolyticus Type III Secretion Systems manipulate host cell MAPK for critical steps in pathogenesis.

    LENUS (Irish Health Repository)

    Matlawska-Wasowska, Ksenia

    2010-12-01

    Vibrio parahaemolyticus is a food-borne pathogen causing inflammation of the gastrointestinal epithelium. Pathogenic strains of this bacterium possess two Type III Secretion Systems (TTSS) that deliver effector proteins into host cells. In order to better understand human host cell responses to V. parahaemolyticus, the modulation of Mitogen Activated Protein Kinase (MAPK) activation in epithelial cells by an O3:K6 clinical isolate, RIMD2210633, was investigated. The importance of MAPK activation for the ability of the bacterium to be cytotoxic and to induce secretion of Interleukin-8 (IL-8) was determined.

  5. Development of III-V-based concentrator solar cells and their application in PV-modules

    International Nuclear Information System (INIS)

    Concentrators have a great potential to achieve cost reduction for solar generated electricity. In this work III-V-based concentrator solar cells for high concentration levels were fabricated. Monolithic and mechanically stacked multi-junction cells were investigated achieving efficiencies up to 33.5% at C=308 (AM1.5d, 1000 W/m2, 25 C). The cells are employed in point-focus Fresnel lens modules. All-glass hermetized modules designed for a concentration level of 120 and 500 obtained efficiencies of up to 24.8% and 21.7%, respectively. The modules were characterized under outdoor conditions at Freiburg, Germany. (orig.)

  6. Caco-2 cell acquisition of dietary iron(III invokes a nanoparticulate endocytic pathway.

    Directory of Open Access Journals (Sweden)

    Dora I A Pereira

    Full Text Available Dietary non-heme iron contains ferrous [Fe(II] and ferric [Fe(III] iron fractions and the latter should hydrolyze, forming Fe(III oxo-hydroxide particles, on passing from the acidic stomach to less acidic duodenum. Using conditions to mimic the in vivo hydrolytic environment we confirmed the formation of nanodisperse fine ferrihydrite-like particles. Synthetic analogues of these (~ 10 nm hydrodynamic diameter were readily adherent to the cell membrane of differentiated Caco-2 cells and internalization was visualized using transmission electron microscopy. Moreover, Caco-2 exposure to these nanoparticles led to ferritin formation (i.e., iron utilization by the cells, which, unlike for soluble forms of iron, was reduced (p=0.02 by inhibition of clathrin-mediated endocytosis. Simulated lysosomal digestion indicated that the nanoparticles are readily dissolved under mildly acidic conditions with the lysosomal ligand, citrate. This was confirmed in cell culture as monensin inhibited Caco-2 utilization of iron from this source in a dose dependent fashion (p<0.05 whilet soluble iron was again unaffected. Our findings reveal the possibility of an endocytic pathway for acquisition of dietary Fe(III by the small intestinal epithelium, which would complement the established DMT-1 pathway for soluble Fe(II.

  7. Outcomes of patients with unresected stage III and stage IV non-small cell lung cancer: A single institution experience

    Directory of Open Access Journals (Sweden)

    Manpreet Singh Tiwana

    2013-01-01

    Full Text Available Introduction: To report on the demographic profile and survival outcomes of North Indian population affected with stage III and stage IV non-small cell lung cancer (NSCLC. Materials and Methods: From November 2008 to January 2012, 138 consecutively diagnosed NSCLC patients were included in this study. The patient, tumor and treatment related factors were analyzed. Median overall survival (OS, Kaplan-Meier survival plots, t-test, Cox proportional hazards models were generated by multivariate analysis [MVA] and analyzed on SPSS software (version 19.0; SPSS, Inc., Chicago, IL. Results: Median OS of stage III patients was 9.26 ± 1.85 months and 2-year survival rate of 13% while stage IV patients had median OS of 5 ± 1.5 months with a 2-year survival rate of 8%. Cox regression modeling for MVA demonstrated higher biologically equivalent dose (BED ( P = 0.01 in stage III while in stage IV non-squamous histology ( P = 0.01, administration of chemotherapy ( P = 0.02, partial responders to chemotherapy ( P = 0.001, higher BED ( P = 0.02, and those with skeletal metastasis alone ( P = 0.17 showed a better OS. Conclusion: Our data showed that a higher BED is associated with favorable outcomes, indicating a role of dose escalated radiation therapy to the primary lesion in both stage III and essentially in stage IV NSCLC. Additionally, optimal use of chemotherapy relates to better survival. The developing, resource restrained nations need to follow an economically feasible multimodality approach.

  8. Role of liver stem cells in hepatocarcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Lei-Bo; Xu; Chao; Liu

    2014-01-01

    Liver cancer is an aggressive disease with a high mortality rate. Management of liver cancer is strongly dependent on the tumor stage and underlying liver disease. Unfortunately, most cases are discovered when the cancer is already advanced, missing the opportunity for surgical resection. Thus, an improved understanding of the mechanisms responsible for liver cancer initiation and progression will facilitate the detection of more reliable tumor markers and the development of new small molecules for targeted therapy of liver cancer. Recently, there is increasing evidence for the "cancer stem cell hypothesis", which postulates that liver cancer originates from the malignant transformation of liver stem/progenitor cells(liver cancer stem cells). This cancer stem cell model has important significance for understanding the basic biology of liver cancer and has profound importance for the development of new strategies for cancer prevention and treatment. In this review, we highlight recent advances in the role of liver stem cells in hepatocarcinogenesis. Our review of the literature shows that identification of the cellular origin and the signaling pathways involved is challenging issues in liver cancer with pivotal implications in therapeutic perspectives. Although the dedifferentiation of mature hepatocytes/cholangiocytes in hepatocarcinogenesis cannot be excluded, neoplastic transformation of a stem cell subpopulation more easily explains hepatocarcinogenesis. Elimination of liver cancer stem cells in liver cancer could result in the degeneration of downstream cells, which makes them potential targets for liver cancer therapies. Therefore, liver stem cells could represent a new target for therapeutic approaches to liver cancer in the near future.

  9. Competition of Escherichia coli DNA polymerases I, II and III with DNA Pol IV in stressed cells.

    Directory of Open Access Journals (Sweden)

    P J Hastings

    Full Text Available Escherichia coli has five DNA polymerases, one of which, the low-fidelity Pol IV or DinB, is required for stress-induced mutagenesis in the well-studied Lac frameshift-reversion assay. Although normally present at approximately 200 molecules per cell, Pol IV is recruited to acts of DNA double-strand-break repair, and causes mutagenesis, only when at least two cellular stress responses are activated: the SOS DNA-damage response, which upregulates DinB approximately 10-fold, and the RpoS-controlled general-stress response, which upregulates Pol IV about 2-fold. DNA Pol III was also implicated but its role in mutagenesis was unclear. We sought in vivo evidence on the presence and interactions of multiple DNA polymerases during stress-induced mutagenesis. Using multiply mutant strains, we provide evidence of competition of DNA Pols I, II and III with Pol IV, implying that they are all present at sites of stress-induced mutagenesis. Previous data indicate that Pol V is also present. We show that the interactions of Pols I, II and III with Pol IV result neither from, first, induction of the SOS response when particular DNA polymerases are removed, nor second, from proofreading of DNA Pol IV errors by the editing functions of Pol I or Pol III. Third, we provide evidence that Pol III itself does not assist with but rather inhibits Pol IV-dependent mutagenesis. The data support the remaining hypothesis that during the acts of DNA double-strand-break (DSB repair, shown previously to underlie stress-induced mutagenesis in the Lac system, there is competition of DNA polymerases I, II and III with DNA Pol IV for action at the primer terminus. Up-regulation of Pol IV, and possibly other stress-response-controlled factor(s, tilt the competition in favor of error-prone Pol IV at the expense of more accurate polymerases, thus producing stress-induced mutations. This mutagenesis assay reveals the DNA polymerases operating in DSB repair during stress and also

  10. Recent advances on antimony(III/V) compounds with potential activity against tumor cells.

    Science.gov (United States)

    Hadjikakou, S K; Ozturk, I I; Banti, C N; Kourkoumelis, N; Hadjiliadis, N

    2015-12-01

    Antimony one of the heavier pnictogens, has been in medical use against microbes and parasites as well. Antimony-based drugs have been prescribed against leishmaniasis since the parasitic transmission of the tropical disease was understood in the beginning of the 20th century. The activity of arsenic against visceral leishmaniasis led to the synthesis of an array of arsenic-containing parasitic agents, among them the less toxic pentavalent antimonials: Stibosan, Neostibosan, and Ureastibamine. Other antimony drugs followed: sodium stibogluconate (Pentostam) and melglumine antimoniate (Glucantim or Glucantime); both continue to be in use today despite their toxic side effects and increasing loss in potency due to the growing resistance of the parasite against antimony. Antimony compounds and their therapeutic potentials are under consideration from many research groups, while a number of early reviews recording advances of antimony biomedical applications are also available. However, there are only few reports on the screening for antitumor potential of antimony compounds. This review focuses upon results obtained on the anti-proliferative activity of antimony compounds in the past years. This survey shows that antimony(III/V) complexes containing various types of ligands such as thiones, thiosemicarbazones, dithiocarbamates, carboxylic acids, or ketones, nitrogen donor ligands, exhibit selectivity against a variety of cancer cells. The role of the ligand type of the complex is elucidated within this review. The complexes and their biological activity are already reported elsewhere. However quantitative structure-activity relationship (QSAR) modeling studies have been carried out and they are reported for the first time here. PMID:26092367

  11. Tamoxifen represses alcohol-induced transcription of RNA polymerase III-dependent genes in breast cancer cells

    OpenAIRE

    Zhong, Qian; Shi, Ganggang; Zhang, Qingsong; Lu, Lei; Levy, Daniel; Zhong, Shuping

    2014-01-01

    Alcohol consumption in women has been associated with an increased risk of breast cancer, particular in estrogen receptor positive (ER+) cases. Deregulation of RNA polymerase III-dependent (Pol III) transcription enhances cellular tRNAs and 5S rRNA production, leading to an increase in translational capacity to promote cell transformation and tumor formation. Our recent studies demonstrated that alcohol induces Brf1 expression and Pol III gene transcription via ER. Here, we report that Tamoxi...

  12. Role of Fe(III) in preventing humic interference during As(III) detection on gold electrode: Spectroscopic and voltammetric evidence

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhong-Gang [Nanomaterials and Environmental Detection Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Department of Chemistry, University of Science and Technology of China, Hefei 230026 (China); Chen, Xing; Jia, Yong; Liu, Jin-Huai [Nanomaterials and Environmental Detection Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Huang, Xing-Jiu, E-mail: xingjiuhuang@iim.ac.cn [Nanomaterials and Environmental Detection Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Department of Chemistry, University of Science and Technology of China, Hefei 230026 (China)

    2014-02-01

    Graphical abstract: - Highlights: • Humic acids interfere with the voltammetric detection of As(III) on gold electrode through adsorption and possible complexation. • Addition of Fe(III) removes this interference and helps in the electroanalytical detection of As(III). • FTIR and XPS studies suggest that the formation of Fe(III)–HA complex prevents adsorption of HA on gold and limits As–HA complex formation. - Abstract: A drawback of As(III) detection using square wave anodic stripping voltammetry (SWASV) is that it is susceptible to interferences from various metals or organic compounds, especially in real sample water. This study attempts to understand the interference of co-existing of Fe(III) and humic acid (HA) molecules to the electrochemical detection of As(III) using Fourier transform infrared (FTIR) spectrum and X-ray photoelectron spectroscopy (XPS). The electrochemical experiments include stripping of As(III) in the solutions containing HA with different concentrations, cyclic voltammetry in 0.5 M H{sub 2}SO{sub 4} in the presence of HA or Fe(III) with/without addition of Fe(III) or HA, and stripping of As(III) in the presence of HA or Fe(III) with/without addition of Fe(III) or HA. FTIR and XPS are employed to confirm the affinity of HA to Fe(III) or As(III) in acidic condition.

  13. Deletion of the topoisomerase III gene in the hyperthermophilic archaeon Sulfolobus islandicus results in slow growth and defects in cell cycle control

    DEFF Research Database (Denmark)

    Li, Xiyang; Guo, Li; Deng, Ling;

    2011-01-01

    Topoisomerase III (topo III), a type IA topoisomerase, is widespread in hyperthermophilic archaea. In order to interrogate the in vivo role of archaeal topo III, we constructed and characterized a topo III gene deletion mutant of Sulfolobus islandicus. The mutant was viable but grew more slowly t...

  14. Preoperative concurrent chemoradiotherapy for unresectable stage III nonsmall cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: We carried out a Phase II trial in an attempt to improve resectability and survivability of inoperable Stage III A and III B nonsmall cell lung cancer (NSCLC) patients by implementing a neoadjuvant chemoradiotherapy treatment program. Methods and Materials: Thirty-six patients with locally advanced Stage III NSCLC received neoadjuvant therapy consisting of 50.4 Gy in 5.5 weeks concurrent with two cycles of chemotherapy, using cisplatin and etoposide. No postsurgical consolidation therapy was given. Results: Assessment at 3 to 6 weeks after treatment suggested that 26 (72%) patients had been rendered resectable. Toxicities were common but usually tolerable; however, one toxic death occurred. Of 24 patients who proceeded to thoracotomy, complete resection was achieved in 20 (56%). There were two surgically related deaths. Surgical-pathological staging showed downstaging in 18 patients, including complete sterilization of the tumor in 3 (8%). The median survival for all 36 patients is 15 months, but at the time of analysis, median survival of resectable patients had not been reached. The actuarial 2-year survival is 39% for all study groups, 57% for resectable patients, and 16% for the remaining (p < 0.005). Conclusions: While this preoperative neoadjuvant appears to improve survival of patients with Stage III NSCLC, comparison with previous reports of other similar trials indicate a superior survival advantage in association with higher doses of radiotherapy

  15. Down-regulated βIII-tubulin Expression Can Reverse Paclitaxel Resistance in A549/Taxol Cells Lines

    Directory of Open Access Journals (Sweden)

    Yinling ZHUO

    2014-08-01

    Full Text Available Background and objective Chemotherapy drug resistance is the primary causes of death in patients with pulmonary carcinoma which make tumor recurrence or metastasis. β-tubulin is the main cell targets of anti-microtubule drug. Increased expression of βIII-tubulin has been implicated in non-small cell lung cancer (NSCLC cell lines. To explore the relationship among the expression level of βIII-tubulin and the sensitivity of A549/Taxolcell lines to Taxol and cell cycles and cell apoptosis by RNA interference-mediated inhibition of βIII-tubulin in A549/Taxol cells. Methods Three pairs of siRNA targetd βIII-tubulin were designed and prepared, which were transfected into A549/Taxol cells using LipofectamineTM 2000. We detected the expression of βIII-tubulin mRNA using Real-time fluorescence qRT-PCR. Tedhen we selected the most efficient siRNA by the expression of βIII-tubulin mRNA in transfected group. βIII-tubulin protein level were mesured by Western blot. The taxol sensitivity in transfected group were evaluated by MTT assay. And the cell apoptosis and cell cycles were determined by flow cytometry. Results βIII-tubulin mRNA levels in A549/Taxol cells were significantly decreased in transfected grop by Real-time qRT-PCR than control groups. And βIII-tubulin siRNA-1 sequence showed the highest transfection efficiency, which was (87.73±4.87% (P<0.01; Western blot results showed that the expressional level of BIII tublin protein was significantly down-reulated in the transfectant cells than thant in the control cells. By MTT assay, we showed that the inhibition ratio of Taxol to A549/Taxol cells transfeced was higher than that of control group (51.77±4.60% (P<0.01. The early apoptosis rate of A549/Taxol cells in transfected group were significantly higher than that of control group (P<0.01; G2-M content in taxol group obviously increased than untreated samples by the cell cycle (P<0.05. Conclusion βIII-tubulin down-regulated significantly

  16. Type III TGFβ receptor and Src direct hyaluronan-mediated invasive cell motility.

    Science.gov (United States)

    Allison, Patrick; Espiritu, Daniella; Barnett, Joey V; Camenisch, Todd D

    2015-03-01

    During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types which contribute to the coronary vessels. This process requires epithelial to mesenchymal transition (EMT) and directed cellular invasion. The Type III Transforming Growth Factor-beta Receptor (TGFβR3) is required for epicardial cell invasion and coronary vessel development. Using primary epicardial cells derived from Tgfbr3(+/+) and Tgfbr3(-/-) mouse embryos, high-molecular weight hyaluronan (HMWHA) stimulated cellular invasion and filamentous (f-actin) polymerization are detected in Tgfbr3(+/+) cells, but not in Tgfbr3(-/-) cells. Furthermore, HMWHA-stimulated cellular invasion and f-actin polymerization in Tgfbr3(+/+) epicardial cells are dependent on Src kinase. Src activation in HMWHA-stimulated Tgfbr3(-/-) epicardial cells is not detected in response to HMWHA. RhoA and Rac1 also fail to activate in response to HMWHA in Tgfbr3(-/-) cells. These events coincide with defective f-actin formation and deficient cellular invasion. Finally, a T841A activating substitution in TGFβR3 drives ligand-independent Src activation. Collectively, these data define a TGFβR3-Src-RhoA/Rac1 pathway that is essential for hyaluronan-directed cell invasion in epicardial cells. PMID:25499979

  17. Scorpion venom component III inhibits cell proliferation by modulating NF-κB activation in human leukemia cells

    OpenAIRE

    SONG, XIANGFENG; Zhang, Guojun; SUN, AIPING; Guo, Jiqiang; TIAN, ZHONGWEI; Wang, Hui; Liu, Yufeng

    2012-01-01

    Scorpion venom contains various groups of compounds that exhibit anticancer activity against a variety of malignancies through a poorly understood mechanism. While the aberrant activation of nuclear factor κB (NF-κB) has been linked with hematopoietic malignancies, we hypothesized that scorpion venom mediates its effects by modulating the NF-κB signaling pathway. In the present study, we examined the effects of scorpion venom component III (SVCIII) on the human leukemia cell lines THP-1 and J...

  18. Heptachlor induced mitochondria-mediated cell death via impairing electron transport chain complex III

    International Nuclear Information System (INIS)

    Highlights: •Heptachlor inhibited mitochondrial electron transport chain complex III activity. •Heptachlor promoted generation of reactive oxygen species. •Heptachlor induced Bax activation. •Heptachlor induced mitochondria-mediated and caspase-dependent apoptosis. -- Abstract: Environmental toxins like pesticides have been implicated in the pathogenesis of Parkinson’s disease (PD). Epidemiological studies suggested that exposures to organochlorine pesticides have an association with an increased PD risk. In the present study, we examined the mechanism of toxicity induced by an organochlorine pesticide heptachlor. In a human dopaminergic neuroblastoma SH-SY5Y cells, heptachlor induced both morphological and functional damages in mitochondria. Interestingly, the compound inhibited mitochondrial electron transport chain complex III activity. Rapid generation of reactive oxygen species and the activation of Bax were then detected. Subsequently, mitochondria-mediated, caspase-dependent apoptosis followed. Our results raise a possibility that an organochlorine pesticide heptachlor can act as a neurotoxicant associated with PD

  19. Heptachlor induced mitochondria-mediated cell death via impairing electron transport chain complex III

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Seokheon; Kim, Joo Yeon; Hwang, Joohyun [Department of Molecular Biology, Sejong University, Seoul 143-747 (Korea, Republic of); Shin, Ki Soon [Department of Biology, Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Kang, Shin Jung, E-mail: sjkang@sejong.ac.kr [Department of Molecular Biology, Sejong University, Seoul 143-747 (Korea, Republic of)

    2013-08-09

    Highlights: •Heptachlor inhibited mitochondrial electron transport chain complex III activity. •Heptachlor promoted generation of reactive oxygen species. •Heptachlor induced Bax activation. •Heptachlor induced mitochondria-mediated and caspase-dependent apoptosis. -- Abstract: Environmental toxins like pesticides have been implicated in the pathogenesis of Parkinson’s disease (PD). Epidemiological studies suggested that exposures to organochlorine pesticides have an association with an increased PD risk. In the present study, we examined the mechanism of toxicity induced by an organochlorine pesticide heptachlor. In a human dopaminergic neuroblastoma SH-SY5Y cells, heptachlor induced both morphological and functional damages in mitochondria. Interestingly, the compound inhibited mitochondrial electron transport chain complex III activity. Rapid generation of reactive oxygen species and the activation of Bax were then detected. Subsequently, mitochondria-mediated, caspase-dependent apoptosis followed. Our results raise a possibility that an organochlorine pesticide heptachlor can act as a neurotoxicant associated with PD.

  20. ALIX and ESCRT-III Coordinately Control Cytokinetic Abscission during Germline Stem Cell Division In Vivo

    Science.gov (United States)

    Eikenes, Åsmund H.; Malerød, Lene; Christensen, Anette Lie; Steen, Chloé B.; Mathieu, Juliette; Nezis, Ioannis P.; Liestøl, Knut; Huynh, Jean-René; Stenmark, Harald; Haglund, Kaisa

    2015-01-01

    Abscission is the final step of cytokinesis that involves the cleavage of the intercellular bridge connecting the two daughter cells. Recent studies have given novel insight into the spatiotemporal regulation and molecular mechanisms controlling abscission in cultured yeast and human cells. The mechanisms of abscission in living metazoan tissues are however not well understood. Here we show that ALIX and the ESCRT-III component Shrub are required for completion of abscission during Drosophila female germline stem cell (fGSC) division. Loss of ALIX or Shrub function in fGSCs leads to delayed abscission and the consequent formation of stem cysts in which chains of daughter cells remain interconnected to the fGSC via midbody rings and fusome. We demonstrate that ALIX and Shrub interact and that they co-localize at midbody rings and midbodies during cytokinetic abscission in fGSCs. Mechanistically, we show that the direct interaction between ALIX and Shrub is required to ensure cytokinesis completion with normal kinetics in fGSCs. We conclude that ALIX and ESCRT-III coordinately control abscission in Drosophila fGSCs and that their complex formation is required for accurate abscission timing in GSCs in vivo. PMID:25635693

  1. The Role of Dihydroorotate Dehydrogenase in Apoptosis Induction in Response to Inhibition of the Mitochondrial Respiratory Chain Complex III

    OpenAIRE

    Khutornenko, A.; Dalina, A.; Chernyak, B.; Chumakov, P; Evstafieva, A.

    2014-01-01

    A mechanism for the induction of programmed cell death (apoptosis) upon dysfunction of the mitochondrial respiratory chain has been studied. Previously, we had found that inhibition of mitochondrial cytochrome bc1, a component of the electron transport chain complex III, leads to activation of tumor suppressor p53, followed by apoptosis induction. The mitochondrial respiratory chain is coupled to the de novo pyrimidine biosynthesis pathway via the mitochondrial enzyme dihydroorotate dehydroge...

  2. Chemical sporulation and germination: cytoprotective nanocoating of individual mammalian cells with a degradable tannic acid-FeIII complex

    Science.gov (United States)

    Lee, Juno; Cho, Hyeoncheol; Choi, Jinsu; Kim, Doyeon; Hong, Daewha; Park, Ji Hun; Yang, Sung Ho; Choi, Insung S.

    2015-11-01

    Individual mammalian cells were coated with cytoprotective and degradable films by cytocompatible processes maintaining the cell viability. Three types of mammalian cells (HeLa, NIH 3T3, and Jurkat cells) were coated with a metal-organic complex of tannic acid (TA) and ferric ion, and the TA-FeIII nanocoat effectively protected the coated mammalian cells against UV-C irradiation and a toxic compound. More importantly, the cell proliferation was controlled by programmed formation and degradation of the TA-FeIII nanocoat, mimicking the sporulation and germination processes found in nature.Individual mammalian cells were coated with cytoprotective and degradable films by cytocompatible processes maintaining the cell viability. Three types of mammalian cells (HeLa, NIH 3T3, and Jurkat cells) were coated with a metal-organic complex of tannic acid (TA) and ferric ion, and the TA-FeIII nanocoat effectively protected the coated mammalian cells against UV-C irradiation and a toxic compound. More importantly, the cell proliferation was controlled by programmed formation and degradation of the TA-FeIII nanocoat, mimicking the sporulation and germination processes found in nature. Electronic supplementary information (ESI) available: Experimental details, LSCM images, and SEM and TEM images. See DOI: 10.1039/c5nr05573c

  3. Role of Menaquinones in Fe(III) Reduction by Membrane Fractions of Shewanella putrefaciens

    OpenAIRE

    Saffarini, Daad A.; Blumerman, Seth L.; Mansoorabadi, Karen J.

    2002-01-01

    Two Tn5-generated mutants of Shewanella putrefaciens with insertions in menD and menB were isolated and analyzed. Both mutants were deficient in the use of several terminal electron acceptors, including Fe(III). This deficiency was overcome by the addition of menaquinone (vitamin K2). Isolated membrane fractions from both mutants were unable to reduce Fe(III) in the absence of added menaquinone when formate was used as the electron donor. These results indicate that menaquinones are essential...

  4. Expression of bovine herpesvirus 1 glycoproteins gI and gIII in transfected murine cells

    International Nuclear Information System (INIS)

    Genes encoding two of the major glycoproteins of bovine herpesvirus 1 (BHV-1), gI and gIII, were cloned into the eucaryotic expression vectors pRSVcat and pSV2neo and transfected into murine LMTK- cells, and cloned cell lines were established. The relative amounts of gI or gIII expressed from the two vectors were similar. Expression of gI was cell associated and localized predominantly in the perinuclear region, but nuclear and plasma membrane staining was also observed. Expression of gI was additionally associated with cell fusion and the formation of polykaryons and giant cells. Expression of gIII was localized predominantly in the nuclear and plasma membranes. Radioimmunoprecipitation in the presence or absence of tunicamycin revealed that the recombinant glycoproteins were proteolytically processed and glycosylated and had molecular weights similar to those of the forms of gI and gIII expressed in BHV-1 infected bovine cells. However, both recombinant glycoproteins were glycosylated to a lesser extent than were the forms found in BHV-1 infected bovine cells. For gI, a deficiency in N-linked glycosylated of the amino-terminal half of the protein was identified; for gIII, a deficiency in O-linked glycosylation was implicated. The reactivity pattern of a panel of gI- and gIII-specific monoclonal antibodies, including six which recognize conformation-dependent epitopes, was found to be unaffected by the glycosylation differences and was identical for transfected of BHV-1-infected murine cells. Use of the transfected cells as targets in immune-mediated cytotoxicity assays demonstrated the functional recognition of recombinant gI and gIII by murine antibody and cytotoxic T lymphocytes

  5. Chlamydia pneumoniae CopD Translocator Protein Plays a Critical Role in Type III Secretion (T3S) and Infection

    OpenAIRE

    Bulir, David C.; Waltho, Daniel A.; Stone, Christopher B.; Mwawasi, Kenneth A.; Nelson, Jordan C.; Mahony, James B.

    2014-01-01

    Pathogenic Gram-negative bacteria use type III secretion (T3S) to inject effector proteins into the host cell to create appropriate conditions for infection and intracellular replication. Chlamydia spp. are believed to use T3S to infect their host cell, and the translocator proteins are an essential component of this system. Chlamydia pneumoniae contains genes encoding two sets of translocator proteins; CopB and CopD, and CopB2 and CopD2. In this study, we identified novel interactions betwee...

  6. Material characterizations and devices tests of solar cells based on III-V elements nitrides

    OpenAIRE

    Gorge, Vanessa

    2012-01-01

    Among III-V nitrides, the InGaN material has intensively been studied since the year 2000 for photovoltaic applications, in particular for multi-junction solar cells, thanks to its large tunable band gap covering almost the entire solar spectrum. Then, it will be possible to reach high efficiency and low cost. However, one of the problems of InGaN material is the absence of lattice-matched substrate leading to high defect density which limits device performances. We have thus studied the feas...

  7. Vorinostat, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

    Science.gov (United States)

    2016-06-20

    Stage II Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  8. The enigmatic role of mast cells in dominant tolerance

    OpenAIRE

    de Vries, Victor C.; Pino-Lagos, Karina; Elgueta, Raul; Noelle, Randolph J.

    2009-01-01

    PURPOSE OF REVIEW: The role of regulatory T cells (Treg) in peripheral tolerance has been studied extensively in transplantation research. Recently, mast cells have been shown to play an indispensable role in allograft tolerance. The purpose of this review is to inform the reader on the current standings of the role of mast cells in dominant tolerance with an emphasis on the interaction of mast cells with Treg.RECENT FINDINGS: Mast cells are required to sustain peripheral tolerance via Treg. ...

  9. Proliferating cell nuclear antigen, p53 and micro vessel density: Grade II vs. Grade III astrocytoma

    Directory of Open Access Journals (Sweden)

    Malhan Priya

    2010-01-01

    Full Text Available Histological classification and grading are prime procedures in the management of patients with astrocytoma, providing vital data for therapeutic decision making and prognostication. However, it has limitations in assessing biological tumor behavior. This can be overcome by using newer immunohistochemical techniques. This study was carried out to compare proliferative indices using proliferating cell nuclear antigen (PCNA, extent of p53 expression and micro vessel morphometric parameters in patients with low grade and anaplastic astrocytoma. Twenty-five patients, each of grade II and grade III astrocytoma were evaluated using monoclonal antibodies to PCNA, p53 protein and factor VIII related antigen. PCNA, p53-labeling indices were calculated along with micro vessel morphometric analysis using Biovis Image plus Software. Patients with grade III astrocytoma had higher PCNA and p53 labeling indices as compared with grade II astrocytoma (29.14 plus/minus 9.87% vs. 16.84 plus/minus 6.57%, p 0.001; 18.18 plus/minus 6.14% vs. 6.14 plus/minus 7.23%, p 0.001, respectively. Micro vessel percentage area of patients with grade III astrocytoma was also (4.26 plus/minus 3.70 vs. 1.05 plus/minus 0.56, p 0.001, higher along with other micro vessel morphometric parameters. Discordance between histology and one or more IHC parameters was seen in 5/25 (20% of patients with grade III astrocytoma and 9/25 (36% of patients with grade II disease. PCNA and p53 labeling indices were positively correlated with Pearson′s correlation, p less than 0.001 for both. Increased proliferative fraction, genetic alterations and neovascularization mark biological aggressiveness in astrocytoma. Immunohistochemical evaluation scores over meet the challenge of accurate prognostication of this potentially fatal malignancy.

  10. Role of polyphenols in cell death control.

    Science.gov (United States)

    Giovannini, Claudio; Masella, Roberta

    2012-05-01

    Dietary consumption of fruit, vegetables, fish, and olive oil has been demonstrated to exert beneficial effects on human health. This finding may be due to the high content of antioxidant compounds including polyphenols. Current evidence strongly supports a contribution of polyphenols to the prevention of several chronic degenerative diseases such as cancer, atherosclerosis and cardiovascular diseases, central nervous system disorders, as well as aging. Apoptosis is a genetically controlled and evolutionarily conserved form of cell death of critical importance for the maintenance of tissue homeostasis in the adult organism. The malfunction of the death machinery may play a primary role in various pathologic processes, leading to proliferative or degenerative diseases. Polyphenols can interact with specific steps and/or proteins regulating the apoptotic process in different ways depending on their concentration, the cell system, the type or stage of the pathological process. Because of their ability to modulate cell death, polyphenols have been proposed as chemopreventive and therapeutic agents. This paper reviews and discusses the last 3-year findings related to the principal molecular mechanisms involved in the control of the balance between apoptosis and cell proliferation exerted by polyphenols. PMID:22584012

  11. The p38-MK2-HuR pathway potentiates EGFRvIII-IL-1β-driven IL-6 secretion in glioblastoma cells.

    Science.gov (United States)

    Gurgis, F M S; Yeung, Y T; Tang, M X M; Heng, B; Buckland, M; Ammit, A J; Haapasalo, J; Haapasalo, H; Guillemin, G J; Grewal, T; Munoz, L

    2015-05-28

    The microenvironment of glioblastoma (GBM) contains high levels of inflammatory cytokine interleukin 6 (IL-6), which contributes to promote tumour progression and invasion. The common epidermal growth factor receptor variant III (EGFRvIII) mutation in GBM is associated with significantly higher levels of IL-6. Furthermore, elevated IL-1β levels in GBM tumours are also believed to activate GBM cells and enhance IL-6 production. However, the crosstalk between these intrinsic and extrinsic factors within the oncogene-microenvironment of GBM causing overproduction of IL-6 is poorly understood. Here, we show that EGFRvIII potentiates IL-1β-induced IL-6 secretion from GBM cells. Importantly, exacerbation of IL-6 production is most effectively attenuated in EGFRvIII-expressing GBM cells with inhibitors of p38 mitogen-activated protein kinase (p38 MAPK) and MAPK-activated protein kinase 2 (MK2). Enhanced IL-6 production and increased sensitivity toward pharmacological p38 MAPK and MK2 inhibitors in EGFRvIII-expressing GBM cells is associated with increased MK2-dependent nuclear-cytoplasmic shuttling and accumulation of human antigen R (HuR), an IL-6 mRNA-stabilising protein, in the cytosol. IL-1β-stimulated activation of the p38 MAPK-MK2-HuR pathway significantly enhances IL-6 mRNA stability in GBM cells carrying EGFRvIII. Further supporting a role for the p38 MAPK-MK2-HuR pathway in the development of inflammatory environment in GBM, activated MK2 is found in more than 50% of investigated GBM tissues and correlates with lower grade and secondary GBMs. Taken together, p38 MAPK-MK2-HuR signalling may enhance the potential of intrinsic (EGFRvIII) and extrinsic (IL-1β) factors to develop an inflammatory GBM environment. Hence, further improvement of brain-permeable and anti-inflammatory inhibitors targeting p38 MAPK, MK2 and HuR may combat progression of lower grade gliomas into aggressive GBMs. PMID:25088200

  12. Permeation of vanadium(III, IV, V)-dipicolinate complexes across MDCK cell monolayer and comparison with Caco-2 cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yue; YANG Xiaoda; WANG Kui

    2005-01-01

    The permeation and cytotoxicity of three insulin-mimetic vanadium(III, IV, V)-dipicolinate complexes were studied using the MDCK cell monolayer in comparison with the Caco-2 cells. On MDCK cell monolayer, the apparent permeation coefficients (Papp) were estimated to be (7.5 ± 1.0)×10-6, (1.0 ± 0.2)×10-6, (1.7±0.4)×10-6 cm/s for V(V), V(IV), and V(III)-dipic complexes, respectively. The permeability of V(V)-dipic complexes is much better than the others, which is in agreement with its better hypoglycemic effect in animal tests. On Caco-2 cell monolayer, Papp were found to be in the range of 1-3×10-6 cm/s and not to be affected by excessive amounts of dipicolinate ligand. By contrast, the permeability in the AP→BL direction across the MDCK monolayer increased greatly in the presence of free ligands, suggesting existence of active transport mechanism of vanadium complex anions on the MDCK cells. The cytotoxicity of the three complexes was found similar and the IC50 were measured in the range of 0.6―0.9 mmol/L for MDCK cells and 1.6―2 mmol/L for Caco-2 cells. The cytotoxicity of three vanadium complexes was conceivably in consistence with their permeability, suggesting that the toxicity, permeation and cellular metabolism of vanadium complexes are closely related.

  13. Cardiotoxin III Inhibits Proliferation and Migration of Oral Cancer Cells through MAPK and MMP Signaling

    Directory of Open Access Journals (Sweden)

    Ching-Yu Yen

    2013-01-01

    Full Text Available Cardiotoxin III (CTXIII, isolated from the snake venom of Formosan cobra Naja naja atra, has previously been found to induce apoptosis in many types of cancer. Early metastasis is typical for the progression of oral cancer. To modulate the cell migration behavior of oral cancer is one of the oral cancer therapies. In this study, the possible modulating effect of CTXIII on oral cancer migration is addressed. In the example of oral squamous carcinoma Ca9-22 cells, the cell viability was decreased by CTXIII treatment in a dose-responsive manner. In wound-healing assay, the cell migration of Ca9-22 cells was attenuated by CTXIII in a dose- and time-responsive manner. After CTXIII treatment, the MMP-2 and MMP-9 protein expressions were downregulated, and the phosphorylation of JNK and p38-MAPK was increased independent of ERK phosphorylation. In conclusion, CTXIII has antiproliferative and -migrating effects on oral cancer cells involving the p38-MAPK and MMP-2/-9 pathways.

  14. The Balance of Cell Surface and Soluble Type III TGF-β Receptor Regulates BMP Signaling in Normal and Cancerous Mammary Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Catherine E. Gatza

    2014-06-01

    Full Text Available Bone morphogenetic proteins (BMPs are members of the TGF-β superfamily that are over-expressed in breast cancer, with context dependent effects on breast cancer pathogenesis. The type III TGF-β receptor (TβRIII mediates BMP signaling. While TβRIII expression is lost during breast cancer progression, the role of TβRIII in regulating BMP signaling in normal mammary epithelium and breast cancer cells has not been examined. Restoring TβRIII expression in a 4T1 murine syngeneic model of breast cancer suppressed Smad1/5/8 phosphorylation and inhibited the expression of the BMP transcriptional targets, Id1 and Smad6, in vivo. Similarly, restoring TβRIII expression in human breast cancer cell lines or treatment with sTβRIII inhibited BMP-induced Smad1/5/8 phosphorylation and BMP-stimulated migration and invasion. In normal mammary epithelial cells, shRNA-mediated silencing of TβRIII, TβRIII over-expression, or treatment with sTβRIII inhibited BMP-mediated phosphorylation of Smad1/5/8 and BMP induced migration. Inhibition of TβRIII shedding through treatment with TAPI-2 or expression of a non-shedding TβRIII mutant rescued TβRIII mediated inhibition of BMP induced Smad1/5/8 phosphorylation and BMP induced migration and/or invasion in both in normal mammary epithelial cells and breast cancer cells. Conversely, expression of a TβRIII mutant, which exhibited increased shedding, significantly reduced BMP-mediated Smad1/5/8 phosphorylation, migration, and invasion. These data demonstrate that TβRIII regulates BMP-mediated signaling and biological effects, primarily through the ligand sequestration effects of sTβRIII in normal and cancerous mammary epithelial cells and suggest that the ratio of membrane bound versus sTβRIII plays an important role in mediating these effects.

  15. Concurrent chemoradiation for stage III non small cell lung cancer: present results and future prospects

    International Nuclear Information System (INIS)

    The prognosis of stage III non small cell lung cancer is reportedly poor, particularly in patients with mediastinal lymph node involvement. These patients may be either good surgical candidates, marginally resectable, or inoperable for technical or medical reasons, but, in any case, surgery and/or radiotherapy are curative in only a minority of them. The high incidence of early distant failures underscores the need for early and effective systemic therapy in association with local treatment, since occult metastatic disease is present in most patients at the time of diagnosis. Recent phase III trials have demonstrated significant benefit to induction chemotherapy prior to irradiation or surgery in reducing the distant metastasis rate. However, poor local control remains a major issue in these locally advanced tumors. In patients with inoperable disease, the concomitant use of chemotherapy along with radiotherapy substantially improves local control. For operable patients, induction chemotherapy with concomitant moderate-dose radiotherapy improves local control as well, and may facilitate surgical resection in marginally operable cases. Currently, a number of phase II clinical trials report encouraging results with concomitant chemoradiotherapy used either prior to surgery or with curative intent in locally advanced non small cell lung cancer. (authors). 27 refs

  16. Radiotherapy alone for elderly patients with stage III non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Kikuo; Hiramoto, Takehiko; Kanehara, Masasi; Doi, Mihoko; Furonaka, Osamu; Miyazu, Yuka; Hada, Yosihiro [National Hospital of Kure, Hiroshima (Japan)

    1999-04-01

    We undertook a retrospective study of elderly patients with stage III non-small cell lung cancer who had been treated solely with radiotherapy during the period 1986 to 1995. Our study was designed to assess the influence of age on survival and malnutrition in patients aged 75 years or older (elderly group) and patients aged 74 years or younger (younger group). Radiotherapy alone resulted in a median survival period of 11.5 months in the younger group and 6.3 months in the elderly group (p=0.0043). With the Cox multivariate model, good performance status, age less than 75 years, and good response were significant favorable independent predictors. Furthermore, the elderly group patients more frequently died of respiratory infections and had lower prognostic nutritional indexes than the younger group patients before and after radiotherapy. These findings suggested elderly patients with stage III non-small cell lung cancer who had been treated with radiotherapy alone had a poor prognosis and that malnutrition caused by radiotherapy was a factor contributing to the risk of death from respiratory infection in such patients. (author)

  17. Radiotherapy alone for elderly patients with stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    We undertook a retrospective study of elderly patients with stage III non-small cell lung cancer who had been treated solely with radiotherapy during the period 1986 to 1995. Our study was designed to assess the influence of age on survival and malnutrition in patients aged 75 years or older (elderly group) and patients aged 74 years or younger (younger group). Radiotherapy alone resulted in a median survival period of 11.5 months in the younger group and 6.3 months in the elderly group (p=0.0043). With the Cox multivariate model, good performance status, age less than 75 years, and good response were significant favorable independent predictors. Furthermore, the elderly group patients more frequently died of respiratory infections and had lower prognostic nutritional indexes than the younger group patients before and after radiotherapy. These findings suggested elderly patients with stage III non-small cell lung cancer who had been treated with radiotherapy alone had a poor prognosis and that malnutrition caused by radiotherapy was a factor contributing to the risk of death from respiratory infection in such patients. (author)

  18. Roles of the Valine Clusters in Domain 3 of the Hemolytic Lectin CEL-III in Its Oligomerization and Hemolytic Abilities

    OpenAIRE

    Hisamatsu, Keigo; Unno, Hideaki; Goda, Shuichiro; Hatakeyama, Tomomitsu

    2009-01-01

    The hemolytic lectin CEL-III and its site-directed mutants were expressed in Escherichia coli cells. Replacement of the valine clusters in domain 3 with alanine residues led to increased self-oligomerization in solution and higher hemolytic activity. The results suggest the involvement of these valine clusters in CEL-III oligomerization and hemolytic activity.

  19. Changes in the BDNF-immunopositive cell population of neocortical layers I and II/III after focal cerebral ischemia in rats.

    Science.gov (United States)

    Choi, Yongwon; Kang, Sung Goo; Kam, Kyung-Yoon

    2015-04-24

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family and is widely distributed in the central nervous system, including the cerebral cortex. BDNF plays an important role in normal neural development, survival of existing neurons, and activity-dependent neuroplasticity. BDNF can also be neuroprotective and evoke neurogenesis in certain pathological conditions, such as cerebral ischemia. Neocortical layer I is an important region that can integrate feedforward and feedback information from other cortical areas and subcortical regions. In addition, it has recently been proposed as a possible source of neuronal progenitor cells after ischemia. Therefore, we investigated changes in the BDNF-immunoreactive cell population of neocortical layers I and II/III after middle cerebral artery occlusion (MCAO)-induced cerebral ischemia in rats. In unaffected condition, the number of BDNF(+) cells in layer I was significantly less than in layer II/III in the cingulate cortex and in the motor and sensory areas. The increase in the number of BDNF(+) cells in layer I 8 days after MCAO was more remarkable than layer II/III, in all regions except the area of cingulate cortex farthest from the infarct core. Only BDNF(+)-Ox-42(+) cells showed a tendency to increase consistently toward the infarct core in both layers I and II/III, implying a major source of BDNF for response to ischemic injury. The present study suggests that some beneficial effects during recovery from ischemic injury, such as increased supportive microglia/macrophages, occur owing to a sensitive response of BDNF in layer I. PMID:25681548

  20. Human T-cell lymphotropic virus type III infection in a cohort of homosexual men in New York City

    International Nuclear Information System (INIS)

    Using blood samples collected since 1978, the authors investigated the epidemiology of human T-cell lymphotropic virus type III (HTLV-III), the etiologic agent of the acquired immunodeficiency syndrome, in a group of 378 homosexually active men who have resided in New York City since the acquire immunodeficiency syndrome epidemic began. The anti-HTLV-III prevalence was 6.6% in sera from 1978 or 1979, and the subsequent annual incidence of seroconversion among susceptible men ranged between 5.5% and 10.6%. The highest incidences were in recent years, even though these men reported a decrease in their sexual activity during this time. These data demonstrate the continuing risk of HTLV-III infections in the homosexual population studied and emphasize the need for more effective prevention of transmission. The year during which antibody was first present was the only factor identified that was associated with altered cell-mediated immunity in antibody-positive men

  1. Human T-cell lymphotropic virus type III infection in a cohort of homosexual men in New York City

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, C.E.; Taylor, P.E.; Zang, E.A.; Morrison, J.M.; Harley, E.J.; de Cordoba, S.R.; Bacino, C.; Ting, R.C.; Bodner, A.J.; Sarngadharan, M.G.; Gallo, R.C.

    1986-04-25

    Using blood samples collected since 1978, the authors investigated the epidemiology of human T-cell lymphotropic virus type III (HTLV-III), the etiologic agent of the acquired immunodeficiency syndrome, in a group of 378 homosexually active men who have resided in New York City since the acquire immunodeficiency syndrome epidemic began. The anti-HTLV-III prevalence was 6.6% in sera from 1978 or 1979, and the subsequent annual incidence of seroconversion among susceptible men ranged between 5.5% and 10.6%. The highest incidences were in recent years, even though these men reported a decrease in their sexual activity during this time. These data demonstrate the continuing risk of HTLV-III infections in the homosexual population studied and emphasize the need for more effective prevention of transmission. The year during which antibody was first present was the only factor identified that was associated with altered cell-mediated immunity in antibody-positive men.

  2. Effect of using heat-inactivated serum with the Abbott human T-cell lymphotropic virus type III antibody test.

    OpenAIRE

    Jungkind, D. L.; DiRenzo, S A; Young, S J

    1986-01-01

    The Abbott enzyme immunoassay (Abbott Laboratories, North Chicago, Ill.) for human T-cell lymphotropic virus type III (HTLV-III) antibody was evaluated to determine the effect of using heat-inactivated (56 degrees C for 30 min) serum as the sample. Each of 58 nonreactive serum samples gave a higher A492 value when tested after heat inactivation. Ten of the samples became reactive after heating. Heat-inactivated serum should not be used in the current Abbott HTLV-III antibody test, because thi...

  3. Expressions of the multidrug resistance-related proteins in the rat olfactory epithelium: a possible role in the phase III xenobiotic metabolizing function.

    Science.gov (United States)

    Kudo, Hideaki; Doi, Yoshiaki; Fujimoto, Sunao

    2010-01-01

    The xenobiotic metabolizing system is considered to play important roles in the olfaction by the chemical homeostasis. Several phase I and phase II xenobiotic metabolizing enzymes are expressed in the olfactory epithelium in vertebrates. Multidrug resistance-related proteins (MRPs) are the phase III xenobiotic metabolizing pumps that eliminate some conjugated ligands from cells. However, the MRP-expressions in the olfactory epithelium have not been confirmed in the mammals. We investigated gene and protein expressions of MRP type 1 (MRP1) and type 2 (MRP2) isoforms in the adult rat olfactory epithelium in order to clarify the existence of phase III xenobiotic metabolizing pumps in the olfactory organs. Expressions of MRP1 mRNA were detected in the nasal cavity by reverse transcriptase polymerase chain reaction (RT-PCR). The nucleoside sequence of the RT-PCR products were completely identical to that found in other organs of rat. On the contrary, the analysis did not detect expressions of MRP2 mRNA in the nasal cavity. By in situ hybridization using a digoxigenin-labeled MRP1 cRNA probe, signals for MRP1 mRNA were observed preferentially in the perinuclear regions of supporting cells. However, the respiratory epithelial cells did not show the signals for MRP1 mRNA. By immunohistochemistry using a specific antibody to MRP1, MRP1-immunoreactivities were seen mainly on the supporting cells. These findings suggest that MRP1 is involved in olfaction as a part of the "olfactory signal termination" by the chemical homeostasis in the "perireceptor events" of the olfactory epithelium. PMID:19879335

  4. Implication of TLR- but not of NOD2-signaling pathways in dendritic cell activation by group B Streptococcus serotypes III and V.

    Directory of Open Access Journals (Sweden)

    Paul Lemire

    Full Text Available Group B Streptococcus (GBS is an important agent of life-threatening invasive infection. It has been previously shown that encapsulated type III GBS is easily internalized by dendritic cells (DCs, and that this internalization had an impact on cytokine production. The receptors underlying these processes are poorly characterized. Knowledge on the mechanisms used by type V GBS to activate DCs is minimal. In this work, we investigated the role of Toll-like receptor (TLR/MyD88 signaling pathway, the particular involvement of TLR2, and that of the intracellular sensing receptor NOD2 in the activation of DCs by types III and V GBS. The role of capsular polysaccharide (CPS, one of the most important GBS virulence factors in bacterial-DC interactions was evaluated using non-encapsulated mutants. Despite differences in the role of CPS between types III and V GBS in bacterial internalization and intracellular survival, no major differences were observed in their capacity to modulate release of cytokines by DC. For both serotypes, CPS had a minor role in this response. Production of cytokines by DCs was shown to strongly rely on MyD88-dependent signaling pathways, suggesting that DCs recognize GBS and become activated mostly through TLR signaling. Yet, GBS-infected TLR2-/- DCs only showed a partial reduction in the production of IL-6 and CXCL1 compared to control DCs. Surprisingly, CXCL10 release by type III or type V GBS-infected DCs was MyD88-independent. No differences in DC activation were observed between NOD2-/- and control DCs. These results demonstrate the involvement of various receptors and the complexity of the cytokine production pathways activated by GBS upon DC infection.

  5. Iron metabolism and cell membranes. III. Iron-induced alterations in HeLa cells.

    Science.gov (United States)

    Jauregui, H. O.; Bradford, W. D.; Arstila, A. U.; Kinney, T. D.; Trump, B. F.

    1975-01-01

    The morphologic characteristics of acute iron loading were studied in HeLa cells incubated in an iron-enriched Eagle's medium containing 500 mug/ml of iron. Chemical studies showed that ferritin synthesis was rapidly induced and the concentration of intracellular ferritin increased up to 72 hours. Closely coupled with an increase in HeLa cell ferritin was a marked decrease in the rate of cell multiplication. The significant ultrastructural findings of iron-induced HeLa cell injury are characterized by the appearance of both autophagic multivesicular and residual bodies over the first 72 hours of iron incubation. The prominence of multivesicular bodies was noted after only 4 hours' incubation, with iron and myelin figures first appearing after 6 hours. Thus, the partial arrest of cell multiplication was associated with an increase in cytoplasmic residual bodies containing iron and other debris. The distribution of intracellular ferritin within HeLa cells differs significantly from the distribution described previously in hepatic parenchymal cells. In HeLa cells, ferritin particles were confined to lysosomal vesicles and were not identified in cell sap, endoplasmic reticulum, or Golgi apparatus. Images Figure 8 Figure 1 Figure 9 Figure 10 Figure 11 Figure 12 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:1155583

  6. Role of the group III metabotropic glutamate receptor in LTP, depotentiation and LTD in dentate gyrus of freely moving rats.

    Science.gov (United States)

    Klausnitzer, J; Kulla, A; Manahan-Vaughan, D

    2004-02-01

    We investigated whether group III metabotropic glutamate (mGlu) receptors are critically involved in the expression of long-term potentiation (LTP), depotentiation, or long-term depression (LTD) in the dentate gyrus of freely moving rats. Male Wistar rats (7 8 weeks) underwent implantation of stimulating and recording electrodes in the medial perforant path and dentate gyrus granule cell layer, respectively. A cannula was permanently implanted into the ipsilateral cerebral ventricle to enable drug administration. Intracerebral injection of the group III mGlu receptor agonist, L(+)-2-amino-4-phosphonobutanoic acid (AP4), significantly inhibited LTP at a concentration which unaffects basal synaptic transmission. Depotentiation. short-term depression (STD) and LTDwere unaffected by the agonist. The antagonist. (R.S)-r-cyclopropyl-4-phosphonophenylglycine (CPPG), inhibited agonist effects. but had no independent effects on basal synaptic transmission. CPPG did not affect the profile of LTP, depotentiation or STD elicited by low frequency stimulation (LFS) at 0.5 or 3 Hz. but significantly impaired LTD expression (at I Hz) and STD elicited at 5 Hz. These findings suggest that activation of group III mGlu receptors is critically required for LTD. but not LTP or depotentiation in the dentate gyrus and provide evidence for the involvement of separate mechanisms underlying LTD and depotentiation. PMID:15080077

  7. Molecular Recognition of Cobalt(III)-ligated Peptides by Serine Proteases: The Role of Electrostatic Effects

    DEFF Research Database (Denmark)

    Bagger, Sven; Wagner, Kim

    1998-01-01

    A series of peptides with a positively charged cobalt(III)-complex group attached to the carboxylate terminal was synthesized. The behaviour of these metallopeptides as acceptor nucleophiles in acyl transfer reactions catalyzed by the three serine proteases bovine pancreatic à-chymotrypsin, porcine...... pancreatic trypsin, and proteinase K from Tritirachium album was examined. The efficiency of the substrates was assessed by kinetic measurement of the partition between aminolysis and hydrolysis. The results are discussed with special reference to coulombic interactions between the metal-ligated substrates...... and charged residues on the enzyme surfaces. The idea of using the metallopeptides in practical enzymatic peptide synthesis is put forward....

  8. Molecular Recognition of Cobalt(III)-ligated Peptides by Serine Proteases: The Role of Electrostatic Effects

    DEFF Research Database (Denmark)

    Bagger, Sven; Wagner, Kim

    1998-01-01

    A series of peptides with a positively charged cobalt(III)-complex group attached to the carboxylate terminal was synthesized. The behaviour of these metallopeptides as acceptor nucleophiles in acyl transfer reactions catalyzed by the three serine proteases bovine pancreatic à-chymotrypsin, porcine...... pancreatic trypsin, and proteinase K from Tritirachium album was examined. The efficiency of the substrates was assessed by kinetic measurement of the partition between aminolysis and hydrolysis. The results are discussed with special reference to coulombic interactions between the metal-ligated substrates...

  9. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    International Nuclear Information System (INIS)

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  10. Photosynthetic activity and protein overexpression found in Cr(III)-tolerant cells of the green algae Dictyosphaerium chlorelloides.

    Science.gov (United States)

    Pereira, M; Bartolomé, C M; Sánchez-Fortún, S

    2014-08-01

    Chromium is an important constituent in effluents obtained from chromium plating industries. Due to the highly toxic nature of Cr(VI), attention has been shifted to less hazardous Cr(III) electroplating processes. This study evaluated aquatic toxicity of Cr(III)-containing laboratory samples representative of effluents from chromium electroplating industries, on the photosynthetic activity exhibited by both Cr(III)-sensitive (Dc1M(wt)) and tolerant (Dc1M(Cr(III)R30)) Dictyosphaerium chlorelloides strains. Additionally, selected de novo-determined peptide sequences, obtained from Dc1M(Cr(III)R30), have been analyzed to evidence the possible Cr(III) toxic mechanism involved in the resistance of these cells to high Cr(III) levels in aquatic environments. Dc1M(Cr(III)R30) strain exhibited a gross photosynthetic balance of about five times lower than that exhibited by Dc1M(wt) strain, demonstrating that Dc1M(Cr(III)R30) has a photosynthetic yield significantly lower than Dc1M(wt). SDS-PAGE of Dc1M(Cr(III)R30) samples showed the presence of at least two protein bands (23.05 and 153.46 KDa, respectively) absent in wild-type strain samples. Although it has achieved a low coincidence between the lower molecular weight band and a GTPase identified from genome of the green alga Chlamydomonas reinhardtii, none of de novo peptide sequences obtained showed a significant MS-BLAST score, so that further studies will be required. PMID:24556547

  11. Physical role for the nucleus in cell migration

    Science.gov (United States)

    Fruleux, Antoine; Hawkins, Rhoda J.

    2016-09-01

    Cell migration is important for the function of many eukaryotic cells. Recently the nucleus has been shown to play an important role in cell motility. After giving an overview of cell motility mechanisms we review what is currently known about the mechanical properties of the nucleus and the connections between it and the cytoskeleton. We also discuss connections to the extracellular matrix and mechanotransduction. We identify key physical roles of the nucleus in cell migration.

  12. Physical role for the nucleus in cell migration.

    Science.gov (United States)

    Fruleux, Antoine; Hawkins, Rhoda J

    2016-09-14

    Cell migration is important for the function of many eukaryotic cells. Recently the nucleus has been shown to play an important role in cell motility. After giving an overview of cell motility mechanisms we review what is currently known about the mechanical properties of the nucleus and the connections between it and the cytoskeleton. We also discuss connections to the extracellular matrix and mechanotransduction. We identify key physical roles of the nucleus in cell migration. PMID:27406341

  13. Role of PU.1 in MHC Class II Expression via CIITA Transcription in Plasmacytoid Dendritic Cells

    Science.gov (United States)

    Miura, Ryosuke; Kasakura, Kazumi; Nakano, Nobuhiro; Hara, Mutsuko; Maeda, Keiko; Okumura, Ko; Ogawa, Hideoki; Yashiro, Takuya; Nishiyama, Chiharu

    2016-01-01

    The cofactor CIITA is a master regulator of MHC class II expression and several transcription factors regulating the cell type-specific expression of CIITA have been identified. Although the MHC class II expression in plasmacytoid dendritic cells (pDCs) is also mediated by CIITA, the transcription factors involved in the CIITA expression in pDCs are largely unknown. In the present study, we analyzed the role of a hematopoietic lineage-specific transcription factor, PU.1, in CIITA transcription in pDCs. The introduction of PU.1 siRNA into mouse pDCs and a human pDC cell line, CAL-1, reduced the mRNA levels of MHC class II and CIITA. When the binding of PU.1 to the 3rd promoter of CIITA (pIII) in CAL-1 and mouse pDCs was analyzed by a chromatin immunoprecipitation assay, a significant amount of PU.1 binding to the pIII was detected, which was definitely decreased in PU.1 siRNA-transfected cells. Reporter assays showed that PU.1 knockdown reduced the pIII promoter activity and that three Ets-motifs in the human pIII promoter were candidates of cis-enhancing elements. By electrophoretic mobility shift assays, it was confirmed that two Ets-motifs, GGAA (-181/-178) and AGAA (-114/-111), among three candidates, were directly bound with PU.1. When mouse pDCs and CAL-1 cells were stimulated by GM-CSF, mRNA levels of PU.1, pIII-driven CIITA, total CIITA, MHC class II, and the amount of PU.1 binding to pIII were significantly increased. The GM-CSF-mediated up-regulation of these mRNAs was canceled in PU.1 siRNA-introduced cells. Taking these results together, we conclude that PU.1 transactivates the pIII through direct binding to Ets-motifs in the promoter in pDCs. PMID:27105023

  14. Combined chemoradiotherapy with daily low-dose cisplatin in stage III non-small cell lung cancer. An interim report

    International Nuclear Information System (INIS)

    To improve the local control of stage III non-small cell lung cancer, we tried concurrent chemoradiotherapy with daily low-dose cisplatin during the first 5 weeks conventional radiotherapy. Ten consecutive patients with stage III non-small cell lung cancer were treated with chemoradiotherapy with 66 Gy in conventional fractionation and concurrent daily low-dose cisplatin (4 mg/m2), which was given 5 days per week (from Monday to Friday) for the first 5 weeks. There was no case with ≥grade 3 toxicity. The median survival was 14.6 months, and the 2-year local progression-free survival rate was 35%. Daily low-dose cisplatin combined with conventional radiotherapy was considered to be feasible and to have the possibility to offer better local control than radiotherapy alone in the treatment of stage III non-small cell lung cancer. (author)

  15. Profile of differentially expressed genes mediated by the type III epidermal growth factor receptor mutation expressed in a small-cell lung cancer cell line

    DEFF Research Database (Denmark)

    Pedersen, M.W.; Andersen, Thomas Thykjær; Ørntoft, Torben Falck;

    2001-01-01

    understanding of how the EGFRvIII contributes to the malignant phenotype is of major importance for future therapy. The GeneChip Hu6800Set developed by Affymetrix was used to identify changes in gene expression caused by the expression of EGFRvIII. The cell line selected for the study was an EGF receptor...... negative small-cell-lung cancer cell line, GLC3, stably transfected with the EGFRvIII gene in a Tet-On system. By comparison of mRNA levels in EGFRvIII-GLC3 with those of Tet-On-GLC3, it was found that the levels of mRNAs encoding several transcription factors (ATF-3, JunD, and c-Myb), cell adhesion......Previous studies have shown a correlation between expression of the EGF receptor type III mutation (EGFRvIII) and a more malignant phenotype of various cancers including: non-small-cell lung cancer, glioblastoma multiforme, prostate cancer and breast cancer. Thus, a detailed molecular genetic...

  16. Scorpion venom component III inhibits cell proliferation by modulating NF-κB activation in human leukemia cells

    Science.gov (United States)

    SONG, XIANGFENG; ZHANG, GUOJUN; SUN, AIPING; GUO, JIQIANG; TIAN, ZHONGWEI; WANG, HUI; LIU, YUFENG

    2012-01-01

    Scorpion venom contains various groups of compounds that exhibit anticancer activity against a variety of malignancies through a poorly understood mechanism. While the aberrant activation of nuclear factor κB (NF-κB) has been linked with hematopoietic malignancies, we hypothesized that scorpion venom mediates its effects by modulating the NF-κB signaling pathway. In the present study, we examined the effects of scorpion venom component III (SVCIII) on the human leukemia cell lines THP-1 and Jurkat and focused on the NF-κB signaling pathway. Our results showed that SVCIII inhibited cell proliferation, caused cell cycle arrest at G1 phase and inhibited the expression of cell cycle regulatory protein cyclin D1 in a dose-dependent manner in THP-1 and Jurkat cells. SVCIII also suppressed the constitutive NF-κB activation through inhibition of the phosphorylation and degradation of IκBα. NF-κB luciferase reporter activity was also inhibited by SVCIII. Our data suggest that SVCIII, a natural compound, may exert its antiproliferative effects by inhibiting the activation of NF-κB and, thus, has potential use in the treatment of hematopoietic malignancies, alone or in combination with other agents. PMID:23060939

  17. Shoot Meristem Function and Leaf Polarity: The Role of Class III HD–ZIP Genes

    OpenAIRE

    Byrne, Mary E

    2006-01-01

    The shoot apical meristem comprises an organized cluster of cells with a central region population of self-maintaining stem cells providing peripheral region cells that are recruited to form differentiated lateral organs. Leaves, the principal lateral organ of the shoot, develop as polar structures typically with distinct dorsoventrality. Interdependent interactions between the meristem and developing leaf provide essential cues that serve both to maintain the meristem and to pattern dorsoven...

  18. Chloroboron (III) subnaphthalocyanine as an electron donor in bulk heterojunction photovoltaic cells

    International Nuclear Information System (INIS)

    In this work, chloroboron (III) subnaphthalocyanine (SubNc) was used as an electron donor, combined with a [6,6]-phenyl-C71-butyric acid methyl ester (PC70BM) or fullerene C70 acceptor in bulk heterojunction photovoltaic cells. In spite of the limited solubility of SubNc in organic solvents, the solution processed device exhibited an efficiency of 4.0% under 1 sun, AM1.5G solar irradiation at room temperature, and 5.0% at 80 ° C due to the temperature-dependence of the carrier mobilities. SubNc:C70 bulk heterojunctions were also fabricated via thermal co-evaporation, demonstrating an efficiency of 4.4%. This result shows that SubNc is a promising material for photovoltaic applications via various processing techniques, such as vacuum deposition and wet coating. (paper)

  19. EGFR kinase-dependent and kinase-independent roles in clear cell renal cell carcinoma.

    Science.gov (United States)

    Cossu-Rocca, Paolo; Muroni, Maria R; Sanges, Francesca; Sotgiu, Giovanni; Asunis, Anna; Tanca, Luciana; Onnis, Daniela; Pira, Giovanna; Manca, Alessandra; Dore, Simone; Uras, Maria G; Ena, Sara; De Miglio, Maria R

    2016-01-01

    Epidermal growth factor receptor (EGFR) is associated with progression of many epithelial malignancies and represents a significant therapeutic target. Although clear cell renal cell carcinoma (CCRCC) has been widely investigated for EGFR molecular alterations, genetic evidences of EGFR gene activating mutations and/or gene amplification have been rarely confirmed in the literature. Therefore, until now EGFR-targeted therapies in clinical trials have been demonstrated unsuccessful. New evidence has been given about the interactions between EGFR and the sodium glucose co-transporter-1 (SGLT1) in maintaining the glucose basal intracellular level to favour cancer cell growth and survival; thus a new functional role may be attributed to EGFR, regardless of its kinase activity. To define the role of EGFR in CCRCC an extensive investigation of genetic changes and functional kinase activities was performed in a series of tumors by analyzing the EGFR mutational status and expression profile, together with the protein expression of downstream signaling pathways members. Furthermore, we investigated the co-expression of EGFR and SGLT1 proteins and their relationships with clinic-pathological features in CCRCC. EGFR protein expression was identified in 98.4% of CCRCC. Furthermore, it was described for the first time that SGLT1 is overexpressed in CCRCC (80.9%), and that co-expression with EGFR is appreciable in 79.4% of the tumours. Moreover, the activation of downstream EGFR pathways was found in about 79.4% of SGLT1-positive CCRCCs. The mutational status analysis of EGFR failed to demonstrate mutations on exons 18 to 24 and the presence of EGFR-variantIII (EGFRvIII) in all CCRCCs analyzed. FISH analysis revealed absence of EGFR amplification, and high polysomy of chromosome 7. Finally, the EGFR gene expression profile showed gene overexpression in 38.2% of CCRCCs. Our study contributes to define the complexity of EGFR role in CCRCC, identifying its bivalent kinase

  20. Enhanced Cr(VI) reduction and As(III) oxidation in ice phase: Important role of dissolved organic matter from biochar

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Xiaoling [Department of Soil and Water Science, University of Florida, Gainesville, FL 32611 (United States); Ma, Lena Q., E-mail: lqma@ufl.edu [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Jiangsu 210046 (China); Department of Soil and Water Science, University of Florida, Gainesville, FL 32611 (United States); Gress, Julia; Harris, Willie [Department of Soil and Water Science, University of Florida, Gainesville, FL 32611 (United States); Li, Yuncong [Soil and Water Science Department, Tropical Research and Education Center, University of Florida, Homestead, FL 33031-3314 (United States)

    2014-02-01

    Graphical abstract: - Highlights: • Biochar-derived dissolved organic matter (DOM) effectively reduced Cr(VI) and oxidized As(III). • Cr(VI) and As(III) could serve as a redox couple. • Cr(VI) and As(III) redox conversion was more effective in the ice phase than aqueous phase. • FTIR and ESR showed that biochar DOM served as both electron donor and acceptor. - Abstract: This study evaluated the impact of DOM from two biochars (sugar beet tailing and Brazilian pepper) on Cr(VI) reduction and As(III) oxidation in both ice and aqueous phases with a soil DOM as control. Increasing DOM concentration from 3 to 300 mg C L{sup −1} enhanced Cr(VI) reduction from 20% to 100% and As(III) oxidation from 6.2% to 25%; however, Cr(VI) reduction decreased from 80–86% to negligible while As(III) oxidation increased from negligible to 18–19% with increasing pH from 2 to 10. Electron spin resonance study suggested semiquinone radicals in DOM were involved in As(III) oxidation while Fourier transform infrared analysis suggested that carboxylic groups in DOM participated in both Cr(VI) reduction and As(III) oxidation. During Cr(VI) reduction, part of DOM (∼10%) was oxidized to CO{sub 2}. The enhanced conversion of Cr(VI) and As(III) in the ice phase was due to the freeze concentration effect with elevated concentrations of electron donors and electron acceptors in the grain boundary. Though DOM enhanced both Cr(VI) reduction and As(III)oxidation, Cr(VI) reduction coupled with As(III) oxidation occurred in absence of DOM. The role of DOM, Cr(VI) and/or As(III) in Cr and As transformation may provide new insights into their speciation and toxicity in cold regions.

  1. Enhanced Cr(VI) reduction and As(III) oxidation in ice phase: Important role of dissolved organic matter from biochar

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • Biochar-derived dissolved organic matter (DOM) effectively reduced Cr(VI) and oxidized As(III). • Cr(VI) and As(III) could serve as a redox couple. • Cr(VI) and As(III) redox conversion was more effective in the ice phase than aqueous phase. • FTIR and ESR showed that biochar DOM served as both electron donor and acceptor. - Abstract: This study evaluated the impact of DOM from two biochars (sugar beet tailing and Brazilian pepper) on Cr(VI) reduction and As(III) oxidation in both ice and aqueous phases with a soil DOM as control. Increasing DOM concentration from 3 to 300 mg C L−1 enhanced Cr(VI) reduction from 20% to 100% and As(III) oxidation from 6.2% to 25%; however, Cr(VI) reduction decreased from 80–86% to negligible while As(III) oxidation increased from negligible to 18–19% with increasing pH from 2 to 10. Electron spin resonance study suggested semiquinone radicals in DOM were involved in As(III) oxidation while Fourier transform infrared analysis suggested that carboxylic groups in DOM participated in both Cr(VI) reduction and As(III) oxidation. During Cr(VI) reduction, part of DOM (∼10%) was oxidized to CO2. The enhanced conversion of Cr(VI) and As(III) in the ice phase was due to the freeze concentration effect with elevated concentrations of electron donors and electron acceptors in the grain boundary. Though DOM enhanced both Cr(VI) reduction and As(III)oxidation, Cr(VI) reduction coupled with As(III) oxidation occurred in absence of DOM. The role of DOM, Cr(VI) and/or As(III) in Cr and As transformation may provide new insights into their speciation and toxicity in cold regions

  2. The role of technology in reducing health care costs. Phase II and phase III.

    Energy Technology Data Exchange (ETDEWEB)

    Cilke, John F.; Parks, Raymond C.; Funkhouser, Donald Ray; Tebo, Michael A.; Murphy, Martin D.; Hightower, Marion Michael; Gallagher, Linda K.; Craft, Richard Layne, II; Garcia, Rudy John

    2004-04-01

    In Phase I of this project, reported in SAND97-1922, Sandia National Laboratories applied a systems approach to identifying innovative biomedical technologies with the potential to reduce U.S. health care delivery costs while maintaining care quality. The effort provided roadmaps for the development and integration of technology to meet perceived care delivery requirements and an economic analysis model for development of care pathway costs for two conditions: coronary artery disease (CAD) and benign prostatic hypertrophy (BPH). Phases II and III of this project, which are presented in this report, were directed at detailing the parameters of telemedicine that influence care delivery costs and quality. These results were used to identify and field test the communication, interoperability, and security capabilities needed for cost-effective, secure, and reliable health care via telemedicine.

  3. Roles of ionizing radiation in cell transformation

    International Nuclear Information System (INIS)

    Earlier the authors described a repair misrepair model (RMR-I) which is applicable for radiations of low LET, e.g., x rays and gamma rays. RMR-II was described later. Here is introduced a mathematical modification of the RMR model, RMR-III, which is intended to describe lethal effects caused by heavily ionizing tracks. 31 references, 4 figures

  4. Preparation and evaluation of [201Tl](III)-DTPA complex for cell labeling

    International Nuclear Information System (INIS)

    Due to interesting physical properties and wide availability of 201Tl as a SPECT radionuclide, the incorporation of this nuclide into DTPA for cell labeling was targeted. Thallium-201 (T1/2 = 3.04 d) in Tl+ form was converted to Tl3+ cation in the presence of O3/6M HCl and di-isopropyl ether, controlled by RTLC/gel electrophoresis methods. The final evaporated activity reacted with cDTPA in normal saline to yield [201Tl](III)DTPA at room temperature after 0.5 hour, followed by solid phase extraction purification using C18 Sep-Pak column (radiochemical yield >95%). Radiochemical purity of more than 99% was obtained using RTLC with specific activity of about 260 GBq/mmol. The stability of the tracer was checked in the final product in the presence of human serum at 37 deg C up to 3 days. The partition coefficient was also measured. The labeled compound was used in red blood cell (RBC) labeling. The cell uptake ratio was determined at 4, 25 and 37 deg C up to 3 hours. (author)

  5. Role of Calmodulin in Cell Proliferation

    Science.gov (United States)

    Chafouleas, J.

    1983-01-01

    Calmodulin levels were found to increase as cells enter plateau. The data suggest that the cells are exiting the cell cycle late in the G sub 1 phase, or that the calmodulin levels in plateau cells are uncoupled to progression into S phase in plateau cells. Upon release, calmodulin levels rapidly decrease. Following this decrease, there is a increase prior to S phase.

  6. ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death.

    Science.gov (United States)

    Raab, M; Gentili, M; de Belly, H; Thiam, H R; Vargas, P; Jimenez, A J; Lautenschlaeger, F; Voituriez, Raphaël; Lennon-Duménil, A M; Manel, N; Piel, M

    2016-04-15

    In eukaryotic cells, the nuclear envelope separates the genomic DNA from the cytoplasmic space and regulates protein trafficking between the two compartments. This barrier is only transiently dissolved during mitosis. Here, we found that it also opened at high frequency in migrating mammalian cells during interphase, which allowed nuclear proteins to leak out and cytoplasmic proteins to leak in. This transient opening was caused by nuclear deformation and was rapidly repaired in an ESCRT (endosomal sorting complexes required for transport)-dependent manner. DNA double-strand breaks coincided with nuclear envelope opening events. As a consequence, survival of cells migrating through confining environments depended on efficient nuclear envelope and DNA repair machineries. Nuclear envelope opening in migrating leukocytes could have potentially important consequences for normal and pathological immune responses. PMID:27013426

  7. Ce(III)/Ce(IV) in methanesulfonic acid as the positive half cell of a redox flow battery

    International Nuclear Information System (INIS)

    The characteristics of the Ce(III)/Ce(IV) redox couple in methanesulfonic acid were studied at a platinum disk electrode (0.125 cm2) over a wide range of electrolyte compositions and temperatures: cerium (III) methanesulfonate (0.1-1.2 mol dm-3), methanesulfonic acid (0.1-5.0 mol dm-3) and electrolyte temperatures (295-333 K). The cyclic voltammetry experiments indicated that the diffusion coefficient of Ce(III) ions was 0.5 x 10-6 cm2 s-1 and that the electrochemical kinetics for the oxidation of Ce(III) and the reduction of Ce(IV) was slow. The reversibility of the redox reaction depended on the electrolyte composition and improved at higher electrolyte temperatures. At higher methanesulfonic acid concentrations, the degree of oxygen evolution decreased by up to 50% when the acid concentration increased from 2 to 5 mol dm-3. The oxidation of Ce(III) and reduction of Ce(IV) were also investigated during a constant current batch electrolysis in a parallel plate zinc-cerium flow cell with a 3-dimensional platinised titanium mesh electrode. The current efficiencies over 4.5 h of the process Ce(III) to Ce(IV) and 3.3 h electrolysis of the reverse reaction Ce(IV) to Ce(III) were 94.0 and 97.6%, respectively. With a 2-dimensional, planar platinised titanium electrode (9 cm2 area), the redox reaction of the Ce(III)/Ce(IV) system was under mass-transport control, while the reaction on the 3-dimensional mesh electrode was initially under charge-transfer control but became mass-transport controlled after 2.5-3 h of electrolysis. The effect of the side reactions (hydrogen and oxygen evolution) on the current efficiencies and the conversion of Ce(III) and Ce(IV) are discussed.

  8. Interaction of atriopeptin III and vasopressin on calcium kinetics and contraction of aortic smooth muscle cells

    International Nuclear Information System (INIS)

    The cellular mechanism of the vasodilatory action of atriopeptin III (APIII) on vasopressin (AVP)-induced Ca2+ mobilization and cell shape change in cultured vascular smooth muscle cells (VSMC) was studied. APIII (10(-8) M) attenuated the increase of intracellular free Ca2+, [Ca2+]i, induced by 10(-8) M AVP (234.0 +/- 14.8 vs. 310.0 +/- 28.4 nM, P less than 0.01). Similar results were obtained in 45Ca2+ efflux experiments. APIII (10(-7) M), however, did not alter AVP-induced inositol trisphosphate (IP3) production, although the levels of inositol-1-phosphate were significantly reduced. The effect of APIII to block or attenuate AVP-induced Ca2+ mobilization was associated with an inhibition of AVP-stimulated cell shape change. The effect of atrial natriuretic factor (ANF) on cell shape, however, occurred at lower ANF concentrations than the effect on the Ca2+ mobilization. APIII stimulated production of cyclic guanosine monophosphate (cGMP) in VSMC. The effect of APIII on AVP-stimulated Ca2+ mobilization was partially mimicked by the stable nucleotide 8-bromo cGMP and was not affected by the soluble guanylate cyclase inhibitor, methylene blue (10(-4) M). These results suggest that APIII exerts its vasodilatory effect, in part, by interference with vasopressor-stimulated Ca2+ mobilization in vascular smooth muscle cells, perhaps by stimulating particulate guanylate cyclase and cGMP. However, an effect of ANF on the contractile mechanism at a site independent of Ca2+ release is also suggested by the present results

  9. Phase III Advanced Anodes and Cathodes Utilized in Energy Efficient Aluminum Production Cells

    Energy Technology Data Exchange (ETDEWEB)

    R.A. Christini; R.K. Dawless; S.P. Ray; D.A. Weirauch, Jr.

    2001-11-05

    During Phase I of the present program, Alcoa developed a commercial cell concept that has been estimated to save 30% of the energy required for aluminum smelting. Phase ii involved the construction of a pilot facility and operation of two pilots. Phase iii of the Advanced Anodes and Cathodes Program was aimed at bench experiments to permit the resolution of certain questions to be followed by three pilot cells. All of the milestones related to materials, in particular metal purity, were attained with distinct improvements over work in previous phases of the program. NiO additions to the ceramic phase and Ag additions to the Cu metal phase of the cermet improved corrosion resistance sufficiently that the bench scale pencil anodes met the purity milestones. Some excellent metal purity results have been obtained with anodes of the following composition: Further improvements in anode material composition appear to be dependent on a better understanding of oxide solubilities in molten cryolite. For that reason, work was commissioned with an outside consultant to model the MeO - cryolite systems. That work has led to a better understanding of which oxides can be used to substitute into the NiO-Fe2O3 ceramic phase to stabilize the ferrites and reduce their solubility in molten cryolite. An extensive number of vertical plate bench electrolysis cells were run to try to find conditions where high current efficiencies could be attained. TiB2-G plates were very inconsistent and led to poor wetting and drainage. Pure TiB2 did produce good current efficiencies at small overlaps (shadowing) between the anodes and cathodes. This bench work with vertical plate anodes and cathodes reinforced the importance of good cathode wetting to attain high current efficiencies. Because of those conclusions, new wetting work was commissioned and became a major component of the research during the third year of Phase III. While significant progress was made in several areas, much work needs to be

  10. DNA damage and repair kinetics of the Alternaria mycotoxins alternariol, altertoxin II and stemphyltoxin III in cultured cells.

    Science.gov (United States)

    Fleck, Stefanie C; Sauter, Friederike; Pfeiffer, Erika; Metzler, Manfred; Hartwig, Andrea; Köberle, Beate

    2016-03-01

    The Alternaria mycotoxins alternariol (AOH) and altertoxin II (ATX II) have previously been shown to elicit mutagenic and genotoxic effects in bacterial and mammalian cells, although with vastly different activities. For example, ATX II was about 50 times more mutagenic than AOH. We now report that stemphyltoxin III (STTX III) is also highly mutagenic. The more pronounced effects of the perylene quinones ATX II and STTX III at lower concentrations compared to the dibenzo-α-pyrone AOH indicate a marked dependence of the genotoxic potential on the chemical structure and furthermore suggest that the underlying modes of action may be different. We have now further investigated the type of DNA damage induced by AOH, ATX II and STTX III, as well as the repair kinetics and their dependence on the status of nucleotide excision repair (NER). DNA double strand breaks induced by AOH due to poisoning of topoisomerase IIα were completely repaired in less than 2h. Under cell-free conditions, inhibition of topoisomerase IIα could also be measured for ATX II and STTX III at low concentrations, but the perylene quinones were catalytic inhibitors rather than topoisomerase poisons and did not induce DSBs. DNA strand breaks induced by ATX II and STTX III were more persistent and not completely repaired within 24h. A dependence of the repair rate on the NER status could only be demonstrated for STTX III, resulting in an accumulation of DNA damage in NER-deficient cells. Together with the finding that the DNA glycosylase formamidopyrimidine-DNA glycosylase (Fpg), but not T4 endonuclease V, is able to generate additional DNA strand breaks measurable by the alkaline unwinding assay, we conclude that the genotoxicity of the perylene quinones with an epoxide group is probably caused by the formation of DNA adducts which may be converted to Fpg sensitive sites. PMID:26994491

  11. Prohibitin( PHB) roles in granulosa cell physiology.

    Science.gov (United States)

    Chowdhury, Indrajit; Thomas, Kelwyn; Thompson, Winston E

    2016-01-01

    Ovarian granulosa cells (GC) play an important role in the growth and development of the follicle in the process known as folliculogenesis. In the present review, we focus on recent developments in prohibitin (PHB) research in relation to GC physiological functions. PHB is a member of a highly conserved eukaryotic protein family containing the repressor of estrogen activity (REA)/stomatin/PHB/flotillin/HflK/C (SPFH) domain (also known as the PHB domain) found in diverse species from prokaryotes to eukaryotes. PHB is ubiquitously expressed in a circulating free form or is present in multiple cellular compartments including mitochondria, nucleus and plasma membrane. In mitochondria, PHB is anchored to the mitochondrial inner membrane and forms complexes with the ATPases associated with proteases having diverse cellular activities. PHB continuously shuttles between the mitochondria, cytosol and nucleus. In the nucleus, PHB interacts with various transcription factors and modulates transcriptional activity directly or through interactions with chromatin remodeling proteins. Many functions have been attributed to the mitochondrial and nuclear PHB complexes such as cellular differentiation, anti-proliferation, morphogenesis and maintenance of the functional integrity of the mitochondria. However, to date, the regulation of PHB expression patterns and GC physiological functions are not completely understood. PMID:26496733

  12. Role of Vibrational Spectroscopy in Stem Cell Research

    OpenAIRE

    AKSOY, Ceren; Severcan, Feride

    2012-01-01

    Recent researches have mainly displayed the significant role of stem cells in tissue renewal and homeostasis with their unique capacity to develop different cell types. These findings have clarified the importance of stem cells to improve the effectiveness of any cell therapy for regenerative medicine. Identification of purity and differentiation stages of stem cells are the greatest challenges of stem cell biology and regenerative medicine. The existing methods to carefully monitor and chara...

  13. Cell-penetration by Co(III)cyclen-based peptide-cleaving catalysts selective for pathogenic proteins of amyloidoses.

    Science.gov (United States)

    Chei, Woo Suk; Lee, Joo-Won; Kim, Jae Bum; Suh, Junghun

    2010-07-15

    Derivatives of the Co(III) complex of 1,4,7,10-tetraazacyclododecane (cyclen) with various organic pendants have been reported as target-selective peptide-cleaving catalysts, which can be exploited as catalytic drugs. In order to provide a firm basis for the catalytic drugs based on Co(III)cyclen, the ability of the Co(III)cyclen-containing peptide-cleaving catalysts to penetrate animal cells such as mouse fibroblast NIH-3T 3 or human embryonic kidney (HEK) 293 cells is demonstrated in the present study. Since the catalysts destroy pathogenic proteins for amyloidoses, results of the present study are expected to initiate extensive efforts to obtain therapeutically safe catalytic drugs for amyloidoses such as Alzheimer's disease, type 2 diabetes mellitus, Parkinson's disease, Huntington's disease, mad cow disease, and so on. PMID:20542701

  14. Type I and III IFNs Produced by Plasmacytoid Dendritic Cells in Response to a Member of the Flaviviridae Suppress Cellular Immune Responses.

    Science.gov (United States)

    Reid, Elizabeth; Juleff, Nicholas; Windsor, Miriam; Gubbins, Simon; Roberts, Lisa; Morgan, Sophie; Meyers, Gregor; Perez-Martin, Eva; Tchilian, Elma; Charleston, Bryan; Seago, Julian

    2016-05-15

    The pestivirus noncytopathic bovine viral diarrhea virus (BVDV) can suppress IFN production in the majority of cell types in vitro. However, IFN is detectable in serum during acute infection in vivo for ∼5-7 d, which correlates with a period of leucopoenia and immunosuppression. In this study, we demonstrate that a highly enriched population of bovine plasmacytoid dendritic cells (DCs) produced IFN in response to BVDV in vitro. We further show that the majority of the IFN produced in response to infection both in vitro and in vivo is type III IFN and acid labile. Further, we show IL-28B (IFN-λ3) mRNA is induced in this cell population in vitro. Supernatant from plasmacytoid DCs harvested postinfection with BVDV or recombinant bovine IFN-α or human IL-28B significantly reduced CD4(+) T cell proliferation induced by tubercle bacillus Ag 85-stimulated monocyte-derived DCs. Furthermore, these IFNs induced IFN-stimulated gene expression predominantly in monocyte-derived DCs. IFN-treated immature DCs derived from murine bone marrow also had a reduced capacity to stimulate T cell proliferative responses to tubercle bacillus Ag 85. Immature DCs derived from either source had a reduced capacity for Ag uptake following IFN treatment that is dose dependent. Immunosuppression is a feature of a number of pestivirus infections; our studies suggest type III IFN production plays a key role in the pathogenesis of this family of viruses. Overall, in a natural host, we have demonstrated a link between the induction of type I and III IFN after acute viral infection and transient immunosuppression. PMID:27053760

  15. Natural montmorillonite induced photooxidation of As(III) in aqueous suspensions: Roles and sources of hydroxyl and hydroperoxyl/superoxide radicals

    International Nuclear Information System (INIS)

    Highlights: • Natural montmorillonite contributes to photochemical oxidation of arsenite. • Ferrous ions significantly affect photochemical behavior of montmorillonite. • HO· and HO2·/O2−· play different roles in this process. -- Abstract: Photooxidation of arsenite(As(III)) in a suspension of natural montmorillonite under the irradiation of metal halide lamp (λ ≥ 313 nm)has been investigated. The results showed that the natural montmorillonite induced the photooxidation of As(III) by generating hydroxyl radicals (HO·) and hydroperoxyl/superoxide radicals (HO2·/O2−·). HO· which was responsible for the As(III) photooxidation. Approximately 38% of HO· was generated by the photolysis of ferric ions, and the formation of the remaining 62% was strongly dependent on the HO2·/O2−·. The presence of free ironions (Fe2+ and Fe3+), made significant contributions to the photogeneration of these reactive oxygen species (ROS). The photooxidation of As(III) in natural montmorillonite suspensions was greatly influenced by the pH values. The photooxidation of As(III) by natural montmorillonite followed the Langmuir–Hinshelwood equation. In addition, the photooxidation of As(III) could be enhanced by the addition of humic acid. This work demonstrates that photooxidation may be an important environmental process for the oxidation of As(III) and may be a way to remove As(III) from acidic surface water containing iron-bearing clay minerals

  16. Improved photodynamic action of nanoparticles loaded with indium (III) phthalocyanine on MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Souto, Carlos Augusto Zanoni [Federal Institute of Espirito Santo (Brazil); Madeira, Klesia Pirola [Federal University of Espirito Santo, Biotechnology Program/RENORBIO, Health Sciences Center (Brazil); Rettori, Daniel [Federal University of Sao Paulo, Department of Exact Sciences and Earth (Brazil); Baratti, Mariana Ozello [University of Campinas, Department of Cellular Biology (Brazil); Rangel, Leticia Batista Azevedo [Federal University of Espirito Santo, Department of Pharmaceutical Sciences (Brazil); Razzo, Daniel [University of Campinas, Department of Physical Chemistry, Institute of Chemistry (Brazil); Silva, Andre Romero da, E-mail: aromero@ifes.edu.br [Federal Institute of Espirito Santo (Brazil)

    2013-09-15

    Indium (III) phthalocyanine (InPc) was encapsulated into nanoparticles of PEGylated poly(d,l-lactide-co-glycolide) (PLGA-PEG) to improve the photobiological activity of the photosensitizer. The efficacy of nanoparticles loaded with InPc and their cellular uptake was investigated with MCF-7 breast tumor cells, and compared with the free InPc. The influence of photosensitizer (PS) concentration (1.8-7.5 {mu}mol/L), incubation time (1-2 h), and laser power (10-100 mW) were studied on the photodynamic effect caused by the encapsulated and the free InPc. Nanoparticles with a size distribution ranging from 61 to 243 nm and with InPc entrapment efficiency of 72 {+-} 6 % were used in the experiments. Only the photodynamic effect of encapsulated InPc was dependent on PS concentration and laser power. The InPc-loaded nanoparticles were more efficient in reducing MCF-7 cell viability than the free PS. For a light dose of 7.5 J/cm{sup 2} and laser power of 100 mW, the effectiveness of encapsulated InPc to reduce the viability was 34 {+-} 3 % while for free InPc was 60 {+-} 7 %. Confocal microscopy showed that InPc-loaded nanoparticles, as well as free InPc, were found throughout the cytosol. However, the nanoparticle aggregates and the aggregates of free PS were found in the cell periphery and outside of the cell. The nanoparticles aggregates were generated due to the particles concentration used in the experiment because of the small loading of the InPc while the low solubility of InPc caused the formation of aggregates of free PS in the culture medium. The participation of singlet oxygen in the photocytotoxic effect of InPc-loaded nanoparticles was corroborated by electron paramagnetic resonance experiments, and the encapsulation of photosensitizers reduced the photobleaching of InPc.

  17. STEM CELLS: Differentiated cells in a back-up role

    OpenAIRE

    Desai, Tushar J.; Krasnow, Mark A.

    2013-01-01

    Two independent studies show that, if push comes to shove, differentiated cells of the stomach and lung can act as adult stem cells generating various cell types of the tissue, including a pool of stem cells.

  18. Neuronal merlin influences ERBB2 receptor expression on Schwann cells through neuregulin 1 type III signalling

    OpenAIRE

    Schulz, Alexander; Kyselyova, Anna; Baader, Stephan L.; Jung, Marie Juliane; Zoch, Ansgar; Mautner, Victor-Felix; Hagel, Christian; Morrison, Helen

    2013-01-01

    Axonal surface proteins encompass a group of heterogeneous molecules, which exert a variety of different functions in the highly interdependent relationship between axons and Schwann cells. We recently revealed that the tumour suppressor protein merlin, mutated in the hereditary tumour syndrome neurofibromatosis type 2, impacts significantly on axon structure maintenance in the peripheral nervous system. We now report on a role of neuronal merlin in the regulation of the axonal surface protei...

  19. Induction chemoradiotherapy followed by surgery for stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    Twenty-five patients with stage III, non-small cell lung cancer were treated with cisplatin-based chemotherapy and thoracic radiation therapy followed by surgery. Thirteen patients had stage IIIA disease and 12, stage IIIB disease. The chemotherapy and radiotherapy were intensively combined with only a few days' interval between them. Radiation therapy delivering a total dose of 50-70 Gy was started 10 days after the beginning of chemotherapy. A few additional courses of chemotherapy were repeated until a thoracotomy was performed. All but two surgically-treated patients underwent tumor resection, with 19 lobectomies and four pneumonectomies. Eighteen patients underwent curative and five, non-curative resections. Pathological examination of the resected specimen provided accurate intrathoracic information. Six patients (24%) showed a pathologically complete response, with no cancer cells detected in the resected specimens. Severe postoperative complications occurred in five patients (20%), with one death. The disease recurred in five of the 18 patients who underwent a curative resection. A second primary tumor developed in two other patients. Seventeen patients (68%) are alive, with a median follow-up of 37 months after thoracotomy. The estimated three-year survival was 67% for all patients. (author)

  20. Concurrent chemo-radiotherapy for stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    In patients with unresectable stage III non-small cell lung cancer, we performed chemotherapy and concurrent thoracic radiotherapy. Thirty-five registered patients were intravenously treated with cisplatin (80mg/m2) on day 1 and vindesine (3mg/m2) on days 1, 3 and were irradiated from days 1 to 10 with single doses of 2.5 Gy up to a total dosage of 20 Gy. Each course lasted 28 days. Patients received 3 courses, and a total dosage of 60 Gy was delivered. Response to this treatment was evaluable in terms of results in 35 patients. Twenty-two patients showed partial response (response rate 62.9%), 10 had no change, and 3 cases had progressive disease. In 7.5 to 37.8 months observation, three PR patients are alive for more than 24 months without recurrence, but eight PR patients died of local relapse, and the median survival time was 15.7 months. Throughout this treatment course, grade 4 leukopenia was noted in 66% and grade 3 thrombocytopenia was observed in 3%. However all were reversible condition and no treatment-related death was observed. However, two cases died due to complications of pulmonary abscess, which occurred in the area of radiation pulmonary fibrosis about one year later after treatment. Although this concurrent chemo-radiotherapy is a tolerable treatment for non-small cell lung cancer and obtained a good response rate, it did not improve the survival rate. (author)

  1. Treatment outcome and toxicity of intensity-modulated (chemo) radiotherapy in stage III non-small cell lung cancer patients

    NARCIS (Netherlands)

    Govaert, S.L.; Troost, E.G.C.; Schuurbiers, O.C.J.; Geus-Oei, L.F. de; Termeer, A.; Span, P.N.; Bussink, J.

    2012-01-01

    ABSTRACT: PURPOSE: The aim of this retrospective cohort study was to assess treatment outcome, and acute pulmonary and esophageal toxicity using intensity modulated (sequential/concurrent chemo)radiotherapy (IMRT) in locally advanced stage III non-small cell lung cancer (NSCLC). METHODS AND MATERIAL

  2. Roles of chemoradio therapy for stage III or IV advanced head and neck cancers

    Energy Technology Data Exchange (ETDEWEB)

    Tachikawa, Takuya; Iwai, Hiroshi; Tsuji, Hiroyuki; Minamino, Masayuki; Yamamoto, Takashi; Yukawa, Hisaya; Inoue, Toshiya; Yamashita, Toshio [Kansai Medical School, Moriguchi, Osaka (Japan)

    2002-03-01

    The effectiveness of chemoradio therapy (CRT), which was performed on 31 patients with advanced head and neck cancers of stage III or IV at Kansai Medical University between September 1999 and December 2000, was examined. The CRT consisted of continuous infusion of 5FU (500 mg/m{sup 2}) for 120 hours, prior to drip infusion of CDDP (50 mg/m{sup 2}) for 2 hours and conventional radiotherapy (2 Gy/day, 5 days/w). The 31 patients with these cancers were divided into two groups; a non-operative group (16 patients) and an operative group (15 patients). The patients in the non-operative group (16 patients) and an operative group (15 patients). The patients in the non-operative group underwent CRT (60-70 Gy of total radiation dose and two courses of chemotherapy) without surgery. The patients in the operative group received surgical treatment followed by CRT (40 Gy of total radiation dose and one course of chemotherapy). The results of CRT indicated 87.1% of the response rate (RR), and 29.0% of the complete response rate (CR) in the group. The CR rate was lower than in other reports. However, the combination of CRT and the subsequent operation indicated a disease-free survival rate of 61.3% and reduction of the recurrence rate to 17.4%. Eight of 9 patients of CR after CRT without surgery revealed NED. On the other hand, the results indicated that all 10 patients of PR after CRT showed tumor residue, 9 of 10 patients of PR showed NED after additional surgery. Therefore, it is likely that the patients of CR do not need the additional surgery, however, the patients of PR are strongly recommended the surgery to improve the local control rate as well as survival rate. Although adverse reactions of CRT on patients included mucositis, leucopenia, thrombopenia and dermatitis, the symptoms ranged within grade 3. (author)

  3. Interaction of antithrombin III with bovine aortic segments. Role of heparin in binding and enhanced anticoagulant activity.

    OpenAIRE

    Stern, D.; Nawroth, P; Marcum, J; Handley, D; Kisiel, W; Rosenberg, R; Stern, K.

    1985-01-01

    Bovine antithrombin III (AT III) interaction with the luminal surface of bovine aortic segments with a continuous layer of endothelium was examined. Incubation of 125I-AT III with vessel segments, previously washed free of endogenous AT III, demonstrated specific, time-dependent binding to the protease inhibitor to the endothelium. Half-maximal binding was observed at an added AT III concentration of 14 nM. Binding of 125I-AT III to the vessel wall was reversible (50% dissociated in 4 min), a...

  4. Metallothionein I+II expression and their role in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, M; Hidalgo, J

    2000-01-01

    -lymphocyte infiltration, and astrogliosis in spinal cord, brain stem, and cerebellum, which peaked 14-18 days after immunization. The remission of symptoms and histopathological changes began at days 19-21 and were completed by days 30-40. MT-I+II expression was increased significantly in EAE infiltrates. In order to......We examined the expression and roles of neuroprotective metallothionein-I+II (MT-I+II) in the rat CNS in experimental autoimmune encephalomyelitis (EAE), an animal model for the human autoimmune disease, multiple sclerosis (MS). EAE caused significant macrophage activation, T...

  5. The role of dental stem cells in regeneration

    OpenAIRE

    MAXIM, MONICA ANGELA; Soritau, Olga; BACIUT, MIHAELA; BRAN, SIMION; BACIUT, GRIGORE

    2015-01-01

    Mesenchymal stem cells (MSCs) are adult stem cells that have the capacity of rising multiple cell types. A rich source of mesenchymal stem cells is represented by the dental tissues: the periodontal ligament, the dental pulp, the apical papilla, the dental follicle and the deciduous teeth. The aim of this review is to characterize the main dental- derived mesenchymal stem cell population, and to show their important role in tissue regeneration based on their properties : the multi-potency, th...

  6. Turn-on fluorogenic and chromogenic detection of Fe(III) and its application in living cell imaging

    Energy Technology Data Exchange (ETDEWEB)

    Sivaraman, Gandhi; Sathiyaraja, Vijayaraj; Chellappa, Duraisamy, E-mail: dcmku123@gmail.com

    2014-01-15

    Two rhodamine-based sensors RDI-1, RDI-2 was designed and synthesized by incorporation of the rhodamine 6G fluorophore and 2-formyl imidazole as the recognizing unit via the imine linkages. RDI-1, RDI-2 exhibits very high selectivity and an excellent sensitivity towards Fe(III) ions in aqueous buffer solution on compared with other probes. The color change from colorless to pink and turn-on fluorescence after binding with iron (III) was observed. Based on jobs plot and ESI-MS studies, the 1:1 binding mode was proposed. Live cell imaging experiments with each probe showed that these probes widely applicable to detect Fe{sup 3+} in living cells. -- Highlights: • Two rhodamine based probes was synthesized and used to recognize iron (III). • The chemosensors can be applied to detect iron(III) ions by color and turn-on fluorescent changes. • The very low detection limit was reported. • The applicability of these probes for live cell fluorescence imaging was studied.

  7. Roles of imprinted genes in neural stem cells.

    Science.gov (United States)

    Hoffmann, Anke; Daniel, Guillaume; Schmidt-Edelkraut, Udo; Spengler, Dietmar

    2014-01-01

    Imprinted genes and neural stem cells (NSC) play an important role in the developing and mature brain. A central theme of imprinted gene function in NSCs is cell survival and G1 arrest to control cell division, cell-cycle exit, migration and differentiation. Moreover, genomic imprinting can be epigenetically switched off at some genes to ensure stem cell quiescence and differentiation. At the genome scale, imprinted genes are organized in dynamic networks formed by interchromosomal interactions and transcriptional coregulation of imprinted and nonimprinted genes. Such multilayered networks may synchronize NSC activity with the demand from the niche resembling their roles in adjusting fetal size. PMID:25431944

  8. Role of growth factors in the growth of normal and transformed cells

    International Nuclear Information System (INIS)

    Growth factors play an important role in the growth of normal cells. However, their untimely and/or excess production leads to neoplastic transformation. The role of growth factors in the growth of normal cells was studied by investigating the mechanism of transmodulation of the cell surface EGF receptor number by protamine. Protamine increased the EGF stimulated mitogenic response in Swiss mouse 3T3 cells and A431 cells by increasing the number of functionally active EGF receptors. Protamine also increased EGF receptor number in plasma membranes and solubilized membranes. This was evidenced by an increase in both 125I-EGF-EGF-receptor complex and EGF stimulated phosphorylation of the EGF receptor. The solubilized EGF receptor was retained on a protamine-agarose gel indicating that protamine might increase EGF receptor number by directly activating cryptic EGF receptors in the plasma membranes. The role of growth factors in neoplastic transformation was studied by investigating the role of the oncogene v-sis in the growth of Simian sarcoma virus (SSV) transformed cells. The product of the oncogene v-sis is 94% homologous to the B chain of PDGF. This study found that (i) v-sis gene product is synthesized as a 32 kDa unglycosylated monomer which is glycosylated, dimerized and proteolytically processed into p36, p72, p68, p58, p44 and p27 mol. wt. species respectively. (ii) p36, p72, p68 and p58 are very likely formed in the endoplasmic reticulum and/or Golgi complex. A fraction of newly synthesized p72, p68 and p58 is degraded intracellularly at a fast rate. (iii) p44 is a secretory product which remains tightly associated with the cell surface. p44 is recaptured by the cells through interaction with cell surface PDGF receptors and degraded into p27. (iv) During long term cultures p44 is extracellularly cleaved into a 27 kDa product

  9. Particle-In-Cell, self-consistent electromagnetic wave emission simulations of type III radio bursts

    CERN Document Server

    Tsiklauri, David

    2010-01-01

    High-resolution, 1.5D Particle-in-Cell, relativistic, fully electromagnetic simulations are used to model electromagnetic wave emission generation in the context of solar type III radio bursts. The model studies generation of electromagnetic waves by a super-thermal, hot beam of electrons injected into a plasma thread that contains uniform longitudinal magnetic field and a parabolic density gradient. In effect, a single magnetic line connecting Sun to earth is considered, for which four cases are studied. (i) We find that the physical system without a beam is stable and only low amplitude level electromagnetic drift waves (noise) are excited. (ii) The beam injection direction is controlled by setting either longitudinal or oblique electron initial drift speed, i.e. by setting the beam pitch angle. In the case of zero pitch angle, the beam excites only electrostatic, standing waves, oscillating at local plasma frequency, in the beam injection spatial location, and only low level electromagnetic drift wave nois...

  10. Biocatalytic role of potato starch synthase III for α-glucan biosynthesis in Synechocystis sp. PCC6803 mutants.

    Science.gov (United States)

    Yoo, Sang-Ho; Lee, Byung-Hoo; Li, Li; Perris, Shayani D N; Spalding, Martin H; Han, Sang Yun; Jane, Jay-lin

    2015-11-01

    A potato starch synthase III (PSSIII) was expressed in the Synechocystis mutants deficient in either glycogen synthase I (M1) or II (M2) to replenish α-(1,4) linkage synthesizing activity, resulting in new mutants, PM1 and PM2, respectively. These mutants were applied to study the role of exogenous plant starch synthase for starch/glycogen biosynthesis mechanism established in the cyanobacteria. The remaining glycogen synthase genes in PM1 and PM2 were further disrupted to make the mutants PM12 and PM21 which contained PSSIII as the sole glycogen/starch synthase. Among wild type and mutants, there were no significant differences in the amount of α-glucan produced. All the mutants harboring active PSSIII produced α-glucans with relatively much shorter and less longer α-1,4 chains than wild-type glycogen, which was exactly in accordance with the increase in glycogen branching enzyme activity. In fact, α-glucan structure of PM1 was very similar to those of PM12 and PM21, and PM2 had more intermediate chains than M2. This result suggests PSSIII may have distributive elongation property during α-glucan synthesis. In conclusion, the Synechocystis as an expression model system of plant enzymes can be applied to determine the role of starch synthesizing enzymes and their association during α-glucan synthesis. PMID:26358554

  11. Role of deoxyribonucleic acid polymerase III in the repair of single-strand breaks produced in Escherichia coli deoxyribonucleic acid by gamma radiation

    International Nuclear Information System (INIS)

    Cell survival, deoxyribonucleic acid (DNA) degradation, and the repair of DNA single-strand breaks were measured for Escherichia coli K-12 pol+, polAl, polC1026(ts), and polAl polC1026(ts) cells after 137Cs γ irradiation. The results indicate that DNA polymerase III is required for growth medium-dependent (type III) repair in polA+ or polA cells and is necessary for growth medium-independent (type II) repair in polA cells. In pol+ or polC cells, DNA polymerase I performs type II repair efficiently. The relative deficiencies of each of these strains in DNA repair generally correlate with their relative sensitivities to cell killing and with the extent of DNA degradation observed

  12. Improved photodynamic action of nanoparticles loaded with indium (III) phthalocyanine on MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Indium (III) phthalocyanine (InPc) was encapsulated into nanoparticles of PEGylated poly(d,l-lactide-co-glycolide) (PLGA-PEG) to improve the photobiological activity of the photosensitizer. The efficacy of nanoparticles loaded with InPc and their cellular uptake was investigated with MCF-7 breast tumor cells, and compared with the free InPc. The influence of photosensitizer (PS) concentration (1.8–7.5 μmol/L), incubation time (1–2 h), and laser power (10–100 mW) were studied on the photodynamic effect caused by the encapsulated and the free InPc. Nanoparticles with a size distribution ranging from 61 to 243 nm and with InPc entrapment efficiency of 72 ± 6 % were used in the experiments. Only the photodynamic effect of encapsulated InPc was dependent on PS concentration and laser power. The InPc-loaded nanoparticles were more efficient in reducing MCF-7 cell viability than the free PS. For a light dose of 7.5 J/cm2 and laser power of 100 mW, the effectiveness of encapsulated InPc to reduce the viability was 34 ± 3 % while for free InPc was 60 ± 7 %. Confocal microscopy showed that InPc-loaded nanoparticles, as well as free InPc, were found throughout the cytosol. However, the nanoparticle aggregates and the aggregates of free PS were found in the cell periphery and outside of the cell. The nanoparticles aggregates were generated due to the particles concentration used in the experiment because of the small loading of the InPc while the low solubility of InPc caused the formation of aggregates of free PS in the culture medium. The participation of singlet oxygen in the photocytotoxic effect of InPc-loaded nanoparticles was corroborated by electron paramagnetic resonance experiments, and the encapsulation of photosensitizers reduced the photobleaching of InPc

  13. The Role of Th17 in Neuroimmune Disorders: A Target for CAM Therapy. Part III

    Directory of Open Access Journals (Sweden)

    Aristo Vojdani

    2011-01-01

    Full Text Available Abundant research has mapped the inflammatory pathways leading to autoimmunity and neuroinflammatory disorders. The latest T helper to be identified, Th17, through its proinflammatory cytokine IL-17, plays a pathogenic role in many inflammatory conditions. Today, healthcare providers have a wealth of anti-inflammatory agents from which to choose. On one hand, pharmaceutical companies market brand-name drugs direct to the public and physicians. Medical botanical knowledge, on the other hand, has been passed down from generation to generation. The demands for natural healing therapies have brought corresponding clinical and laboratory research studies to elucidate the medicinal properties of alternative practices. With a variety of options, it can be difficult to pinpoint the proper anti-inflammatory agent for each case presented. In this review, the authors highlight a vast array of anti-inflammatory medicaments ranging from drugs to vitamins and from botanicals to innate molecules. This compilation may serve as a guide for complimentary and alternative healthcare providers who need to target neuroinflammation driven by Th17 and its inflammatory cytokine IL-17. By understanding the mechanisms of anti-inflammatory agents, CAM practitioners can tailor therapeutic interventions to fit the needs of the patient, thereby providing faster relief from inflammatory complaints.

  14. Giant Cell Tumor: Role of Conservative Treatment

    Institute of Scientific and Technical Information of China (English)

    Anatolii Diedkov[1; Pavlo Kovalchuk[1; Marija Kukushkina[2; Sergey Bojchuk[1; Viktor Kostyuk[1

    2014-01-01

    Giant cell tumor is aggressive bone tumor. Surgical treatment is considered to be the only effective method of treatment ofthese tumors. The problem of inoperable patients with giant cell tumors is a challenge. A total of 8 patients had giant cell bone tumorsof pelvis and sacrum. 3 patients were treated by bisphosphonates, radiation therapy and embolization of tumor-nutrient arteries. 5patients received denosumab. The efficiency was assessed according to clinical data and CT scan control. Median follow up is 28months. All 8 patients had reduction of pain intensity. Treatment with denosumab demonstrated more than 30% tumor regression. Allof the patients are in remission.

  15. Adhesion in the stem cell niche: biological roles and regulation

    OpenAIRE

    Chen, Shuyi; Lewallen, Michelle; Xie, Ting

    2013-01-01

    Stem cell self-renewal is tightly controlled by the concerted action of stem cell-intrinsic factors and signals within the niche. Niche signals often function within a short range, allowing cells in the niche to self-renew while their daughters outside the niche differentiate. Thus, in order for stem cells to continuously self-renew, they are often anchored in the niche via adhesion molecules. In addition to niche anchoring, however, recent studies have revealed other important roles for adhe...

  16. Role of inositol phospholipid signaling in natural killer cell biology

    OpenAIRE

    Gumbleton, Matthew; Kerr, William G.

    2013-01-01

    Natural killer (NK) cells are important for host defense against malignancy and infection. At a cellular level NK cells are activated when signals from activating receptors exceed signaling from inhibitory receptors. At a molecular level NK cells undergo an education process to both prevent autoimmunity and acquire lytic capacity. Mouse models have shown important roles for inositol phospholipid signaling in lymphocytes. NK cells from mice with deletion in different members of the inositol ph...

  17. Predictors of Local Recurrence After Rituximab-Based Chemotherapy Alone in Stage III and IV Diffuse Large B-Cell Lymphoma: Guiding Decisions for Consolidative Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Jegadeesh, Naresh; Rajpara, Raj; Esiashvili, Natia; Shi, Zheng [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Liu, Yuan [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia (United States); Okwan-Duodu, Derrick [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Flowers, Christopher R. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Medical Oncology, Emory University, Atlanta, Georgia (United States); Khan, Mohammad K., E-mail: drkhurram2000@gmail.com [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2015-05-01

    Purpose: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials: Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these, 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome. Results: The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ≥5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ≥5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ≥15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV≥15 (P=.10). Conclusions: Advanced-stage DLBCL patients with stage III disease or with disease ≥5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ≥15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy.

  18. Predictors of Local Recurrence After Rituximab-Based Chemotherapy Alone in Stage III and IV Diffuse Large B-Cell Lymphoma: Guiding Decisions for Consolidative Radiation

    International Nuclear Information System (INIS)

    Purpose: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials: Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these, 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome. Results: The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ≥5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ≥5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ≥15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV≥15 (P=.10). Conclusions: Advanced-stage DLBCL patients with stage III disease or with disease ≥5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ≥15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy

  19. Phase III trial comparing chemotherapy plus once-daily or twice-daily radiotherapy in Stage III non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: This Phase III study was performed to determine whether chemotherapy plus b.i.d. or q.d. radiotherapy (RT) resulted in superior survival for patients with Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: Patients with Stage III NSCLC and an Eastern Cooperative Oncology Group performance status of ≤1 were randomized to receive either standard q.d. RT (60 Gy in 30 daily fractions) or split-course b.i.d. RT (30 Gy in 20 fractions b.i.d.) followed by a 2-week break and then 30 Gy in 20 fractions b.i.d. Both arms included etoposide and cisplatin (EP) during RT. Results: Between December 1994 and February 1999, 246 patients were accrued and 234 were deemed eligible and included in the analyses. Of the 234 patients, 123 had Stage IIIa disease and 111 had Stage IIIb disease. The incidence of severe (Grade 3 or greater) acute nonhematologic toxicity (q.d. RT, 53% vs. b.i.d. RT, 65%) and severe (Grade 3 or greater) hematologic toxicities (thrombocytopenia, 41% q.d. RT vs. 39% b.i.d. RT; neutropenia, 80% q.d. RT vs. 81% b.i.d. RT) was not significantly different between the treatment arms. Five patients (3 in q.d. RT group and 2 in b.i.d. RT group) died as a result of acute toxicity. The follow-up ranged from 2 to 73 months (median 43). No significant differences were found between the q.d. and b.i.d. RT arms in terms of time to progression (p=0.9; median 9.4 and 9.6 months, respectively), overall survival (p=0.4; median 14 and 15 months and 2-year survival rate 37% and 40%, respectively), and cumulative incidence of local failure (p=0.6; 2-year rate 45% and 41%, respectively). Conclusion: This program of split-course b.i.d. RT plus EP was not superior to standard q.d. RT plus EP. The toxicity, tumor control, and survival rates were similar with either b.i.d. or q.d. RT. Our future efforts will concentrate on new combinations of systemic therapy and innovative methods of administering increasing doses of RT

  20. Programmed cell death and its role in inflammation

    Institute of Scientific and Technical Information of China (English)

    Yong Yang; Ge-Ning Jiang; Peng Zhang; Jie Fan

    2015-01-01

    Cell death plays an important role in the regulation of inflammation and may be the result of inflammation. The maintenance of tissue homeostasis necessitates both the recognition and removal of invading microbial pathogens as well as the clearance of dying cells. In the past few decades, emerging knowledge on cell death and inflammation has enriched our molecular understanding of the signaling pathways that mediate various programs of cell death and multiple types of inflammatory responses. This review provides an overview of the major types of cell death related to inflammation. Modification of cell death pathways is likely to be a logical therapeutic target for inflammatory diseases.

  1. Collective Behavior of Brain Tumor Cells: the Role of Hypoxia

    Science.gov (United States)

    Khain, Evgeniy; Katakowski, Mark; Hopkins, Scott; Szalad, Alexandra; Zheng, Xuguang; Jiang, Feng; Chopp, Michael

    2013-03-01

    We consider emergent collective behavior of a multicellular biological system. Specifically we investigate the role of hypoxia (lack of oxygen) in migration of brain tumor cells. We performed two series of cell migration experiments. The first set of experiments was performed in a typical wound healing geometry: cells were placed on a substrate, and a scratch was done. In the second set of experiments, cell migration away from a tumor spheroid was investigated. Experiments show a controversy: cells under normal and hypoxic conditions have migrated the same distance in the ``spheroid'' experiment, while in the ``scratch'' experiment cells under normal conditions migrated much faster than under hypoxic conditions. To explain this paradox, we formulate a discrete stochastic model for cell dynamics. The theoretical model explains our experimental observations and suggests that hypoxia decreases both the motility of cells and the strength of cell-cell adhesion. The theoretical predictions were further verified in independent experiments.

  2. Prognostic Role of BRAF Mutation in Stage II/III Colorectal Cancer Receiving Curative Resection and Adjuvant Chemotherapy: A Meta-Analysis Based on Randomized Clinical Trials

    Science.gov (United States)

    Cao, Ying; Fang, Xuefeng; Zhong, Chenhan; Li, Dan; Yuan, Ying

    2016-01-01

    Background and Objective Studies examining the prognostic value of the BRAF mutation on relapse-free survival (RFS), disease-free survival (DFS) and overall survival (OS) in stage II/III colorectal cancer (CRC) patients receiving curative resection and adjuvant chemotherapy so far showed discrepant results. Therefore, a meta-analysis of relevant studies was performed for clarification. Methods Randomized trials of stage II/III colorectal cancer treated with curative resection followed by adjuvant chemotherapy were selected to conduct a meta-analysis. The necessary descriptive and statistical information such as hazard ratios (HRs) and 95% confidence intervals (CIs) were derived from published survival data. Results Seven phase III randomized clinical trials (RCTs) including 1,035 BRAF mutation stage II/III CRC patients receiving curative resection and adjuvant chemotherapy were analyzed. Overall, BRAF mutation resulted in poorer OS (HR = 1.42, 95% CI: 1.25–1.60; P < 0.00001), and poorer DFS (HR = 1.26, 95% CI: 1.07–1.48, P = 0.006) compared with BRAF wild-type CRC. The prognostic role on RFS could not be elucidated in the meta-analysis because of limited data. Conclusions BRAF mutation was significantly related with shorter DFS and OS among stage II/III CRC patients receiving adjuvant chemotherapy after curative resection. Its prognostic role for RFS needs to be further analyzed when more data is available. PMID:27138801

  3. Role of autophagy in the regulation of epithelial cell junctions.

    Science.gov (United States)

    Nighot, Prashant; Ma, Thomas

    2016-01-01

    Autophagy is a cell survival mechanism by which bulk cytoplasmic material, including soluble macromolecules and organelles, is targeted for lysosomal degradation. The role of autophagy in diverse cellular processes such as metabolic stress, neurodegeneration, cancer, aging, immunity, and inflammatory diseases is being increasingly recognized. Epithelial cell junctions play an integral role in the cell homeostasis via physical binding, regulating paracellular pathways, integrating extracellular cues into intracellular signaling, and cell-cell communication. Recent data indicates that cell junction composition is very dynamic. The junctional protein complexes are actively regulated in response to various intra- and extra-cellular clues by intracellular trafficking and degradation pathways. This review discusses the recent and emerging information on how autophagy regulates various epithelial cell junctions. The knowledge of autophagy regulation of epithelial junctions will provide further rationale for targeting autophagy in a wide variety of human disease conditions. PMID:27583189

  4. Comparison of outcomes in patients with stage III versus limited stage IV non-small cell lung cancer

    International Nuclear Information System (INIS)

    Standard therapy for metastatic non small cell lung cancer (NSCLC) includes palliative systemic chemotherapy and/or radiotherapy. Recent studies of patients with limited metastases treated with curative-intent stereotactic body radiation therapy (SBRT) have shown encouraging survival. We hypothesized that patients treated with SBRT for limited metastases have comparable outcomes with those treated with curative-intent radiation for Stage III NSCLC. We retrospectively reviewed the records of NSCLC patients treated with curative-intent radiotherapy at the University of Rochester from 2000-2008. We identified 3 groups of patients with NSCLC: stage III, stage IV, and recurrent stage IV (initial stage I-II). All stage IV NSCLC patients treated with SBRT had ≤ 8 lesions. Of 146 patients, 88% had KPS ≥ 80%, 30% had > 5% weight loss, and 95% were smokers. The 5-year OS from date of NSCLC diagnosis for stage III, initial stage IV and recurrent stage IV was 7%, 14%, and 27% respectively. The 5-year OS from date of metastatic diagnosis was significantly (p < 0.00001) superior among those with limited metastases (≤ 8 lesions) versus stage III patients who developed extensive metastases not amenable to SBRT (14% vs. 0%). Stage IV NSCLC is a heterogeneous patient population, with a selected cohort apparently faring better than Stage III patients. Though patients with limited metastases are favorably selected by virtue of more indolent disease and/or less bulky disease burden, perhaps staging these patients differently is appropriate for prognostic and treatment characterization. Aggressive local therapy may be indicated in these patients, though prospective clinical studies are needed

  5. Postnatal development of layer III pyramidal cells in the primary visual, inferior temporal, and prefrontal cortices of the marmoset

    OpenAIRE

    Hirosato eAoi; Tomofumi eOga; Tetsuya eSasaki; Ichiro eFujita; Noritaka eIchinohe

    2013-01-01

    Abnormalities in the processes of the generation and/or pruning of dendritic spines have been implicated in several mental disorders including autism and schizophrenia. We have chosen to examine the common marmoset (Callithrix jacchus) as a primate model to explore the processes. As a first step, we studied the postnatal development of basal dendritic trees and spines of layer-III pyramidal cells in the primary visual sensory cortex (V1), a visual association cortex (inferior temporal area, T...

  6. The role of red blood cells in inflammation and remodeling

    OpenAIRE

    Fredriksson, Karin

    2004-01-01

    Besides being carriers of oxygen and carbon dioxide, red blood cells (RBCs) also have a scavenger function, binding inflammatory mediators to surface receptors. Animal and experimental models have suggested a role for RBCs in inflammatory and fibrotic responses and patients with idiopathic pulmonary hemosiderosis, a disease characterized by lung hemorrhage, frequently develop fibrosis. Fibroblasts, the resident cell in the connective tissue, play an active role in tissue rem...

  7. Innate Lymphoid Cells: Roles In Tumour Genesis And Progression

    OpenAIRE

    Jovanovic Ivan; Gajovic Nevena; Radosavljevic Gordana; Pantic Jelena; Pejnovic Nada; Arsenijevic Nebojsa; Lukic Miodrag L.

    2015-01-01

    Innate lymphoid cells (ILCs) represent the most recently identified members of the innate immune system. These cells play important roles in inflammation, tissue remodelling and metabolic disease. ILCs can be subdivided into three major groups according to their cytokine production. The role of ILCs in tumourigenesis and tumour progression is not completely clarified. In this review, we discuss whether and how ILCs are involved in tumour genesis, growth and metastasis.

  8. Innate Lymphoid Cells: Roles In Tumour Genesis And Progression

    Directory of Open Access Journals (Sweden)

    Jovanovic Ivan

    2015-06-01

    Full Text Available Innate lymphoid cells (ILCs represent the most recently identified members of the innate immune system. These cells play important roles in inflammation, tissue remodelling and metabolic disease. ILCs can be subdivided into three major groups according to their cytokine production. The role of ILCs in tumourigenesis and tumour progression is not completely clarified. In this review, we discuss whether and how ILCs are involved in tumour genesis, growth and metastasis.

  9. Functional role of inorganic trace elements in angiogenesis part III: (Ti, Li, Ce, As, Hg, Va, Nb and Pb).

    Science.gov (United States)

    Saghiri, Mohammad Ali; Orangi, Jafar; Asatourian, Armen; Sorenson, Christine M; Sheibani, Nader

    2016-02-01

    Many essential elements exist in nature with significant influence on human health. Angiogenesis is vital in developmental, repair, and regenerative processes, and its aberrant regulation contributes to pathogenesis of many diseases including cancer. Thus, it is of great importance to explore the role of these elements in such a vital process. This is third in a series of reviews that serve as an overview of the role of inorganic elements in regulation of angiogenesis and vascular function. Here we will review the roles of titanium, lithium, cerium, arsenic, mercury, vanadium, niobium, and lead in these processes. The roles of other inorganic elements in angiogenesis were discussed in part I (N, Fe, Se, P, Au, and Ca) and part II (Cr, Si, Zn, Cu, and S) of these series. The methods of exposure, structure, mechanisms, and potential activities of these elements are briefly discussed. An electronic search was performed on the role of these elements in angiogenesis from January 2005 to April 2014. These elements can promote and/or inhibit angiogenesis through different mechanisms. The anti-angiogenic effect of titanium dioxide nanoparticles comes from the inhibition of angiogenic processes, and not from its toxicity. Lithium affects vasculogenesis but not angiogenesis. Nanoceria treatment inhibited tumor growth by inhibiting angiogenesis. Vanadium treatment inhibited cell proliferation and induced cytotoxic effects through interactions with DNA. The negative impact of mercury on endothelial cell migration and tube formation activities was dose and time dependent. Lead induced IL-8 production, which is known to promote tumor angiogenesis. Thus, understanding the impact of these elements on angiogenesis will help in development of new modalities to modulate angiogenesis under various conditions. PMID:26638864

  10. Role of Innate Lymphoid Cells in Lung Disease

    Directory of Open Access Journals (Sweden)

    SayedMehran Marashian

    2015-10-01

    Full Text Available  Innate lymphoid cells (ILCs are identified as novel population of hematopoietic cells which protect the body by coordinating the innate immune response against a wide range of threats including infections, tissue damages and homeostatic disturbances. ILCs, particularly ILC2 cells, are found throughout the body including the brain. ILCs are morphologically similar to lymphocytes, express and release high levels of T-helper (Th1, Th2 and Th17 cytokines but do not express classical cell-surface markers that are associated with other immune cell lineages.Three types of ILCs (ILC1, 2 & 3 have been reported depending upon the cytokines produced. ILC1 cells encompass natural killer (NK cells and interferon (IFN-g releasing cells; ILC2 cells release the Th2 cytokines, IL-5, IL-9 and IL-13 in response to IL-25 and IL-33; and ILC3 cells which release IL-17 and IL-22. ILC2 cells have been implicated inmucosal reactions occurring in animal models of allergic asthma and virus-induced lung disorders resulting in the regulation of airway remodeling and tissue homeostasis.There is evidence for increased ILC2 cell numbers in allergic responses in man but little is known about the role of ILCs in chronic obstructive pulmonary disease (COPD. Further understanding of the characteristics of ILCs such as their origin, location and phenotypes and function would help to clarify the role of these cells in the pathogenesis of various lung diseases.In this review we will focus on the role of ILC2 cells and consider their origin, function,location and possible role in the pathogenesis of the chronic inflammatory disorders such as asthma and COPD.   

  11. Natural montmorillonite induced photooxidation of As(III) in aqueous suspensions: Roles and sources of hydroxyl and hydroperoxyl/superoxide radicals

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yajie [Department of Environmental Science, Hubei Key Lab of Biomass Resource Chemistry and Environmental Biotechnology, School of Resources and Environmental Science, Wuhan University, 430079 (China); School of Chemistry and Environmental Science, Guizhou Minzu University, Guiyang 550025 (China); Xu, Jing [Department of Environmental Science, Hubei Key Lab of Biomass Resource Chemistry and Environmental Biotechnology, School of Resources and Environmental Science, Wuhan University, 430079 (China); Li, Jinjun, E-mail: ljj0410@163.com [Department of Environmental Science, Hubei Key Lab of Biomass Resource Chemistry and Environmental Biotechnology, School of Resources and Environmental Science, Wuhan University, 430079 (China); Wu, Feng, E-mail: fengwu@whu.edu.cn [Department of Environmental Science, Hubei Key Lab of Biomass Resource Chemistry and Environmental Biotechnology, School of Resources and Environmental Science, Wuhan University, 430079 (China)

    2013-09-15

    Highlights: • Natural montmorillonite contributes to photochemical oxidation of arsenite. • Ferrous ions significantly affect photochemical behavior of montmorillonite. • HO· and HO{sub 2}·/O{sub 2}{sup −}· play different roles in this process. -- Abstract: Photooxidation of arsenite(As(III)) in a suspension of natural montmorillonite under the irradiation of metal halide lamp (λ ≥ 313 nm)has been investigated. The results showed that the natural montmorillonite induced the photooxidation of As(III) by generating hydroxyl radicals (HO·) and hydroperoxyl/superoxide radicals (HO{sub 2}·/O{sub 2}{sup −}·). HO· which was responsible for the As(III) photooxidation. Approximately 38% of HO· was generated by the photolysis of ferric ions, and the formation of the remaining 62% was strongly dependent on the HO{sub 2}·/O{sub 2}{sup −}·. The presence of free ironions (Fe{sup 2+} and Fe{sup 3+}), made significant contributions to the photogeneration of these reactive oxygen species (ROS). The photooxidation of As(III) in natural montmorillonite suspensions was greatly influenced by the pH values. The photooxidation of As(III) by natural montmorillonite followed the Langmuir–Hinshelwood equation. In addition, the photooxidation of As(III) could be enhanced by the addition of humic acid. This work demonstrates that photooxidation may be an important environmental process for the oxidation of As(III) and may be a way to remove As(III) from acidic surface water containing iron-bearing clay minerals.

  12. On the Role of the $\\Omega\\Gamma$ Limit in the Formation of Population III Massive Stars

    CERN Document Server

    Lee, Hunchul

    2016-01-01

    We explore the role of the modified Eddington limit due to rapid rotation (the so-called $\\Omega\\Gamma-$limit) in the formation of Population III stars. We performed one-dimensional stellar evolution simulations of mass-accreting zero-metallicity protostars at a very high rate ($\\dot{M} \\sim 10^{-3}~\\mathrm{M_\\odot~yr^{-1}}$) and dealt with stellar rotation as a separate post-process. The protostar would reach the Keplerian rotation very soon after the onset of mass accretion, but mass accretion would continue as stellar angular momentum is transferred outward to the accretion disk by viscous stress. The protostar envelope expands rapidly when the stellar mass reaches $5\\sim7~\\mathrm{M_\\odot}$ and the Eddington factor sharply increases. This makes the protostar rotate critically at a rate that is significantly below the Keplerian value (i.e., the $\\Omega\\Gamma-$limit). The resultant positive gradient of the angluar velocity in the boundary layer between the protostar and the Keplerian disk prohibits angular m...

  13. Small molecule inhibitors of the Yersinia type III secretion system impair the development of Chlamydia after entry into host cells

    Directory of Open Access Journals (Sweden)

    Henriques-Normark Birgitta

    2009-04-01

    Full Text Available Abstract Background Chlamydiae are obligate intracellular pathogens that possess a type III secretion system to deliver proteins into the host cell during infection. Small molecule inhibitors of type III secretion in Yersinia, termed INPs (Innate Pharmaceuticals AB were reported to strongly inhibit Chlamydia growth in epithelial cells. In this study we have analyzed the effect of these drugs on bacterial invasiveness. Results We demonstrate that INPs affect Chlamydia growth in a dose dependent manner after bacterial invasion. The efficiency of C. trachomatis L2 and C. caviae GPIC entry into host cells was not altered in the presence of INPs. In C. caviae, entry appears to proceed normally with recruitment of actin and the small GTPases Rac, Cdc42 and Arf6 to the site of bacterial entry. Conclusion INPs have a strong inhibitory effect on Chlamydia growth. However, bacterial invasion is not altered in the presence of these drugs. In the light of these results, we discuss several hypotheses regarding the mode of action of INPs on type III secretion during the Chlamydia infectious cycle.

  14. The Role of Treg Cells in the Cancer Immunological Response

    Directory of Open Access Journals (Sweden)

    Stephen M. Ansell

    2009-01-01

    Full Text Available Problem statement: T cell-mediated immunosuppression has been observed for decades without clarification as to which factor was responsible for this observation. The identification of CD4+CD25+ regulatory T (Treg cells represents a milestone in the filed of immunology and provides an explanation for T-cell-mediated immunosuppression. Although Treg cells were originally identified for their ability to prevent organ-specific autoimmune disease in mice, emerging evidence suggests that Treg cells play a pivotal role in tumor immunity and contribute to tumor growth and progression, thereby having an important impact on the outcome of cancer patients. Approach: This article reviewed the medical literature to describe how Treg cells affect anti-tumor immunity. Results: Treg cells suppressed anti-tumor immunity by inhibiting the effector functions of tumor-specific T cells and NK cells. Importantly, tumor cells played an active role in recruiting and generating Treg cells and creating a suppressive tumor microenvironment. Strategies to deplete Treg cells or inhibit their function had yielded promising results by enhancing anti-tumor immunity in experimental studies as well as clinical practice. Conclusion: A better understanding of the pathophysiology of Treg cells not only increased our knowledge in a variety of aspects of immunology but also potentially benefited cancer patients.

  15. Correlation of F-18 FDG PET with morphometric tumor response after neoadjuvant chemoradiation in locally advanced (stage III) non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Aim: To determine the role of 2-[(18)F] fluoro-2- deoxy-D-glucose (FDG) positron emission tomography (PET) in morphometric tumor response after neoadjuvant chemoradiation, findings in 32 patients were analyzed prospectively in an ongoing multicenter trial (LUCAS-MD, Germany). Material and Methods: Inclusion criteria was histologically confirmed NSCLC stage IIIA/IIIB. For staging all patients received a PET scan in addition to a spiral CT and/or MRI before therapy. Neoadjuvant treatment consisted of 2-3 cycles of chemotherapy with paclitaxel (225 mg/m2) and carboplatin (AUC 6), each d1 q22 and a block of chemoradiation (45Gy, 1.5Gy b.i.d., concomitant with paclitaxel (50 mg/m2) and carboplatin (AUC = 2), each d1, d8, d15) followed by surgery. All patients received a second PET after completion of neoadjuvant therapy prior to surgery. Whole-body PET (ECAT Exact 47) studies (attenuation corrected, iteratively reconstructed) were obtained 60 min. after injection of 6 MBq/kg body weight F-18 FDG. For semi-quantitative analysis, the tumor standardized uptake values (SUV), the tumor to background SUV ratio (T/B ratio), the metabolic tumor diameter (MTD) and the metabolic tumor index (MTI = SUV x MTD) were assessed in all primary tumors and in metastatic lymph nodes. Additionally, image fusion of PET with CT data was applied (using a HERMES Computer, Nuclear Diagnostics, Sweden). Results: So far, all patients (7/32) with complete metabolic response in lymph node metastases detected by PET, had no vital tumor cells (morphometric regression grade III). In primary tumors showing complete metabolic response, the regression grade was IIB (less than 10% vital tumor cells) or III. Conclusion: Morphometric tumor response after neoadjuvant therapy correlates strongly with metabolic remission by FDG-PET. PET precedes the tumor response as measured by CT after neoadjuvant treatment and may predict the long term therapeutic outcome in stage III NSCLC

  16. Repair of UV induced DNA lesions in ribosomal gene chromatin and the role of "Odd" RNA polymerases (I and III).

    Science.gov (United States)

    Charton, Romain; Guintini, Laetitia; Peyresaubes, François; Conconi, Antonio

    2015-12-01

    In fast growing eukaryotic cells, a subset of rRNA genes are transcribed at very high rates by RNA polymerase I (RNAPI). Nuclease digestion-assays and psoralen crosslinking have shown that they are open; that is, largely devoid of nucleosomes. In the yeast Saccharomyces cerevisae, nucleotide excision repair (NER) and photolyase remove UV photoproducts faster from open rRNA genes than from closed and nucleosome-loaded inactive rRNA genes. After UV irradiation, rRNA transcription declines because RNAPI halt at UV photoproducts and are then displaced from the transcribed strand. When the DNA lesion is quickly recognized by NER, it is the sub-pathway transcription-coupled TC-NER that removes the UV photoproduct. If dislodged RNAPI are replaced by nucleosomes before NER recognizes the lesion, then it is the sub-pathway global genome GG-NER that removes the UV photoproducts from the transcribed strand. Also, GG-NER maneuvers in the non-transcribed strand of open genes and in both strands of closed rRNA genes. After repair, transcription resumes and elongating RNAPI reopen the rRNA gene. In higher eukaryotes, NER in rRNA genes is inefficient and there is no evidence for TC-NER. Moreover, TC-NER does not occur in RNA polymerase III transcribed genes of both, yeast and human fibroblast. PMID:26411875

  17. Role of dendritic cells in the induction of regulatory T cells

    Directory of Open Access Journals (Sweden)

    Kushwah Rahul

    2011-05-01

    Full Text Available Abstract Dendritic cells (DCs play a key role in initiating immune responses and maintaining immune tolerance. In addition to playing a role in thymic selection, DCs play an active role in tolerance under steady state conditions through several mechanisms which are dependent on IL-10, TGF-β, retinoic acid, indoleamine-2,3,-dioxygenase along with vitamin D. Several of these mechanisms are employed by DCs in induction of regulatory T cells which are comprised of Tr1 regulatory T cells, natural and inducible foxp3+ regulatory T cells, Th3 regulatory T cells and double negative regulatory T cells. It appears that certain DC subsets are highly specialized in inducing regulatory T cell differentiation and in some tissues the local microenvironment plays a role in driving DCs towards a tolerogenic response. In this review we discuss the recent advances in our understanding of the mechanisms underlying DC driven regulatory T cell induction.

  18. Role of Dendritic Cells in Immune Dysfunction

    Science.gov (United States)

    Savary, Cherylyn A.

    1997-01-01

    Specific aims include: (1) Application of the bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC); (2) Based on clues from spaceflight: compare the frequency and function of DC in normal donors and immunocompromised cancer patients; and (3) Initiate studies on the efficiency of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in animal models of experimental fungal infections.

  19. Induction of Intracellular Ca2+ and pH Changes in Sf9 Insect Cells by Rhodojaponin-III, A Natural Botanic Insecticide Isolated from Rhododendron molle

    Directory of Open Access Journals (Sweden)

    Yan-Bo Zhang

    2011-04-01

    Full Text Available Many studies on intracellular calcium ([Ca2+]i and intracellular pH (pHi have been carried out due to their importance in regulation of different cellular functions. However, most of the previous studies are focused on human or mammalian cells. The purpose of the present study was to characterize the effect of Rhodojaponin-III (R-III on [Ca2+]i and pHi and the proliferation of Sf9 cells. R-III strongly inhibited Sf9 cells proliferation with a time- and dose-dependent manner. Flow cytometry established that R-III interfered with Sf9 cells division and arrested them in G2/M. By using confocal scanning technique, effects of R-III on intracellular free calcium ([Ca2+]i and intracellular pH (pHi in Sf9 cells were determined. R-III induced a significant dose-dependent (1, 10, 100, 200 μg/mL increase in [Ca2+]i and pHi of Sf9 cells in presence of Ca2+-containing solution (Hanks and an irreversible decrease in the absence of extra cellular Ca2+. We also found that both extra cellular Ca2+ and intracellular Ca2+ stores contributed to the increase of [Ca2+]i, because completely treating Sf9 cells with CdCl2 (5 mM, a Ca2+ channels blocker, R-III (100 μg/mL induced a transient elevation of [Ca2+]i in case of cells either in presence of Ca2+ containing or Ca2+ free solution. In these conditions, pHi showed similar changes with that of [Ca2+]i on the whole. Accordingly, we supposed that there was a certain linkage for change of [Ca2+]i, cell cycle arrest, proliferation inhibition in Sf9 cells induced by R-III.

  20. The Role of Everolimus in Renal Cell Carcinoma

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    Malek Meskawi

    2015-12-01

    Full Text Available Everolimus (RAD001 is an orally administered agent that inhibits the mammalian target of rapamycin serine-threonine kinase. A phase III pivotal trial on everolimus, published in 2008, provided the first evidence for the efficacy of sequential therapy for patients with metastatic clear cell renal cell carcinoma (RCC. In this study, everolimus was used after failure of one or several previous lines of therapy, and it demonstrated a 3-month survival benefit relative to placebo. Currently, based on the level 1 evidence, everolimus represents the molecule of choice for third-line therapy after failure of previous two tyrosine kinase inhibitors (TKIs. However, second-line use after failure of one TKI is challenged by two new molecules (nivolumab and cabozantinib, which proved to have better efficacy with similar toxicity profile. In non-clear cell metastatic RCC, the current evidence recommends everolimus as a second-line therapy after failure of previous first-line sunitinib.

  1. Role of Fetal Stem Cells in Maternal Tissue Regeneration

    OpenAIRE

    Zhong, Jiang F; Weiner, Leslie P.

    2007-01-01

    Microchimerism refers to the status of harboring cells from another individual at low levels. It is well known that cells traffic bidirectionally between fetus and mother during pregnancy. This situation resembles a naturally occurring long lasting fetal stem cell transplantation. The fetus acts as the donor and the mother acts as the recipient. To study the role of microchimerism in tissue regeneration, we constructed a murine microchimerism model with wild type C57BL/6J female mice carrying...

  2. Photon confinement in high-efficiency, thin-film III-V solar cells obtained by epitaxial lift-off

    International Nuclear Information System (INIS)

    Using the epitaxial lift-off (ELO) technique, a III-V device structure can be separated from its GaAs substrate by selective wet etching of a thin release layer. The thin-film structures obtained by the ELO process can be cemented or van der Waals bonded on arbitrary smooth surface carriers for further processing. It is shown that the ELO method, initially able to separate millimetre-sized GaAs layers with a lateral etch rate of about 1 mm/h, has been developed to a process capable to free the entire 2-in. epitaxial structures from their substrates with etch rates up to 30 mm/h. With these characteristics the method has a large potential for the production of high efficiency thin-film solar cells. By choosing the right deposition and ELO strategy, the thin-film III-V cells can be adequately processed on both sides allowing for an entire range of new cell structures. In the present work, the performance of semi-transparent bifacial solar cells, produced by the deposition of metal grid contacts on both sides, was evaluated. Reflection of light at the rear side of the bifacial GaAs solar cells was found to result in an enhanced collection probability of the photon-induced carriers compared to that of regular III-V cells on a GaAs substrate. To enhance this effect, thin-film GaAs cells with gold mirror back contacts were prepared. Even in their present premature stage of development, these single-junction thin-film cells reached a record efficiency of 24.5% which is already very close to the 24.9% efficiency that was obtained with a regular GaAs cell on a GaAs substrate. From this it could be concluded that, as a result of the photon confinement, ELO cells require a significantly thinner base layer than regular GaAs cells while at the same time they have the potential to reach a higher efficiency

  3. A possible role for the canonical Wnt pathway in endocrine cell development in chicks

    International Nuclear Information System (INIS)

    Wnt signalling is involved in many developmental processes such as proliferation, differentiation, cell fate decisions, and morphogenesis. However, little is known about Wnt signalling during pancreas development. Multiple Wnt ligands and Frizzled receptors are expressed in the embryonic mouse pancreas, the surrounding mesenchyme, and have also been detected in the chicken endoderm during development. The aim of this study was to investigate the role of canonical Wnt signalling on endocrine cell development by use of the in ovo electroporation of the chicken endoderm. Overexpression with a constitutive active form of β-catenin in combination with Ngn3 resulted in reduced numbers of glucagon cells. dnLEF-1 or naked-1 did not alter endocrine cell differentiation when co-expressed with Ngn3, but dnLEF-1 appeared to have some potential for inhibiting delamination of Ngn3 cells. In addition, neuronal β-III-tubulin, which had previously been considered a specific marker for neuronal cells, was observed in the pancreas and was upregulated in the electroporated Ngn3 cells and thus may be a new endocrine marker in the chicken

  4. Functional redundancy between DNA ligases I and III in DNA replication in vertebrate cells

    OpenAIRE

    Arakawa, Hiroshi; Bednar, Theresa; Wang, Minli; Paul, Katja; Mladenov, Emil; Bencsik-Theilen, Alena A.; Iliakis, George

    2011-01-01

    In eukaryotes, the three families of ATP-dependent DNA ligases are associated with specific functions in DNA metabolism. DNA ligase I (LigI) catalyzes Okazaki-fragment ligation at the replication fork and nucleotide excision repair (NER). DNA ligase IV (LigIV) mediates repair of DNA double strand breaks (DSB) via the canonical non-homologous end-joining (NHEJ) pathway. The evolutionary younger DNA ligase III (LigIII) is restricted to higher eukaryotes and has been associated with base excisio...

  5. Membrane-surfactant interactions. The role of surfactant in mitochondrial complex III-phospholipid-Triton X-100 mixed micelles

    International Nuclear Information System (INIS)

    Complex III (ubiquinol-cytochrome c reductase) was purified from beef heart mitochondria in the form of protein-phospholipid-Triton X-100 mixed micelles (about 1:80:100 molar ratio). Detergent may be totally removed by sucrose density gradient centrifugation, and the resulting lipoprotein complexes retain full enzyme activity. In order to understand the role of surfactant in the mixed micelles, and the interaction of Triton X-100 with integral membrane proteins and phospholipid bilayers, both the protein-lipid-surfactant mixed micelles and the detergent-free lipoprotein system were examined from the point of view of particle size and ultrastructure, enzyme activity, tryptophan fluorescence quenching, 31P NMR, and Fourier transform infrared spectroscopy. The NMR and IR spectroscopic studies show that surfactant withdrawal induces a profound change in phospholipid architecture, from a micellar to a lamellar-like phase. However, electron microscopic observations fail to reveal the existence of lipid bilayers in the absence of detergent. We suggest that, under these conditions, the lipid:protein molar ratio (80:1) is too low to permit the formation of lipid bilayer planes, but the relative orientation and mobility of phospholipids with respect to proteins is similar to that of the lamellar phase. Protein conformational changes are also detected as a consequence of surfactant removal. Fourier transform infrared spectroscopy indicates an increase of peptide beta-structure in the absence of Triton X-100; changes in the amide II/amide I intensity ratio are also detected, although the precise meaning of these observations is unclear

  6. The role of Chromium III in the organism and its possible use in diabetes and obesity treatment

    Directory of Open Access Journals (Sweden)

    Sławomir Lewicki

    2014-06-01

    Full Text Available introduction. Diabetes and obesity are diseases characterized by their increasing incidence every year. When comparing with healthy subjects, the serum levels of chromium (Cr are lowered in these two diseases. Several studies conducted in laboratory animals with experimentally- induced diabetes demonstrated that supplementation with chromium ions (III decreased glucose concentration in the blood, reduced the probability of atherosclerosis and heart attack, lowered the levels of cholesterol and low density lipoprotein (LDL. The Importance of chromium is actually challenged due to lack of clear manifestations of Cr deficiency in humans and animals. objective. The aim of this review was to present current knowledge about Cr its role in the organism and possible mechanisms of its action also in metabolic disorders such as diabetes or obesity. state of knowledge. In the last decade, Cr was established to be rather a beneficial than essential trace element in mammals, and has gained popularity as a nutritional supplement and a component of many multivitamin/mineral formulations, fortified food and energy drinks. Cr supplements are widespread for diabetes and obesity treatment, despite conflicting reports on its efficacy. It was suggested that Cr shows a beneficial influence upon glucose and lipid disturbances. conclusions. The recent clinical trials provided evidence both in favor and against the importance of Cr in healthy and ill organisms. Unfortunately, also the molecular mechanism by which chromium affects glucose and lipid metabolism is still unclear. Beneficial effects of diet supplementation with different sources of Cr 3+ can be potentially explained by rather pharmacological than nutritional effects.

  7. Role of Dendritic Cells in Immune Dysfunction

    Science.gov (United States)

    Savary, Cherylyn A.

    1998-01-01

    The specific aims of the project were: (1) Application of the NASA bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC). (2) Compare the frequency and function of DC in normal donors and immunocompromised cancer patients. (3) Analyze the effectiveness of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in a murine model of experimental fungal disease. Our investigations have provided new insight into DC immunobiology and have led to the development of methodology to evaluate DC in blood of normal donors and patients. Information gained from these studies has broadened our understanding of possible mechanisms involved in the immune dysfunction of space travelers and earth-bound cancer patients, and could contribute to the design of novel therapies to restore/preserve immunity in these individuals. Several new avenues of investigation were also revealed. The results of studies completed during Round 2 are summarized.

  8. Role of Iron(III)-salen Chloride as Oxidizing Agent with Thiodiglycolic Acid: The Effect of Axial Ligands

    OpenAIRE

    Perumal Subramaniam; Thangadurai Vanitha; Thiruttimuthu Kodispathi; Chandra Raj Shanmuga Sundari

    2014-01-01

    En este trabajo se estudia la sulfoxidación del ácido tio - diglicólico con cloruro de Fe(III)-salen, que actúa como agente oxi - dante en un medio 50% acetonitrilo-agua. Se observa un desplaza - miento importante hacia el rojo del valor del λ max del FeIII-salen en medio acuoso. El estudio cinético espectrofotométrico indica que el [FeIII(salen)]+ es la especie oxidante activa y que se sigue una cinética Michaelis-Menten, con respecto al sustrato. La velocidad de reacción es altamente sensib...

  9. Organometallic iron(III-salophene exerts cytotoxic properties in neuroblastoma cells via MAPK activation and ROS generation.

    Directory of Open Access Journals (Sweden)

    Kyu Kwang Kim

    Full Text Available The objective of the present study was to investigate the specific effects of Iron(III-salophene (Fe-SP on viability, morphology, proliferation, cell cycle progression, ROS generation and pro-apoptotic MAPK activation in neuroblastoma (NB cells. A NCI-DTP cancer screen revealed that Fe-SP displayed high toxicity against cell lines of different tumor origin but not tumor type-specificity. In a viability screen Fe-SP exhibited high cytotoxicity against all three NB cell lines tested. The compound caused cell cycle arrest in G1 phase, suppression of cells progressing through S phase, morphological changes, disruption of the mitochondrial membrane depolarization potential, induction of apoptotic markers as well as p38 and JNK MAPK activation, DNA degradation, and elevated generation of reactive oxygen species (ROS in SMS-KCNR NB cells. In contrast to Fe-SP, non-complexed salophene or Cu(II-SP did not raise ROS levels in NB or SKOV-3 ovarian cancer control cells. Cytotoxicity of Fe-SP and activation of caspase-3, -7, PARP, pro-apoptotic p38 and JNK MAPK could be prevented by co-treatment with antioxidants suggesting ROS generation is the primary mechanism of cytotoxic action. We report here that Fe-SP is a potent growth-suppressing and cytotoxic agent for in vitro NB cell lines and, due to its high tolerance in previous animal toxicity studies, a potential therapeutic drug to treat NB tumors in vivo.

  10. Three new chondrosarcoma cell lines: one grade III conventional central chondrosarcoma and two dedifferentiated chondrosarcomas of bone

    International Nuclear Information System (INIS)

    Chondrosarcoma is the second most common primary sarcoma of bone. High-grade conventional chondrosarcoma and dedifferentiated chondrosarcoma have a poor outcome. In pre-clinical research aiming at the identification of novel treatment targets, the need for representative cell lines and model systems is high, but availability is scarce. We developed and characterized three cell lines, derived from conventional grade III chondrosarcoma (L835), and dedifferentiated chondrosarcoma (L2975 and L3252) of bone. Proliferation and migration were studied and we used COBRA-FISH and array-CGH for karyotyping and genotyping. Immunohistochemistry for p16 and p53 was performed as well as TP53 and IDH mutation analysis. Cells were injected into nude mice to establish their tumorigenic potential. We show that the three cell lines have distinct migrative properties, L2975 had the highest migration rate and showed tumorigenic potential in mice. All cell lines showed chromosomal rearrangements with complex karyotypes and genotypic aberrations were conserved throughout late passaging of the cell lines. All cell lines showed loss of CDKN2A, while TP53 was wild type for exons 5–8. L835 has an IDH1 R132C mutation, L2975 an IDH2 R172W mutation and L3252 is IDH wild type. Based on the stable culturing properties of these cell lines and their genotypic profile resembling the original tumors, these cell lines should provide useful functional models to further characterize chondrosarcoma and to evaluate new treatment strategies

  11. Role of Kupffer cells in the pathogenesis of liver disease

    Institute of Scientific and Technical Information of China (English)

    George Kolios; Vassilis Valatas; Elias Kouroumalis

    2006-01-01

    Kupffer cells, the resident liver macrophages have long been considered as mostly scavenger cells responsible for removing particulate material from the portal circulation. However, evidence derived mostly from animal models, indicates that Kupffer cells may be implicated in the pathogenesis of various liver diseases including viral hepatitis, steatohepatitis, alcoholic liver disease, intrahepatic cholostasis, activation or rejection of the liver during liver transplantation and liver fibrosis. There is accumulating evidence, reviewed in this paper, suggesting that Kupffer cells may act both as effector cells in the destruction of hepatocytes by producing harmful soluble mediators as well as antigen presenting cells during viral infections of the liver. Moreover they may represent a significant source of chemoattractant molecules for cytotoxic CD8 and regulatory T cells. Their role in fibrosis is well established as they are one of the main sources of TGFβ1 production, which leads to the transformation of stellate cells into myofibroblasts. Whether all these variable functions in the liver are mediated by different Kupffer cell subpopulations remains to be evaluated. In this review we propose a model that demonstrates the role of Kupffer cells in the pathogenesis of liver disease.

  12. The significant role of mast cells in cancer.

    Science.gov (United States)

    Khazaie, Khashayarsha; Blatner, Nichole R; Khan, Mohammad Wasim; Gounari, Fotini; Gounaris, Elias; Dennis, Kristen; Bonertz, Andreas; Tsai, Fu-Nien; Strouch, Matthew J; Cheon, Eric; Phillips, Joseph D; Beckhove, Philipp; Bentrem, David J

    2011-03-01

    Mast cells (MC) are a bone marrow-derived, long-lived, heterogeneous cellular population that function both as positive and negative regulators of immune responses. They are arguably the most productive chemical factory in the body and influence other cells through both soluble mediators and cell-to-cell interaction. MC are commonly seen in various tumors and have been attributed alternatively with tumor rejection or tumor promotion. Tumor-infiltrating MC are derived both from sentinel and recruited progenitor cells. MC can directly influence tumor cell proliferation and invasion but also help tumors indirectly by organizing its microenvironment and modulating immune responses to tumor cells. Best known for orchestrating inflammation and angiogenesis, the role of MC in shaping adaptive immune responses has become a focus of recent investigations. MC mobilize T cells and antigen-presenting dendritic cells. They function as intermediaries in regulatory T cells (Treg)-induced tolerance but can also modify or reverse Treg-suppressive properties. The central role of MC in the control of innate and adaptive immunity endows them with the ability to tune the nature of host responses to cancer and ultimately influence the outcome of disease and fate of the cancer patient. PMID:21287360

  13. Fluorescence detection of telomerase activity in cancer cell extracts based on autonomous exonuclease III-assisted isothermal cycling signal amplification.

    Science.gov (United States)

    Ding, Caifeng; Li, Xiaoqian; Wang, Wei; Chen, Yaoyao

    2016-09-15

    Based on the extension reaction of a telomerase substrate (TS) primer in the presence of the telomerase, strand-displacement process to perform more stable longer duplex chain, and stepwise hydrolysis of mononucleotides from the blunt or the recessed 3'-hydroxyl termini of duplex DNA in the presence of Exonuclease III (Exo III), an amplified fluorescence detection of telomerase activity in the cancer cells was described in this manuscript. A fluorescence probe DNA, a quencher DNA, and a TS primer were mixed to construct a three-chain DNA structure and a two-chain DNA structure because the amount of the TS primer was less than the other two DNA. In the presence of the telomerase, the quencher DNA was replaced from the probe DNA and the telomerase activity could be determined with the fluorescence enhancement. The telomerase activity in HeLa extracts equivalent to 6-2000 cells was detected by this method. Moreover, the strategy was further proved by using telomerase extracted from Romas cells. With the multiple rounds of isothermal strand displacement and the hydrolysis process, constituted consecutive of signal amplification for the novel detection paradigm that allowed measuring of telomerase activity in crude cancer cell extracts confirmed the reliability and practicality of the protocol, which reveal this platform holds great promise in the biochemical assay for the telomerase activity in early diagnosis for cancers. PMID:27108253

  14. Subsets of regulatory T cells and their roles in allergy.

    Science.gov (United States)

    Zhang, Huiyun; Kong, Hui; Zeng, Xiaoning; Guo, Lianyi; Sun, Xiaoyun; He, Shaoheng

    2014-01-01

    In recent years, it is recognized that acquired immunity is controlled by regulatory T cell (Treg). Since fundamental pathophysiological changes of allergy are mainly caused by hyperresponsiveness of immune system to allergens that acquires after birth, Tregs likely play key roles in the pathogenesis of allergy, particularly during the sensitization phase. However, accumulated information indicate that there are several distinctive subtypes of Tregs in man, and each of them seems to play different role in controlling immune system, which complicates the involvement of Tregs in allergy. The aim of the present study is to attempt to classify subtypes of Tregs and summarize their roles in allergy. Tregs should include natural Tregs (nTreg) including inducible costimulator (ICOS)(+) Tregs, inducible/adaptive Tregs (iTreg), interleukin (IL)-10-producing type 1 Tregs (Tr1 cells), CD8(+) Tregs and IL-17-producing Tregs. These cells share some common features including expression of Foxp3 (except for Tr1 cells), and secretion of inhibitory cytokine IL-10 and/or TGF-β. Furthermore, it is noticeable that Tregs likely contribute to allergic disorders such as dermatitis and airway inflammation, and play a crucial role in the treatment of allergy through their actions on suppression of effector T cells and inhibition of activation of mast cells and basophils. Modulation of functions of Tregs may provide a novel strategy to prevent and treat allergic diseases. PMID:24886492

  15. Calreticulin: Roles in Cell-Surface Protein Expression

    Directory of Open Access Journals (Sweden)

    Yue Jiang

    2014-09-01

    Full Text Available In order to perform their designated functions, proteins require precise subcellular localizations. For cell-surface proteins, such as receptors and channels, they are able to transduce signals only when properly targeted to the cell membrane. Calreticulin is a multi-functional chaperone protein involved in protein folding, maturation, and trafficking. However, evidence has been accumulating that calreticulin can also negatively regulate the surface expression of certain receptors and channels. In these instances, depletion of calreticulin enhances cell-surface expression and function. In this review, we discuss the role of calreticulin with a focus on its negative effects on the expression of cell-surface proteins.

  16. Role of Exosome Shuttle RNA in Cell-to-Cell Communication.

    Science.gov (United States)

    Zhang, Wei; Peng, Peng; Shen, Keng

    2016-08-01

    There are several ways that transpire in cell-to-cell communication,with or without cell contact. Exosomes play an important role in cell-to-cell communication,which do not need cell contact,as that can result in a relatively long-distance influence. Exosome contains RNA components including mRNA and micro-RNA,which are protected by exosomes rigid membranes. This allows those components be passed long distance through the circulatory system. The mRNA components are far different from their donor cells,and the micro-RNA components may reflect the cell they originated. In this article we review the role of exosomes in cell-to-cell communication,with particular focus on their potentials in both diagnostic and therapeutic applications. PMID:27594165

  17. CARI III Inhibits Tumor Growth in a Melanoma-Bearing Mouse Model through Induction of G0/G1 Cell Cycle Arrest

    Directory of Open Access Journals (Sweden)

    Hye-Jin Park

    2014-09-01

    Full Text Available Mushroom-derived natural products have been used to prevent or treat cancer for millennia. In this study, we evaluated the anticancer effects of CARI (Cell Activation Research Institute III, which consists of a blend of mushroom mycelia from Phellinus linteus grown on germinated brown rice, Inonotus obliquus grown on germinated brown rice, Antrodia camphorata grown on germinated brown rice and Ganoderma lucidum. Here, we showed that CARI III exerted anti-cancer activity, which is comparable to Dox against melanoma in vivo. B16F10 cells were intraperitoneally injected into C57BL6 mice to develop solid intra-abdominal tumors. Three hundred milligrams of the CARI III/kg/day p.o. regimen reduced tumor weight, comparable to the doxorubicin (Dox-treated group. An increase in life span (ILS% = 50.88% was observed in the CARI III-administered group, compared to the tumor control group. CARI III demonstrates anti-proliferative activity against B16F10 melanoma cells through inducing G0/G1 cell cycle arrest. CARI III inhibits the expression of cyclin D1, CDK4 and CDK2 and induces p21. Therefore, CARI III could be a potential chemopreventive supplement to melanoma patients.

  18. CARI III inhibits tumor growth in a melanoma-bearing mouse model through induction of G0/G1 cell cycle arrest.

    Science.gov (United States)

    Park, Hye-Jin

    2014-01-01

    Mushroom-derived natural products have been used to prevent or treat cancer for millennia. In this study, we evaluated the anticancer effects of CARI (Cell Activation Research Institute) III, which consists of a blend of mushroom mycelia from Phellinus linteus grown on germinated brown rice, Inonotus obliquus grown on germinated brown rice, Antrodia camphorata grown on germinated brown rice and Ganoderma lucidum. Here, we showed that CARI III exerted anti-cancer activity, which is comparable to Dox against melanoma in vivo. B16F10 cells were intraperitoneally injected into C57BL6 mice to develop solid intra-abdominal tumors. Three hundred milligrams of the CARI III/kg/day p.o. regimen reduced tumor weight, comparable to the doxorubicin (Dox)-treated group. An increase in life span (ILS% = 50.88%) was observed in the CARI III-administered group, compared to the tumor control group. CARI III demonstrates anti-proliferative activity against B16F10 melanoma cells through inducing G0/G1 cell cycle arrest. CARI III inhibits the expression of cyclin D1, CDK4 and CDK2 and induces p21. Therefore, CARI III could be a potential chemopreventive supplement to melanoma patients. PMID:25221864

  19. Sophisticated Functions for a Simple Molecule: The Role of Glucosylceramides in Fungal Cells

    Directory of Open Access Journals (Sweden)

    Leonardo Nimrichter

    2008-01-01

    Full Text Available It is well known that mammalian glycosphingolipids (GSL play key roles in different physiological and pathophysiological processes. The simplest GSL, glucosylceramide (GlcCer, is formed through the enzymatic transfer of glucose to a ceramide moiety. In mammalian cells this molecule is the building block for the synthesis of lactosylceramides and many other complex GSLs. In fungal cells GlcCer is a major neutral GSL that has been considered during decades merely as a structural component of cell membranes. The recent literature, however, describes the participation of fungal GlcCer in vital processes such as secretion, cell wall assembly, recognition by the immune system and regulation of virulence. In this review we discuss the most recent information regarding fungal GlcCer, including (i new aspects of GlcCer metabolism, (ii the involvement of these molecules in virulence mechanisms, (iii their role as targets of new antifungal drugs and immunotherapeutic agents and, finally, (v their potential participation on cellular signaling in response to different stimuli.

  20. Role of radiation therapy in large cell lymphoma

    International Nuclear Information System (INIS)

    This paper compares the results of treatment for large cell lymphoma with use of radiation therapy (RT), chemotherapy (CT), or both. The authors retrospectively studied 142 patients with large cell lymphoma. Seventy-two has stage I or II disease and 70, stage III or IV; 37% had B symptoms. CT was used in 66 patients, RT in 22, both in 46, and surgery with or without RT or CT in eight. CT regimens were CHOP, 38 patients; C-MOPP/COPP, 25; CHOP-bleo/BACOP, 15; COP-BLAN-MEL, 8; M-BACOD, 8; COP/CVP, 5; COP-BLAM, 5; and other regimens, 12. Statistical analysis showed that age, stage B symptoms, and treatment were significant variables determining survival. In stages I and II, the 5-year survival rate with RT plus CT was 65%; with CT, 35%; and with RT, 9% (P = < .01)

  1. Antigen I/II encoded by integrative and conjugative elements of Streptococcus agalactiae and role in biofilm formation.

    Science.gov (United States)

    Chuzeville, Sarah; Dramsi, Shaynoor; Madec, Jean-Yves; Haenni, Marisa; Payot, Sophie

    2015-11-01

    Streptococcus agalactiae (i.e. Group B streptococcus, GBS) is a major human and animal pathogen. Genes encoding putative surface proteins and in particular an antigen I/II have been identified on Integrative and Conjugative Elements (ICEs) found in GBS. Antigens I/II are multimodal adhesins promoting colonization of the oral cavity by streptococci such as Streptococcus gordonii and Streptococcus mutans. The prevalence and diversity of antigens I/II in GBS were studied by a bioinformatic analysis. It revealed that antigens I/II, which are acquired by horizontal transfer via ICEs, exhibit diversity and are widespread in GBS, in particular in the serotype Ia/ST23 invasive strains. This study aimed at characterizing the impact on GBS biology of proteins encoded by a previously characterized ICE of S. agalactiae (ICE_515_tRNA(Lys)). The production and surface exposition of the antigen I/II encoded by this ICE was examined using RT-PCR and immunoblotting experiments. Surface proteins of ICE_515_tRNA(Lys) were found to contribute to GBS biofilm formation and to fibrinogen binding. Contribution of antigen I/II encoded by SAL_2056 to biofilm formation was also demonstrated. These results highlight the potential for ICEs to spread microbial adhesins between species. PMID:26232503

  2. Impact of Consolidation Radiation Therapy in Stage III-IV Diffuse Large B-cell Lymphoma With Negative Post-Chemotherapy Radiologic Imaging

    International Nuclear Information System (INIS)

    Purpose: While consolidation radiation therapy (i.e., RT administered after chemotherapy) is routine treatment for patients with early-stage diffuse large B-cell lymphoma (DLBCL), the role of consolidation RT in stage III-IV DLBCL is controversial. Methods and Materials: Cases of patients with stage III-IV DLBCL treated from 1991 to 2009 at Duke University, who achieved a complete response to chemotherapy were reviewed. Clinical outcomes were calculated using the Kaplan-Meier method and were compared between patients who did and did not receive RT, using the log-rank test. A multivariate analysis was performed using Cox proportional hazards model. Results: Seventy-nine patients were identified. Chemotherapy (median, 6 cycles) consisted of anti-CD20 antibody rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 65%); cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; 22%); or other (13%). Post-chemotherapy imaging consisted of positron emission tomography (PET)/computed tomography (CT) (73%); gallium with CT (14%); or CT only (13%). Consolidation RT (median, 25 Gy) was given to involved sites of disease in 38 (48%) patients. Receipt of consolidation RT was associated with improved in-field control (92% vs. 69%, respectively, p = 0.028) and event-free survival (85% vs. 65%, respectively, p = 0.014) but no difference in overall survival (85% vs. 78%, respectively, p = 0.15) when compared to patients who did not receive consolidation RT. On multivariate analysis, no RT was predictive of increased risk of in-field failure (hazard ratio [HR], 8.01, p = 0.014) and worse event-free survival (HR, 4.3, p = 0.014). Conclusions: Patients with stage III-IV DLBCL who achieve negative post-chemotherapy imaging have improved in-field control and event-free survival with low-dose consolidation RT.

  3. Impact of Consolidation Radiation Therapy in Stage III-IV Diffuse Large B-cell Lymphoma With Negative Post-Chemotherapy Radiologic Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Dorth, Jennifer A., E-mail: jennifer.dorth@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Prosnitz, Leonard R. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Broadwater, Gloria [Cancer Statistical Center, Duke University Medical Center, Durham, North Carolina (United States); Diehl, Louis F.; Beaven, Anne W. [Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina (United States); Coleman, R. Edward [Department of Radiology, Division of Nuclear Medicine, Duke University Medical Center, Durham, North Carolina (United States); Kelsey, Chris R. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

    2012-11-01

    Purpose: While consolidation radiation therapy (i.e., RT administered after chemotherapy) is routine treatment for patients with early-stage diffuse large B-cell lymphoma (DLBCL), the role of consolidation RT in stage III-IV DLBCL is controversial. Methods and Materials: Cases of patients with stage III-IV DLBCL treated from 1991 to 2009 at Duke University, who achieved a complete response to chemotherapy were reviewed. Clinical outcomes were calculated using the Kaplan-Meier method and were compared between patients who did and did not receive RT, using the log-rank test. A multivariate analysis was performed using Cox proportional hazards model. Results: Seventy-nine patients were identified. Chemotherapy (median, 6 cycles) consisted of anti-CD20 antibody rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 65%); cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; 22%); or other (13%). Post-chemotherapy imaging consisted of positron emission tomography (PET)/computed tomography (CT) (73%); gallium with CT (14%); or CT only (13%). Consolidation RT (median, 25 Gy) was given to involved sites of disease in 38 (48%) patients. Receipt of consolidation RT was associated with improved in-field control (92% vs. 69%, respectively, p = 0.028) and event-free survival (85% vs. 65%, respectively, p = 0.014) but no difference in overall survival (85% vs. 78%, respectively, p = 0.15) when compared to patients who did not receive consolidation RT. On multivariate analysis, no RT was predictive of increased risk of in-field failure (hazard ratio [HR], 8.01, p = 0.014) and worse event-free survival (HR, 4.3, p = 0.014). Conclusions: Patients with stage III-IV DLBCL who achieve negative post-chemotherapy imaging have improved in-field control and event-free survival with low-dose consolidation RT.

  4. Comorbidity and Karnofksy performance score are independent prognostic factors in stage III non-small-cell lung cancer: an institutional analysis of patients treated on four RTOG studies

    International Nuclear Information System (INIS)

    Purpose: To determine the prognostic role of comorbidity in Stage III non-small cell lung cancer (NSCLC) treated definitively with radiotherapy alone. Methods and Materials: A total of 112 patients with clinical Stage III NSCLC (American Joint Commission on Cancer 1997) enrolled in four Radiation Therapy Oncology Group studies (83-11, 84-03, 84-07, and 88-08 nonchemotherapy arms) at a single institution were analyzed retrospectively for overall survival (OS) and comorbidity. Of the 112 patients, 105 (94%) completed their assigned radiotherapy. The median assigned dose was 50.4 Gy to the lymphatics (range 45-50.4 Gy) and 70.2 Gy to the primary tumor (range 60-79.2 Gy). Comorbidity was rated retrospectively using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and Charlson scales. Karnofsky performance scores (KPSs) and weight loss were prospectively recorded. Because only 8 patients had a KPS of 70). Results: The median survival was 10.39 months (range 7.87-12.91). The 2-, 3-, and 5-year OS rate was 20.5%, 12.5%, and 7.1%, respectively. On univariate analysis, clinical stage (IIIA vs. IIIB) was found to be a statistically significant factor influencing OS (p=0.026), and the histologic features, grade, tumor size as measured on CT scans, age, tobacco use, weight loss ≥5%, and total dose delivered to the primary tumor were not. A KPS of ≤70 (p=0.001), the presence of a CIRS-G score of 4 (extremely severe; p=0.0002), and a severity index of >2 (p2 were independently associated with inferior OS; clinical tumor stage was not found to be an independent prognostic factor. Conclusion: KPS and comorbidity are important independent prognostic factors in Stage III NSCLC. Comorbidity should be included in protocols studying advanced stage NSCLC and used for stratification

  5. Regulatory T Cells and Their Role in Animal Disease.

    Science.gov (United States)

    Veiga-Parga, T

    2016-07-01

    In humans and mouse models, Foxp3(+) regulatory T cells are known to control all aspects of immune responses. However, only limited information exists on these cells' role in diseases of other animals. In this review, we cover the most important features and different types of regulatory T cells, which include those that are thymus-derived and peripherally induced, the mechanisms by which they control immune responses by targeting effector T cells and antigen-presenting cells, and most important, their role in animal health and diseases including cancer, infections, and other conditions such as hypersensitivities and autoimmunity. Although the literature regarding regulatory T cells in domestic animal species is still limited, multiple articles have recently emerged and are discussed. Moreover, we also discuss the evidence suggesting that regulatory T cells might limit the magnitude of effector responses, which can have either a positive or negative result, depending on the context of animal and human disease. In addition, the issue of plasticity is discussed because plasticity in regulatory T cells can result in the loss of their protective function in some microenvironments during disease. Lastly, the manipulation of regulatory T cells is discussed in assessing the possibility of their use as a treatment in the future. PMID:26945003

  6. Role(s) of IL-2 inducible T cell kinase and Bruton's tyrosine kinase in mast cell response to lipopolysaccharide.

    Science.gov (United States)

    Huang, Weishan; August, Avery

    2016-06-01

    Mast cells play critical roles during immune responses to the bacterial endotoxin lipopolysaccharide (LPS) that can lead to fatal septic hypothermia [1], [2], [3]. IL-2 inducible T cell kinase (ITK) and Bruton's tyrosine kinase (BTK) are non-receptor tyrosine kinases that act downstream of numerous receptors, and have been shown to modulate mast cell responses downstream of FcεRIα [4], however, their roles in regulating mast cell responses to endotoxic stimuli were unclear. We found that the absence of ITK and BTK alters the mast cell response to LPS, and leads to enhanced pro-inflammatory cytokine production by mast cells and more severe LPS-induced hypothermia in mice [5]. Here, we detail our investigation using microarray analysis to study the transcriptomic profiles of mast cell responses to LPS, and the roles of ITK and/or BTK expression in this process. Mouse whole genome array data of WT, Itk (-/-) , Btk (-/-) , and Itk (-/-)  Btk (-/-) bone marrow-derived mast cells (BMMCs) stimulated by PBS (control) or LPS for 1 h were used in our latest research article [5] and is available in the Gene Expression Omnibus under accession number GSE64287. PMID:27081634

  7. Overexpression of DNA ligase III in mitochondria protects cells against oxidative stress and improves mitochondrial DNA base excision repair

    DEFF Research Database (Denmark)

    Akbari, Mansour; Keijzers, Guido; Maynard, Scott;

    2014-01-01

    Base excision repair (BER) is the most prominent DNA repair pathway in human mitochondria. BER also results in a temporary generation of AP-sites, single-strand breaks and nucleotide gaps. Thus, incomplete BER can result in the generation of DNA repair intermediates that can disrupt mitochondrial...... rotenone. Our results suggest that the amount of DNA ligase III in mitochondria may be critical for cell survival following prolonged oxidative stress, and demonstrate a functional link between mitochondrial DNA damage and repair, cell survival upon oxidative stress, and removal of dysfunctional...... DNA replication and transcription and generate mutations. We carried out BER analysis in highly purified mitochondrial extracts from human cell lines U2OS and HeLa, and mouse brain using a circular DNA substrate containing a lesion at a specific position. We found that DNA ligation is significantly...

  8. Monolithic in-based III-V compound semiconductor focal plane array cell with single stage CCD output

    Science.gov (United States)

    Fossum, Eric R. (Inventor); Cunningham, Thomas J. (Inventor); Krabach, Timothy N. (Inventor); Staller, Craig O. (Inventor)

    1995-01-01

    A monolithic semiconductor imager includes an indium-based III-V compound semiconductor monolithic active layer of a first conductivity type, an array of plural focal plane cells on the active layer, each of the focal plane cells including a photogate over a top surface of the active layer, a readout circuit dedicated to the focal plane cell including plural transistors formed monolithically with the monolithic active layer and a single-stage charge coupled device formed monolithically with the active layer between the photogate and the readout circuit for transferring photo-generated charge accumulated beneath the photogate during an integration period to the readout circuit. The photogate includes thin epitaxial semiconductor layer of a second conductivity type overlying the active layer and an aperture electrode overlying a peripheral portion of the thin epitaxial semiconductor layer, the aperture electrode being connectable to a photogate bias voltage.

  9. Clinical role in biopsy after interstitial irradiation to squamous cell carcinoma of tongue

    International Nuclear Information System (INIS)

    The clinical role of biopsy after interstitial irradiation therapy was evaluated in 44 patients with squamous cell carcinoma of tongue on which biopsy was done in our hospital. More residual tumors were observed in the induration-positive groups compared to those of the induration-negative groups. No tumor was histologically observed in 71.4% of the induration-positive groups. On the adjacent and covering mucous membranes, epithelial dysplasia was detected in 15 patients, 1 of them was Grade III and 9 were Grade IV. Two patients had recurrence. In the initial stage of interstitial irradiation, reaction of stoma showed decrease of edema, inflammatory cell infiltration, regeneration and dilation of vessels after 6 weeks. The regeneration of collagen fiber increased within 3-14 weeks after irradiation, followed by decrease of its activity. After interstitial irradiation, 2 of 9 Grade IIb patients treated by surgery and 2 by re-interstitial irradiation survived. One of 3 Grade III patients manifested recurrence and was treated by surgery. All patients were alive. Fourteen of 17 Grade IV patients under careful observation were still alive. Eleven of 15 patients treated by total neck dissection after interstitial irradiation survived. Four Grade IV patients showed recurrence. Two-year primary lesion control rate was 91.2% and the survival rate for 5 year was 74.0%. (S.Y.). 54 refs

  10. Switching roles: the functional plasticity of adult tissue stem cells.

    Science.gov (United States)

    Wabik, Agnieszka; Jones, Philip H

    2015-05-01

    Adult organisms have to adapt to survive, and the same is true for their tissues. Rates and types of cell production must be rapidly and reversibly adjusted to meet tissue demands in response to both local and systemic challenges. Recent work reveals how stem cell (SC) populations meet these requirements by switching between functional states tuned to homoeostasis or regeneration. This plasticity extends to differentiating cells, which are capable of reverting to SCs after injury. The concept of the niche, the micro-environment that sustains and regulates stem cells, is broadening, with a new appreciation of the role of physical factors and hormonal signals. Here, we review different functions of SCs, the cellular mechanisms that underlie them and the signals that bias the fate of SCs as they switch between roles. PMID:25812989

  11. Roles of tRNA in cell wall biosynthesis

    DEFF Research Database (Denmark)

    Dare, Kiley; Ibba, Michael

    2012-01-01

    Recent research into various aspects of bacterial metabolism such as cell wall and antibiotic synthesis, degradation pathways, cellular stress, and amino acid biosynthesis has elucidated roles of aminoacyl-transfer ribonucleic acid (aa-tRNA) outside of translation. Although the two enzyme families...... specificity of this diverse enzymatic family is necessary to aid current efforts in designing potential bactericidal agents. These two enzyme families are linked only by the substrate with which they modify the cell wall, aa-tRNA; their structure, cell wall modification processes and the physiological changes...... responsible for cell wall modifications, aminoacyl-phosphatidylglycerol synthases (aaPGSs) and Fem, were discovered some time ago, they have recently become of intense interest for their roles in the antimicrobial resistance of pathogenic microorganisms. The addition of positively charged amino acids to...

  12. Role of "electron shuttles" in the bioreduction of Fe(III) oxides in humid forest tropical soils.

    Science.gov (United States)

    Peretyazhko, T.; Sposito, G.

    2004-12-01

    Dissimilatory iron-reducing bacteria (DIRB) can reduce Fe(III) oxides either by direct contact between the organisms and the oxide surface or by indirect mechanisms not involving contact. These latter mechanisms can include (i) "electron shuttling" or (ii) soluble Fe(III) complexation with subsequent reduction. In the presence of humic substances, indirect Fe(III) reduction occurs, particularly by mechanism (i). Important electron-accepting groups in humic substances include quinone moieties, complexed Fe(III) and conjugated aromatic moieties. A model compound frequently used to study mechanism (i) is anthraquinone-2,6-disulfonate (AQDS), which is believed to function as an "electron shuttle" in a manner similar to humic substances. We are currently investigating Fe(III) reduction in humid tropical forest soils as affected by "electron shuttles," using AQDS and humic substances in our experiments. The soil samples were collected at the bottom of a toposequence in the Luquillo Experimental Forest, Puerto Rico. Development of anaerobic conditions in these soils occurs due to high precipitation and runoff water inputs. Fourteen-day anoxic incubations of soil suspensions amended with AQDS showed enhanced production of both soluble and particulate forms of Fe(II) as compared to non-amended soil suspensions. Our data indicated clearly that DIRB in the soil could utilize added "electron shuttles" effectively to reduce Fe(III). To examine factors controlling Fe(III) reduction by humic acid (HA), three IHSS HA samples (soil, peat and Leonardite) were both abiotically reduced by H2 treatment and microbially reduced by incubation with a filtrate from a soil suspension, then titrated with three different oxidants (iodine, cyanoferrate, and ferric citrate) to provide chemical and biological estimates of electron-accepting capacity at pH 5 and 7. The results will be discussed in terms of the three oxidants used, the properties of the HA samples, pH, and the effects of chemical

  13. The role of calcium in cell injury. A review.

    Science.gov (United States)

    Trump, B F; Berezesky, I K; Laiho, K U; Osornio, A R; Mergner, W J; Smith, M W

    1980-01-01

    The role of calcium in cell injury is currently under investigation in many laboratories. It appears that movement of calcium between extra- to intracellular compartments and between various intracellular compartments plays a key role in determining many important reactions of cells both to lethal and sublethal injuries of diverse types as well as in adaptive new steady states. Prevention and/or modification of calcium movements has implication for the control of cell population growth, the prevention of cancer, and the retrieval of victims of shock, myocardial infarction and stroke. Regardless of what type of initial injury occurs, for example ischemia or direct cell membrane damage, the cell undergoes calcium accumulation either by impaired energy metabolism and/or plasmalemmal alterations. This elevated intracellular calcium concentration is responsible for cytoskeletal modifications which alter cell shape, the activation of phospholipases which results in perpetuation of membrane damage and finally, mitochondrial calcification. Although such changes have been partially characterized biochemically and morphologically, some obscure points continue to need clarification. The importance of determing the event(s) responsible for cell death is directly related to the potential capability of their manipulation. Therefore, this could result in the development and/or modification of pharmacologic interventions for the control and prevention of many human diseases. It is the purpose of this paper to review the present state of the art regarding the role of calcium in cell injury, to put it into perspective concerning organelle changes from the standpoint of morphology, and to indicate the present and future role of analytical microscopy in furthering the understanding of these processes. PMID:6999604

  14. Role of pancreatic stellate cells in chemoresistance in pancreatic cancer

    OpenAIRE

    McCarroll, Joshua A.; Naim, Stephanie; Sharbeen, George; Russia, Nelson; Lee, Julia; Kavallaris, Maria; Goldstein, David; Phillips, Phoebe A.

    2014-01-01

    Pancreatic cancer is highly chemoresistant. A major contributing factor is the characteristic extensive stromal or fibrotic reaction, which comprises up to 90% of the tumor volume. Over the last decade there has been intensive research into the role of the pro-fibrogenic pancreatic stellate cells (PSCs) and their interaction with pancreatic cancer cells. As a result of the significant alterations in the tumor microenvironment following activation of PSCs, tumor progression, and chemoresistanc...

  15. Salmonella Type III Secretion-Associated Protein InvE Controls Translocation of Effector Proteins into Host Cells

    OpenAIRE

    Kubori, Tomoko; Galán, Jorge E.

    2002-01-01

    Salmonella enterica encodes a type III secretion system (TTSS) within a pathogenicity island located at centisome 63 (SPI-1), which is essential for its pathogenicity. This system mediates the transfer of a battery of bacterial proteins into the host cell with the capacity to modulate cellular functions. The transfer process is dependent on the function of protein translocases SipB, SipC, and SipD. We report here that Salmonella protein InvE, which is also encoded within SPI-1, is essential f...

  16. Role of stem/progenitor cells in reparative disorders

    Directory of Open Access Journals (Sweden)

    Pretheeban Thavaneetharajah

    2012-12-01

    Full Text Available Abstract Adult stem cells are activated to proliferate and differentiate during normal tissue homeostasis as well as in disease states and injury. This activation is a vital component in the restoration of function to damaged tissue via either complete or partial regeneration. When regeneration does not fully occur, reparative processes involving an overproduction of stromal components ensure the continuity of tissue at the expense of its normal structure and function, resulting in a “reparative disorder”. Adult stem cells from multiple organs have been identified as being involved in this process and their role in tissue repair is being investigated. Evidence for the participation of mesenchymal stromal cells (MSCs in the tissue repair process across multiple tissues is overwhelming and their role in reparative disorders is clearly demonstrated, as is the involvement of a number of specific signaling pathways. Transforming growth factor beta, bone morphogenic protein and Wnt pathways interact to form a complex signaling network that is critical in regulating the fate choices of both stromal and tissue-specific resident stem cells (TSCs, determining whether functional regeneration or the formation of scar tissue follows an injury. A growing understanding of both TSCs, MSCs and the complex cascade of signals regulating both cell populations have, therefore, emerged as potential therapeutic targets to treat reparative disorders. This review focuses on recent advances on the role of these cells in skeletal muscle, heart and lung tissues.

  17. 125I brachytherapy combined with chemotherapy for patients with inoperable stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To assess the therapeutic effect of radioactive seed 125I brachytherapy combined with GP chemotherapy regimen (gemcitabine 1000 mg/m2, cisplatin 75 mg/m2) for inoperable stage III non-small cell lung cancer (NSCLC). Methods: Thirty-nine documented inoperable stage III NSCLC patients, enrolled between January 2005 and June 2008 for the study group, were treated with the combination of 125I brachytherapy and GP regimen. The brachytherapy methods were conducted according to TPS and each patient was treated under those patients were treated with standard GP regimen. Chest CT scans were performed every three months post-procedurally, until disease progression or recurrence. The follow-up time was up to twenty four months after treatment. In the control group, equal amount of III stage NSCLC patients were treated with standard GP regimen alone. Chi-square test and survival analysis with Kaplan-Meier and Log-rank were used to compare the differences of recent (3 months after therapy) efficiency, survival rate, survival time between two groups. Results: The re-cent effective rates of the study group (71.8%, 28/39) and control group (61.5%, 24/39) were not statistical different (χ2=0.93, P>0.05), yet the tumor CR rates in two groups showed significant disparity (χ2=4.48, P2=1.57, P>0.05). However, significant differences (χ2=4.07, 4.63,both P125I brachytherapy combined with GP regimen chemotherapy could be an effective treatment method and could improve the tumor CR rate and survival rate for patients with inoperable stage III NSCLC. (authors)

  18. Role of allogeneic stem cell transplantation in mantle cell lymphoma.

    Science.gov (United States)

    Cohen, Jonathon B; Burns, Linda J; Bachanova, Veronika

    2015-04-01

    Despite a wide spectrum of treatment options, mantle cell lymphoma (MCL) remains a challenging hematologic malignancy to manage. Advances in front-line therapy, including the monoclonal antibody rituximab and increasing use of cytarabine, have improved remission rates. Autologous hematopoietic cell transplantation (HCT) can effectively consolidate remission of MCL, leading to encouraging survival beyond 5 yr. However, nearly all patients with MCL will relapse and require salvage therapy. Novel agents such as ibrutinib, bortezomib, and lenalidomide have dramatically expanded the options for treating relapsed MCL. In this review, we summarize the clinical evidence supporting the use of allogeneic donor HCT in MCL and make recommendations on indications for its use. Data suggest that allogeneic donor HCT is the only curative therapy for patients with poor prognosis or aggressive MCL. Patient selection, timing, and optimal use remain a matter of scientific debate and given the rapidly changing therapeutic landscape of MCL, the outcomes of allogeneic HCT should be interpreted in the context of novel therapeutics. PMID:25154430

  19. Uranium(VI) reduction by nanoscale zero-valent iron in anoxic batch systems: The role of Fe(II) and Fe(III)

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Sen; Chen, Yongheng; Xiang, Wu; Bao, Zhengyu; Liu, Chongxuan; Deng, Baolin

    2014-12-01

    The role of Fe(II) and Fe(III) on U(VI) reduction by nanoscale zerovalent iron (nanoFe0) was investigated using two iron chelators 1,10-phenanthroline and triethanolamine (TEA) under a CO2-free anoxic condition. The results showed U(VI) reduction was strongly inhibited by 1,10-phenanthroline and TEA in a pH range from 6.92 to 9.03. For instance, at pH 6.92 the observed U(VI) reduction rates decreased by 80.7% and 82.3% in the presence of 1,10-phenanthroline and TEA, respectively. The inhibition was attributed to the formation of stable complexes between 1,10-phenanthroline and Fe(II) or TEA and Fe(III). In the absence of iron chelators, U(VI) reduction can be enhanced by surface-bound Fe(II) on nanoFe0. Our results suggested that Fe(III) and Fe(II) probably acted as an electron shuttle to mediate the transfer of electrons from nanoFe0 to U(VI), therefore a combined system with Fe(II), Fe(III) and nanoFe0 can facilitate the U(VI) reductive immobilization in the contaminated groundwater.

  20. Inflammatory role of the acinar cells during acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Isabel; De; Dios

    2010-01-01

    Pancreatic acinar cells are secretory cells whose main function is to synthesize, store and f inally release digestive enzymes into the duodenum. However, in response to noxious stimuli, acinar cells behave like real inflammatory cells because of their ability to activate signalling transduction pathways involved in the expression of inflammatory mediators. Mediated by the kinase cascade, activation of Nuclear factor-κB, Activating factor-1 and Signal transducers and activators of transcription transcription factors has been demonstrated in acinar cells, resulting in overexpression of inflammatory genes. In turn, kinase activity is down-regulated by protein phosphatases and the f inal balance between kinase and phosphatase activity will determine the capability of the acinar cells to produce inflammatory factors. The kinase/ phosphatase pair is a redox-sensitive system in which kinase activation overwhelms phosphatase activity under oxidant conditions. Thus, the oxidative stress developed within acinar cells at early stages of acute pancreatitis triggers the activation of signalling pathways involved in the up-regulation of cytokines, chemokines and adhesion molecules. In this way, acinar cells trigger the release of the f irst inflammatory signals which can mediate the activation and recruitment of circulating inflammatorycells into the injured pancreas. Accordingly, the role of acinar cells as promoters of the inflammatory response in acute pancreatitis may be considered. This concept leads to amplifying the focus from leukocyte to acinar cells themselves, to explain the local inflammation in early pancreatitis.

  1. Role of plasmacytoid dendritic cell subsets in allergic asthma

    OpenAIRE

    Maazi, Hadi; Lam, Jonathan; Lombardi, Vincent; Akbari, Omid

    2013-01-01

    Plasmacytoid dendritic cells (pDCs) are major type-I interferon producing cells that play important roles in antiviral immunity and tolerance induction. These cells share a common DC progenitor with conventional DCs and Fms-like tyrosine kinase-3 ligand is essential for their development. Several subsets of pDCs have been identified to date including CCR9+, CD9+ and CD2+ pDCs. Recently, three subsets of pDCs were described namely, CD8α−β−, CD8α+β− and CD8α+β+ subsets. Interestingly, CD8α+β− a...

  2. Role of Ikaros in T-cell acute lymphoblastic leukemia

    OpenAIRE

    Kastner, Philippe; Chan, Susan

    2011-01-01

    Ikaros is a zinc finger transcriptional regulator encoded by the Ikzf1 gene. Ikaros displays crucial functions in the hematopoietic system and its loss of function has been linked to the development of lymphoid leukemia. In particular, Ikaros has been found in recent years to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia. Its role in T-cell leukemia, however, has been more controversial. While Ikaros deficiency appears to be very frequent in murine T-cell l...

  3. The Role of Plant Hormones in Nematode Feeding Cell Formation

    NARCIS (Netherlands)

    Goverse, A.; Bird, D.

    2011-01-01

    In this Chapter, we discuss recent advances in the role of plant hormones in the molecular mechanisms underlying feeding cell formation both by cyst (CN) and root-knot nematodes (RKN). Phytohormones are small signalling molecules that regulate plant growth and development, including the formation of

  4. The role of EBNA binding proteins in cell transformation

    OpenAIRE

    Darekar, Suhas

    2013-01-01

    Epstein - Barr virus (EBV) infects m ajority of the human population and maintains sub - cl inical infection . However , under certain conditions it is associated with several B - cell malignancies , such as Burkitt lymphoma, Hodgkin’s lymphoma etc. Moreover , EBV also plays a causative role in a cquired immunodeficiency syndrome ( AIDS ) associated lymph omas and post - transplant l...

  5. Superselective intra-arterial infusion chemotherapy for stage III/IV squamous cell carcinomas of the oral cavity: Midterm results

    International Nuclear Information System (INIS)

    Purpose: We performed superselective intra-arterial infusion chemotherapy (SIC) according to a protocol in which drug distribution is evaluated by the use of interventional radiology (IVR)-computed tomography (CT) system, and the chemotherapy is combined with medium-dose conformal radiation therapy (CRT). We analyzed retrospectively the factors that affect the midterm survival ratio, including local response, for stage III and IV squamous cell carcinomas of the oral cavity. Materials and methods: Forty consecutive patients with stage III and IV squamous cell carcinomas of the oral cavity and who had undergone both SIC and CRT were enrolled. A microcatheter was placed in the appropriate feeding artery of the tumor and cisplatin (50 mg/body) was infused twice. CRT was administered with a dual-energy (4 and 10 MV) linear accelerator. The total and daily doses delivered were 30 and 2.0 Gy, respectively. Histopathologic effects were classified into five grades: grade 0 or 1 was defined as a poor response, and grade II or higher as a good response. Age, sex, stage, local response to treatment, mode of invasion and lymph node metastasis were analyzed, and differences in the midterm survival ratio were assessed. Results: The 3-year survival ratio of the 40 cases was 67%. A good local response (III or IV) was achieved in 75% of the cases. The survival ratio of the good local response group was significantly better than that of the poor response group (p = 0.04). Mode of invasion (p = 0.03) and lymph node metastasis (p = 0.01) were also predictive of survival. In the multivariable analysis of survival, however, no variables including good local response (p = 0.12), were predictive. Conslusion: Our new protocol improved local response, but it did not contribute to the survival ratio

  6. The putative role of mast cells in lung transplantation.

    Science.gov (United States)

    Jungraithmayr, W

    2015-03-01

    Mast cells (MCs) were primarily recognized as effector cells of allergy. These cells are acting predominantly at the interface between the host and the external environment, such as skin, gastrointestinal and the respiratory tract. Only recently, MCs have gained increased recognition as cells of functional plasticity with immune-regulatory properties that influence both the innate and the adaptive immune response in inflammatory disorders, cancer and transplantation. Through the secretion of both proinflammatory and antiinflammatory mediators, MCs can either ameliorate or deteriorate the course and outcome in lung transplantation. Recent research from other models recognized the immune-protective activity of MCs including its role as an important source of IL-10 and TGF-β for the modulation of alloreactive T cell responses or assistance in Treg activity. This paper summarizes the current understanding of MCs in lung transplantation and discusses MC-mediated immune-mechanisms by which the outcome of the engrafted organ is modulated. PMID:25693471

  7. Role of topology in complex functional networks of beta cells.

    Science.gov (United States)

    Cherubini, Christian; Filippi, Simonetta; Gizzi, Alessio; Loppini, Alessandro

    2015-10-01

    The activity of pancreatic β cells can be described by biological networks of coupled nonlinear oscillators that, via electrochemical synchronization, release insulin in response to augmented glucose levels. In this work, we analyze the emergent behavior of regular and percolated β-cells clusters through a stochastic mathematical model where "functional" networks arise. We show that the emergence and robustness of the synchronized dynamics depend both on intrinsic and extrinsic parameters. In particular, cellular noise level, glucose concentration, network spatial architecture, and cell-to-cell coupling strength are the key factors for the generation of a rhythmic and robust activity. Their role in the functional network topology associated with β-cells clusters is analyzed and discussed. PMID:26565267

  8. Outcome of patients with stage II and III nonseminomatous germ cell tumors: Results of a single center

    Directory of Open Access Journals (Sweden)

    Ataergin S

    2007-01-01

    Full Text Available Background: The prognostic factors in nonseminomatous germ cell tumors have been mainly derived from the analysis of stage I tumors. Aims: The aim of this study was to evaluate some prognostic factors and the outcome of patients with stage II and III nonseminomatous germ cell tumors according to risk groups treated between 1993 and 2002. Settings and Design: Patients were retrospectively classified as good, intermediate and poor risk groups according to International Germ Cell Cancer Consensus Group. Materials and Methods: Biopsy specimens of 58 patients with stage II and III nonseminomatous germ cell tumors were analyzed by means of tumor histopathology, primary localization site of the tumor, relapse sites, initial serum tumor marker levels, the presence of persistent serum tumor marker elevation and the patients′ outcome. Statistical Analysis :0 Kruskall Wallis test and Mann-Whitney U test were used to determine the differences between the groups. Kaplan-Meier method was used for survival analysis and log rank test was used to compare the survival probabilities of groups. Cox proportional hazard analysis was used to determine the prognostic factors in univariate and multivariate analysis. Results: Five-year overall and disease-free survival rates were calculated as 85% and 75% in stage II; 44% and 29% in stage III cases, respectively. Fifty-seven percent of patients were classified in good risk, 9% in intermediate risk and 27% in poor risk groups. Five-year overall survival rates were 97%, 75% and 7% ( P < 0.001 and disease-free survival rates were 83%, 34% and 7% ( P < 0.001 in good, intermediate and poor risk groups, respectively. Analysis of the prognostic factors revealed that the localization site of the primary tumor ( P < 0.001, the initial stage of disease ( P < 0.001, the initial serum AFP level (p: 0.001, the initial β -HCG level (p: 0.0048, the presence of yolk sac and choriocarcinoma components in tumor (p: 0.003 and p: 0

  9. Role of calcium in differentiation of murine erythroleukemia cells

    Institute of Scientific and Technical Information of China (English)

    ZHUDAN; NONGGAOHE; 等

    1993-01-01

    Calcium plays a crucial role in the normal and abnomal cell metabolism.The role of calcium in the differentiation process of murine erythroleukemia cells(MELC)remains controversial.Here,based upon quantitative measurement of fluorescence in single cells,a method was developed to investigate the intracellular free calcium[Ca2+]i concentration and DNA contents simultaneously,by employing the fluorescent probe,fluo-3 acetoxymethyl ester and DNA dye Hoechst 33342.During MELC differentiation.[Ca2+]i concentration incresed.We also demonstrated that calcium ionophore,A23187,enhanced the HMB-induced MELC differentiation,while verapamil,an inhibitor of calcuim uptake,slightly reduced differentiation.These results suggested that an increase in the [Ca2+]i level was an essential step in HMBA-induced MELC differentiation.

  10. Phase I-II Study of Clofarabine-Melphalan-Alemtuzumab Conditioning for Allogeneic Hematopoietic Cell Transplantation

    OpenAIRE

    van Besien, Koen; Stock, Wendy; Rich, Elizabeth; Odenike, Olatoyosi; Godley, Lucy A.; O’Donnell, Peter H.; Kline, Justin; Nguyen, Vu; del Cerro, Paula; LARSON, RICHARD A.; Artz, Andrew S.

    2011-01-01

    We conducted a phase I-II study of transplantation conditioning with clofarabine-melphalan-alemtuzumab for patients with advanced hematologic malignancies. Ten patients were accrued to the phase I portion, which utilized an accelerated titration design. No dose-limiting toxicity was observed, and clofarabine 40 mg/m2 × 5, melphalan 140 mg/m2 × 1, and alemtuzumab 20 mg × 5 was adopted for the phase II study, which accrued 72 patients. Median age was 54 years. There were 44 patients with acute ...

  11. Physiological role of group III metabotropic glutamate receptors in visually responsive neurons of the rat superficial superior colliculus.

    Science.gov (United States)

    Cirone, J; Salt, T E

    2000-03-01

    There is evidence from immunohistochemical and in situ hybridization studies for the presence of Group I, II and III metabotropic glutamate receptors (mGluRs) in the rat superficial superior colliculus (SSC). The purpose of this study was to investigate if manipulation of Group III mGluRs affects visual responses in the SSC. Drugs were applied by iontophoresis and single neuron activity was recorded extracellularly. L-AP4 (Group III agonist) resulted in a reduction of visual responses in most neurons, but also a potentiation in others. The effect of L-AP4 is drug- and stereospecific in that application of D-AP4 did not significantly affect visual responses. L-AP4 application also resulted in a potentiation of the response to iontophoretically applied NMDA. The effects of MPPG and CPPG (Group III antagonists) were compared with the effect of L-AP4 in the same neuron and were found to produce the opposite effect to L-AP4. Furthermore, the effect of L-AP4 could be blocked by coapplication of MPPG or CPPG. Presynaptic depression of glutamate release is a possible mechanism by which L-AP4 could reduce visual responses in the SSC whereas the potentiation of visual responses by L-AP4 could be due to a reduction of GABAergic inhibition. The finding that MPPG and CPPG, as well as antagonizing the L-AP4 effect, have a direct effect on visual responses suggests that Group III mGluRs are activated by endogenous transmitter released during visual stimulation. PMID:10762314

  12. The role of Protein Kinase Cη in T cell biology

    Directory of Open Access Journals (Sweden)

    Nicholas R.J. Gascoigne

    2012-06-01

    Full Text Available Protein kinase Cη (PKCη is a member of the novel PKC subfamily, which also includes δ, ε, and θ isoforms. Compared to the other novel PKCs, the function of PKCη in the immune system is largely unknown. Several studies have started to reveal the role of PKCη, particularly in T cells. PKCη is highly expressed in T cells, and is upregulated during thymocyte positive selection. Interestingly, like the θ isoform, PKCη is also recruited to the immunological synapse that is formed between a T cell and an antigen-presenting cell. However, unlike PKCθ, which becomes concentrated to the central region of the synapse, PKCη remains in a diffuse pattern over the whole area of the synapse, suggesting distinctive roles of these two isoforms in signal transduction. Although PKCη is dispensable for thymocyte development, further analysis of PKCη− or PKCθ−deficient and double knockout mice revealed the redundancy of these two isoforms in thymocyte development. In contrast, PKCη rather than PKCθ, plays an important role for T cell homeostatic proliferation, which requires recognition of self-antigen. Another piece of evidence demonstrating that PKCη and PKCθ have isoform specific as well as redundant roles come from the analysis of CD4 to CD8 T cell ratios in the periphery of these knockout mice. Deficiency in PKCη or PKCθ had opposing effects as PKCη knockout mice had a higher ratio of CD4 to CD8 T cells compared to that of wild-type mice, whereas PKCθ-deficient mice had a lower ratio. Biochemical studies showed that calcium flux and NFκB translocation is impaired in PKCη-deficient T cells upon TCR crosslinking stimulation, a character shared with PKCθ-deficient T cells. However, unlike the case with PKCθ, the mechanistic study of PKCη is at early stage and the signaling pathways involving PKCη, at least in T cells, are essentially unknown. In this review, we will cover the topics mentioned above as well as provide some

  13. Long-term results of a randomized phase III trial of TPF induction chemotherapy followed by surgery and radiation in locally advanced oral squamous cell carcinoma

    OpenAIRE

    Zhong, Lai-ping; Zhang, Chen-Ping; Ren, Guo-xin; Guo, Wei; William, William N.; Hong, Christopher S.; Sun, Jian; ZHU, HAN-GUANG; Tu, Wen-yong; Li, Jiang; Cai, Yi-li; Yin, Qiu-ming; WANG, LI-ZHEN; Wang, Zhong-he; Hu, Yong-jie

    2015-01-01

    Previously, we conducted a randomized phase III trial of TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy in surgically managed locally advanced oral squamous cell carcinoma (OSCC) and found no improvement in overall survival. This study reports long-term follow-up results from our initial trial. All patients had clinical stage III or IVA locally advanced OSCC. In the experimental group, patients received two cycles of TPF induction chemotherapy (75mg/m2 docetaxel d1, 75m...

  14. CARI III Inhibits Tumor Growth in a Melanoma-Bearing Mouse Model through Induction of G0/G1 Cell Cycle Arrest

    OpenAIRE

    Hye-Jin Park

    2014-01-01

    Mushroom-derived natural products have been used to prevent or treat cancer for millennia. In this study, we evaluated the anticancer effects of CARI (Cell Activation Research Institute) III, which consists of a blend of mushroom mycelia from Phellinus linteus grown on germinated brown rice, Inonotus obliquus grown on germinated brown rice, Antrodia camphorata grown on germinated brown rice and Ganoderma lucidum. Here, we showed that CARI III exerted anti-cancer activity, which is comparable ...

  15. Influence of clinical characteristics on radiation therapy effect in patients with stage III non-small-cell lung cancer at non-standard fractionation modes

    International Nuclear Information System (INIS)

    A comparative analysis of different modes of radiotherapy fractionation with modification using etoposide and cisplatin in patients with non-small-cell lung cancer is given. The general condition of the patient, the form of the macroscopic tumor growth, the degree of tumor regression are prognostically significant for stage III non-small-cell lung cancer

  16. The role of physical rehabilitation in stem cell transplantation patients.

    Science.gov (United States)

    Steinberg, Amir; Asher, Arash; Bailey, Charlotte; Fu, Jack B

    2015-08-01

    The purpose of this paper is to review the evidence for the role of physical rehabilitation in stem cell transplantation patients. We will also review the literature and discuss professional experiences on how rehabilitation can play a role in stem cell transplant care and survivorship. Hematopoietic stem cell transplantation (HCT) is a procedure that has evolved substantially over the years to help treat multiple conditions, particularly hematologic malignancies. HCT can be very stressful on the body and can leave patients weakened and sometimes quite debilitated. Supportive care measures have advanced to improve the quality of life and overall survival of HCT survivors. One key component of improved supportive care is gaining increased attention, and that is physical medicine and rehabilitation. Its role in HCT survivorship care is expanding, and new insight and research within the discipline have focused on fatigue, inflammation, exercise, and the development of structured rehabilitation programs to improve the musculoskeletal sequelae of transplantation. This literature review has demonstrated the utility of physical rehabilitation in HCT, its impact on cancer-related fatigue, and to outline the current state of the literature on these topics. The paper delves into a background of HCT. Cancer-related fatigue in HCT is then discussed and summarized, and the role that exercise plays in modifying such fatigue is outlined. We then outline the models and the impact that physical rehabilitation may play in HCT recipients. PMID:25971213

  17. The Role Of Nitric Oxide After Repeated Low Dose Photodynamic Treatments In Prostate Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Valentina Rapozzi

    2015-08-01

    Full Text Available Photodynamic therapy (PDT is a clinically approved treatment that causes a selective cytotoxic effect in cancer cells. In addition to the production of singlet oxygen and reactive oxygen species, PDT can induce the release of nitric oxide (NO by up-regulating nitric oxide synthases (NOS. Since non-optimal PDT often causes tumor recurrence, understanding of the molecular pathways involved in the photoprocess is a challenging task for scientists. The present study has examined the response of the PC3 human metastatic prostate cancer cell line, following repeated low-dose pheophorbide a treatments, mimicking non-optimal PDT treatment. The analysis was focused on the NF-kB/YY1/RKIP circuitry as it is (i dysregulated in cancer cells (ii modulated by NO and (iii correlated with the epithelial to mesenchymal transition (EMT. We hypothesized that a repeated treatment of non-optimal PDT induces low levels of NO that lead to cell growth and EMT via regulation of the above circuitry. The expressions of gene products involved in the circuitry and in EMT were analyzed by western blot. The findings demonstrate the cytoprotective role of NO following non-optimal PDT treatments that was corroborated by the use of l-NAME, an inhibitor of NOS.

  18. Alcoholic hepatitis: The pivotal role of Kupffer cells.

    Science.gov (United States)

    Suraweera, Duminda B; Weeratunga, Ashley N; Hu, Robert W; Pandol, Stephen J; Hu, Richard

    2015-11-15

    Kupffer cells play a central role in the pathogenesis of alcoholic hepatitis (AH). It is believed that alcohol increases the gut permeability that results in raised levels of serum endotoxins containing lipopolysaccharides (LPS). LPS binds to LPS-binding proteins and presents it to a membrane glycoprotein called CD14, which then activates Kupffer cells via a receptor called toll-like receptor 4. This endotoxin mediated activation of Kupffer cells plays an important role in the inflammatory process resulting in alcoholic hepatitis. There is no effective treatment for AH, although notable progress has been made over the last decade in understanding the underlying mechanism of alcoholic hepatitis. We specifically review the current research on the role of Kupffer cells in the pathogenesis of AH and the treatment strategies. We suggest that the imbalance between the pro-inflammatory and the anti-inflammatory process as well as the increased production of reactive oxygen species eventually lead to hepatocyte injury, the final event of alcoholic hepatitis. PMID:26600966

  19. Alcoholic hepatitis: The pivotal role of Kupffer cells

    Institute of Scientific and Technical Information of China (English)

    Duminda; B; Suraweera; Ashley; N; Weeratunga; Robert; W; Hu; Stephen; J; Pandol; Richard; Hu

    2015-01-01

    Kupffer cells play a central role in the pathogenesis of alcoholic hepatitis(AH). It is believed that alcohol increases the gut permeability that results in raised levels of serum endotoxins containing lipopolysaccharides(LPS). LPS binds to LPS-binding proteins and presents it to a membrane glycoprotein called CD14, which then activates Kupffer cells via a receptor called tolllike receptor 4. This endotoxin mediated activation of Kupffer cells plays an important role in the inflammatory process resulting in alcoholic hepatitis. There is no effective treatment for AH, although notable progress has been made over the last decade in understanding the underlying mechanism of alcoholic hepatitis. We specifically review the current research on the role of Kupffer cells in the pathogenesis of AH and the treatment strategies. We suggest that the imbalance between the pro-inflammatory and the anti-inflammatory process as well as the increased production of reactive oxygen species eventually lead to hepatocyte injury, the final event of alcoholic hepatitis.

  20. Role of T Follicular Helper cells in Multiple Sclerosis

    Science.gov (United States)

    Schmitt, Nathalie

    2015-01-01

    Multiple Sclerosis (MS) is a chronic, inflammatory and neurodegenerative disease which results from the destruction of myelin and associated collateral tissue damage within the central nervous system (CNS). MS is a highly diverse disease with different clinical profiles. During the past decade, several new treatment options have been introduced, but no treatment completely stops the disease progression. Therefore deeper understanding of the disease mechanism is necessary to develop novel therapeutic strategies. While yet to be proven, there is evidence suggesting the involvement of T follicular helper (Tfh) cells, a CD4 T cell subset specialized for the provision of help to B cells, in the pathogenesis of MS. In this review, I will discuss the potential pathogenic roles of Tfh cells in the course of MS. PMID:26082945

  1. Role of Ikaros in T-cell acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    Philippe; Kastner; Susan; Chan

    2011-01-01

    Ikaros is a zinc finger transcriptional regulator encoded by the Ikzf1 gene.Ikaros displays crucial functions in the hematopoietic system and its loss of function has been linked to the development of lymphoid leukemia.In particular,Ikaros has been found in recent years to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia.Its role in T-cell leukemia,however,has been more controversial.While Ikaros deficiency appears to be very frequent in murine T-cell leukemias,loss of Ikaros appears to be rare in human T-cell acute lymphoblastic leukemia (T-ALL).We review here the evidence linking Ikaros to T-ALL in mouse and human systems.

  2. Role of Dicer on tumorigenesis in glioma cells

    Institute of Scientific and Technical Information of China (English)

    Anling Zhang; Lei Han; Guangxiu Wang; Zhifan Jia; Peiyu Pu; Chunsheng Kang

    2010-01-01

    Micro RNAs(miRNAs)are non-coding,single-stranded RNAs that regulate target gene expression by repressing translation or promoting RNA cleavage.Recent studies show that miRNA expression is globally decreased in some human tumors.Dicer is an essential component of the miRNA processing machinery.To determine whether global reduction of miRNA effects tumorigenesis,small interfering RNA were designed to target Dicer to restrain whole miRNA expression in the glioblastoma cell line-TJ905.With effective knock-down of Dicer,tumor cells were invasive and proliferative,and globally impaired miRNA processing enhanced proliferation and invasiveness of glioma cells in vitro.Suppression of Dicer expression resulted in a more aggressive glioma phenotype,which suggests that global reduction of miRNA expression could have an oncogenic role in glioblastoma cells.

  3. Concurrent chemoradiotherapy with low dose weekly gemcitabine in stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    Combined chemoradiotherapy (CRT) is the treatment of choice for stage III NSCLC. Gemcitabine (G) is a novel deoxycitidine analogue that has been proven to be a potent radiosensitizer. Twenty-two consecutive patients were treated with concurrent CRT to demonstrate the tolerability and efficacy of low dose G given weekly as radiosensitizer in stage III NSCLC. Patients with KPS ≥70, adequate bone marrow reserve, with no prior radiotherapy (RT) and surgery were included. Eighteen patients had received prior induction chemotherapy (CT). G (75 mg/m2/week) was infused over 1 hour for 6 weeks. Thoracic RT was given two hours later over 6 weeks at 1.8 Gy/day fractions (total dose of 61.2 Gy). Pulmonary toxicity was evaluated with computed tomography scans in 6 weeks. Median age was 60 years (range, 48–75), median follow-up was 15 months (range, 2–40). Sixty-eight percent of patients were male and median KPS score was 90. Conformal 3D-RT planning was used in 64% of patients. G was given for a median of 5 weeks (range 1–9). Twelve patients (54.6%) received all planned CT. G was stopped because of intolerance in 6 and death in 2 patients. Seven patients (31.8%) had radiation pneumonitis. Twenty patients were evaluated for overall response, 1 patient (4.5%) had clinical CR, 81.8% had PR while 9.5% had SD. Median overall survival (OS) was 14 ± 5 months (95% CI 3–25). One- and 2-year OS rates were 55% and 38%. Sixteen patients died of disease-related events (6 with progression of primary tumor, 8 due to metastatic disease), 2 patients died of other causes. One- and 2-year progression-free survival and local control rates were 56%, 27% and 79%, 51%, respectively. G might be used as radiosensitizer for patients with stage III NSCLC who could not receive full doses CT with concurrent RT

  4. The JNKs differentially regulate RNA polymerase III transcription by coordinately modulating the expression of all TFIIIB subunits

    OpenAIRE

    Zhong and, Shuping; Johnson, Deborah L.

    2009-01-01

    RNA polymerase (pol) III-dependent transcription is subject to stringent regulation by tumor suppressors and oncogenic proteins and enhanced RNA pol III transcription is essential for cellular transformation and tumorigenesis. Since the c-Jun N-terminal kinases (JNKs) display both oncogenic and tumor suppressor properties, the roles of these proteins in regulating RNA pol III transcription were examined. In both mouse and human cells, loss or reduction in JNK1 expression represses RNA pol III...

  5. The role of fibrocytes in sickle cell lung disease.

    Directory of Open Access Journals (Sweden)

    Joshua J Field

    Full Text Available BACKGROUND: Interstitial lung disease is a frequent complication in sickle cell disease and is characterized by vascular remodeling and interstitial fibrosis. Bone marrow-derived fibrocytes have been shown to contribute to the pathogenesis of other interstitial lung diseases. The goal of this study was to define the contribution of fibrocytes to the pathogenesis of sickle cell lung disease. METHODOLOGY/PRINCIPAL FINDINGS: Fibrocytes were quantified and characterized in subjects with sickle cell disease or healthy controls, and in a model of sickle cell disease, the NY1DD mouse. The role of the chemokine ligand CXCL12 in trafficking of fibrocytes and phenotype of lung disease was examined in the animal model. We found elevated concentration of activated fibrocytes in the peripheral blood of subjects with sickle cell disease, which increased further during vaso-occlusive crises. There was a similar elevations in the numbers and activation phenotype of fibrocytes in the bone marrow, blood, and lungs of the NY1DD mouse, both at baseline and under conditions of hypoxia/re-oxygenation. In both subjects with sickle cell disease and the mouse model, fibrocytes expressed a hierarchy of chemokine receptors, with CXCR4 expressed on most fibrocytes, and CCR2 and CCR7 expressed on a smaller subset of cells. Depletion of the CXCR4 ligand, CXCL12, in the mouse model resulted in a marked reduction of fibrocyte trafficking into the lungs, reduced lung collagen content and improved lung compliance and histology. CONCLUSIONS: These data support the notion that activated fibrocytes play a significant role in the pathogenesis of sickle cell lung disease.

  6. The Role of Heat Shock Proteins in Pathogenesis of Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Adi Prayitno

    2013-07-01

    Full Text Available Cell in the distress situation, denaturation of proteins may occur, and may also respond by expressing stress proteins. However, such homeostasis effort does not always succeed and even may lead to disease, including cancer. In distress situation also ensue much protein misfolding. Objective: This research were to explain the role of heat shock protein 40 (Hsp40 and Hsp70 in pathogenesis of occurred oral squamous cell carcinoma (OSCC patient which realized human papilloma virus (HPV infection. Material and Method: Tissue biopsy frozen section were taken from BOSC and OSCC patients was cut into three part. Parrafin blocks were made from cutting I, which was subsequently stains with HE to ascertain the type of neoplasm. Cutting II was subjected to DNA isolation. The DNA isolation results were subjected to PCR to amplify L1-HPV gene for fixed the HPV stressoor. Protein isolation was treated from Cutting III, folloewd with Blottdot test by using antibody monoclonal anti Hsp40 and Hsp70 and continued with measurement using densitometer to find the concentration of Hsp40 and Hsp70. The collected data were analyzed with F Test (Manova and discriminant analysis. Result: This experiment showed the differences in concentration of Hsp40 (p<=0,070 and Hsp70 (p<=0,006 between beningn oral squamous cell (BOSC and OSCC patients which realized HPV infection. Conclusion: This experiment proved that OSCC patients which realized HPV infection indicated an up regulated of Hsp70 concentration, so that there was occurs misfolding of the proteins cell. The misfolding was ensue obstacle of apoptosis and to raise cell proliferation which to storm carcinogenesis. An up regulated of Hsp40 was role as co-chaperone.DOI: 10.14693/jdi.v16i2.91 

  7. A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Jeremy P. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Murphy, James D. [Department of Radiation Medicine and Applied Science, University of California– San Diego, Moores Cancer Center, La Jolla, California (United States); Hanlon, Alexandra L. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); University of Pennsylvania School of Nursing, Philadelphia, Pennsylvania (United States); Le, Quynh-Thu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Loo, Billy W., E-mail: BWLoo@Stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Diehn, Maximilian, E-mail: diehn@Stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California (United States)

    2014-03-15

    Purpose: Concerns have been raised about the potential for worse treatment outcomes because of dosimetric inaccuracies related to tumor motion and increased toxicity caused by the spread of low-dose radiation to normal tissues in patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy (IMRT). We therefore performed a population-based comparative effectiveness analysis of IMRT, conventional 3-dimensional conformal radiation therapy (3D-CRT), and 2-dimensional radiation therapy (2D-RT) in stage III NSCLC. Methods and Materials: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify a cohort of patients diagnosed with stage III NSCLC from 2002 to 2009 treated with IMRT, 3D-CRT, or 2D-RT. Using Cox regression and propensity score matching, we compared survival and toxicities of these treatments. Results: The proportion of patients treated with IMRT increased from 2% in 2002 to 25% in 2009, and the use of 2D-RT decreased from 32% to 3%. In univariate analysis, IMRT was associated with improved overall survival (OS) (hazard ratio [HR] 0.90, P=.02) and cancer-specific survival (CSS) (HR 0.89, P=.02). After controlling for confounders, IMRT was associated with similar OS (HR 0.94, P=.23) and CSS (HR 0.94, P=.28) compared with 3D-CRT. Both techniques had superior OS compared with 2D-RT. IMRT was associated with similar toxicity risks on multivariate analysis compared with 3D-CRT. Propensity score matched model results were similar to those from adjusted models. Conclusions: In this population-based analysis, IMRT for stage III NSCLC was associated with similar OS and CSS and maintained similar toxicity risks compared with 3D-CRT.

  8. A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: Concerns have been raised about the potential for worse treatment outcomes because of dosimetric inaccuracies related to tumor motion and increased toxicity caused by the spread of low-dose radiation to normal tissues in patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy (IMRT). We therefore performed a population-based comparative effectiveness analysis of IMRT, conventional 3-dimensional conformal radiation therapy (3D-CRT), and 2-dimensional radiation therapy (2D-RT) in stage III NSCLC. Methods and Materials: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify a cohort of patients diagnosed with stage III NSCLC from 2002 to 2009 treated with IMRT, 3D-CRT, or 2D-RT. Using Cox regression and propensity score matching, we compared survival and toxicities of these treatments. Results: The proportion of patients treated with IMRT increased from 2% in 2002 to 25% in 2009, and the use of 2D-RT decreased from 32% to 3%. In univariate analysis, IMRT was associated with improved overall survival (OS) (hazard ratio [HR] 0.90, P=.02) and cancer-specific survival (CSS) (HR 0.89, P=.02). After controlling for confounders, IMRT was associated with similar OS (HR 0.94, P=.23) and CSS (HR 0.94, P=.28) compared with 3D-CRT. Both techniques had superior OS compared with 2D-RT. IMRT was associated with similar toxicity risks on multivariate analysis compared with 3D-CRT. Propensity score matched model results were similar to those from adjusted models. Conclusions: In this population-based analysis, IMRT for stage III NSCLC was associated with similar OS and CSS and maintained similar toxicity risks compared with 3D-CRT

  9. EGFRvIII-specific chimeric antigen receptor T cells migrate to and kill tumor deposits infiltrating the brain parenchyma in an invasive xenograft model of glioblastoma.

    Directory of Open Access Journals (Sweden)

    Hongsheng Miao

    Full Text Available Glioblastoma (GBM is the most common primary malignant brain tumor in adults and is uniformly lethal. T-cell-based immunotherapy offers a promising platform for treatment given its potential to specifically target tumor tissue while sparing the normal brain. However, the diffuse and infiltrative nature of these tumors in the brain parenchyma may pose an exceptional hurdle to successful immunotherapy in patients. Areas of invasive tumor are thought to reside behind an intact blood brain barrier, isolating them from effective immunosurveillance and thereby predisposing the development of "immunologically silent" tumor peninsulas. Therefore, it remains unclear if adoptively transferred T cells can migrate to and mediate regression in areas of invasive GBM. One barrier has been the lack of a preclinical mouse model that accurately recapitulates the growth patterns of human GBM in vivo. Here, we demonstrate that D-270 MG xenografts exhibit the classical features of GBM and produce the diffuse and invasive tumors seen in patients. Using this model, we designed experiments to assess whether T cells expressing third-generation chimeric antigen receptors (CARs targeting the tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, would localize to and treat invasive intracerebral GBM. EGFRvIII-targeted CAR (EGFRvIII+ CAR T cells demonstrated in vitro EGFRvIII antigen-specific recognition and reactivity to the D-270 MG cell line, which naturally expresses EGFRvIII. Moreover, when administered systemically, EGFRvIII+ CAR T cells localized to areas of invasive tumor, suppressed tumor growth, and enhanced survival of mice with established intracranial D-270 MG tumors. Together, these data demonstrate that systemically administered T cells are capable of migrating to the invasive edges of GBM to mediate antitumor efficacy and tumor regression.

  10. Advances in High-Efficiency III-V Multijunction Solar Cells

    Directory of Open Access Journals (Sweden)

    Richard R. King

    2007-01-01

    Full Text Available The high efficiency of multijunction concentrator cells has the potential to revolutionize the cost structure of photovoltaic electricity generation. Advances in the design of metamorphic subcells to reduce carrier recombination and increase voltage, wide-band-gap tunnel junctions capable of operating at high concentration, metamorphic buffers to transition from the substrate lattice constant to that of the epitaxial subcells, concentrator cell AR coating and grid design, and integration into 3-junction cells with current-matched subcells under the terrestrial spectrum have resulted in new heights in solar cell performance. A metamorphic Ga0.44In0.56P/Ga0.92In0.08As/ Ge 3-junction solar cell from this research has reached a record 40.7% efficiency at 240 suns, under the standard reporting spectrum for terrestrial concentrator cells (AM1.5 direct, low-AOD, 24.0 W/cm2, 25∘C, and experimental lattice-matched 3-junction cells have now also achieved over 40% efficiency, with 40.1% measured at 135 suns. This metamorphic 3-junction device is the first solar cell to reach over 40% in efficiency, and has the highest solar conversion efficiency for any type of photovoltaic cell developed to date. Solar cells with more junctions offer the potential for still higher efficiencies to be reached. Four-junction cells limited by radiative recombination can reach over 58% in principle, and practical 4-junction cell efficiencies over 46% are possible with the right combination of band gaps, taking into account series resistance and gridline shadowing. Many of the optimum band gaps for maximum energy conversion can be accessed with metamorphic semiconductor materials. The lower current in cells with 4 or more junctions, resulting in lower I2R resistive power loss, is a particularly significant advantage in concentrator PV systems. Prototype 4-junction terrestrial concentrator cells have been grown by metal-organic vapor-phase epitaxy, with preliminary measured

  11. Role of cell adhesion signal molecules in hepatocellular carcinoma cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Jian-Min Su; Li-Ying Wang; Yu-Long Liang; Xi-Liang Zha

    2005-01-01

    AIM: Cell adhesion molecules and their signal molecules play a very important role in carcinogenesis. The aim of this study is to elucidate the role of these molecules and the signal molecules of integrins and E-cadherins, such as (focal adhesion kinase) FAK, (integrin linked kinase)ILK, and β-catenin in hepatocellular carcinoma cell apoptosis.METHODS: We first synthesized the small molecular compound, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and identified it, by element analysis and 1H NMR. To establish the apoptosis model of the SMMC-7721 hepatocellular carcinoma cell, we treated cells with DCVC in EBSS for different concentrations or for various length times in the presence of 20 μmol/L N,N-diphenyl-p-phenylenediamine,which blocks necrotic cell death and identified this model by flow cytometry and DNA ladder. Then we studied the changes of FAK, ILK, β-catenin, and PKB in this apoptotic model by Western blot.RESULTS: We found that the loss or decrease of cell adhesion signal molecules is an important reason in apoptosis of SMMC-7721 hepatocellular carcinoma cell and the apoptosis of SMMC-7721 cell was preceded by the loss or decrease of FAK, ILK, PKB, and β-catenin or the damage of cell-matrix and cell-cell adhesion.CONCLUSION: Our results suggested that the decrease of adhesion signal molecules, FAK, ILK, PKB, and β-catenin,could induce hepatocellular carcinoma cell apoptosis.

  12. Role of Inflammation and Substrate Stiffness in Cancer Cell Transmigration

    Science.gov (United States)

    Hamilla, Susan; Stroka, Kimberly; Aranda-Espinoza, Helim

    2013-03-01

    Cancer metastasis, the ability for cancer cells to break away from the primary tumor site and spread to other organs of the body, is one of the main contributing factors to the deadliness of the disease. One of the rate-limiting steps in cancer metastasis that is not well understood is the adhesion of tumor cells to the endothelium followed by transmigration. Other factors include substrate stiffness and inflammation. To test these parameters, we designed an in vitro model of transendothelial migration. Our results suggest that cancer cell transmigration is a two-step process in which they first incorporate into the endothelium before migrating through. It was observed that the cumulative fraction of cancer cells that incorporate into the endothelium increases over time. Unlike leukocytes, which can directly transmigrate through the endothelium, cancer cells appear to have a two-step process of transmigration. Our results indicate that inflammation does not act as a signal for cancer cells to localize at specific sites and transmigrate similarly to leukocytes. Cancer cell transmigration also does not vary with substrate stiffness indicating that tissue stiffness may not play a role in cancer's propensity to metastasize to certain tissues.

  13. Role of mast cells in gastrointestinal mucosal defense.

    Science.gov (United States)

    Penissi, Alicia B; Rudolph, María I; Piezzi, Ramón S

    2003-08-01

    The purpose of this review, based on studies from our laboratory as well as from others, is to summarize salient features of mast cell immunobiology and to describe their associations with gastrointestinal mucosal defense. Gastrointestinal mast cells are involved in many pathologic effects, such as food hypersensitivity. On the other hand, they also play a protective role in defense against parasitic and microbial infections. Thus, they have both positive and negative effects, but presently the mechanisms that control the balance of these various effects are poorly known. It has been suggested that stabilization of mast cells may be a key mechanism to protect the gastrointestinal tract from injury. Few molecules are known to possess both mast cell stabilizing and gastrointestinal cytoprotective activity. These include zinc compounds, sodium cromoglycate, FPL 52694, ketotifen, aloe vera, certain flavonoids such as quercetin, some sulfated proteoglycans such as chondroitin sulfate and dehydroleucodine. Dehydroleucodine, a sesquiterpene lactone isolated from Artemisia douglasiana Besser, exhibits anti-inflammatory and gastrointestinal cytoprotective action. The lactone stimulates mucus production, and inhibits histamine and serotonin release from intestinal mast cells. The lactone could act as a selective mast cell stabilizer by releasing cytoprotective factors and inhibiting pro-inflammatory mast cell mediators. PMID:14510234

  14. On the role of ploidy in cell radiosensitivity

    International Nuclear Information System (INIS)

    Sensitivity of experimentally obtained diploid cells of naturally occuring haplonts Pichia pinus and Pichia quilliermondii to gamma-quanta and α-particles has been shown to be twice as high as that of haploid cells and, therefore, independent of the ploidy, as calculated per one set of chromosomes. In this respect, the haplonts under study are similar to diplonts Saccharomyces cerevisiae, carrying rad 51 mutation, and drastically different from Saccharomyces cerevisiae of ''wild type'' whose haploid cells are much more radiosensitive than diploids. It has also been found that relative biological effectiveness (RBE) of α-particles for yeasts of the strains under study decreases, with increasing radiosensitivity, varying from 4.6 to 1.0. It is concluded that: (1) similar lesions lay the basis of radiation damage to both haploid and diploid yeast cells; the probability of formation of these lesions is conditioned by the dimensions of the ''target'' (DNA content) and the effectiveness of the repair systems, (2) the presence in the cell of at least two sets of chromosomes is necessary for productive work of the repair systems, (3) a higher radioresistance of diploid cells as compared to haploids in diplonts is mainly due to the effective work of the repair systems, (4) a higher radiosensitivity of diploid cells as compared to haploids in haplonts is perhaps due to a deficiency of these yeasts in repair systems, (5) an important role is ascribed to repair processes in the estimation of RBE of radiations possessing different LET

  15. The Role of Myeloma Cells to Osteoclast Activation

    Directory of Open Access Journals (Sweden)

    Bahare Sadeghi

    2010-01-01

    Full Text Available Objective: Multiple myeloma (MM is a hematological malignancy characterized by osteolyticbone disease which is associated with severe bone pain and pathological bonefractures. The receptor activator of nuclear factor κB (RANK and receptor activator ofnuclear factor κB ligand (RANKL system has an important role in regulation of boneremodeling process. The aim of this study was to evaluate the expression of the RANK/RANKL molecules by the myeloma cells derived from patients and myeloma cell lineU-266.Materials and Methods: Myeloma cells derived from 7 myeloma patients and plasma cellleukemia were included into this study to evaluate the expression of the RANK/RANKLmolecules by the reverse transcriptions-polymerase chain reaction (RT-PCR method atthe mRNA level. As well as human myeloma cell line U266, U937, RPMI-8866 and Helawere used as control groups.Results: In this study we show the expression of RANK and its ligand at the mRNA levelin U-266 (myeloma cell line and plasma cells derived from patients by the RT-PCR technique.Conclusion: Our results demonstrate that expression of RANK and RANKL by plasmacells can contribute to induction of osteoclasts and plasma cell activation which elevatesbone resorption in myeloma patients.

  16. Role of everolimus in the treatment of renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Saby George

    2009-08-01

    Full Text Available Saby George1, Ronald M Bukowski21University of Texas Health Sciences Center, MC-8221, Division of Hematology and Oncology, San Antonio, Texas, USA; 2CCF Lerner College of Medicine Division of Hematology and Oncology, Cleveland, Ohio, USAAbstract: The therapeutic options in metastatic renal cell carcinoma have been recently expanded by the discovery of the VHL gene, the mutation of which is associated with development of clear cell carcinoma, and overexpression of the angiogenesis pathway, resulting in a very vascular tumor. This breakthrough in science led to the development of a variety of small molecules inhibiting the VEGF-dependent angiogenic pathway, such as sunitinib and sorafenib. These agents prolong overall and progression-free survival, respectively. The result was the development of robust front-line therapies which ultimately fail and are associated with disease progression. In this setting, there existed an unmet need for developing second-line therapies for patients with refractory metastatic renal cell carcinoma (MRCC. Everolimus (RAD 001 is an oral inhibitor of the mammalian target of rapamycin (mTOR pathway. The double-blind, randomized, placebo-controlled phase III trial of everolimus (RECORD-1 conducted in MRCC patients after progression on sunitinib or sorafenib, or both, demonstrated a progression-free survival benefit favoring the study drug (4.9 months vs 1.9 months, HR 0.33, 95% CI 0.25 to 0.43, P ≤ 0 0.001. Everolimus thus established itself as a standard of care in the second-line setting for patients with MRCC who have failed treatment with VEGF receptor inhibitors.Keywords: mTOR inhibitor, mammalian target of rapamycin inhibitor, signal transduction inhibitor, renal cell carcinoma, targeted therapy

  17. Sterile inflammation - do innate lymphoid cell subsets play a role?

    OpenAIRE

    Walsh, Patrick

    2012-01-01

    PUBLISHED The recent identification of several novel innate lymphoid cell (iLC) subsets has increased our understanding of the mechanisms which link the innate and adaptive immune systems. While the contribution of these subsets toward the pathogenesis of human disease remains largely to be determined, it seems likely that they will play a particularly important role in sterile inflammatory settings where the innate response is seen as a critical mediator of inflammation. Several recent st...

  18. Role of TAZ in cancer stem cells and Wnt signaling

    OpenAIRE

    Azzolin, Luca

    2013-01-01

    The transcriptional co-activator TAZ, known Hippo transducer together with his paralogue YAP, has recently emerged as important player in processes like organ growth and tumorigenesis. Here we focused on two aspects of TAZ biology: the first regards the role of TAZ as molecular determinant of breast cancer stem cells (CSCs); the second is the characterization of TAZ as downstream mediator of Wnt signaling. Using a bioinformatic approach, we discovered that more-malignant/CSC-enriched prim...

  19. Subsets of regulatory T cells and their roles in allergy

    OpenAIRE

    ZHANG, HUIYUN; Kong, Hui; Zeng, Xiaoning; Guo, Lianyi; Sun, Xiaoyun; He, Shaoheng

    2014-01-01

    In recent years, it is recognized that acquired immunity is controlled by regulatory T cell (Treg). Since fundamental pathophysiological changes of allergy are mainly caused by hyperresponsiveness of immune system to allergens that acquires after birth, Tregs likely play key roles in the pathogenesis of allergy, particularly during the sensitization phase. However, accumulated information indicate that there are several distinctive subtypes of Tregs in man, and each of them seems to play diff...

  20. Role of NK, NKT cells and macrophages in liver transplantation

    Science.gov (United States)

    Fahrner, René; Dondorf, Felix; Ardelt, Michael; Settmacher, Utz; Rauchfuss, Falk

    2016-01-01

    Liver transplantation has become the treatment of choice for acute or chronic liver disease. Because the liver acts as an innate immunity-dominant organ, there are immunological differences between the liver and other organs. The specific features of hepatic natural killer (NK), NKT and Kupffer cells and their role in the mechanism of liver transplant rejection, tolerance and hepatic ischemia-reperfusion injury are discussed in this review. PMID:27468206

  1. The role of regulatory T cells in cancer immunology

    OpenAIRE

    Whiteside TL

    2015-01-01

    Theresa L Whiteside University of Pittsburgh Cancer Institute, Pittsburgh, PA, US Abstract: Regulatory T cells (Treg) are generally considered to be significant contributors to tumor escape from the host immune system. Emerging evidence suggests, however, that in some human cancers, Treg are necessary to control chronic inflammation, prevent tissue damage, and limit inflammation-associated cancer development. The dual role of Treg in cancer and underpinnings of Treg diversity are not well und...

  2. New III-V cell design approaches for very high efficiency. Annual subcontract report, 1 August 1991--31 July 1992

    Energy Technology Data Exchange (ETDEWEB)

    Lundstrom, M.S.; Melloch, M.R.; Lush, G.B.; Patkar, M.P.; Young, M.P. [Purdue Univ., Lafayette, IN (United States)

    1993-04-01

    This report describes to examine new solar cell desip approaches for achieving very high conversion efficiencies. The program consists of two elements. The first centers on exploring new thin-film approaches specifically designed for M-III semiconductors. Substantial efficiency gains may be possible by employing light trapping techniques to confine the incident photons, as well as the photons emitted by radiative recombination. The thin-film approach is a promising route for achieving substantial performance improvements in the already high-efficiency, single-junction, III-V cell. The second element of the research involves exploring desip approaches for achieving high conversion efficiencies without requiring extremely high-quality material. This work has applications to multiple-junction cells, for which the selection of a component cell often involves a compromise between optimum band pp and optimum material quality. It could also be a benefit manufacturing environment by making the cell`s efficiency less dependent on materialquality.

  3. Pathophysiological consequences of hemolysis. Role of cell-free hemoglobin

    Directory of Open Access Journals (Sweden)

    Tomasz Misztal

    2011-09-01

    Full Text Available Abundant hemolysis is associated with a number of inherent and acquired diseases including sickle-cell disease (SCD, polycythemia, paroxysmal nocturnal hemoglobinuria (PNH and drug-induced hemolytic anemia. Despite different etiopathology of hemolytic diseases, many concomitant symptoms are comparable and include e.g. hypertension, hemoglobinuria and hypercoagulation state. Studies in the last years have shown a growing list of mechanisms lying at the basis of those symptoms, in particular irreversible reaction between cell-free hemoglobin (Hb and nitric oxide (NO – endogenous vasorelaxant and anti-thrombotic agent. Saturation of protective physiological cell-free Hb-scavenging mechanisms results in accumulation of Hb in plasma and hemoglobinemia. Extensive hemoglobinemia subsequently leads to hemoglobinuria, which may cause kidney damage and development of Fanconi syndrome. A severe problem in patients with SCD and PNH is pulmonary and systemic hypertension. It may lead to circulation failure, including stroke, and it is related to abolition of NO bioavailability for vascular smooth muscle cells. Thrombotic events are the major cause of death in SCD and PNH. It ensues from lack of platelet inhibition evoked by Hb-mediated NO scavenging. A serious complication that affects patients with excessive hemolysis is erectile dysfunction. Also direct cytotoxic, prooxidant and proinflammatory effects of cell-free hemoglobin and heme compose the clinical picture of hemolytic diseases. The pathophysiological role of plasma Hb, mechanisms of its elimination, and direct and indirect (via NO scavenging deleterious effects of cell-free Hb are presented in detail in this review. Understanding the critical role of hemolysis and cell-free Hb is important in the perspective of treating patients with hemolytic diseases and to design new effective therapies in future.

  4. Role of Geminin in cell fate determination of hematopoietic stem cells (HSCs).

    Science.gov (United States)

    Yasunaga, Shin'ichiro; Ohno, Yoshinori; Shirasu, Naoto; Zhang, Bo; Suzuki-Takedachi, Kyoko; Ohtsubo, Motoaki; Takihara, Yoshihiro

    2016-09-01

    Geminin exerts two distinct molecular roles. Geminin negatively regulates DNA replication licensing through the direct interaction with Cdt1 to prevent re-replication in proliferating cells. Geminin also regulates chromatin remodeling through the direct interaction with Brahma/Brg1 to maintain undifferentiated states of stem cells. We previously uncovered that Polycomb-group complex 1 and Hoxb4/Hoxa9, well-known intrinsic factors that are essential for maintaining the hematopoietic stem cell (HSC) activity, alternatively act as ubiquitin-proteasome systems for Geminin protein to reduce the protein expression level, and sustain the HSC activity. Thus, Geminin is presumed to play an important role in determining cell fate, i.e., turning on and off cellular quiescence and proliferation/differentiation, in HSCs. We recently generated recombinant cell-penetrating Geminin (CP-Geminin), enabling rapid incorporation and withdraw of Geminin protein in cells. CP-Geminin may be useful in regulating the cell cycle and chromatin configuration. In this article, we summarize current information on the molecular functions of Geminin and the regulatory system for Geminin protein expression, and argue for the molecular role of Geminin in cell fate determination of HSCs, and future perspective of a new technology for manipulating the activities of HSCs and cancer stem cells (CSCs). PMID:27422432

  5. High Efficiency Quantum Dot III-V Thermophotovoltaic Cell for Space Power Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Quantum dots are nanoscale materials that have already improved the performance of optical sensors, lasers, light emitting diodes and solar cells. The unique...

  6. Graphene-Based Counter Electrode for Co(III/II) Mediated Dye-sensitized Solar Cells

    Czech Academy of Sciences Publication Activity Database

    Kavan, Ladislav; Yum, J. H.; Graetzel, M.

    Strasbourg: European Materials Research Society, 2013. XVI2. [E- MRS 2013 SPRING MEETING. 26.05.2013-31.05.2013, Strasbourg] Institutional support: RVO:61388955 Keywords : graphene * solar cells Subject RIV: CG - Electrochemistry

  7. Antigen modulation of the immune response. III. Evaluation of the hypothetical short-lived memory cell

    International Nuclear Information System (INIS)

    The putative short-lived memory cells, whose existence has been suggested by the results of secondary adoptive transfer experiments, were investigated. On the basis of the following evidences we have concluded that the short-lived memory cell is probably an artifact of the adoptive transfer technique: when immune thoracic duct lymphocytes, known to consist predominantly of long-lived memory cells, were transferred to irradiated recipients and challenged at various times after transfer, approximately 80 to 90 percent of the initial response was absent by Day 14 challenge; preirradiating adoptive recipients with increasing dose of x-irradiation tended to lengthen the observed half life of memory cells; single or multiple treatments of immune donors with 0.3 mg Vinblastin before transfer resulted in neither a depression of the initial secondary response nor an alteration in the rate of decline of the memory potential; reconstitution of irradiated hosts with normal spleen cells one day before transfer of memory cells and challenge resulted in inhibition of the adoptive secondary response; and the transfer of memory cells to antigen free intermediate hosts, in which they were allowed to reside for one day or fourteen days before transfer to irradiated recipients, resulted in only a slight decline in their capacity to respond. We propose that the rapid decline of memory potential in adoptive recipients challenged at various times after transfer is due to modulating effects by the hosts as it recovers from irradiation. These effects may be the result of cell crowding or the loss of irradiation-produced stimulatory factors. The relevance of these findings to adoptive transfer systems in general and the secondary response of intact animals is discussed

  8. LuIII Parvovirus Selectively and Efficiently Targets, Replicates in, and Kills Human Glioma Cells

    OpenAIRE

    Paglino, Justin C.; Ozduman, Koray; van den Pol, Anthony N.

    2012-01-01

    Because productive infection by parvoviruses requires cell division and is enhanced by oncogenic transformation, some parvoviruses may have potential utility in killing cancer cells. To identify the parvovirus(es) with the optimal oncolytic effect against human glioblastomas, we screened 12 parvoviruses at a high multiplicity of infection (MOI). MVMi, MVMc, MVM-G17, tumor virus X (TVX), canine parvovirus (CPV), porcine parvovirus (PPV), rat parvovirus 1A (RPV1A), and H-3 were relatively ineff...

  9. Interaction of Cosup(III) complexes with radiation on 'in vitro' mammalian cells and on molecular systems

    International Nuclear Information System (INIS)

    Cosup(III) complexes could be considered as potential radiosensitizers in dependence of the electronic configuration of the metal. Due to the high redox state that causes its powerful electrophilia they possibly act through electron-affinic mechanisms. In this paper the effect of [Co(NH3)5Cl]Cl2 on TC.SV-40 hamster cells is reported, in aerobic and hypoxic conditions, and its action, at a non-toxic concentration, in a combined treatment with X-rays. Results show the small protection induced by the product in the survival curves. As a contribution to the knowledge of its possible mechanism of action some molecular proofs and the interaction test with -SHNP cellular groups are made. A high degree of reaction is observed as is the case with good radiosensitizers but at molecular level the behaviour of the complex formed between DNA and the product reveals mutual protection due to their corresponding radiodegradation. (orig.)

  10. Role of mucosal dendritic cells in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Jan Hendrik Niess

    2008-01-01

    The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents.These local immune responses require a tight control,the outcome of which is in most cases the induction of tolerance.Local T cell immunity is an important compartment of the specific intestinal immune system.T cell reactivity is programmed during the initial stage of its activation by professional presenting cells.Mucosal dendritic cells(DCs)are assumed to play key roles in regulating immune responses in the antigen-rich gastrointestinal environment.Mucosal DCs are a heterogeneous population that can either initiate(innate and adaptive)immune responses,or control intestinal inflammation and maintain tolerance.Defects in this regulation are supposed to lead to the two major forms of inflammatory bowel disease(IBD),Crohn's disease(CD)and ulcerative colitis(UC).This review will discuss the emerging role of mucosal DCs in regulating intestinal inflammation and immune responses.(C)2008 The WJG Press.All rights reserved.

  11. Tumor Necrosis Factor-alpha Potentiates the Cytotoxicity of Amiodarone in Hepa1c1c7 Cells: Roles of Caspase Activation and Oxidative Stress

    OpenAIRE

    Lu, Jingtao; Miyakawa, Kazuhisa; Roth, Robert A.; Ganey, Patricia E.

    2012-01-01

    Amiodarone (AMD), a class III antiarrhythmic drug, causes idiosyncratic hepatotoxicity in human patients. We demonstrated previously that tumor necrosis factor-alpha (TNF-α) plays an important role in a rat model of AMD-induced hepatotoxicity under inflammatory stress. In this study, we developed a model in vitro to study the roles of caspase activation and oxidative stress in TNF potentiation of AMD cytotoxicity. AMD caused cell death in Hepa1c1c7 cells, and TNF cotreatment potentiated its t...

  12. Insight into the roles of structures and energy levels of mono- and bis-β-diketones on sensitizing Nd(iii) NIR-luminescence.

    Science.gov (United States)

    Li, Bing; Li, Hongfeng; Chen, Peng; Sun, Wenbin; Wang, Cheng; Gao, Ting; Yan, Pengfei

    2016-07-28

    Three neodymium complexes Nd(TTA)3(DMSO)2 (1, TTA = 2-thenoyltrifluoroacetone), Nd2(BDT)3(DMSO)6 (2, BDT = bis(4,4,4-trifluoro-1,3-dioxobutyl)thiophene) and Nd2(BTT)3(DMSO)4 (3, BTT = bis(4,4,4-trifluoro-1,3-dioxobutyl)(2,2'-bithiophene)) constructed from three thiophene-based β-diketonate ligands, were prepared for the purpose of building the relationships between the structures, energy levels of the complexes and NIR luminescence properties of Nd(iii) ions. X-ray crystallographical analysis reveals that complex 1 is a mononuclear structure, the central Nd(iii) ion is coordinated by eight oxygen atoms from three mono-β-diketones (TTA) and two DMSO, whereas, complexes 2 and 3 adopt triple-stranded dinuclear structures, in which the two Nd(iii) ions are wrapped by three bis-β-diketones, the central Nd(iii) ions are nine and eight coordinated by oxygen atoms from ligands and the coordinated DMSO molecules. The photophysical properties related to the electronic transition are characterized by the absorbance spectra, the excitation spectra, the phosphorescence spectra, the emission spectra, the emission quantum yields, and the emission lifetimes. The luminescence quantum yields experiment reveals that the dinuclear complexes (0.49% and 0.33% for 2 and 3) show higher luminescence efficiencies compared to the mononuclear complex 1 (0.22%). This enhancement is mainly attributed to their binuclear structures, which effectively represses the nonradiative transition caused by high-energy oscillators in ligands and/or solvents. On the other hand, the energy level matching also plays an important role in this enhancement. PMID:27346610

  13. The role of Cajal cells in chronic prostatitis.

    Science.gov (United States)

    Haki Yuksel, Ozgur; Urkmez, Ahmet; Verit, Ayhan

    2016-01-01

    Types of prostatitis can be defined as groups of syndromes in adult men associated with infectious and noninfectious causes characterized frequently by lower abdominal and perineal signs and diverse clinical symptoms and complications. Etiopathogenesis of chronic prostatitis is not well defined. Moreover, its treatment outcomes are not satisfactory. Presence of c-kit positive interstitial cells in human prostate is already known. It has been demonstrated that these cells can be pacemaker cells which trigger spontaneous slow-wave electrical activity in the prostate and can be responsible for the transport of glandular secretion from acinar cells into major and minor prostatic ducts and finally into urethra. In the light of all these data, when presence of a possible inflammatory pathology is thought to involve prostate that secretes and has a reservoir which drains its secretion (for prostate, prostatic urethra), two points are worth mentioning. Impairment of secretion mechanism and collection of secretion within the organ with reflux of the microbial material from its reservoir back into prostate gland. Both of these potential conditions can be explained by ductal neuromuscular mechanism, which induces secretion. We think that in this neuromuscular mechanism interstitial Cajal cells have an important role in chronic prostatitis. Our hypothesis is that curability of prostatitis is correlated with the number of Cajal cells not subjected to apoptosis. PMID:27377090

  14. Role of mitochondria on muscle cell death and meat tenderization.

    Science.gov (United States)

    Sierra, Verónica; Oliván, Mamen

    2013-05-01

    The possibility that mitochondria are involved in cellular dysfunction is particularly high in situations associated with increases in free radical activity, like hypoxia or ischemia; therefore its potential role in the muscle post-mortem metabolism is reviewed. In the dying muscle, different routes of cell death catabolism (apoptosis, autophagy) may occur having great influence on the process of conversion of muscle into meat. Mitochondria are the first and also one of the main organelles affected by post-mortem changes; therefore they are decisive in the subsequent cellular responses influencing the pathway to cell demise and thus, the final meat quality. Depending on the cell death programme followed by muscle cells after exsanguination, diverse proteases would be activated to a different extent, which is also reviewed in order to understand how they affect meat tenderization. This review also summarizes recent patents relating cell death processes and meat tenderness. Further research is encouraged as there is still a need of knowledge on cell death post-mortem processes to increase our understanding of the conversion of muscle into meat. PMID:23432120

  15. The Role of Lipid Domains in Bacterial Cell Processes

    Directory of Open Access Journals (Sweden)

    Katarína Muchová

    2013-02-01

    Full Text Available Membranes are vital structures for cellular life forms. As thin, hydrophobic films, they provide a physical barrier separating the aqueous cytoplasm from the outside world or from the interiors of other cellular compartments. They maintain a selective permeability for the import and export of water-soluble compounds, enabling the living cell to maintain a stable chemical environment for biological processes. Cell membranes are primarily composed of two crucial substances, lipids and proteins. Bacterial membranes can sense environmental changes or communication signals from other cells and they support different cell processes, including cell division, differentiation, protein secretion and supplementary protein functions. The original fluid mosaic model of membrane structure has been recently revised because it has become apparent that domains of different lipid composition are present in both eukaryotic and prokaryotic cell membranes. In this review, we summarize different aspects of phospholipid domain formation in bacterial membranes, mainly in Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. We describe the role of these lipid domains in membrane dynamics and the localization of specific proteins and protein complexes in relation to the regulation of cellular function.

  16. Granulosa cell proliferation differentiation and its role in follicular development

    Institute of Scientific and Technical Information of China (English)

    LU Cuiling; YANG Wei; HU Zhaoyuan; LIU Yixun

    2005-01-01

    Granuiosa cells (GCs) are the most important cells in the ovary that undergo serious changes morphologically and physiologically during the processes of follicular proliferation, differentiation, ovulation, lutenization and atresia. Oocyte (OC) directs GC proliferation and differentiation, while GCs influence OC maturation. Many ovarian factors are involved in the regulation of these processes via different molecular mechanisms and signal pathways. P38MAPK can selectively regulate steroidogenesis in GCs controlled by FSH; Transcript factors LRH-1 and DAX-1 play an important role in this process; FSH induces GC prolfferation and differentiation by stimulating PCNA and StAR expression and steroidogenesis. Activated ERK1/2 signal pathway may be involved in the FSH-regulated GC proliferation and differentiation. Therefore, GC is an ideal model for studying cell proliferation, differentiation and interaction,as well as signal transduction. This review briefly summarizes the latest data in the literature, including the results achieved in our laboratory.

  17. Fibroblast growth factor signaling and inhibition in non-small cell lung cancer and their role in squamous cell tumors

    International Nuclear Information System (INIS)

    With the introduction of targeted agents primarily applicable to non-small cell lung cancer (NSCLC) of adenocarcinoma histology, there is a heightened unmet need in the squamous cell carcinoma population. Targeting the angiogenic fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling pathway is among the strategies being explored in squamous NSCLC; these efforts are supported by growth-promoting effects of FGF signaling in preclinical studies (including interactions with other pathways) and observations suggesting that FGF/FGFR-related aberrations may be more common in squamous versus adenocarcinoma and other histologies. A number of different anti-FGF/FGFR approaches have shown promise in preclinical studies. Clinical trials of two multitargeted tyrosine kinase inhibitors are restricting enrollment to patients with squamous NSCLC: a phase I/II trial of nintedanib added to first-line gemcitabine/cisplatin and a phase II trial of ponatinib for previously treated advanced disease, with the latter requiring not only squamous disease but also a confirmed FGFR kinase amplification or mutation. There are several ongoing clinical trials of multitargeted agents in general NSCLC populations, including but not limited to patients with squamous disease. Other FGF/FGFR-targeted agents are in earlier clinical development. While results are awaited from these clinical investigations in squamous NSCLC and other disease settings, additional research is needed to elucidate the role of FGF/FGFR signaling in the biology of NSCLC of different histologies

  18. Techno-Economic Analysis of Three Different Substrate Removal and Reuse Strategies for III-V Solar Cells

    Energy Technology Data Exchange (ETDEWEB)

    Ward, J. Scott; Remo, Timothy; Horowitz, Kelsey; Woodhouse, Michael; Sopori, Bhushan; VanSant, Kaitlyn; Basore, Paul

    2016-09-01

    The high cost of wafers suitable for epitaxial deposition of III-V solar cells has been a primary barrier to widespread use of these cells in low-concentration and one-sun terrestrial solar applications. A possible solution is to reuse the substrate many times, thus spreading its cost across many cells. We performed a bottom-up techno-economic analysis of three different strategies for substrate reuse in high-volume manufacturing: epitaxial lift-off, spalling, and the use of a porous germanium release layer. The analysis shows that the potential cost reduction resulting from substrate reuse is limited in all three strategies--not by the number of reuse cycles achievable, but by the costs that are incurred in each cycle to prepare the substrate for another epitaxial deposition. The dominant substrate-preparation cost component is different for each of the three strategies, and the cost-ranking of these strategies is subject to change if future developments substantially reduce the cost of epitaxial deposition.

  19. Galectin-1-mediated cell adhesion, invasion and cell death in human anaplastic large cell lymphoma: Regulatory roles of cell surface glycans

    OpenAIRE

    Suzuki, Osamu; Abe, Masafumi

    2014-01-01

    Galectin-1 is known to be one of the extracellular matrix proteins. To elucidate the biological roles of galectin-1 in cell adhesion and invasion of human anaplastic large cell lymphoma, we performed cell adhesion and invasion assays using the anaplastic large cell lymphoma cell line H-ALCL, which was previously established in our laboratory. From the cell surface lectin array, treatment with neuraminidase from Arthrobacter ureafaciens which cleaves all linkage types of cell surface sialic ac...

  20. Highly efficient multiple-layer CdS quantum dot sensitized III-V solar cells.

    Science.gov (United States)

    Lin, Chien-Chung; Han, Hau-Vei; Chen, Hsin-Chu; Chen, Kuo-Ju; Tsai, Yu-Lin; Lin, Wein-Yi; Kuo, Hao-Chung; Yu, Peichen

    2014-02-01

    In this review, the concept of utilization of solar spectrum in order to increase the solar cell efficiency is discussed. Among the three mechanisms, down-shifting effect is investigated in detail. Organic dye, rare-earth minerals and quantum dots are three most popular down-shift materials. While the enhancement of solar cell efficiency was not clearly observed in the past, the advances in quantum dot fabrication have brought strong response out of the hybrid platform of a quantum dot solar cell. A multiple layer structure, including PDMS as the isolation layer, is proposed and demonstrated. With the help of pulse spray system, precise control can be achieved and the optimized concentration can be found. PMID:24749412

  1. Specific inhibition of secreted NRG1 types I-II by heparin enhances Schwann Cell myelination.

    Science.gov (United States)

    Eshed-Eisenbach, Yael; Gordon, Aaron; Sukhanov, Natalya; Peles, Elior

    2016-07-01

    Primary cultures of mixed neuron and Schwann cells prepared from dorsal root ganglia (DRG) are extensively used as a model to study myelination. These dissociated DRG cultures have the particular advantage of bypassing the difficulty in purifying mouse Schwann cells, which is often required when using mutant mice. However, the drawback of this experimental system is that it yields low amounts of myelin. Here we report a simple and efficient method to enhance myelination in vitro. We show that the addition of heparin or low molecular weight heparin to mixed DRG cultures markedly increases Schwann cells myelination. The myelin promoting activity of heparin results from specific inhibition of the soluble immunoglobulin (Ig)-containing isoforms of neuregulin 1 (i.e., NRG1 types I and II) that negatively regulates myelination. Heparin supplement provides a robust and reproducible method to increase myelination in a simple and commonly used culture system. GLIA 2016;64:1227-1234. PMID:27143444

  2. Engrailed-2 might play an anti-oncogenic role in clear-cell renal cell carcinoma.

    Science.gov (United States)

    Lai, Cai-Yong; Xu, Yin; Yu, Gan-Shen; Wu, Xun; Li, Yun-Fei; Pan, Bin; Heng, Bao-Li; Xue, Yi-Jun; Su, Ze-Xuan

    2016-06-01

    Our preliminary study indicated that Engrailed-2 (EN2) is downregulated but also ectopically expressed in clear-cell renal cell carcinoma (CCRCC), and the absence of EN2 expression was associated with poor histological grade. However, the specific roles of EN2 in CCRCC have yet to be elucidated. In the present study, we examined the effects of inhibiting EN2 expression by human renal tubular epithelial cells (HK-2) and overexpressing EN2 by human clear-cell renal cells (786-O). Results showed that EN2 inhibition accelerated HK-2 cell proliferation, shortened the cell cycle, reduced apoptosis, and acted more invasively. By contrast, EN2 overexpression in 786-O cells decelerated the proliferative ability of 786-O, increased the percentage of cell apoptosis, and weakened the invasive ability. Overall, the results demonstrated that EN2 might play an anti-oncogenic role in oncogenesis and development of CCRCC, thereby maintaining the normal growth of human renal tubular epithelial cells. PMID:26948025

  3. Mechanical properties of mammalian single smooth muscle cells. III. Passive properties of pig detrusor and human a terme uterus cells.

    NARCIS (Netherlands)

    J.J. Glerum (Jacobus); R. van Mastrigt (Ron); A.J. van Koeveringe (Bram)

    1990-01-01

    textabstractCells isolated from pig urinary bladders and pregnant full term human uteruses were attached longitudinally between a microforce transducer and a length displacement apparatus. Cells were stretched by applying a series of ramp-like length changes of 0.2 s duration and 10.0 microns amplit

  4. The effect of tumor volume and its change on survival in stage III non-small cell lung cancer treated with definitive concurrent chemoradiotherapy

    International Nuclear Information System (INIS)

    To investigate a prognostic role of gross tumor volume (GTV) changes on survival outcomes following concurrent chemoradiotherapy (CCRT) in stage III non-small-cell lung cancer (NSCLC) patients. We enrolled 191 patients with stage III NSCLC from 2001 to 2009 undergoing definitive CCRT. The GTV of 157 patients was delineated at the planning CT prior to CCRT and with a follow-up CT 1 month after CCRT. We assessed the volumetric parameters of pre-treatment GTV (GTVpre) post-treatment GTV (GTVpost), and volume reduction ratio of GTV (VRR). The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and locoregional progression-free survival (LRPFS). The best cut-off value was defined as that which exhibited the maximum difference between the two groups. The median follow-up duration was 52.7 months in surviving patients. Median survival, 3-year OS, PFS and LRPFS rates were 25.5 months, 36.4%, 23.0%, and 45.0%, respectively. The selected cut-off values were 50 cm3 for GTVpre, 20 cm3 for GTVpost, and 50% for VRR. The smaller GTVpre and GTVpost values were associated with better OS (p < 0.001 and p = 0.015) and PFS (p = 0.001 and p = 0.004), respectively, upon univariate analysis. The higher VRR of > 50% was associated with a trend toward poorer OS (p = 0.004) and PFS (p = 0.054). Upon multivariate analysis, smaller GTVpre indicated significantly improved OS (p = 0.001), PFS (p = 0.013) and LRPFS (p = 0.002), while smaller GTVpost was marginally significant for PFS (p = 0.086). Higher VRR was associated with a trend toward poorer OS (p = 0.075). In patients with stage III NSCLC undergoing definitive CCRT, GTVpre was an independent prognostic factor of survival. Notably, improved outcome was not correlated with higher VRR after short-term follow-up with CT alone. The online version of this article (doi:10.1186/s13014-014-0283-6) contains supplementary material, which is available to authorized users

  5. The role and importance of club cells (Clara cells) in the pathogenesis of some respiratory diseases.

    Science.gov (United States)

    Rokicki, Wojciech; Rokicki, Marek; Wojtacha, Jacek; Dżeljijli, Agata

    2016-03-01

    The report presents the cellular structure of the respiratory system as well as the history of club cells (Clara cells), their ultrastructure, and location in the airways and human organs. The authors discuss the biochemical structure of proteins secreted by these cells and their importance for the integrity and regeneration of the airway epithelium. Their role as progenitor cells for the airway epithelium and their involvement in the biotransformation of toxic xenobiotics introduced into the lungs during breathing is emphasized. This is followed by a discussion of the clinical aspects associated with club cells, demonstrating that tracking the serum concentration of club cell-secreted proteins is helpful in the diagnosis of a number of lung tissue diseases. Finally, suggestions are provided regarding the possible use of proteins secreted by club cells in the treatment of serious respiratory conditions. PMID:27212975

  6. Targeting cancer stem cells: emerging role of Nanog transcription factor

    Directory of Open Access Journals (Sweden)

    Wang ML

    2013-09-01

    Full Text Available Mong-Lien Wang,1 Shih-Hwa Chiou,2,3 Cheng-Wen Wu1,4–61Institute of Biochemistry and Molecular Biology, 2Institute of Pharmacology, National Yang Ming University, Taipei, Taiwan; 3Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan; 4Institute of Microbiology and Immunology, 5Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan; 6Institute of Biomedical Science, Academia Sinica, Taipei, TaiwanAbstract: The involvement of stemness factors in cancer initiation and progression has drawn much attention recently, especially after the finding that introducing four stemness factors in somatic cells is able to reprogram the cells back to an embryonic stem cell-like state. Following accumulating data revealing abnormal elevated expression levels of key stemness factors, like Nanog, Oct4, and Sox2, in several types of cancer stem cells; the importance and therapeutic potential of targeting these stemness regulators in cancers has turned to research focus. Nanog determines cell fate in both embryonic and cancer stem cells; activating Nanog at an inappropriate time would result in cancer stem cells rather than normal pluripotent stem cells or differentiated somatic cells. Upregulated Nanog is correlated with poor survival outcome of patients with various types of cancer. The discoveries of downstream regulatory pathways directly or indirectly mediated by Nanog indicate that Nanog regulates several aspects of cancer development such as tumor cell proliferation, self-renewal, motility, epithelial-mesenchymal transition, immune evasion, and drug-resistance, which are all defined features for cancer stem cells. The current review paper illustrates the central role of Nanog in the regulatory networks of cancer malignant development and stemness acquirement, as well as in the communication between cancer cells and the surrounding stroma. Though a more defined model is needed to test the

  7. Dose-rate effects in mammalian cells in culture. III. Comparison of cell killing and cell proliferation during continuous irradiation for six different cell lines

    International Nuclear Information System (INIS)

    The effects of continuous irradiation over a wide range of dose rates were studied for six different mammalian cell lines in regard to cell survival and proliferation. Cell lines were chosen in which such characteristics as population doubling time, chromosome number, DNA content, acute dose-survival curve parameters, and division delay were as diverse as possible. There was no correlation between the minimum dose rate necessary to stop cell population growth and any of the above listed characteristics, with the exception of division delay following acute doses. In general, the longer the division delay (min/rad), the lower the dose rate required to stop cell population growth. The effects of cell-cycle redistribution during continuous irradiaton in regard to cell survival were dramatic. In some cases a reduction in dose rate resulted in an increase in cell killing for a given total dose. This occurred only when dose rates were sufficient to stop cell population growth and after exposure times sufficient to allow for the occurrence of cell-cycle redistribution

  8. Role of mitochondrial function in cell death and body metabolism.

    Science.gov (United States)

    Lee, Myung-Shik

    2016-01-01

    Mitochondria are the key players in apoptosis and necrosis. Mitochondrial DNA (mtDNA)-depleted r0 cells were resistant to diverse apoptosis inducers such as TNF-alpha, TNFSF10, staurosporine and p53. Apoptosis resistance was accompanied by the absence of mitochondrial potential loss or cytochrome c translocation. r0 cells were also resistant to necrosis induced by reactive oxygen species (ROS) donors due to upregulation of antioxidant enzymes such as manganese superoxide dismutase. Mitochondria also has a close relationship with autophagy that plays a critical role in the turnover of senescent organelles or dysfunctional proteins and may be included in 'cell death' category. It was demonstrated that autophagy deficiency in insulin target tissues such as skeletal muscle induces mitochondrial stress response, which leads to the induction of FGF21 as a 'mitokine' and affects the whole body metabolism. These results show that mitochondria are not simply the power plants of cells generating ATP, but are closely related to several types of cell death and autophagy. Mitochondria affect various pathophysiological events related to diverse disorders such as cancer, metabolic disorders and aging. PMID:27100503

  9. The Role of the Immune Response in Merkel Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Triozzi, Pierre L., E-mail: triozzp@ccf.org [Taussig Cancer Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (United States); Fernandez, Anthony P. [Departments of Dermatology and Anatomic Pathology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (United States)

    2013-02-28

    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies.

  10. The Role of the Immune Response in Merkel Cell Carcinoma

    International Nuclear Information System (INIS)

    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies

  11. Resolving the role of actoymyosin contractility in cell microrheology.

    Directory of Open Access Journals (Sweden)

    Christopher M Hale

    Full Text Available Einstein's original description of Brownian motion established a direct relationship between thermally-excited random forces and the transport properties of a submicron particle in a viscous liquid. Recent work based on reconstituted actin filament networks suggests that nonthermal forces driven by the motor protein myosin II can induce large non-equilibrium fluctuations that dominate the motion of particles in cytoskeletal networks. Here, using high-resolution particle tracking, we find that thermal forces, not myosin-induced fluctuating forces, drive the motion of submicron particles embedded in the cytoskeleton of living cells. These results resolve the roles of myosin II and contractile actomyosin structures in the motion of nanoparticles lodged in the cytoplasm, reveal the biphasic mechanical architecture of adherent cells-stiff contractile stress fibers interdigitating in a network at the cell cortex and a soft actin meshwork in the body of the cell, validate the method of particle tracking-microrheology, and reconcile seemingly disparate atomic force microscopy (AFM and particle-tracking microrheology measurements of living cells.

  12. CD155/PVR plays a key role in cell motility during tumor cell invasion and migration

    International Nuclear Information System (INIS)

    Invasion is an important early step of cancer metastasis that is not well understood. Developing therapeutics to limit metastasis requires the identification and validation of candidate proteins necessary for invasion and migration. We developed a functional proteomic screen to identify mediators of tumor cell invasion. This screen couples Fluorophore Assisted Light Inactivation (FALI) to a scFv antibody library to systematically inactivate surface proteins expressed by human fibrosarcoma cells followed by a high-throughput assessment of transwell invasion. Using this screen, we have identified CD155 (the poliovirus receptor) as a mediator of tumor cell invasion through its role in migration. Knockdown of CD155 by FALI or by RNAi resulted in a significant decrease in transwell migration of HT1080 fibrosarcoma cells towards a serum chemoattractant. CD155 was found to be highly expressed in multiple cancer cell lines and primary tumors including glioblastoma (GBM). Knockdown of CD155 also decreased migration of U87MG GBM cells. CD155 is recruited to the leading edge of migrating cells where it colocalizes with actin and αv-integrin, known mediators of motility and adhesion. Knockdown of CD155 also altered cellular morphology, resulting in cells that were larger and more elongated than controls when plated on a Matrigel substrate. These results implicate a role for CD155 in mediating tumor cell invasion and migration and suggest that CD155 may contribute to tumorigenesis

  13. Roles of Nrf2 in cell proliferation and differentiation.

    Science.gov (United States)

    Murakami, Shohei; Motohashi, Hozumi

    2015-11-01

    The Keap1-Nrf2 system plays pivotal roles in defense mechanisms by regulating cellular redox homeostasis. Nrf2 is an inducible transcription factor that activates a battery of genes encoding antioxidant proteins and phase II enzymes in response to oxidative stress and electrophilic xenobiotics. The activity of Nrf2 is regulated by Keap1, which promotes the ubiquitination and subsequent degradation of Nrf2 under normal conditions and releases the inhibited Nrf2 activity upon exposure to the stresses. Though an impressive contribution of the Keap1-Nrf2 system to the protection from exogenous and endogenous electrophilic insults has been well established, a line of evidence has suggested that the Keap1-Nrf2 system has various novel functions, particularly in cell proliferation and differentiation. Because the proliferation and differentiation of diverse cell types are often influenced and modulated by the cellular redox balance, Nrf2 has been considered to control these cellular processes by regulating the cellular levels of reactive oxygen species (ROS). In addition, analyses of the genome-wide distribution of Nrf2 have identified new sets of Nrf2 target genes whose products are involved in cell proliferation and differentiation but not necessarily in the regulation of oxidative stress. Considering the most characteristic features of Nrf2 as an inducible transcription factor, a newly emerged concept proposes that the Keap1-Nrf2 system translates environmental stresses into regulatory network signals in cell fate determination. In this review, we introduce the contribution of Nrf2 to lineage-specific differentiation, maintenance and differentiation of stem cells, and proliferation of normal and cancer cells, and we discuss how the response to fluctuating environments modulates cell behavior through the Keap1-Nrf2 system. PMID:26119783

  14. Characterization of screen printed carbon counter electrodes for Co(II)/(III) mediated photoelectrochemical cells

    Energy Technology Data Exchange (ETDEWEB)

    Ghamouss, Fouad [CEISAM, Universite de Nantes, CNRS, 2 rue de la Houssiniere, B.P. 92208, 44322, Nantes cedex 3 (France); Pitson, Robbin [Gwent Electronics Materials Ltd, Monmouth House, Mamhilad Park, Pontypool, NP4 0HZ (United Kingdom); Odobel, Fabrice [CEISAM, Universite de Nantes, CNRS, 2 rue de la Houssiniere, B.P. 92208, 44322, Nantes cedex 3 (France); Boujtita, Mohammed, E-mail: mohammed.boujtita@univ-nantes.f [CEISAM, Universite de Nantes, CNRS, 2 rue de la Houssiniere, B.P. 92208, 44322, Nantes cedex 3 (France); Caramori, Stefano [Dipartmento di Chimica, Universita di Ferrara, Via L.Borsari, 46, 44100 Ferrara (Italy); Bignozzi, Carlo A., E-mail: g4s@unife.i [Dipartmento di Chimica, Universita di Ferrara, Via L.Borsari, 46, 44100 Ferrara (Italy)

    2010-09-01

    A screen printed carbon electrode associated with Tris(4,4'-di-tert-butyl-2,2'-bipyridine)Cobalt(II) as redox mediator was investigated as possible alternative to the volatile and corrosive iodide/triodide system in dye sensitized solar cells (DSSCs). We report here a first study on the screen printing technology for the manufacturing of an advanced and stable carbon cathode for dye sensitized solar cell. The electrode surface was characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) while the electrochemical response towards the cobalt complex was evaluated by using cyclic voltammetry. Photocurrent-voltage characteristics of DSSCs based on the new cathode/Cobalt complex system were 30% lower than those recorded with Pt/iodide.

  15. Graphene Nanoplatelet Cathode for Co(III)/(II) Mediated Dye-Sensitized Solar Cells

    Czech Academy of Sciences Publication Activity Database

    Kavan, Ladislav; Yum, J. H.; Nazeeruddin, M. K.; Grätzel, M.

    2011-01-01

    Roč. 5, č. 11 (2011), s. 9171-9178. ISSN 1936-0851 R&D Projects: GA MŠk LC510; GA AV ČR IAA400400804; GA AV ČR KAN200100801 Institutional research plan: CEZ:AV0Z40400503 Keywords : graphene * dye sensitized solar cell * cobalt redox shuttle Subject RIV: CG - Electrochemistry Impact factor: 10.774, year: 2011

  16. WHAT WAS THE ROLE OF THE SUPERVISORY COMMITTEE RECOMMENDATIONS FOR CREDIT INSTITUTIONS AND THE REQUIREMENTS OF BASEL III

    Directory of Open Access Journals (Sweden)

    MEDAR LUCIAN-ION

    2010-12-01

    Full Text Available The economic downturn and financial crisis has negative impacted the European banking system, which determined the Basel Committee on Banking Supervision, after the implementation of "Basel I and Basel II", to conduct a new series of recommendations. The economic crisis has affected all types banking products and services, all models of supervision and all evaluation methods known. Credit institutions innovations, on the ease of promoting new products and services, absence amid of high quality capital who can absorb losses in the limit of liquidity, led to a deadlock on lending activity. Supervisory Committee appointed by the new "Basel III" recommendations, requires the introduction of minimum global standards for measuring and monitoring liquidity risk and also requires banks to triple quality capital reserve by 2015-2019, up to a 7% capital adequacy.

  17. Role of alpha 2,3-sialyltransferases ST3Gal III and ST3Gal IV in pancreatic ductal adenocarcinoma

    OpenAIRE

    Pérez Garay, Marta

    2011-01-01

    Este trabajo demuestra que los genes que codifican para los enzimas beta-galactosido alfa-2,3-sialiltransferasa 3 (ST3Gal III), y en menor medida beta-galactosido alfa-2,3-sialiltransferasa 4 (ST3Gal IV), están directamente implicados en etapas clave de la progresión tumoral como la adhesión, la migración y la formación de metástasis en las líneas de adenocarcinoma pancreático humano Capan-1 y MDAPanc-28. También, que las Especies Reactivas del Oxígeno (ROS) generadas durante los procesos de ...

  18. Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

    International Nuclear Information System (INIS)

    For patients with metastatic renal cell cancer (mRCC) who progressed on vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs) that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part). In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus induced Treg expansion in patients with metastatic renal cell

  19. Combining advanced radiotherapy technologies to maximize safety and tumor control probability in stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    Background: The goal of the current study was to investigate the tumor control probability (TCP) of advanced radiotherapy technologies for stage III non-small cell lung cancer (NSCLC) and to evaluate potential interplay effects between their applications. Materials and methods: Three-dimensional conformal radiotherapy (3D-CRT) with conventionally fractionated doses of 66 Gy served as reference for 13 patients with stage III NSCLC. Isotoxic dose escalation relative to the corresponding 3D-CRT plans was performed for three technologies and their combinations: intensity-modulated radiotherapy (IMRT), IMRT with a simultaneous integrated boost (IMRT-SIB) of 10% to the gross tumor volume (GTV), and adaptive re-planning twice during the treatment course (ART). All analyses were based on accumulated dose distributions using deformable image registration of CT images, which were acquired weekly during the treatment course. Results: IMRT reduced the mean lung dose (MLD) by 5.6% ± 3.8% compared to 3D-CRT. ART resulted in lung sparing of 7.9% ± 4.8% and 9.2% ± 3.9% in 3D-CRT and IMRT planning, respectively. IMRT and ART escalated the irradiation dose by 6.6% ± 3.2% and 8.8% ± 6.3%, respectively, which was not statistically different. For the 7 patients with the largest GTVs, IMRT-SIB was superior to IMRT and ART with dose escalation of 11.9% ± 3.7%. The combination of ART, IMRT, and SIB achieved maximum dose escalation in all 13 patients by 17.1% ± 5.4% on average, which increased TCP from 19.9% ± 7.0 to 37.1% ± 10.1%. Adaptive re-planning was required to continuously conform the escalated and hypofractionated SIB doses to the shrinking tumor. Conclusion: Combining advanced radiotherapy technologies is considered as a safe and effective strategy to maximize local tumor control probability in stage III NSCLC. (orig.)

  20. Role of CaECM25 in cell morphogenesis, cell growth and virulence in Candida albicans

    Institute of Scientific and Technical Information of China (English)

    ZHANG TingTing; LI WanJie; LI Di; WANG Yue; SANG JianLi

    2008-01-01

    Candida albicans is the most prominent opportunistic fungal pathogen in humans. Multiple factors are associated with the virulence of C. albicans, including morphogenesis, cell wall organization and growth rate. Here, we describe the identification and functional characterization of CaECM25, a gene that has not been reported before. We constructed Caecm25△/△ mutants and investigated the role of the gene In morphogenesis, cell wall organization and virulence. CaECM25 deletion resulted in defects in cell separation, a slower growth rate, reduced filamentous growth and attenuated adherence to plastic surfaces. The Caecm25△/△ mutant was also significantly less virulent than wild type when tested for systemic infection in mice. Therefore, CaECM25 plays important roles in morphogenesis, cell wall organization and virulence.

  1. Role of CaECM25 in cell morphogenesis, cell growth and virulence in Candida albicans

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Candida albicans is the most prominent opportunistic fungal pathogen in humans. Multiple factors are associated with the virulence of C. albicans, including morphogenesis, cell wall organization and growth rate. Here, we describe the identification and functional characterization of CaECM25, a gene that has not been reported before. We constructed Caecm25?/? mutants and investigated the role of the gene in morphogenesis, cell wall organization and virulence. CaECM25 deletion resulted in defects in cell separation, a slower growth rate, reduced filamentous growth and attenuated adherence to plastic surfaces. The Caecm25?/? mutant was also significantly less virulent than wild type when tested for systemic infection in mice. Therefore, CaECM25 plays important roles in morphogenesis, cell wall organization and virulence.

  2. Treatment-related death in patients with small-cell lung cancer in phase III trials over the last two decades.

    Directory of Open Access Journals (Sweden)

    Nobuaki Ochi

    Full Text Available INTRODUCTION: Treatment-related death (TRD remains a serious problem in small-cell lung cancer (SCLC, despite recent improvements in supportive care. However, few studies have formally assessed time trends in the proportion of TRD over the past two decades. The aim of this study was to determine the frequency and pattern of TRD over time. METHODS: We examined phase 3 trials conducted between 1990 and 2010 to address the role of systemic treatment for SCLC. The time trend was assessed using linear regression analysis. RESULTS: In total, 97 trials including nearly 25,000 enrolled patients were analyzed. The overall TRD proportion was 2.95%. Regarding the time trend, while it was not statistically significant, it tended to decrease, with a 0.138% decrease per year and 2.76% decrease per two decades. The most common cause of death was febrile neutropenia without any significant time trend in its incidence over the years examined (p = 0.139. However, deaths due to febrile neutropenia as well as all causes in patients treated with non-platinum chemotherapy increased significantly (p = 0.033. CONCLUSIONS: The overall TRD rate has been low, but not negligible, in phase III trials for SCLC over the past two decades.

  3. Lymphokine-activated killer cell phenomenon. III. Evidence that IL-2 is sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer cells

    OpenAIRE

    1983-01-01

    Purified interleukin 2 (IL-2) was found to be sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer (LAK) cells. The LAK activation factor was directly and consistently associated with IL-2 activity using classic protein purification techniques, adsorption to IL-2-dependent cell lines, and inhibition with anti-Tac antibody. As yet, no other cytokines have been found that perform the same role.

  4. Concurrent gemcitabine and 3D radiotherapy in patients with stage III unresectable non-small cell lung cancer

    International Nuclear Information System (INIS)

    Stage III unresectable non-small cell lung cancer (NSCLC) is preferably treated with concurrent schedules of chemoradiotherapy, but none is clearly superior Gemcitabine is a radiosensitizing cytotoxic drug that has been studied in phase 1 and 2 studies in this setting. The aim of this study was to describe outcome and toxicity of low-dose weekly gemcitabine combined with concurrent 3-dimensional conformal radiotherapy (3D-CRT). Treatment consisted of two cycles of a cisplatin and gemcitabine followed by weekly gemcitabine 300 mg/m2 during 5 weeks of 3D-CRT, 60 Gy in 5 weeks (hypofractionated-accelerated). Overall survival (OS), progression-free survival (PFS), and treatment related toxicity according to Common Toxicity Criteria of Adverse Events (CTCAE) version 3.0 were assessed. Between February 2002 and August 2008, 318 patients were treated. Median age was 64 years (range 36–86); 72% were male, WHO PS 0/1/2 was 44/53/3%. Median PFS was 15.5 months (95% confidence interval [CI], 12.9-18.1) and median OS was 24.6 months (95% CI., 21.0-28.1). Main toxicity (CTCAE grade ≥3) was dysphagia (12.6%), esophagitis (9.6%), followed by radiation pneumonitis (3.0%). There were five treatment related deaths (1.6%), two due to esophagitis and three due to radiation pneumonitis. Concurrent low-dose gemcitabine and 3D-CRT provides a comparable survival and toxicity profile to other available treatment schemes for unresectable stage III

  5. Phosphorescence imaging of homocysteine and cysteine in living cells based on a cationic iridium(III) complex.

    Science.gov (United States)

    Xiong, Liqin; Zhao, Qiang; Chen, Huili; Wu, Yanbo; Dong, Zesheng; Zhou, Zhiguo; Li, Fuyou

    2010-07-19

    Homocysteine (Hcy) and cysteine (Cys) are crucial to the physiological balance in living systems. Specific detection of intracellular Hcy and Cys is of growing importance. Herein, we demonstrated phosphorescence imaging of intracellular Hcy and Cys using a cationic iridium(III) complex Ir(pba)(2)(bpy)(+).PF(6)(-) [pba = 4-(2-pyridyl)benzaldehyde, bpy = bipyridine] containing aldehyde groups as a luminescent probe. Upon addition of Hcy or Cys to a semiaqueous solution of Ir(pba)(2)(bpy)(+), a change in luminescence from yellow to red was visible to the naked eye. The successful chemical reaction of the aldehyde in Ir(pba)(2)(bpy)(+) with Hcy and Cys to form thiazinane and thiazolidine was confirmed by (1)H NMR. Moreover, complexation with Hcy and Cys disturbed the p-pi conjugation between the aldehyde group and the bpy moiety, and led to the excited states switching to [dpi(Ir)-pi(N(wedge)N)*] (3)MLCT and [pi(C(wedge)N)-pi(N(wedge)N)*] (3)LLCT from (pi-pi*)(pba(-)) (3)IL. Furthermore, the MTT assay was used to determine that the probe has low cytotoxicity. Importantly, cell imaging experiments demonstrated that the probe is membrane permeable and can monitor the changes of Hcy/Cys within living cells in a ratiometric mode. PMID:20565069

  6. Treatment outcome and toxicity of intensity-modulated (chemo radiotherapy in stage III non-small cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Govaert Stephanie LA

    2012-09-01

    Full Text Available Abstract Purpose The aim of this retrospective cohort study was to assess treatment outcome, and acute pulmonary and esophageal toxicity using intensity modulated (sequential/concurrent chemoradiotherapy (IMRT in locally advanced stage III non-small cell lung cancer (NSCLC. Methods and materials Eighty-six patients with advanced stage NSCLC, treated with either IMRT only (66 Gy or combined with (sequential or concurrent chemotherapy were retrospectively included in this study. Overall survival and metastasis-free survival were assessed as well as acute pulmonary and esophageal toxicity using the RTOG Acute Radiation Morbidity Scoring Criteria. Results Irrespective of the treatment modality, the overall survival rate for patients receiving 66 Gy was 71% (±11%; 95% CI after one year and 56% (±14% after two years resulting in a median overall survival of 29.7 months. Metastasis-free survival was 73% (±11% after both one and two years. There were no statistically significant differences between the treatment groups. Treatment related esophageal toxicity was significantly more pronounced in the concurrent chemoradiotherapy group (p = 0.013 with no differences in pulmonary toxicity. Conclusions This retrospective cohort study in advanced non-small cell lung cancer patients shows that IMRT is an effective technique with acceptable acute toxicity, also when (sequentially or concomitantly combined with chemotherapy.

  7. Treatment outcome and toxicity of intensity-modulated (chemo) radiotherapy in stage III non-small cell lung cancer patients

    International Nuclear Information System (INIS)

    The aim of this retrospective cohort study was to assess treatment outcome, and acute pulmonary and esophageal toxicity using intensity modulated (sequential/concurrent chemo)radiotherapy (IMRT) in locally advanced stage III non-small cell lung cancer (NSCLC). Eighty-six patients with advanced stage NSCLC, treated with either IMRT only (66 Gy) or combined with (sequential or concurrent) chemotherapy were retrospectively included in this study. Overall survival and metastasis-free survival were assessed as well as acute pulmonary and esophageal toxicity using the RTOG Acute Radiation Morbidity Scoring Criteria. Irrespective of the treatment modality, the overall survival rate for patients receiving 66 Gy was 71% (±11%; 95% CI) after one year and 56% (±14%) after two years resulting in a median overall survival of 29.7 months. Metastasis-free survival was 73% (±11%) after both one and two years. There were no statistically significant differences between the treatment groups. Treatment related esophageal toxicity was significantly more pronounced in the concurrent chemoradiotherapy group (p = 0.013) with no differences in pulmonary toxicity. This retrospective cohort study in advanced non-small cell lung cancer patients shows that IMRT is an effective technique with acceptable acute toxicity, also when (sequentially or concomitantly) combined with chemotherapy

  8. Role of laminin receptor in tumor cell migration

    DEFF Research Database (Denmark)

    Wewer, U M; Taraboletti, G; Sobel, M E;

    1987-01-01

    Polyclonal antisera were made against biochemically purified laminin receptor protein as well as against synthetic peptides deduced from a complementary DNA clone corresponding to the COOH-terminal end of the laminin receptor (U.M. Wewer et al., Proc. Natl. Acad. Sci. USA, 83: 7137-7141, 1986...... human carcinoma cells in vivo exhibited a marked cytoplasmic immunoreactivity for the receptor antigen. Together these findings indicate a specific role for the laminin receptor in laminin-mediated migration and that the ligand binding of the laminin receptor is encompassed in the COOH-terminal end of...

  9. Concomitant radio chemotherapy with cisplatin-etoposide in inoperable non small cells bronchial neoplasms stage III: toward an improvement of local control and of survive

    International Nuclear Information System (INIS)

    The addition of etoposide to cisplatin in the framework of a concomitant radio chemotherapy is susceptible to improve the local control of the non at small cells bronchial carcinomas with an improvement of survive until two years. Results with fifty patients stage III are described

  10. EGFRvIII deletion mutations in pediatric high-grade glioma and response to targeted therapy in pediatric glioma cell lines

    DEFF Research Database (Denmark)

    Bax, Dorine A; Gaspar, Nathalie; Little, Suzanne E;

    2009-01-01

    erlotinib despite expressing wild-type PTEN. Phosphorylated receptor tyrosine kinase profiling showed a specific activation of platelet-derived growth factor receptor alpha/beta in EGFRvIII-transduced pediatric glioblastoma cells, and targeted coinhibition with erlotinib and imatinib leads to enhanced...

  11. Apoptotic cell-based therapies against transplant rejection: role of recipient’s dendritic cells

    Science.gov (United States)

    Larregina, Adriana T.

    2010-01-01

    One of the ultimate goals in transplantation is to develop novel therapeutic methods for induction of donor-specific tolerance to reduce the side effects caused by the generalized immunosuppression associated to the currently used pharmacologic regimens. Interaction or phagocytosis of cells in early apoptosis exerts potent anti-inflammatory and immunosuppressive effects on antigen (Ag)-presenting cells (APC) like dendritic cells (DC) and macrophages. This observation led to the idea that apoptotic cell-based therapies could be employed to deliver donor-Ag in combination with regulatory signals to recipient’s APC as therapeutic approach to restrain the anti-donor response. This review describes the multiple mechanisms by which apoptotic cells down-modulate the immuno-stimulatory and pro-inflammatory functions of DC and macrophages, and the role of the interaction between apoptotic cells and APC in self-tolerance and in apoptotic cell-based therapies to prevent/treat allograft rejection and graft-versus-host disease in murine experimental systems and in humans. It also explores the role that in vivo-generated apoptotic cells could have in the beneficial effects of extracorporeal photopheresis, donor-specific transfusion, and tolerogenic DC-based therapies in transplantation. PMID:20140521

  12. Allergen recognition by innate immune cells: critical role of dendritic and epithelial cells.

    Science.gov (United States)

    Salazar, Fabián; Ghaemmaghami, Amir M

    2013-01-01

    Allergy is an exacerbated response of the immune system against non-self-proteins called allergens and is typically characterized by biased type-2 T helper cell and deleterious IgE mediated immune responses. The allergic cascade starts with the recognition of allergens by antigen presenting cells, mainly dendritic cells (DCs), leading to Th2 polarization, switching to IgE production by B cells, culminating in mast cell sensitization and triggering. DCs have been demonstrated to play a crucial role in orchestrating allergic diseases. Using different C-type lectin receptors DCs are able to recognize and internalize a number of allergens from diverse sources leading to sensitization. Furthermore, there is increasing evidence highlighting the role of epithelial cells in triggering and modulating immune responses to allergens. As well as providing a physical barrier, epithelial cells can interact with allergens and influence DCs behavior through the release of a number of Th2 promoting cytokines. In this review we will summarize current understanding of how allergens are recognized by DCs and epithelial cells and what are the consequences of such interaction in the context of allergic sensitization and downstream events leading to allergic inflammation. Better understanding of the molecular mechanisms of allergen recognition and associated signaling pathways could enable developing more effective therapeutic strategies that target the initial steps of allergic sensitization hence hindering development or progression of allergic diseases. PMID:24204367

  13. Functional role of regulatory T cells in B cell lymphoma and related mechanisms.

    Science.gov (United States)

    Wu, Wei; Wan, Jun; Xia, Ruixiang; Huang, Zhenqi; Ni, Jing; Yang, Mingzhen

    2015-01-01

    B cell lymphoma (BCL) has a higher degree of malignancy and complicated pathogenic mechanism. Regulatory T cells (Treg cells) are known to exert certain immune suppression functions, in addition to immune mediating effects. Recent studies have revealed the role of Treg cells in pathogenesis and progression of multiple malignant tumors. This study therefore investigated the functional role and related mechanism of Treg cells in BCL. A cohort of thirty patients who were diagnosed with BCL in our hospital between January 2013 and December 2014. Another thirty healthy individuals were recruited. Peripheral blood mononuclear cells (PBMCs) were separated and analyzed for the ratio of CD4+/CD25+ Treg cells. The mRNA expression levels of Foxp3, transforming growth factor (TGF)-β1 and interleukin (IL)-10 genes were quantified by real-time PCR, while their serum levels were determined by enzyme-linked immunosorbent assay (ELISA). Meanwhile all laboratory indexes for patients were monitored during the complete remission (CR) stage. BCL patients significantly elevated ratio of CD4+/CD25+ Treg cells, which were decreased at CR stage. mRNA levels of Foxp3, TGF-β1 and IL-10, in addition to protein levels of TGF-β1 and IL-10 were potentiated in lymphoma patients but decreased in CR patients (Pregulating cytokines, thereby facilitating the pathogenesis and progression of lymphoma. PMID:26464657

  14. Functional Role of Dendritic Cells in Patients with Unstable Angina

    Institute of Scientific and Technical Information of China (English)

    LI Dazhu; Sharma Ranjit; ZENG Qiutang

    2005-01-01

    To investigate the function of dendritic cells (DC) in patients with unstable angina, 10 mL of blood was drawn from 30 subjects. 15 patients diagnosed as having unstable angina and 15 healthy subjects were included in an observation and a control groups respectively. The mononuclear cells were separated from the peripheral blood and cultured in RPMI1640 supplemented with recombinant human granulocyte/macrophage-colony stimulating factor (rh GM-CSF) and recombinant human interleukin-4 (rh IL-4) to induce dendritic cells. The shape and ultrastructure of DC was examined with electronic microscope. The phenotype of DC was analyzed with FACS and the alloantigen presenting capacity of DC was evaluated by mixed lymphocyte reaction (MLR). The expression rate of CD86 of DC in patients with unstable angina was (40.7±3.6) %, which was obviously higher than that of normal DC (29.6±2.5 %) (P<0.001). The capacity of the DCs in unstable angina patients to induce allogenic T cells (OD 2.73±1.10), was significantly higher than that of the normal DC (OD:0.9±0.21) (P<0.005). It is suggested that the function of DC in patients with unstable angina is increased, which may play an important role in the initiation of immune reaction in the plaque.

  15. Neurorestorative Role of Stem Cells in Alzheimer's Disease: Astrocyte Involvement.

    Science.gov (United States)

    Choi, Sung S; Lee, Sang-Rae; Lee, Hong J

    2016-01-01

    Neurogenesis is maintained in both neonatal and adult brain, although it is dramatically reduced in aged neurogenic brain region such as the subgranular layer and subventricular zone of the dentate gyrus (DG). Astrocytes play important roles for survival and maintenance of neurons as well as maintenance of neurogenic niche in quiescent state. Aβ can induce astrocyte activation which give rise to produce reactive oxygen species (ROS) and cytotoxic cytokines and chemokines, and subsequently induce neuronal death. Unfortunately, the current therapeutic medicines have been limited to reduce the symptoms and delay the pathogenesis of Alzheimer's disease (AD), but not to cure it. Stem cells enhance neurogenesis and Aβ clearing as well as improved cognitive impairment. Neurotrophins and growth factors which are produced from both stem cells and astrocytes also have neuroprotective effects via neurogenesis. Secreted factors from both astrocytes and neural stem cells also are influenced in neurogenesis and neuron survival in neurodegenerative diseases. Transplanted stem cells overexpressing neurogenic factors may be an effective and therapeutic tool to enhance neurogenesis for AD. PMID:27018261

  16. RNase III mediated cleavage of the coding region of mraZ mRNA is required for efficient cell division in Corynebacterium glutamicum.

    Science.gov (United States)

    Maeda, Tomoya; Tanaka, Yuya; Takemoto, Norihiko; Hamamoto, Nagisa; Inui, Masayuki

    2016-03-01

    The Corynebacterium glutamicum R cgR_1959 gene encodes an endoribonuclease of the RNase III family. Deletion mutant of cgR_1959 (Δrnc mutant) showed an elongated cell shape, and presence of several lines on the cell surface, indicating a required of RNase III for maintaining normal cell morphology in C. glutamicum. The level of mraZ mRNA was increased, whereas cgR_1596 mRNA encoding a putative cell wall hydrolase and ftsEX mRNA were decreased in the Δrnc mutant. The half-life of mraZ mRNA was significantly prolonged in the Δrnc and the Δpnp mutant strains. This indicated that the degradation of mraZ mRNA was performed by RNase III and the 3'-to-5' exoribonuclease, PNPase. Northern hybridization and primer extension analysis revealed that the cleavage site for mraZ mRNA by RNase III is in the coding region. Overproduction of MraZ resulted in an elongated cell shape. The expression of ftsEX decreased while that of cgR_1596 unchanged in an MraZ-overexpressing strain. An electrophoretic mobility shift assay and a transcriptional reporter assay indicate that MraZ is a transcriptional repressor of ftsEX in C. glutamicum. These results indicate that RNase III is required for efficient expression of MraZ-dependent ftsEX and MraZ-independent cgR_1596. PMID:26713407

  17. Microimaging FT-IR of oral cavity tumours. Part III: Cells, inoculated tissues and human tissues

    Science.gov (United States)

    Conti, C.; Ferraris, P.; Giorgini, E.; Pieramici, T.; Possati, L.; Rocchetti, R.; Rubini, C.; Sabbatini, S.; Tosi, G.; Mariggiò, M. A.; Lo Muzio, L.

    2007-05-01

    The biochemistry of healthy and tumour cell cultures, inoculated tissues and oral cavity tissues have been studied by FT-IR Microscopy with the aim to relate spectral patterns with microbiological and histopathological findings. 'Supervised' and 'unsupervised' procedures of data handling afforded a satisfactory degree of accordance between spectroscopic and the other two techniques. In particular, changes in frequency and intensity of proteins, connective and nucleic acids vibrational modes as well as the visualization of biochemical single wave number or band ratio images, allowed an evaluation of the pathological changes. The spectroscopic patterns of inoculated tissues resulted quite similar to human tissues; differences of both types of sections with cellular lines could be explained by the influence of the environment.

  18. Role of NSO compounds during primary cracking of a Type II kerogen and a Type III lignite

    Science.gov (United States)

    Behar, F.; Lorant, F.; Lewan, M.

    2008-01-01

    The aim of this work is to follow the generation of NSO compounds during the artificial maturation of an immature Type II kerogen and a Type III lignite in order to determine the different sources of the petroleum potential during primary cracking. Experiments were carried out in closed system pyrolysis in the temperature range from 225 to 350 ??C. Two types of NSOs were recovered: one is soluble in n-pentane and the second in dichloromethane. A kinetic scheme was optimised including both kerogen and NSO cracking. It was validated by complementary experiments carried out on isolated asphaltenes generated from the Type II kerogen and on the total n-pentane and DCM extracts generated from the Type III lignite. Results show that kerogen and lignite first decompose into DCM NSOs with minor generation of hydrocarbons. Then, the main source of petroleum potential originates from secondary cracking of both DCM and n-pentane NSOs through successive decomposition reactions. These results confirm the model proposed by Tissot [Tissot, B., 1969. Premie??res donne??es sur les me??canismes et la cine??tique de la formation du pe??trole dans les bassins se??dimentaires. Simulation d'un sche??ma re??actionnel sur ordinateur. Oil and Gas Science and Technology 24, 470-501] in which the main source of hydrocarbons is not the insoluble organic matter, but the NSO fraction. As secondary cracking of the NSOs largely overlaps that of the kerogen, it was demonstrated that bulk kinetics in open system is a result of both kerogen and NSO cracking. Thus, another kinetic scheme for primary cracking in open system was built as a combination of kerogen and NSO cracking. This new kinetic scheme accounts for both the rate and amounts of hydrocarbons generated in a closed pyrolysis system. Thus, the concept of successive steps for hydrocarbon generation is valid for the two types of pyrolysis system and, for the first time, a common kinetic scheme is available for extrapolating results to natural

  19. Cell layer-specific distribution of transiently expressed barley ESCRT-III component HvVPS60 in developing barley endosperm.

    Science.gov (United States)

    Hilscher, Julia; Kapusi, Eszter; Stoger, Eva; Ibl, Verena

    2016-01-01

    The significance of the endosomal sorting complexes required for transport (ESCRT)-III in cereal endosperm has been shown by the identification of the recessive mutant supernumerary aleurone layer1 (SAL1) in maize. ESCRT-III is indispensable in the final membrane fission step during biogenesis of multivesicular bodies (MVBs), responsible for protein sorting to vacuoles and to the cell surface. Here, we annotated barley ESCRT-III members in the (model) crop Hordeum vulgare and show that all identified members are expressed in developing barley endosperm. We used fluorescently tagged core ESCRT-III members HvSNF7a/CHMP4 and HvVPS24/CHMP3 and the associated ESCRT-III component HvVPS60a/CHMP5 for transient localization studies in barley endosperm. In vivo confocal microscopic analyses show that the localization of recombinantly expressed HvSNF7a, HvVPS24 and HvVPS60a differs within barley endosperm. Whereas HvSNF7a induces large agglomerations, HvVPS24 shows mainly cytosolic localization in aleurone and subaleurone. In contrast, HvVPS60a localizes strongly at the plasma membrane in aleurone. In subaleurone, HvVPS60a was found to a lesser extent at the plasma membrane and at vacuolar membranes. These results indicate that the steady-state association of ESCRT-III may be influenced by cell layer-specific protein deposition or trafficking and remodelling of the endomembrane system in endosperm. We show that sorting of an artificially mono-ubiquitinated Arabidopsis plasma membrane protein is inhibited by HvVPS60a in aleurone. The involvement of HvVPS60a in different cell layer-specific trafficking pathways, reflected by localization of HvVPS60a at the plasma membrane in aleurone and at the PSV membrane in subaleurone, is discussed. PMID:25796522

  20. Cell wall-bound cationic and anionic class III isoperoxidases of pea root: biochemical characterization and function in root growth.

    Science.gov (United States)

    Kukavica, Biljana M; Veljovicc-Jovanovicc, Sonja D; Menckhoff, Ljiljana; Lüthje, Sabine

    2012-07-01

    Cell wall isolated from pea roots was used to separate and characterize two fractions possessing class III peroxidase activity: (i) ionically bound proteins and (ii) covalently bound proteins. Modified SDS-PAGE separated peroxidase isoforms by their apparent molecular weights: four bands of 56, 46, 44, and 41kDa were found in the ionically bound fraction (iPOD) and one band (70kDa) was resolved after treatment of the cell wall with cellulase and pectinase (cPOD). Isoelectric focusing (IEF) patterns for iPODs and cPODs were significantly different: five iPODs with highly cationic pI (9.5-9.2) were detected, whereas the nine cPODs were anionic with pI values between pH 3.7 and 5. iPODs and cPODs showed rather specific substrate affinity and different sensitivity to inhibitors, heat, and deglycosylation treatments. Peroxidase and oxidase activities and their IEF patterns for both fractions were determined in different zones along the root and in roots of different ages. New iPODs with pI 9.34 and 9.5 were induced with root growth, while the activity of cPODs was more related to the formation of the cell wall in non-elongating tissue. Treatment with auxin that inhibits root growth led to suppression of iPOD and induction of cPOD. A similar effect was obtained with the widely used elicitor, chitosan, which also induced cPODs with pI 5.3 and 5.7, which may be specifically related to pathogen defence. The differences reported here between biochemical properties of cPOD and iPOD and their differential induction during development and under specific treatments implicate that they are involved in specific and different physiological processes. PMID:22760472

  1. Role for protein geranylgeranylation in adult T-cell leukemia cell survival

    International Nuclear Information System (INIS)

    Adult T-cell leukemia (ATL) is a fatal lymphoproliferative disease that develops in human T-cell leukemia virus type I (HTLV-I)-infected individuals. Despite the accumulating knowledge of the molecular biology of HTLV-I-infected cells, effective therapeutic strategies remain to be established. Recent reports showed that the hydroxyl-3-methylglutaryl (HMG)-CoA reductase inhibitor statins have anti-proliferative and apoptotic effects on certain tumor cells through inhibition of protein prenylation. Here, we report that statins hinder the survival of ATL cells and induce apoptotic cell death. Inhibition of protein geranylgeranylation is responsible for these effects, since simultaneous treatment with isoprenoid precursors, geranylgeranyl pyrophosphate or farnesyl pyrophosphate, but not a cholesterol precursor squalene, restored the viability of ATL cells. Simvastatin inhibited geranylgeranylation of small GTPases Rab5B and Rac1 in ATL cells, and a geranylgeranyl transferase inhibitor GGTI-298 reduced ATL cell viability more efficiently than a farnesyl transferase inhibitor FTI-277. These results not only unveil an important role for protein geranylgeranylation in ATL cell survival, but also implicate therapeutic potentials of statins in the treatment of ATL

  2. The role of mismatch repair in small-cell lung cancer cells

    DEFF Research Database (Denmark)

    Hansen, L T; Thykjaer, T; Ørntoft, T F; Rasmussen, L J; Keller, P; Spang-Thomsen, M; Edmonston, T Bocker; Schmutte, C; Fishel, R; Petersen, L Nørgård

    2003-01-01

    The role of mismatch repair (MMR) in small-cell lung cancer (SCLC) is controversial, as the phenotype of a MMR-deficiency, microsatellite instability (MSI), has been reported to range from 0 to 76%. We studied the MMR pathway in a panel of 21 SCLC cell lines and observed a highly heterogeneous...... pattern of MMR gene expression. A significant correlation between the mRNA and protein levels was found. We demonstrate that low hMLH1 gene expression was not linked to promoter CpG methylation. One cell line (86MI) was found to be deficient in MMR and exhibited resistance to the alkylating agent MNNG...

  3. The Role of Mesenchymal Stem Cell in Cancer Development

    Directory of Open Access Journals (Sweden)

    Hiroshi eYagi

    2013-11-01

    Full Text Available The role of mesenchymal stem cells (MSCs in cancer development is still controversial. MSCs may promote tumor progression through immune modulation, but other tumor suppressive effects of MSCs have also been described. The discrepancy between these results may arise from issues related to different tissue sources, individual donor variability, and injection timing of MSCs. The expression of critical receptors such as Toll-like receptor (TLR is variable at each time point of treatment, which may also determine the effects of MSCs on tumor progression. However, factors released from malignant cells, as well as surrounding tissues and the vasculature, are still regarded as a black box. Thus, it is still difficult to clarify the specific role of MSCs in cancer development. Whether MSCs support or suppress tumor progression is currently unclear, but it is clear that systemically administered MSCs can be recruited and migrate toward tumors. These findings are important because they can be used as a basis for initiating studies to explore the incorporation of engineered MSCs as novel anti-tumor carriers, for the development of tumor-targeted therapies.

  4. Role of Cell-Cell bond for the viability and the function of vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    M. Mura

    2010-01-01

    Full Text Available Vascular smooth muscle cell (VSMC viability and homeostasis is regulated by cell-matrix and cell-cell contact: disruption of these interactions are responsible of a switch from a mature to a high proliferative phenotype. VSMCs migration, rate of growth and apoptosis, and the extent of their extracellular matrix (ECM deposition can be also modulated by proatherogenic peptides. Among them, ATII induces the transactivation of IGF I R, which, together with the binding protein IGFBP3, represents a determinant of cell survival, growth and proliferation. Aim of our in vitro study was to verify the role of elective cell-cell bond in moulating the response to ATII. Thus, we evaluated viability, proliferation, IGFIR, IGFBP3 expression and the long term survival and production of ECM in a provisional tissue. A7r5 cell-line was used in adherent cultures or incubated in agarose-coated culture plates to inhibit cell-matrix interactions. Cells, treated or not with ATII 100 nM, were evaluated for apoptosis rate, cell cycle, IGFIR and IGFBP3 protei expression. Fibrin provisional tissue was developed polymerizing a fibrin solution. cantaining A7r5 cells with thrombin. Histological stainings for ECM components were performed on sections of prvisional tissue. An exclusive cell-cell contact resulted to monolayer cell cultures. ATII did not affect the cell survival in both culture conditions, but promoted a 10% decrease in "S" phase and an increases IGFIR expression only in adherent cells. while suspended cell aggregates were resistant to ATII administration; IGFBP3 was reduced both in ATII treated adherent cells and in floating clustered cells, irrespective of the treatmentn. VSMC conditioning in agarose-coated plates before seeding in fibrin provisional matrix reduced, but not abolished, the cell ability to colonize the clot and to produce ECM. This study demonstrates that the elective cell-cell contact induces a quiescent status in cells lacking of cell

  5. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Scagliotti, G.V.; Parikh, P.; Pawel, J. von;

    2008-01-01

    Purpose Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. Patients and Methods This noninferiority, phase III, randomized study...... neutropenia (P = .002); and alopecia (P common. Conclusion In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin....../gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type Udgivelsesdato: 2008/7/20...

  6. Role of CD40 ligation in dendritic cell semimaturation

    Directory of Open Access Journals (Sweden)

    Gerlach Anna-Maria

    2012-04-01

    Full Text Available Abstract Background DC are among the first antigen presenting cells encountering bacteria at mucosal surfaces, and play an important role in maintenance of regular homeostasis in the intestine. Upon stimulation DC undergo activation and maturation and as initiators of T cell responses they have the capacity to stimulate naïve T cells. However, stimulation of naïve murine DC with B. vulgatus or LPS at low concentration drives DC to a semimature (sm state with low surface expression of activation-markers and a reduced capacity to activate T-cells. Additionally, semimature DC are nonresponsive to subsequent TLR stimulation in terms of maturation, TNF-α but not IL-6 production. Ligation of CD40 is an important mechanism in enhancing DC maturation, function and capacity to activate T-cells. We investigated whether the DC semimaturation can be overcome by CD40 ligation. Results Upon CD40 ligation smDC secreted IL-12p40 but not the bioactive heterodimer IL-12p70. Additionally, CD40 ligation of smDC resulted in an increased production of IL-6 but not in an increased expression of CD40. Analysis of the phosphorylation pattern of MAP kinases showed that in smDC the p38 phosphorylation induced by CD40 ligation is inhibited. In contrast, phosphorylation of ERK upon CD40 ligation was independent of the DC maturation state. Conclusion Our data show that the semimature differentiation state of DC can not be overcome by CD40 ligation. We suggest that the inability of CD40 ligation in overcoming DC semimaturation might contribute to the tolerogenic phenotype of semimature DC and at least partially account for maintenance of intestinal immune homeostasis.

  7. Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells

    International Nuclear Information System (INIS)

    Notch signaling has been implicated in the regulation of cell-fate decisions such as self-renewal of adult stem cells and differentiation of progenitor cells along a particular lineage. Moreover, depending on the cellular and developmental context, the Notch pathway acts as a regulator of cell survival and cell proliferation. Abnormal expression of Notch receptors has been found in different types of epithelial metaplastic lesions and neoplastic lesions, suggesting that Notch may act as a proto-oncogene. The vertebrate Notch1 and Notch4 homologs are involved in normal development of the mammary gland, and mutated forms of these genes are associated with development of mouse mammary tumors. In order to determine the role of Notch signaling in mammary cell-fate determination, we have utilized a newly described in vitro system in which mammary stem/progenitor cells can be cultured in suspension as nonadherent 'mammospheres'. Notch signaling was activated using exogenous ligands, or was inhibited using previously characterized Notch signaling antagonists. Utilizing this system, we demonstrate that Notch signaling can act on mammary stem cells to promote self-renewal and on early progenitor cells to promote their proliferation, as demonstrated by a 10-fold increase in secondary mammosphere formation upon addition of a Notch-activating DSL peptide. In addition to acting on stem cells, Notch signaling is also able to act on multipotent progenitor cells, facilitating myoepithelial lineage-specific commitment and proliferation. Stimulation of this pathway also promotes branching morphogenesis in three-dimensional Matrigel cultures. These effects are completely inhibited by a Notch4 blocking antibody or a gamma secretase inhibitor that blocks Notch processing. In contrast to the effects of Notch signaling on mammary stem/progenitor cells, modulation of this pathway has no discernable effect on fully committed, differentiated, mammary epithelial cells. These studies

  8. [Photodynamic therapy in combined treatment of stage III non-small cell lung carcinoma].

    Science.gov (United States)

    Akopov, A L; Rusanov, A A; Molodtsova, V P; Chistiakov, I V; Kazakov, N V; Urtenova, M A; Rait, Makhmud; Papaian, G V

    2013-01-01

    The aim of the study was to evaluate the effectiveness of combined treatment of locally advanced lung cancer with the use of neoadjuvant chemotherapy and surgery with the use of pre- and intraoperative photodynamic therapy. 20 patients with IIIa (n=7) and IIIb (n=13) stage of non-small cell lung carcinoma were included. At the time of diagnosis the surgical treatment was decided to abstain because of the trachea invasion in 9 patients, wide mediastinal invasion in 2 patients and contralateral mediastinal lymph nodes metastases in 2 patients; pneumonectomy was not possible due to the poor respiratory function in 7 patients. Neoadjuvant therapy included 3 courses of chemotherapy and endobronchial photodynamic therapy. During the operation, along with the lung resection (pneumonectomy - 15, lobectomy - 5), photodynamic therapy of the resection margins were carried out. No adjuvant treatment was done. Preoperative treatment led to partial regress of the disease in all cases; the goal of surgery was the complete tumor removal. No complications of the photodynamic therapy were observed. 18 surgical interventions were radical and two non-complete microscopically (R1). Postoperative morbidity was 20%, one patient died due to massive gastrointestinal bleeding. The average follow-up period was 18 months: 19 patients were alive, of them 18 with no signs of the disease recurrence. The first experience of the combined use of neoadjuvant chemotherapy and surgery with pre- and intraoperative photodynamic therapy demonstrates safety and efficacy of the suggested treatment tactics. PMID:23612332

  9. Sequential chemoradiotherapy for stage I/II nasal natural killer/T cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Young Joo [Ulsan University Hospital, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Ahn, Yong Chan; Kim, Won Seog; Ko, Young Hyeh [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2004-09-15

    Authors would report the results of sequential CHOP chemotherapy (cyclophosphamide, adriamycin, vincristine, and prednisone) and involved field radiotherapy (IFRT) for early stage nasal natural killer/T-cell lymphoma (NKTCL). Fourteen among 17 patients, who were registered at the Samsung Medical Center tumor registry with stage I and II nasal NKTCL from March 1995 to December 1999 received this treatment protocol. Three to four cycles of CHOP chemotherapy were given at 3 weeks' interval, which was followed by local IFRT including the known tumor extent and the adjacent draining lymphatics. Favorable responses after chemotherapy (before IFRT) were achievable only in seven patients (5 CR's + 2 PR's: 50%), while seven patients showed disease progression. There were six patients with local failures, two with distant relapses, and none with regional lymphatic failure. The actuarial overall survival and progression-free survival at 3 years were 50.0% and 42.9%. All the failures and deaths occurred within 13 months of the treatment start. The factors that correlated with the improved survival were the absence of 'B' symptoms, the favorable response to chemotherapy and overall treatment, and the low risk by international prognostic index on univariate analyses. Compared with the historic treatment results by IFRT either alone or followed by chemotherapy, the current trial failed to demonstrate advantages with respect to the failure pattern and survival. Development of new treatment strategy in combining IFRT and chemotherapy is required for improving outcomes.

  10. 25 Role of Myeloid Derived Suppressor Cells in Asthma

    OpenAIRE

    Nelson, Allison; Parkerson, Jim; Lockey, Richard F.; Mohapatra, Subhra; Mohapatra, Shyam; Nagaraj, Srinivas

    2012-01-01

    Background We know that a heterogeneous group of myeloid cells termed myeloid derived suppressor cells (MDSC) accumulate in almost all pathological conditions, which elicit an inflammatory signal. The exact role played by these cells in asthma is not known. In this study we investigated the function and role of these cells in asthma. Methods Accumulation of MDSC and other subsets of myeloid cells were analyzed from peripheral blood mononuclear cells from patients with non-severe asthma (FEV1)...

  11. Role of microbial Fe(III) reduction and solution chemistry in aggregation and settling of suspended particles in the Mississippi River Delta plain, Louisiana, USA

    Science.gov (United States)

    Jaisi, D.P.; Ji, S.; Dong, H.; Blake, R.E.; Eberl, D.D.; Kim, J.

    2008-01-01

    River-dominated delta areas are primary sites of active biogeochemical cycling, with productivity enhanced by terrestrial inputs of nutrients. Particle aggregation in these areas primarily controls the deposition of suspended particles, yet factors that control particle aggregation and resulting sedimentation in these environments are poorly understood. This study was designed to investigate the role of microbial Fe(III) reduction and solution chemistry in aggregation of suspended particles in the Mississippi Delta. Three representative sites along the salinity gradient were selected and sediments were collected from the sediment-water interface. Based on quantitative mineralogical analyses 88-89 wt.% of all minerals in the sediments are clays, mainly smectite and illite. Consumption of SO421 and the formation of H2S and pyrite during microbial Fe(III) reduction of the non-sterile sediments by Shewanella putrefaciens CN32 in artificial pore water (APW) media suggest simultaneous sulfate and Fe(III) reduction activity. The pHPZNPC of the sediments was ??? 3.5 and their zeta potentials at the sediment-water interface pH (6.9-7.3) varied from -35 to -45 mV, suggesting that both edges and faces of clay particles have negative surface charge. Therefore, high concentrations of cations in pore water are expected to be a predominant factor in particle aggregation consistent with the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Experiments on aggregation of different types of sediments in the same APW composition revealed that the sediment with low zeta potential had a high rate of aggregation. Similarly, addition of external Fe(II) (i.e. not derived from sediments) was normally found to enhance particle aggregation and deposition in all sediments, probably resulting from a decrease in surface potential of particles due to specific Fe(II) sorption. Scanning and transmission electron microscopy (SEM, TEM) images showed predominant face-to-face clay aggregation in native

  12. Collective motion of cells crawling on a substrate: roles of cell shape and contact inhibition

    CERN Document Server

    Schnyder, Simon Kaspar; Molina, John Jairo; Yamamoto, Ryoichi

    2016-01-01

    Contact inhibition plays a crucial role in the motility of cells, the process of wound healing, and the formation of tumors. By mimicking the mechanical motion of calls crawling on a substrate using a pseudopod, we constructed a minimal model for migrating cells which gives rise to contact inhibition of locomotion (CIL) naturally. The model cell consists of two disks, one in the front (a pseudopod) and the other one in the back (cell body), connected by a finitely extensible spring. Despite the simplicity of the model, the cells' collective behavior is highly nontrivial, depending on the shape of cells and whether CIL is enabled or not. Cells with a small front circle (i.e. a narrow pseudopod) form immobile colonies. In contrast, cells with a large front circle (i.e. such as a lamellipodium) exhibit coherent migration without any explicit alignment mechanism being present in the model. This suggests that crawling cells often exhibit broad fronts because it helps them avoid clustering. Upon increasing the dens...

  13. Emerging role of SOX11 in mantle cell lymphoma

    Directory of Open Access Journals (Sweden)

    Kuci V

    2015-02-01

    Full Text Available Venera Kuci,1,2,* Lena Nordström,1,2,* Mats Jerkeman,3 Sara Ek1,2 1Department of Immunotechnology, Lund University, Lund, Sweden; 2CREATE Health, Lund University, Lund, Sweden; 3Department of Oncology, Lund University, Lund, Sweden *These authors contributed equally to this work Abstract: During recent years the neural transcription factor SOX11 has been established as an important biomarker for mantle cell lymphoma. SOX11 is both a diagnostic and prognostic antigen, and may potentially be used for treatment selection for younger patients, in relation to protocols including high dose chemotherapy. The molecular pathways involved are still not fully elucidated and, as SOX11 can interact with several co-transcription factors, functional assays need to be carefully designed to pinpoint SOX11-specific function in a defined cellular context. Furthermore, as SOX11 belongs to a large family of homologous proteins, analysis of SOX11 has been limited by the availability of specific antibodies for detection and pull-down. In this review, we discuss the emerging role of SOX11 in mantle cell lymphoma and discuss the potential impact in relation to tumorigenesis, diagnostics, prognostics, and therapy. Keywords: SOX11, mantle cell lymphoma, diagnostic

  14. Roles of host cell factors in circularization of retroviral DNA

    International Nuclear Information System (INIS)

    Early during retroviral infection, a fraction of the linear reverse-transcribed viral DNA genomes become circularized by cellular enzymes, thereby inactivating the genomes for further replication. Prominent circular DNA forms include 2-long-terminal repeat (LTR) circles, made by DNA end joining, and 1-LTR circles, produced in part by homologous recombination. These reactions provide a convenient paradigm for analyzing the cellular machinery involved in DNA end joining in vertebrate cells. In previous studies, we found that inactivating components of the nonhomologous DNA end-joining (NHEJ) pathway--specifically Ku, ligase 4, or XRCC4--blocked formation of 2-LTR circles. Here we report that inactivating another NHEJ component, the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), had at most modest effects on 2-LTR circle formation, providing informative parallels with other end-joining reactions. We also analyzed cells mutant in components of the RAD50/MRE11/NBS1 nuclease and found a decrease in the relative amount of 1-LTR circles, opposite to the effects of NHEJ mutants. In MRE11-mutant cells, a MRE11 gene mutant in the nuclease catalytic site failed to restore 1-LTR circle formation, supporting a model for the role of MRE11 in 1-LTR circle formation. None of the cellular mutations showed a strong effect on normal integration, consistent with the idea that the cellular pathways leading to circularization are not involved in productive integration

  15. The role of mast cells in functional GI disorders.

    Science.gov (United States)

    Wouters, Mira M; Vicario, Maria; Santos, Javier

    2016-01-01

    Functional gastrointestinal disorders (FGIDs) are characterized by chronic complaints arising from disorganized brain-gut interactions leading to dysmotility and hypersensitivity. The two most prevalent FGIDs, affecting up to 16-26% of worldwide population, are functional dyspepsia and irritable bowel syndrome. Their etiopathogenic mechanisms remain unclear, however, recent observations reveal low-grade mucosal inflammation and immune activation, in association with impaired epithelial barrier function and aberrant neuronal sensitivity. These findings come to challenge the traditional view of FGIDs as pure functional disorders, and relate the origin to a tangible organic substrate. The mucosal inflammatory infiltrate is dominated by mast cells, eosinophils and intraepithelial lymphocytes in the intestine of FGIDs. It is well established that mast cell activation can generate epithelial and neuro-muscular dysfunction and promote visceral hypersensitivity and altered motility patterns in FGIDs, postoperative ileus, food allergy and inflammatory bowel disease. This review will discuss the role of mucosal mast cells in the gastrointestinal tract with a specific focus on recent advances in disease mechanisms and clinical management in irritable bowel syndrome and functional dyspepsia. PMID:26194403

  16. Role of nuclear receptors in breast cancer stem cells

    Science.gov (United States)

    Papi, Alessio; Orlandi, Marina

    2016-01-01

    The recapitulation of primary tumour heterogenity and the existence of a minor sub-population of cancer cells, capable of initiating tumour growth in xenografts on serial passages, led to the hypothesis that cancer stem cells (CSCs) exist. CSCs are present in many tumours, among which is breast cancer. Breast CSCs (BCSCs) are likely to sustain the growth of the primary tumour mass, as well as to be responsible for disease relapse and metastatic spreading. Consequently, BCSCs represent the most significant target for new drugs in breast cancer therapy. Both the hypoxic condition in BCSCs biology and pro-inflammatory cytokine network has gained increasing importance in the recent past. Breast stromal cells are crucial components of the tumours milieu and are a major source of inflammatory mediators. Recently, the anti-inflammatory role of some nuclear receptors ligands has emerged in several diseases, including breast cancer. Therefore, the use of nuclear receptors ligands may be a valid strategy to inhibit BCSCs viability and consequently breast cancer growth and disease relapse. PMID:27022437

  17. Roles of regulatory T cells in cancer immunity.

    Science.gov (United States)

    Takeuchi, Yoshiko; Nishikawa, Hiroyoshi

    2016-08-01

    CD4(+) regulatory T cells (Tregs) expressing the transcription factor FoxP3 are highly immune suppressive and play central roles in the maintenance of self-tolerance and immune homeostasis, yet in malignant tumors they promote tumor progression by suppressing effective antitumor immunity. Indeed, higher infiltration by Tregs is observed in tumor tissues, and their depletion augments antitumor immune responses in animal models. Additionally, increased numbers of Tregs and, in particular, decreased ratios of CD8(+) T cells to Tregs among tumor-infiltrating lymphocytes are correlated with poor prognosis in various types of human cancers. The recent success of cancer immunotherapy represented by immune checkpoint blockade has provided a new insight in cancer treatment, yet more than half of the treated patients did not experience clinical benefits. Identifying biomarkers that predict clinical responses and developing novel immunotherapies are therefore urgently required. Cancer patients whose tumors contain a large number of neoantigens stemming from gene mutations, which have not been previously recognized by the immune system, provoke strong antitumor T-cell responses associated with clinical responses following immune checkpoint blockade, depending on the resistance to Treg-mediated suppression. Thus, integration of a strategy restricting Treg-mediated immune suppression may expand the therapeutic spectrum of cancer immunotherapy towards patients with a lower number of neoantigens. In this review, we address the current understanding of Treg-mediated immune suppressive mechanisms in cancer, the involvement of Tregs in cancer immunotherapy, and strategies for effective and tolerable Treg-targeted therapy. PMID:27160722

  18. Fusion Power Demonstration III

    International Nuclear Information System (INIS)

    This is the third in the series of reports covering the Fusion Power Demonstration (FPD) design study. This volume considers the FPD-III configuration that incorporates an octopole end plug. As compared with the quadrupole end-plugged designs of FPD-I and FPD-II, this octopole configuration reduces the number of end cell magnets and shortens the minimum ignition length of the central cell. The end-cell plasma length is also reduced, which in turn reduces the size and cost of the end cell magnets and shielding. As a contiuation in the series of documents covering the FPD, this report does not stand alone as a design description of FPD-III. Design details of FPD-III subsystems that do not differ significantly from those of the FPD-II configuration are not duplicated in this report

  19. The history of NATO TNF policy: The role of studies, analysis and exercises conference proceedings. Volume 3: Papers by Gen. Robert C. Richardson III (Ret.)

    Energy Technology Data Exchange (ETDEWEB)

    Rinne, R.L. [ed.

    1994-02-01

    This conference was organized to study and analyze the role of simulation, analysis, modeling, and exercises in the history of NATO policy. The premise was not that the results of past studies will apply to future policy, but rather that understanding what influenced the decision process-and how-would be of value. The structure of the conference was built around discussion panels. The panels were augmented by a series of papers and presentations focusing on particular TNF events, issues, studies, or exercises. The conference proceedings consist of three volumes. Volume 1 contains the conference introduction, agenda, biographical sketches of principal participants, and analytical summary of the presentations and discussion panels. Volume 2 contains a short introduction and the papers and presentations from the conference. This volume contains selected papers by Brig. Gen. Robert C. Richardson III (Ret.).

  20. Adhesion of different cell cycle human hepatoma cells to endothelial cells and roles of integrin β1

    Institute of Scientific and Technical Information of China (English)

    Guan-Bin Song; Jian Qin; Qing Luo; Xiao-Dong Shen; Run-Bin Yan; Shao-Xi Cai

    2005-01-01

    AIM: To investigate the adhesive mechanical properties of different cell cycle human hepatoma cells (SMMC-7721)to human umbilical vein endothelial cells (ECV-304),expression of adhesive molecule integrinβ1 in SMMC-7721cells and its contribution to this adhesive course.METHODS: Adhesive force of SMMC-7721 cells to endothelialcells was measured using micropipette aspiration technique.Synchronous G1 and S phase SMMC-7721 cells wereachieved by thymine-2-deoxyriboside and colchicinessequential blockage method and double thymine-2-deoxyriboside blockage method, respectively. Synchronousrates of SMMC-7721 cells and expression of integrinβ1 inSMMC-7721 cells were detected by flow cytometer.RESULTS: The percentage of cell cycle phases of generalSMMC-7721 cells was 11.01% in G2/M phases, 53.51% inG0/G1 phase, and 35.48% in S phase. The synchronous ratesof G1 and S phase SMMC-7721 cells amounted to 74.09%and 98.29%, respectively. The adhesive force of SMMC-7721cells to endothelial cells changed with the variations ofadhesive time and presented behavior characteristics ofadhesion and de-adhesion. S phase SMMC-7721 cells had higheradhesive forces than G1 phase cells [(307.65±92.10)× 10-10Nvs (195.42±60.72)×10-10N, P<0.01]. The expressivefluorescent intensity of integrinβ1 in G1 phase SMMC-7721cells was depressed more significantly than the values ofS phase and general SMMC-7721cells. The contribution ofadhesive integrinβ1 was about 53% in this adhesive course.CONCLUSION: SMMC-7721 cells can be synchronizedpreferably in G1 and S phases with thymine-2-deoxyribosideand colchicines. The adhesive molecule integrinβ1 expressesa high level in SMMC-7721 cells and shows differences invarious cell cycles, suggesting integrin β1 plays an importantrole in adhesion to endothelial cells. The change of adhesiveforces in different cell cycle SMMC-7721 cells indicatesthat S phase cells play predominant roles possibly whilethey interact with endothelial cells.

  1. Type III methyltransferase M.NgoAX from Neisseria gonorrhoeae FA1090 regulates biofilm formation and human cell invasion

    Directory of Open Access Journals (Sweden)

    Agnieszka eKwiatek

    2015-12-01

    Full Text Available Neisseria gonorrhoeae is the etiological factor of the sexually transmitted gonorrhea disease that may lead, under specific conditions, to systemic infections. The gonococcal genome encodes many Restriction Modification (RM systems, which main biological role is to defend the pathogen from potentially harmful foreign DNA. However, RM systems seem also to be involved in several other functions. In this study, we examined the effect of inactivation the N. gonorrhoeae FA1090 ngo0545 gene encoding M.NgoAX methyltransferase on the global gene expression, biofilm formation, interactions with human epithelial host cells and overall bacterial growth. Expression microarrays showed at least a two-fold deregulation of a total of 121 genes in the NgoAX knock-out mutant compared to the wt strain under standard grow conditions. As determined by the assay with crystal violet, the NgoAX knock-out strain formed a slightly larger biofilm biomass per cell than the wt strain (OD570/600 = 13.8  2.24 and 9.35  2.06, respectively. SCLM observations showed that the biofilm formed by the gonococcal ngo0545 gene mutant is more relaxed and dispersed than the one formed by the wt strain. Thickness of the biofilm formed by both strains was 48.3 (14.9 µm for the mutant and 28.6 (4.0 µm for the wt. This more relaxed feature of the biofilm in respect to adhesion and bacterial interactions seems advantageous for pathogenesis of the NgoAX-deficient gonococci at the stage of human epithelial cell invasion. Indeed, the overall adhesion of mutant bacterial cells to human cells was lower than adhesion of the wt gonococci (adhesion index = 0.672 ( 0.2 and 2.15 ( 1.53, respectively; yet, a higher number of mutant than wt bacteria were found inside the Hec-1-B epithelial cells (invasion index = 3.38 ( 0.93  105 for mutant and 4.67 ( 3.09  104 for the wt strain. These results indicate that NgoAX-deficient cells have lower ability to attach to human cells

  2. Determination of the flows profile in the role of power in the central thimble of TRIGA Mark III Reactor

    International Nuclear Information System (INIS)

    The overall objective of the thesis project is to determine the flow profiles sub cadmic and epi cadmic in the central thimble to different powers and operation times of TRIGA Mark III Reactor, using activation foils as detectors. In the reactor operation, it is necessary to know the neutron flow profile for to realize other tasks as: the radioisotopes production, research in reactors physics and fuel burning. The distribution of the neutron flow, accurately reflects what is happening in the reactor core, plus the flows value in this distribution is directly related to the power generated. For this reason it is performed the sub cadmic flow measurement with energies between 0 and 0.4 eV (energy of the cadmium cut Ecd ∼ 0.4 eV) and epi cadmic flow with energies greater than 0.4 eV, in the central thimble powers to the powers of 10, 100 W, 1, 10 100 Kw and 1 MW. The method used is known as flakes activation, which is to be arranged by placing flakes ( 3 mm of diameter and 0.0508 mm of thickness) of a given material (either Au, In, Cu, Mn, etc.) into an aluminum tube outside diameter equal to 6.35 mm, alternating flakes with lids covered and discovered of cadmium (3.4 mm of diameter and 0.508 mm of thickness) and separated by lucite pieces of 3 mm of diameter and 25.4 mm in length. After irradiating the flakes for some time, is measured the gamma activity of each of them, using a hyper pure germanium detector of high resolution. Already known gamma activity, proceed to calculate the epi cadmic and sub cadmic flows using a computer program in Fortran language, called Caflu. (Author)

  3. Gender difference in treatment outcomes in patients with stage III non-small cell lung cancer receiving concurrent chemoradiotherapy

    International Nuclear Information System (INIS)

    The objective of this study was to identify any gender differences in the outcomes of concurrent platinum-based chemotherapy and thoracic radiotherapy for unresectable stage III non-small cell lung cancer (NSCLC). A comparative retrospective review of the clinical characteristics and treatment outcomes between female and male NSCLC patients receiving chemoradiotherapy. Of a total of 204 patients, 44 (22%) were females and 160 (78%) were males. There was no difference in age, body weight loss, performance status or disease stage between the sexes, whereas never-smokers and adenocarcinoma were more common in female patients (55% vs. 3%, P80% of the patients, respectively, of both sexes. Grade 3-4 neutropenia was observed in 64% of the female patients and 63% of the male patients. Severe esophagitis was encountered in <10% of the patients, irrespective of the sex. The response rate was higher in the female than in the male patients (93% vs. 79%, P=0.028), but the median progression-free survival did not differ between the sexes. The median survival time in the female and male patients was 22.3 and 24.3 months, respectively (P=0.64). This study failed to show any gender differences in the survival or toxicity among patients treated by concurrent chemoradiotherapy. These results contrast with the better survival in female patients undergoing surgery for localized disease or chemotherapy for metastatic disease. (author)

  4. Role of Th9 cells and Th17 cells in the pathogenesis of malignant ascites

    Institute of Scientific and Technical Information of China (English)

    Xian-Wen Yang; Hai-Xing Jiang; Xiao-Li Huang; Shi-Jia Ma; Shan-Yu Qin

    2015-01-01

    Objective:To assess the role of Th9 and Th17 cells in malignant ascites (MA). Methods: MA from 30 hepatic carcinoma patients and benign ascites from 30 cirrhotic patients were collected. Corresponding peripheral blood samples from these hepatic carcinoma and cirrhotic patients as well as 30 healthy subjects were collected. The frequency of Th9 and Th17 cells was tested by flow cytometry. Serum levels of interleukin (IL)-9 and IL-17 were examined byELISA. Results: The observed frequency of Th9 and Th17 cells, and the IL-9 and IL-17 serum levels were significantly higher in MA patients than those in cirrhotic patients and healthy control samples (P Conclusions:The increased frequency of Th9 and Th17 cells in MA patients suggests that these two T cell subsets play a synergistic role in MA pathogenesis. This study also demonstrated that Th9 and Th17 cells may perform their biological functions in conjunction with IL-9 production.

  5. Syntrophin proteins as Santa Claus: role(s) in cell signal transduction.

    Science.gov (United States)

    Bhat, Hina F; Adams, Marvin E; Khanday, Firdous A

    2013-07-01

    Syntrophins are a family of cytoplasmic membrane-associated adaptor proteins, characterized by the presence of a unique domain organization comprised of a C-terminal syntrophin unique (SU) domain and an N-terminal pleckstrin homology (PH) domain that is split by insertion of a PDZ domain. Syntrophins have been recognized as an important component of many signaling events, and they seem to function more like the cell's own personal 'Santa Claus' that serves to 'gift' various signaling complexes with precise proteins that they 'wish for', and at the same time care enough for the spatial, temporal control of these signaling events, maintaining overall smooth functioning and general happiness of the cell. Syntrophins not only associate various ion channels and signaling proteins to the dystrophin-associated protein complex (DAPC), via a direct interaction with dystrophin protein but also serve as a link between the extracellular matrix and the intracellular downstream targets and cell cytoskeleton by interacting with F-actin. They play an important role in regulating the postsynaptic signal transduction, sarcolemmal localization of nNOS, EphA4 signaling at the neuromuscular junction, and G-protein mediated signaling. In our previous work, we reported a differential expression pattern of alpha-1-syntrophin (SNTA1) protein in esophageal and breast carcinomas. Implicated in several other pathologies, like cardiac dys-functioning, muscular dystrophies, diabetes, etc., these proteins provide a lot of scope for further studies. The present review focuses on the role of syntrophins in membrane targeting and regulation of cellular proteins, while highlighting their relevance in possible development and/or progression of pathologies including cancer which we have recently demonstrated. PMID:23263165

  6. Activation of cord T lymphocytes. III. Role of LFA-1/ICAM-1 and CD2/LFA-3 adhesion molecules in CD3-induced proliferative response.

    Science.gov (United States)

    Gerli, R; Agea, E; Muscat, C; Tognellini, R; Fiorucci, G; Spinozzi, F; Cernetti, C; Bertotto, A

    1993-04-15

    As cord T cells, a model of antigen (Ag)-unprimed cell, display a functional defect when stimulated through the CD3 molecule, the role of lymphocyte function-associated antigen 1(LFA-1)/intercellular adhesion molecule 1 (ICAM-1) and CD2/lymphocyte function-associated antigen 3 (LFA-3) receptor-ligand pairs in cord CD3-triggered T-cell activation was analyzed using specific monoclonal antibodies (mAb) against each adhesion molecule. The addition of anti-CD11a, anti-CD18, or anti-CD2 to both adult and cord peripheral blood mononuclear cells (PBMC) cultures led to a decrease in CD3-induced proliferation. In contrast, CD3-stimulated cord, but not adult, PBMC proliferation was markedly enhanced when anti-CD54 or anti-CD58 were added. Despite the fact that ICAM-1 and LFA-3 molecules were virtually absent on cord resting T cells, mAb against these two molecules boosted both mitogenesis of and interleukin (IL)-2 production by purified cord T cells stimulated with plastic immobilized anti-CD3. Cord T-cell supernatant levels of interferon-gamma (IFN-gamma) were undetectable with CD3 stimulation, slightly raised with CD58/CD3 costimulation, but normal when T cells were preincubated with IL-2 for 24 hr before being costimulated with anti-CD3/CD58. Evidence that IL-2 and IFN-gamma play a pivotal role in fully activating cord T cells came from the demonstration that IL-2 and IFN-gamma are able to bypass the CD3-proliferative defect through differential up-regulation of the adhesion molecules. It would, therefore, seem that ICAM-1 and LFA-3 molecules are crucially implicated in the CD3-activation pathway of Ag-unprimed T cells. PMID:7684326

  7. ROLE OF LIVER SINUSOIDAL CELLS AND BONE MARROW CELLS IN REALIZATION OF REGENERATIVE STRATEGY OF NORMAL AND DAMAGED LIVER

    Directory of Open Access Journals (Sweden)

    A. V. Lyundup

    2010-06-01

    Full Text Available Sinusoidal cells play the key role at all kinds of liver regeneration (physiological, reparative, fibrogenetic, which vector depends on adaptative reserves of these cells (first of all Ito cells stressful damaging factors affect. It was demonstrated that under reparative liver regeneration the recovery of hepatocytes pool originates not only from mitosis, but from regional stem cells – oval cells, Ito cells and from migrating bone marrow cells. Fibrogenetic liver regeneration occurs as a result of inhibiting stem cell function of Ito cells and bone marrow cells

  8. Prognostic Value and Reproducibility of Pretreatment CT Texture Features in Stage III Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fried, David V. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, Texas (United States); Tucker, Susan L. [Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhou, Shouhao [Division of Quantitative Sciences, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mawlawi, Osama [Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, Texas (United States); Ibbott, Geoffrey [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, Texas (United States); Court, Laurence E., E-mail: LECourt@mdanderson.org [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, Texas (United States)

    2014-11-15

    Purpose: To determine whether pretreatment CT texture features can improve patient risk stratification beyond conventional prognostic factors (CPFs) in stage III non-small cell lung cancer (NSCLC). Methods and Materials: We retrospectively reviewed 91 cases with stage III NSCLC treated with definitive chemoradiation therapy. All patients underwent pretreatment diagnostic contrast enhanced computed tomography (CE-CT) followed by 4-dimensional CT (4D-CT) for treatment simulation. We used the average-CT and expiratory (T50-CT) images from the 4D-CT along with the CE-CT for texture extraction. Histogram, gradient, co-occurrence, gray tone difference, and filtration-based techniques were used for texture feature extraction. Penalized Cox regression implementing cross-validation was used for covariate selection and modeling. Models incorporating texture features from the 33 image types and CPFs were compared to those with models incorporating CPFs alone for overall survival (OS), local-regional control (LRC), and freedom from distant metastases (FFDM). Predictive Kaplan-Meier curves were generated using leave-one-out cross-validation. Patients were stratified based on whether their predicted outcome was above or below the median. Reproducibility of texture features was evaluated using test-retest scans from independent patients and quantified using concordance correlation coefficients (CCC). We compared models incorporating the reproducibility seen on test-retest scans to our original models and determined the classification reproducibility. Results: Models incorporating both texture features and CPFs demonstrated a significant improvement in risk stratification compared to models using CPFs alone for OS (P=.046), LRC (P=.01), and FFDM (P=.005). The average CCCs were 0.89, 0.91, and 0.67 for texture features extracted from the average-CT, T50-CT, and CE-CT, respectively. Incorporating reproducibility within our models yielded 80.4% (±3.7% SD), 78.3% (±4.0% SD), and 78

  9. Hyperfractionated Radiotherapy and Concurrent Chemotherapy for Stage III Unascertainable Non Small Cell Lung Cancer : Preliminary Report for Response and Toxicity

    International Nuclear Information System (INIS)

    Lung cancer study group at Asan Medical Center has conducted the second prospective study to determine the efficacy and feasibility of MVP chemotherapy with concurrent hyperfractionated radiotherapy for patients with stage III unresectable non-small cell lung cancer(NSCLC). All eligible patients with stage III unresectable NSCLC were treated with hyperfractionated radiotherapy( 120 cGy/fx BID, 6480 cGY/54fx) and concurrent 2 cycles of MVP(Motomycin C 6 mg/m2 , d2 and d29, Vinblastin 6 mg/m2 , d2 and d29, Cisplatin 6 mg/m2 , d1 and d28) chemotherapy. Between Aug. 1993 and Nov. 1994, 62 patients entered this study ; 6(10%) had advanced stage IIIa and 56(90%) had IIIb disease including 1 with pleural effusion and 10 with supraclavicular metastases. Among 62 Patients, 48(77%) completed planned therapy. Fourteen patients refused further treatment during chemoradiotherapy. Of 46 patients evaluable for response, 34(74%) showed major response including 10(22%) with complete and 24(52%) with partial responses. Of 48 patients evaluable for toxicity, 13(27%) showed grade IV hematologic toxicity but treatment delay did not exceed 5 days. Two patients died of sepsis during chemoradiotherapy. Server weight(more than 10%) occurred in 9 patients(19%) during treatment. Nine patients(19%) developed radiation pneumonitis. Six of these patients had grad I(mild) pneumonitis with radiographic changes within the treatment fields. Three other patients had grade II pneumonitis, but none of theses patients had continuous symptoms after steroid treatment. Concurrent chemoradiotherapy for patients with advanced NSCLC was well tolerated with acceptable toxicity and achieved higher response rates than the first study, but rather low compliance rate(7%) in this study is worrisome. We need to improve nutritional support during treatment and to use G-CSF to improve leukopenia and if necessary, supportive care will given as in patients. Longer follow-up and larger sample size is needed to observe

  10. Prognostic Value and Reproducibility of Pretreatment CT Texture Features in Stage III Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: To determine whether pretreatment CT texture features can improve patient risk stratification beyond conventional prognostic factors (CPFs) in stage III non-small cell lung cancer (NSCLC). Methods and Materials: We retrospectively reviewed 91 cases with stage III NSCLC treated with definitive chemoradiation therapy. All patients underwent pretreatment diagnostic contrast enhanced computed tomography (CE-CT) followed by 4-dimensional CT (4D-CT) for treatment simulation. We used the average-CT and expiratory (T50-CT) images from the 4D-CT along with the CE-CT for texture extraction. Histogram, gradient, co-occurrence, gray tone difference, and filtration-based techniques were used for texture feature extraction. Penalized Cox regression implementing cross-validation was used for covariate selection and modeling. Models incorporating texture features from the 33 image types and CPFs were compared to those with models incorporating CPFs alone for overall survival (OS), local-regional control (LRC), and freedom from distant metastases (FFDM). Predictive Kaplan-Meier curves were generated using leave-one-out cross-validation. Patients were stratified based on whether their predicted outcome was above or below the median. Reproducibility of texture features was evaluated using test-retest scans from independent patients and quantified using concordance correlation coefficients (CCC). We compared models incorporating the reproducibility seen on test-retest scans to our original models and determined the classification reproducibility. Results: Models incorporating both texture features and CPFs demonstrated a significant improvement in risk stratification compared to models using CPFs alone for OS (P=.046), LRC (P=.01), and FFDM (P=.005). The average CCCs were 0.89, 0.91, and 0.67 for texture features extracted from the average-CT, T50-CT, and CE-CT, respectively. Incorporating reproducibility within our models yielded 80.4% (±3.7% SD), 78.3% (±4.0% SD), and 78

  11. Biochemical and Structural Properties of Mouse Kynurenine Aminotransferase III

    Energy Technology Data Exchange (ETDEWEB)

    Han, Q.; Robinson, H; Cai, T; Tagle, D; Li, J

    2009-01-01

    Kynurenine aminotransferase III (KAT III) has been considered to be involved in the production of mammalian brain kynurenic acid (KYNA), which plays an important role in protecting neurons from overstimulation by excitatory neurotransmitters. The enzyme was identified based on its high sequence identity with mammalian KAT I, but its activity toward kynurenine and its structural characteristics have not been established. In this study, the biochemical and structural properties of mouse KAT III (mKAT III) were determined. Specifically, mKAT III cDNA was amplified from a mouse brain cDNA library, and its recombinant protein was expressed in an insect cell protein expression system. We established that mKAT III is able to efficiently catalyze the transamination of kynurenine to KYNA and has optimum activity at relatively basic conditions of around pH 9.0 and at relatively high temperatures of 50 to 60C. In addition, mKAT III is active toward a number of other amino acids. Its activity toward kynurenine is significantly decreased in the presence of methionine, histidine, glutamine, leucine, cysteine, and 3-hydroxykynurenine. Through macromolecular crystallography, we determined the mKAT III crystal structure and its structures in complex with kynurenine and glutamine. Structural analysis revealed the overall architecture of mKAT III and its cofactor binding site and active center residues. This is the first report concerning the biochemical characteristics and crystal structures of KAT III enzymes and provides a basis toward understanding the overall physiological role of mammalian KAT III in vivo and insight into regulating the levels of endogenous KYNA through modulation of the enzyme in the mouse brain.

  12. Differentiation of glioblastoma multiforme stem-like cells leads to downregulation of EGFR and EGFRvIII and decreased tumorigenic and stem-like cell potential

    DEFF Research Database (Denmark)

    Stockhausen, Marie-Thérése; Kristoffersen, Karina; Stobbe, Louise;

    2014-01-01

    Glioblastoma multiforme (GBM) is the most common and devastating primary brain tumor among adults. Despite recent treatment progress, most patients succumb to their disease within 2 years of diagnosis. Current research has highlighted the importance of a subpopulation of cells, assigned brain...... cancer stem-like cells (bCSC), to play a pivotal role in GBM malignancy. bCSC are identified by their resemblance to normal neural stem cells (NSC), and it is speculated that the bCSC have to be targeted in order to improve treatment outcome for GBM patients. One hallmark of GBM is aberrant expression......, differentiation is induced. Furthermore, we show that differentiation leads to decreased tumorigenic and stem cell-like potential of the neurosphere cultures and that by specifically inhibiting EGFR signaling it is possible to target the bCSC population. Our results suggest that differentiation therapy, possibly...

  13. Role of axial base coordination in isonitrile binding and chalcogen atom transfer to vanadium(III) complexes.

    Science.gov (United States)

    Majumdar, Subhojit; Stauber, Julia M; Palluccio, Taryn D; Cai, Xiaochen; Velian, Alexandra; Rybak-Akimova, Elena V; Temprado, Manuel; Captain, Burjor; Cummins, Christopher C; Hoff, Carl D

    2014-10-20

    The enthalpy of oxygen atom transfer (OAT) to V[(Me3SiNCH2CH2)3N], 1, forming OV[(Me3SiNCH2CH2)3N], 1-O, and the enthalpies of sulfur atom transfer (SAT) to 1 and V(N[t-Bu]Ar)3, 2 (Ar = 3,5-C6H3Me2), forming the corresponding sulfides SV[(Me3SiNCH2CH2)3N], 1-S, and SV(N[t-Bu]Ar)3, 2-S, have been measured by solution calorimetry in toluene solution using dbabhNO (dbabhNO = 7-nitroso-2,3:5,6-dibenzo-7-azabicyclo[2.2.1]hepta-2,5-diene) and Ph3SbS as chalcogen atom transfer reagents. The V-O BDE in 1-O is 6.3 ± 3.2 kcal·mol(-1) lower than the previously reported value for 2-O and the V-S BDE in 1-S is 3.3 ± 3.1 kcal·mol(-1) lower than that in 2-S. These differences are attributed primarily to a weakening of the V-Naxial bond present in complexes of 1 upon oxidation. The rate of reaction of 1 with dbabhNO has been studied by low temperature stopped-flow kinetics. Rate constants for OAT are over 20 times greater than those reported for 2. Adamantyl isonitrile (AdNC) binds rapidly and quantitatively to both 1 and 2 forming high spin adducts of V(III). The enthalpies of ligand addition to 1 and 2 in toluene solution are -19.9 ± 0.6 and -17.1 ± 0.7 kcal·mol(-1), respectively. The more exothermic ligand addition to 1 as compared to 2 is opposite to what was observed for OAT and SAT. This is attributed to less weakening of the V-Naxial bond in ligand binding as opposed to chalcogen atom transfer and is in keeping with structural data and computations. The structures of 1, 1-O, 1-S, 1-CNAd, and 2-CNAd have been determined by X-ray crystallography and are reported. PMID:25280113

  14. Role of TRPM2 in H(2O(2-induced cell apoptosis in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Lei Sun

    Full Text Available Melastatin-like transient receptor potential channel 2 (TRPM2 is an oxidant-sensitive and cationic non-selective channel that is expressed in mammalian vascular endothelium. Here we investigated the functional role of TRPM2 channels in hydrogen peroxide (H(2O(2-induced cytosolic Ca(2+ ([Ca(2+](i elavation, whole-cell current increase, and apoptotic cell death in murine heart microvessel endothelial cell line H5V. A TRPM2 blocking antibody (TM2E3, which targets the E3 region near the ion permeation pore of TRPM2, was developed. Treatment of H5V cells with TM2E3 reduced the [Ca(2+](i rise and whole-cell current change in response to H(2O(2. Suppressing TRPM2 expression using TRPM2-specific short hairpin RNA (shRNA had similar inhibitory effect. H(2O(2-induced apoptotic cell death in H5V cells was examined using MTT assay, DNA ladder formation analysis, and DAPI-based nuclear DNA condensation assay. Based on these assays, TM2E3 and TRPM2-specific shRNA both showed protective effect against H(2O(2-induced apoptotic cell death. TM2E3 and TRPM2-specific shRNA also protect the cells from tumor necrosis factor (TNF-α-induced cell death in MTT assay. In contrast, overexpression of TRPM2 in H5V cells resulted in an increased response in [Ca(2+](i and whole-cell currents to H(2O(2. TRPM2 overexpression also aggravated the H(2O(2-induced apoptotic cell death. Downstream pathways following TRPM2 activation was examined. Results showed that TRPM2 activity stimulated caspase-8, caspase-9 and caspase-3. These findings strongly suggest that TRPM2 channel mediates cellular Ca(2+ overload in response to H(2O(2 and contribute to oxidant-induced apoptotic cell death in vascular endothelial cells. Down-regulating endogenous TRPM2 could be a means to protect the vascular endothelial cells from apoptotic cell death.

  15. A Phase I/II Radiation Dose Escalation Study With Concurrent Chemotherapy for Patients With Inoperable Stages I to III Non-Small-Cell Lung Cancer: Phase I Results of RTOG 0117

    International Nuclear Information System (INIS)

    Purpose: In preparation for a Phase III comparison of high-dose versus standard-dose radiation therapy, this Phase I/II study was initiated to establish the maximum tolerated dose of radiation therapy in the setting of concurrent chemotherapy, using three-dimensional conformal radiation therapy for non-small-cell lung cancer. Methods and Materials: Eligibility included patients with histologically proven, unresectable Stages I to III non-small-cell lung cancer. Concurrent chemotherapy consisted of paclitaxel, 50 mg/m2, and carboplatin, AUC of 2, given weekly. The radiation dose was to be sequentially intensified by increasing the daily fraction size, starting from 75.25 Gy/35 fractions. Results: The Phase I portion of this study accrued 17 patients from 10 institutions and was closed in January 2004. After the initial 8 patients were accrued to cohort 1, the trial closed temporarily on September 26, 2002, due to reported toxicity. Two acute treatment-related dose-limiting toxicities (DLTs) were reported at the time: a case of grade 5 and grade 3 radiation pneumonitis. The protocol, therefore, was revised to de-escalate the radiation therapy dose (74 Gy/37 fractions). Patients in cohort 1 continued to develop toxicity, with 6/8 (75%) patients eventually developing grade ≥3 events. Cohort 2 accrued 9 patients. There was one DLT, a grade 3 esophagitis, in cohort 2 in the first 5 patients (1/5 patients) and no DLTs for the next 2 patients (0/2 patients). Conclusions: The maximum tolerated dose was determined to be 74 Gy/37 fractions (2.0 Gy per fraction) using three-dimensional conformal radiation therapy with concurrent paclitaxel and carboplatin therapy. This dose level in the Phase II portion has been well tolerated, with low rates of acute and late lung toxicities.

  16. Role of Histone Acetylation in Cell Cycle Regulation.

    Science.gov (United States)

    Koprinarova, Miglena; Schnekenburger, Michael; Diederich, Marc

    2016-01-01

    Core histone acetylation is a key prerequisite for chromatin decondensation and plays a pivotal role in regulation of chromatin structure, function and dynamics. The addition of acetyl groups disturbs histone/DNA interactions in the nucleosome and alters histone/histone interactions in the same or adjacent nucleosomes. Acetyl groups can also provide binding sites for recruitment of bromodomain (BRD)-containing non-histone readers and regulatory complexes to chromatin allowing them to perform distinct downstream functions. The presence of a particular acetylation pattern influences appearance of other histone modifications in the immediate vicinity forming the "histone code". Although the roles of the acetylation of particular lysine residues for the ongoing chromatin functions is largely studied, the epigenetic inheritance of histone acetylation is a debated issue. The dynamics of local or global histone acetylation is associated with fundamental cellular processes such as gene transcription, DNA replication, DNA repair or chromatin condensation. Therefore, it is an essential part of the epigenetic cell response to processes related to internal and external signals. PMID:26303420

  17. Role of Public Participation and Communications in a Greenfield Nuclear Power Plant Project in Finland. Annex III

    International Nuclear Information System (INIS)

    In January 2008, Fennovoima Oy launched an EIA procedure regarding the construction of a new greenfield nuclear power plant in Finland. The EIA dealt with the construction of a power plant consisting of one or two reactors with an electrical output of 1500-2500 MW to one of the following municipalities: Pyhaejoki, Ruotsinpyhtaeae or Simo. The EIA procedure was concluded in 2009, when the Ministry of Employment and the Economy (MoEE) gave its final statement. Following the approval of the EIA, the Finnish Government and Parliament gave Fennovoima a Decision in Principle (DiP) in 2010, which granted Fennovoima the right to build a new nuclear power plant. The role of public participation in Finnish EIA procedures is briefly introduced in this Annex and illustrates the interaction between the participation and communication procedures and project development. The Fennovoima EIA procedure is used as a case example, but the principles of the role of public participation and communications apply to other large scale EIAs. Introduction to Public Participation and Communications in Environmental Impact Assessments: The EIA procedure is the key tool for communications in the early project development phase. The objective of the procedure is to improve the EIA and to align its consideration in planning and decision making. Another objective is to increase the availability of information to all citizens and the possibilities of public participation in the planning of projects. The Finnish EIA procedure does not require the plant design or layout to be strictly defined, and the EIA report is not a licence but a prerequisite for several licences. The linkages between procedure, public participation and communications in the Fennovoima EIA is shown. It also illustrates activities required by law, other means of public participation commonly part of the EIA procedure and examples of the supporting communication efforts. The figure shows that interaction between the project

  18. The role of Pbx1 in T cells

    Institute of Scientific and Technical Information of China (English)

    Mayami Sengupta; Laurence Morel

    2011-01-01

    Tissue and organ differentiation is tightly controlled to ensure proper development and function of the growing embryo as well as cells such as lymphocytes that differentiate throughout the adult stage.Therefore it is vital that the genes and the protein they encode that are involved in these processes function accurately.Hence,any mutation or error that occurs along the way can result in extensive damage,which is expressed in various ways in the embryo and can result in immune pathogenesis,including immunodeficiency and autoimmune diseases,when lymphocyte development is altered.A number of studies have been carried out to look at the genes regulating transcription in tissue differentiation,including the transcription factors Pbx1.This gene is of particular interest to us as we have identified that it is associated with systemic lupus erythematosus susceptibility (Cuda et al.,in press).This perspective summarizes the known roles of Pbx1 in tissue differentiation as well as our recent findings associating genetic variations in Pbx1 to lupus susceptibility,and we will speculate on how this gene controls the maintenance of immune tolerance in T cells.

  19. The role of primary radiotherapy for squamous cell carcinoma of the supraglottic larynx

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Won Taek; Kim, Dong Won; Kwon, Byung Hyun; Nam, Ji Ho [College of Medicine, Pusan National Univ, Pusan (Korea, Republic of); Hur, Won Joo [College of Medicine, Donga Univ, Pusan (Korea, Republic of)

    2000-12-01

    First of all, this study was performed to assess the result of curative radiotherapy and to evaluate different possible prognostic factors for squamous cell carcinoma of the supraglottic larynx treated at the Pusan National University Hospital. The second goal of this study was by comparing our data with those of other study groups, to determine the better treatment policy of supraglottic cancer in future. Thirty-two patients with squamous cell carcinoma of the supraglottic larynx were treated with radiotherapy at Pusan National University Hospital, from August 1985 to December 1996. Minimum follow-up period was 29 months. Twenty-seven patients (84.4%.) were followed up over 5 years. Radiotherapy was delivered with 6 MV photons to the primary laryngeal tumor and regional lymphatics with shrinking field technique. All patients received radiotherapy under conventional fractionated schedule (once a. day). Median total tumor dose was 70.2 Gy (range, 55.8 to 75.6 Gy) on primary or gross tumor lesion. Thirteen patients had induction chemotherapy with cisplatin and 5-fluorouracil (1-3 cycles). Patient distribution, according to the different stages, were as follows: stage I, 5/32 (15.6%); stage II, 10/32 (31.3%); stage III, 8/32 (25%); stage IV, 9/32 (28. 1 %). The 5-year overall survival rate of the whole series (32 patients) was 51.7%. The overall survival rate at 5-years was 80% in stage I, 66.7% in stage II, 42.9% in stage III, 25% in stage IV.(p= 0,0958). The 5-year local control rates after radiotherapy were as follows: stage I, 100%; stage II, 60%; stage III, 62.5%; stage lV, 44.4% (p=0.233). Overall vocal preservation rates was 65.6%,100% in stage I, 70% in stage II, 62.5% in stage III, 44.4% in stage IV (p=0.210). There was no statistical significance in survival and local control rate between neoadjuvant chemotherapy followed by radiotherapy group and radiotherapy alone group. Severe laryngeal edema was found in 2 cases after radiotherapy. emergent tracheostomy

  20. Asymmetric cell division and its role in cell fate determination in the green alga Tetraselmis indica

    Indian Academy of Sciences (India)

    Mani Arora; Arga Chandrashekar Anil; Karl Burgess; Jane Delany; Ehsan Mesbahi

    2015-12-01

    The prasinophytes (early diverging Chlorophyta), consisting of simple unicellular green algae, occupy a critical position at the base of the green algal tree of life, with some of its representatives viewed as the cell form most similar to the first green alga, the `ancestral green flagellate'. Relatively large-celled unicellular eukaryotic phytoflagellates (such as Tetraselmis and Scherffelia), traditionally placed in Prasinophyceae but now considered as members of Chlorodendrophyceae (core Chlorophyta), have retained some primitive characteristics of prasinophytes. These organisms share several ultrastructural features with the other core chlorophytes (Trebouxiophyceae, Ulvophyceae and Chlorophyceae). However, the role of Chlorodendrophycean algae as the evolutionary link between cellular individuality and cellular cooperation has been largely unstudied. Here, we show that clonal populations of a unicellular chlorophyte, Tetraselmis indica, consist of morphologically and ultrastructurally variant cells which arise through asymmetric cell division. These cells also differ in their physiological properties. The structural and physiological differences in the clonal cell population correlate to a certain extent with the longevity and function of cells.

  1. Role of stem cells in large bowel carcinogenesis

    Directory of Open Access Journals (Sweden)

    N. A. Nefedova

    2015-10-01

    Full Text Available Сancer stem cells (CSC play a significant role in the development and progression of colorectal cancer. They are capable of self-senewal and multipotent differentiation. CSC can be formed from stem cells or mutant by dedifferentiation of crypt epithelial cells. Recently, much attention is paid to CSC in colon cancer, but very little has been published regarding their expression in colon polyps. In 2010 The World Health Organization attributed the so-called serrated lesions, including hyperplastic polyp, serrated sessile adenoma and traditional serrated adenoma to a group of precancerous lesions of the colon in addition to the classical tubular, villous and tubulo-villous adenomas. Despite the large number of publications devoted to the newly selected category, a full understanding of the processes involved in the formation of polyps and their progression into colon cancer, there is still no. Identification of CSC in colon polyps will assess their potential malignancy conduct adequate therapy, determine the amount of the operation and further treatment strategy. This in turn will contribute to the early detection and prevention of cancer. Identification of CSC, an assessment of their localization and distribution in tubular adenomas, serrated adenoma broad-based, traditional serrated adenoma and hyperplastic polyps allow to evaluate the potential of malignancy and prognosis for each of the polyps. In this regard, the definition of markers characteristic of colon CSC, is interesting not only from a scientific, but also from a practical point of view.

  2. The DNA polymerase III holoenzyme contains γ and is not a trimeric polymerase

    Science.gov (United States)

    Dohrmann, Paul R.; Correa, Raul; Frisch, Ryan L.; Rosenberg, Susan M.; McHenry, Charles S.

    2016-01-01

    There is widespread agreement that the clamp loader of the Escherichia coli replicase has the composition DnaX3δδ’χψ. Two DnaX proteins exist in E. coli, full length τ and a truncated γ that is created by ribosomal frameshifting. τ binds DNA polymerase III tightly; γ does not. There is a controversy as to whether or not DNA polymerase III holoenzyme (Pol III HE) contains γ. A three-τ form of Pol III HE would contain three Pol IIIs. Proponents of the three-τ hypothesis have claimed that γ found in Pol III HE might be a proteolysis product of τ. To resolve this controversy, we constructed a strain that expressed only τ from a mutated chromosomal dnaX. γ containing a C-terminal biotinylation tag (γ-Ctag) was provided in trans at physiological levels from a plasmid. A 2000-fold purification of Pol III* (all Pol III HE subunits except β) from this strain contained one molecule of γ-Ctag per Pol III* assembly, indicating that the dominant form of Pol III* in cells is Pol III2τ2 γδδ’χψ. Revealing a role for γ in cells, mutants that express only τ display sensitivity to ultraviolet light and reduction in DNA Pol IV-dependent mutagenesis associated with double-strand-break repair, and impaired maintenance of an F’ episome. PMID:26786318

  3. The role of the substrate on the dispersion in accumulation in III-V compound semiconductor based metal-oxide-semiconductor gate stacks

    International Nuclear Information System (INIS)

    Dispersion in accumulation is a widely observed phenomenon in metal-oxide-semiconductor gate stacks based on III-V compound semiconductors. The physical origin of this phenomenon is attributed to border traps located in the dielectric material adjacent to the semiconductor. Here, we study the role of the semiconductor substrate on the electrical quality of the first layers at atomic layer deposited (ALD) dielectrics. For this purpose, either Al2O3 or HfO2 dielectrics with variable thicknesses were deposited simultaneously on two technology important semiconductors—InGaAs and InP. Significantly larger dispersion was observed in InP based gate stacks compared to those based on InGaAs. The observed difference is attributed to a higher border trap density in dielectrics deposited on InP compared to those deposited on InGaAs. We therefore conclude that the substrate plays an important role in the determination of the electrical quality of the first dielectric monolayers deposited by ALD. An additional observation is that larger dispersion was obtained in HfO2 based capacitors compared to Al2O3 based capacitors, deposited on the same semiconductor. This phenomenon is attributed to the lower conduction band offset rather than to a higher border trap density

  4. The role of the substrate on the dispersion in accumulation in III-V compound semiconductor based metal-oxide-semiconductor gate stacks

    Energy Technology Data Exchange (ETDEWEB)

    Krylov, Igor, E-mail: krylov@tx.technion.ac.il [The Russell Berrie Nanotechnology Institute, Technion – Israel Institute of Technology, Haifa 32000 (Israel); Ritter, Dan [The Russell Berrie Nanotechnology Institute, Technion – Israel Institute of Technology, Haifa 32000 (Israel); Department of Electrical Engineering, Technion – Israel Institute of Technology, Haifa 32000 (Israel); Eizenberg, Moshe [The Russell Berrie Nanotechnology Institute, Technion – Israel Institute of Technology, Haifa 32000 (Israel); Department of Materials Science and Engineering, Technion – Israel Institute of Technology, Haifa 32000 (Israel)

    2015-09-07

    Dispersion in accumulation is a widely observed phenomenon in metal-oxide-semiconductor gate stacks based on III-V compound semiconductors. The physical origin of this phenomenon is attributed to border traps located in the dielectric material adjacent to the semiconductor. Here, we study the role of the semiconductor substrate on the electrical quality of the first layers at atomic layer deposited (ALD) dielectrics. For this purpose, either Al{sub 2}O{sub 3} or HfO{sub 2} dielectrics with variable thicknesses were deposited simultaneously on two technology important semiconductors—InGaAs and InP. Significantly larger dispersion was observed in InP based gate stacks compared to those based on InGaAs. The observed difference is attributed to a higher border trap density in dielectrics deposited on InP compared to those deposited on InGaAs. We therefore conclude that the substrate plays an important role in the determination of the electrical quality of the first dielectric monolayers deposited by ALD. An additional observation is that larger dispersion was obtained in HfO{sub 2} based capacitors compared to Al{sub 2}O{sub 3} based capacitors, deposited on the same semiconductor. This phenomenon is attributed to the lower conduction band offset rather than to a higher border trap density.

  5. New targeted treatments for non-small-cell lung cancer - role of nivolumab.

    Science.gov (United States)

    Zago, Giulia; Muller, Mirte; van den Heuvel, Michel; Baas, Paul

    2016-01-01

    Non-small-cell lung cancer (NSCLC) is often diagnosed at an advanced stage of disease, where it is no longer amenable to curative treatment. During the last decades, the survival has only improved significantly for lung cancer patients who have tumors harboring a driver mutation. Therefore, there is a clear unmet need for effective therapies for patients with no mutation. Immunotherapy has emerged as an effective treatment for different cancer types. Nivolumab, a monoclonal inhibitory antibody against PD-1 receptor, can prolong survival of NSCLC patients, with a manageable toxicity profile. In two Phase III trials, nivolumab was compared to docetaxel in patients with, respectively, squamous (CheckMate 017) and non-squamous NSCLC (CheckMate 057). In both trials, nivolumab significantly reduced the risk of death compared to docetaxel (41% and 27% lower risk of death for squamous and non-squamous NSCLC, respectively). Therefore, nivolumab has been approved in the US and in Europe as second-line treatment for advanced NSCLC. Unfortunately, accurate predictive factors for patient selection are lacking, making it difficult to decide who will benefit and who will not. Currently, there are many ongoing trials that evaluate the efficacy of nivolumab in different settings and in combination with other agents. This paper reviews the present literature about the role of nivolumab in the treatment of NSCLC. Particular attention has been given to efficacy studies, toxicity profile, and current and emerging predictive factors. PMID:27536062

  6. Analysis of a Mathematical Model of Lithium-Sulfur Cells Part III: Electrochemical Reaction Kinetics, Transport Properties and Charging

    International Nuclear Information System (INIS)

    Highlights: • The discharge behavior of Li-S cells in wide range of exchange current densities of electrochemical reactions is studied. • Among all reduction reactions, 1/2 S8(l)+e−⇌1/2 S82− and 1/2 S22−+e−⇌2S2− play the most important role in capacity performance. • Low diffusion increases the precipitation of polysulfides in separator which may block the anode surface. • Large solubility of Li2S is needed for the model to be able to simulate the charging process. - Abstract: Sensitivity analysis of a mathematical model of a lithium-sulfur (Li-S) battery was performed by investigating the response of the model to variation of the exchange current densities, diffusion coefficients, and cathode thickness over a wide range; the results of the analysis were used to explain the some aspects of the behavior of the system which may be seen in experiments. In particular, among all the exchange current densities, the exchange current density of the elemental sulfur reduction has the most significant effect on the discharge capacity of the cell. The variation of the diffusion coefficients was also analyzed, providing information on the non-uniformity of precipitants in the cell after discharge. An optimum cathode thickness was presented to gain the highest capacity of the cell. Finally, the simulation of charging was studied, showing that the model needs a large solubility product of di-lithium sulfide to be able to simulate the charge process of a cell

  7. Role of the tryptophan residue in the vicinity of the catalytic center of exonuclease III family AP endonucleases: AP site recognition mechanism

    OpenAIRE

    Kaneda, Kohichi; Sekiguchi, Junichi; Shida, Toshio

    2006-01-01

    The mechanisms by which AP endonucleases recognize AP sites have not yet been determined. Based on our previous study with Escherichia coli exonuclease III (ExoIII), the ExoIII family AP endonucleases probably recognize the DNA-pocket formed at an AP site. The indole ring of a conserved tryptophan residue in the vicinity of the catalytic site presumably intercalates into this pocket. To test this hypothesis, we constructed a series of mutants of ExoIII and human APE1. Trp-212 of ExoIII and Tr...

  8. Head and neck squamous cell cancer (stages III and IV) induction chemotherapy assessment: value of FDG volumetric imaging parameters

    International Nuclear Information System (INIS)

    To evaluate whether the change in the metabolic tumour volume (MTV) or total lesion glycolysis (TLG) of the primary tumour, before and after induction chemotherapy, predicts outcome for patients with advanced head and neck squamous cell cancer (SCC). Twenty-eight patients with advanced (American Joint Committee on Cancer stage III and IV) head and neck SCC who underwent positron emission tomography (PET)/CT were included in this retrospective study. Primary tumour MTV and TLG were measured using gradient and fixed percentage threshold segmentations. Outcome endpoint was disease progression or mortality. Pearson correlation, Bland-Altman and receiver operator characteristic analysis were performed. The Pearson's correlation coefficients between percentage changes (pre- and post-induction chemotherapy) from gradient MTV (MTVG) and the 38% SUVmax threshold MTV (MTV38) was 0.96 and between MTVG and the 50% threshold MTV (MTV50) was 0.95 (PG and TLG38 was 0.94 and between TLGG and TLG50 was 0.96 (PG and MTV50. The areas under the curve for predicting progression or mortality were 0.76 (P=0.03) for MTVG and 0.82 for TLGG (P=0.009). Optimum cut points of a 42% reduction in MTVG and a 55% reduction in the TLGG predict event-free survival with a sensitivity of 62.5% and a specificity of 90% and a hazards ratio of 6.25. A reduction in primary tumour MTV of at least 42% or in TLG of at least 55% after induction chemotherapy may predict event-free survival in patients with advanced head and neck SCC.

  9. Clinical outcome of whole body gamma knife therapy inoperable stage I/II non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the efficacy and toxicity of hypofractionated stereotactic body radiotherapy (SBRT) in patients with inoperable stage I/II non-small cell lung cancer. Methods: Forty-three such patients were treated with home-manufactored stereotaetic gamma-ray whole-body therapeutic system (whole body gamma-knife radiotherapy, QGD; OUR International Technology and Science Co., LTD, Shenzhen, China) with 30 rotary, conical-surface 60Co sources on the target volume. For whole body γ-knife treatment, a stereotactic body frame for exact tumor localization, reproducible vacuum fixation, low-speed computed tomography simulation were conducted, which was followed by three-dimensional conformal radio-therapy planning. A total dose of 50 Gy was delivered at 5 Gy/fraction to the 50% isodose line covering the planned target volume, with a total dose of 70 Gy delivered at 7 Gy/fraction to the gross target volume. The median follow-up duration was 27 months. Results: Three to six months after treatment, the complete response rate for whole body-gamma knife radiotherapy was 63%, and the overall response rate was 95%. The 1-, 2-, and 3-year local control rates were all 95 %. In stage I patients, the 1-, 2-, and 3-year overall survival rate was 100%, 91% and 91% respectively. In patients with stage II, it was 73%, 64% and 64%, respectively. In patients with stage I + II, it was 88%, 78%, and 78%. Only 2% (1/43) of the patients had grade 3 pneumonitis. Conclusion: Our highly focused stereotactic body radiotherapy method has resulted in promising local control and survival with minimal toxicity. (authors)

  10. Preliminary investigation of stereotactic body radiation therapy for medically inoperable stage I/II non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the therapeutic efficacy and treatment-related toxicity of stereotactic body radiation therapy (SBRT) in patients with medically inoperable stage I/II non-small cell lung cancer (NSCLC). Methods: SBRT was applied to 30 patients, including clinically staged T1, T2 (≤5 cm) or T3 (chest wall primary tumors only), N0, M0 ,biopsy-confirmed NSCLC. All patients were precluded from lobotomy because of physical condition or comorbidity. No patients developed tumors of any T-stage in the proximal zone. SBRT was performed with the total dose of 50 Gy to 70 Gy in 10 - 11 fractions during 12 - 15 days. prescription line was set onthe edge of the PTV. Results: The follow-up rate was 100%. The number of patients who completed the 1-, and 2-year follow-up were 15, and 10, respectively. All 30 patients completed therapy as planned. The complete response (CR), partial response (PR) and stable disease (SD) rates were 37%, 53% and 3%, respectively. With a median follow-up of 16 months (range, 4-36 months), Kaplan-Meier local control at 2 years was 94%. The 2-year overall survival was 84% and the 2-year cancer specific survival was 90%. Seven patients(23%) developed Grade 2 pneumonitis, no grade > 2 acute or late lung toxicity was observed. No one developed chest wall pain. Conclusions: It is feasible to deliver 50 Gy to 70 Gy of SBRT in 10 - 11 fractions for medically inoperable patients with stage I / II NSCLC. It was associated with low incidence of toxicities and provided sustained local tumor control.The preliminary investigation indicated the cancer specific survival probability of SBRT was high. It is necessary to perform similar investigation in a larger number of patients with long-term follow-up. (authors)

  11. Efficacy of the smaller target volume for stage III non-small cell lung cancer treated with intensity-modulated radiotherapy

    OpenAIRE

    LIANG, XIANGCUN; Yu, Huiming; Yu, Rong; Xu, Gang; Guangying ZHU

    2015-01-01

    The present study reports the local recurrence, distant metastasis, progression-free survival, overall survival and radiation toxicity between two arms of stage III non-small cell lung cancer (NSCLC) treated with intensity-modulated radiotherapy (IMRT); one arm with clinical target volume (CTV) and the other without CTV. The two arms of local recurrence, distant metastasis, progression-free survival, overall survival, grade 3–4 radiation esophagitis and hematological toxicity had no statistic...

  12. Impact of KRAS mutation on response and outcome of patients with stage III non-squamous non-small cell lung cancer

    OpenAIRE

    Yagishita, Shigehiro; Horinouchi, Hidehito; Sunami, Kuniko S; Kanda, Shintaro; Fujiwara, Yutaka; Nokihara, Hiroshi; Yamamoto, Noboru; Sumi, Minako; Shiraishi, Kouya; Kohno, Takashi; Furuta, Koh; Tsuta, Koji; Tamura, Tomohide; Ohe, Yuichiro

    2015-01-01

    The frequency and clinical profile of patients with stage III non-small cell lung cancer harboring KRAS mutations have not yet been well documented. Here, we analyzed hotspot KRAS mutations using high-resolution melting analyses in tumor specimens from patients who received chemoradiotherapy between January 2001 and December 2010 at the National Cancer Center Hospital. The associations between the presence of KRAS mutations and the response rate, relapse-free survival, first relapse sites, su...

  13. Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome.

    Science.gov (United States)

    Kim, Ji-Hee; Hwang, Kyu-Hee; Lkhagvadorj, Sayamaa; Jung, Jae Hung; Chung, Hyun Chul; Park, Kyu-Sang; Kong, In Deok; Eom, Minseob; Cha, Seung-Kuy

    2016-05-01

    Klotho functions as a tumor suppressor predominantly expressed in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC). Altered expression and/or activity of growth factor receptor have been implicated in ccRCC development. Although Klotho suppresses a tumor progression through growth factor receptor signaling including insulin-like growth factor-1 receptor (IGF-1R), the role of Klotho acting on IGF-1R in ccRCC and its clinical relevance remains obscure. Here, we show that Klotho is favorable prognostic factor for ccRCC and exerts tumor suppressive role for ccRCC through inhibiting IGF-1R signaling. Our data shows the following key findings. First, in tumor tissues, the level of Klotho and IGF-1R expression are low or high, respectively, compared to that of adjacent non-neoplastic parenchyma. Second, the Klotho expression is clearly low in higher grade of ccRCC and is closely associated with clinical outcomes in tumor progression. Third, Klotho suppresses IGF-1-stimulated cell proliferation and migration by inhibiting PI3K/Akt pathway. These results provide compelling evidence supporting that Klotho acting on IGF-1R signaling functions as tumor suppressor in ccRCC and suggest that Klotho is a potential carcinostatis substance for ccRCC. PMID:27162484

  14. Mathematics III

    OpenAIRE

    Viader Canals, Pelegrí

    2013-01-01

    Apunts de l'assignatura Mathematics III del Grau en International Business Economics del curs 2012-2013. Conté : Diagonalization, Difference Equations, Differential Equations, Lagrange-Kuhn-Tucker, Second order Difference Equations.

  15. Roles of membrane trafficking in plant cell wall dynamics

    OpenAIRE

    Ebine, Kazuo; Ueda, Takashi

    2015-01-01

    The cell wall is one of the characteristic components of plant cells. The cell wall composition differs among cell types and is modified in response to various environmental conditions. To properly generate and modify the cell wall, many proteins are transported to the plasma membrane or extracellular space through membrane trafficking, which is one of the key protein transport mechanisms in eukaryotic cells. Given the diverse composition and functions of the cell wall in plants, the transpor...

  16. Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells.

    Science.gov (United States)

    Wu, S; Wright, R A; Rockey, P K; Burgett, S G; Arnold, J S; Rosteck, P R; Johnson, B G; Schoepp, D D; Belagaje, R M

    1998-01-01

    Cloning and expression in a stable mammalian cell line co-transfected with a glutamate transporter (RGT cells) were used as tools for studying the functions and pharmacological properties of group III metabotropic glutamate receptors (mGluRs). Complementary DNAs (cDNAs) encoding the human mGluR4, human mGluR7, and human mGluR8 were isolated from human cerebellum, fetal brain or retinal cDNA libraries. The human mGluR4, mGluR7 and mGluR8 receptors were 912, 915 and 908 amino acid residues long and share 67-70% amino acid similarity with each other and 42-45% similarity with the members of mGluR subgroups I and II. The human mGluR4 and mGluR7 had amino acid identity of 96% and 99.5% with rat mGluR4 and 7, respectively, whereas the human mGluR8 has 98.8% amino acid identity with the mouse mGluR8. The nucleotide and amino acid sequences in the coding region of human mGluR4 and mGluR7 were found to be identical to the previously published sequences by Flor et al. and Makoff et al. Following stable expression in RGT cells, highly significant inhibitions of forskolin stimulation of cAMP production by group III agonists were found for each receptor. The relative potencies of the group III agonist L-AP4 varied greatly between the group III clones, being mGluR8>mGluR4 > mGluR7. The reported group II mGluR agonist L-CCG-I was a highly potent mGluR8 agonist (EC50=0.35 microM), with significant agonist activities at both mGluR4 (EC50=3.7 microM) and mGluR7 (EC50=47 microM). The antagonist potency of the purported group III mGluR antagonist MPPG also varied among the receptors being human mGluR8 > mGluR4 = mGluR7. The expression and second messenger coupling of human group III mGluRs expressed in the RGT cell line are useful to clearly define the subtype selectivities of mGluR ligands. PMID:9473604

  17. Mutations in the Borrelia burgdorferi Flagellar Type III Secretion System Genes fliH and fliI Profoundly Affect Spirochete Flagellar Assembly, Morphology, Motility, Structure, and Cell Division

    Science.gov (United States)

    Gao, Lihui; Zhao, Xiaowei; Liu, Jun; Norris, Steven J.

    2015-01-01

    ABSTRACT The Lyme disease spirochete Borrelia burgdorferi migrates to distant sites in the tick vectors and mammalian hosts through robust motility and chemotaxis activities. FliH and FliI are two cytoplasmic proteins that play important roles in the type III secretion system (T3SS)-mediated export and assembly of flagellar structural proteins. However, detailed analyses of the roles of FliH and FliI in B. burgdorferi have not been reported. In this study, fliH and fliI transposon mutants were utilized to dissect the mechanism of the Borrelia type III secretion system. The fliH and fliI mutants exhibited rod-shaped or string-like morphology, greatly reduced motility, division defects (resulting in elongated organisms with incomplete division points), and noninfectivity in mice by needle inoculation. Mutants in fliH and fliI were incapable of translational motion in 1% methylcellulose or soft agar. Inactivation of either fliH or fliI resulted in the loss of the FliH-FliI complex from otherwise intact flagellar motors, as determined by cryo-electron tomography (cryo-ET). Flagellar assemblies were still present in the mutant cells, albeit in lower numbers than in wild-type cells and with truncated flagella. Genetic complementation of fliH and fliI mutants in trans restored their wild-type morphology, motility, and flagellar motor structure; however, full-length flagella and infectivity were not recovered in these complemented mutants. Based on these results, disruption of either fliH or fliI in B. burgdorferi results in a severe defect in flagellar structure and function and cell division but does not completely block the export and assembly of flagellar hook and filament proteins. PMID:25968649

  18. Role of Metallothionein1H in Cisplatin Resistance of Non-Small Cell Lung Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Xin-fang Hou; Qing-xia Fan; Liu-xing Wang; Shi-xin Lu

    2009-01-01

    Objective: Despite platinum-based adjuvant chemotherapy has improved greatly patients' outcomes, drug resistance poses a major impediment to the successful use of such an effective agent. Metallothioneins(MTs) are known to play putative roles in cancer cell proliferation, apoptosis, differentiation, drug resistance and prognosis. The present studiy was to investigte the role of metallethioein1H(MT1H) in cisplatin resistance of human non-small cell lung cancer(NSCLC) cell lines in vitro or its possible molecular mechanisms. Methods: MT1H mRNA expression in A549 and A549/DDP cells was detected by RT-PCR. A recombinant eukaryotic expression plasmid pcDNA3.1(-)-MT1H was constructed and transfected into A549 cells which express no MT1H. MT1H siRNA was transfected into A549/DDP cells which express MT1H highly. MT1H expression was detected by RT-PCR and Immunoblot. The chemosensitivity to cisplatin was assessed by MTT assay. Apoptosis rate was determined by Tunel and FCM. Bcl-2 and Bax were determined by immunohistochemistry. Results: MT1H mRNA was expressed in A549/DDP but not in A549. After transfection of MT1H, MT1H expression was enhanced and the chemosensitivity to cisplatin was decreased in A549 cells. Inversely, after transfection of MT1H siRNA, MT1H expression was decreased and the chemosensitivity to cisplatin was increased in A549/DDP. The apoptosis rate induced by cisplatin was increased and Bcl-2 was down-regulated but Bax showed little change in A549/DDP cells interferred with MT1H siRNA. Conclusion: MT1H overexpression can promote drug resistance in A549 cells . Down-regulation of MT1H interfered with siRNA can effectively reverses the drug resistance in A549/DDP cells by down-regulating the expression of Bcl-2 and increasing cisplatin induced apoptosis. SiRNA targeting MT1H combined with chemotherapy may be a very promising strategy for treatment of lung cancer.

  19. Basel III

    OpenAIRE

    Štrbová, Barbora

    2014-01-01

    The aim of this thesis is to analyze current capital adequacy in Europe under regulatory framework Basel III and compare the state of its implementation within European banks and Slovak financial sector, which is represented by two Slovak case banks. Firstly it is focused on the two previous regulatory frameworks, especially on their capital adequacy and three-pillar structure of Basel II. Then we proceed to present the new regulatory framework Basel III. The third regulatory framework of the...

  20. Role of Stem Cells in Treatment of Neurological Disorder

    OpenAIRE

    Ul Hassan, Ashfaq; Hassan, Ghulam; Rasool, Zahida

    2009-01-01

    Stem cells or mother or queen of all cells are pleuropotent and have the remarkable potential to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person or animal is alive. When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood c...

  1. DMPD: Nitric oxide and cell viability in inflammatory cells: a role for NO inmacrophage function and fate. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15691589 Nitric oxide and cell viability in inflammatory cells: a role for NO inmac...(.png) (.svg) (.html) (.csml) Show Nitric oxide and cell viability in inflammatory cells: a role for NO inma...ty in inflammatory cells: a role for NO inmacrophage function and fate. Authors Bosca L, Zeini M, Traves PG,

  2. WtsE, an AvrE-family type III effector protein of Pantoea stewartii subsp. stewartii, causes cell death in non-host plants.

    Science.gov (United States)

    Ham, Jong Hyun; Majerczak, Doris; Ewert, Sophie; Sreerekha, Mysore-Venkatarau; Mackey, David; Coplin, David

    2008-09-01

    Pantoea stewartii subsp. stewartii (Pnss) causes Stewart's bacterial wilt of sweet corn and leaf blight of maize. The pathogenicity of Pnss depends on synthesis of extracellular polysaccharide and an Hrp type III secretion system. WtsE, a type III secreted effector protein, is essential for the virulence of Pnss on corn. It belongs to the AvrE family of effectors, which includes DspA/E from Erwinia amylovora and AvrE1 from Pseudomonas syringae. Previously, WtsE was shown to cause disease-associated cell death in its host plant, sweet corn. Here, we examine the biological activity of WtsE in several non-host plants. WtsE induced cell death in Nicotiana benthamiana, tobacco, beet and Arabidopsis thaliana when it was transiently produced in plant cells following agroinfiltration or translocated into plant cells from Pnss, Escherichia coli or Pseudomonas syringae pv. phaseolicola (Pph). WtsE-induced cell death in N. benthamiana, tobacco and beet resembled a hypersensitive response and in N. benthamiana it was delayed by cycloheximide. Interestingly, WtsE strongly promoted the growth of Pnss in N. benthamiana prior to the onset of cell death. Deletion derivatives of WtsE that failed to induce cell death in N. benthamiana and tobacco also did not complement wtsE mutants of Pnss for virulence in sweet corn, indicating a correlation between the two activities. WtsE also induced cell death in A. thaliana, where it suppressed basal defences induced by Pph. Thus, WtsE has growth-promoting, defence-suppressing and cell death-inducing activities in non-host plants. Expression of WtsE also prevented the growth of yeast, possibly due to an innate toxicity to eukaryotic cells. PMID:19018993

  3. Cytotoxic effects of bromelain in human gastrointestinal carcinoma cell lines (MKN45, KATO-III, HT29-5F12, and HT29-5M21

    Directory of Open Access Journals (Sweden)

    Amini A

    2013-04-01

    Full Text Available Afshin Amini, Anahid Ehteda, Samar Masoumi Moghaddam, Javed Akhter, Krishna Pillai, David Lawson Morris Department of Surgery, St George Hospital, University of New South Wales, Sydney, NSW, Australia Background: Bromelain is a pineapple stem extract with a variety of therapeutic benefits arising from interaction with a number of different biological processes. Several preclinical studies and anecdotal clinical observations have reported the anticancer properties of bromelain. In the present study, we investigated the cytotoxic effects of bromelain in four human cancer cell lines of gastrointestinal origin and the mechanisms involved. Methods: The gastric carcinoma cell lines (KATO-III and MKN45 and two chemoresistant subpopulations of the HT29 colon adenocarcinoma cell line (HT29-5M21 and HT29-5F12 were treated with a range of concentrations of bromelain, as well as with cisplatin as a positive control. The effect of bromelain on the growth and proliferation of cancer cells was determined using a sulforhodamine B assay after 72 hours of treatment. Expression of apoptosis-associated proteins in MKN45 cells treated with bromelain was analyzed by Western blotting. Results: Data from our sulforhodamine B assay showed that bromelain inhibited proliferation of HT29-5F12, HT29-5M21, MKN45, and KATO-III cells, with respective half maximal inhibitory concentration values of 29, 34, 94, and 142 µg/mL. Analyzing the expression of proapoptotic and antiapoptotic proteins in bromelain-treated MKN45 cells, we observed activation of the caspase system, cleavage of PARP and p53, overexpression of cytochrome C, attenuation of phospho-Akt and Bcl2, and removal of MUC1. Apart from the caspase-dependent apoptosis observed, emergence of cleaved p53 supports a direct, extranuclear apoptotic function of p53. Moreover, interrupted Akt signaling and attenuation of Bcl2 and MUC1 oncoproteins suggest impaired survival of cancer cells. Conclusion: Our findings

  4. A Burkholderia pseudomallei type III secreted protein, BopE, facilitates bacterial invasion of epithelial cells and exhibits guanine nucleotide exchange factor activity

    OpenAIRE

    M.P. Stevens; Friebel, A; Taylor, L A; Wood, M W; Brown, P. J.; Hardt, W D; Galyov, E E

    2003-01-01

    We report the characterization of BopE, a type III secreted protein that is encoded adjacent to the Burkholderia pseudomallei bsa locus and is homologous to Salmonella enterica SopE/SopE2. Inactivation of bopE impaired bacterial entry into HeLa cells, indicating that BopE facilitates invasion. Consistent with this notion, BopE expressed in eukaryotic cells induced rearrangements in the subcortical actin cytoskeleton, and purified BopE exhibited guanine nucleotide exchange factor activity for ...

  5. New Roles for Mast Cells in Modulating Allergic Reactions and Immunity Against Pathogens

    OpenAIRE

    Hofmann, Alison M.; Abraham, Soman N.

    2009-01-01

    Mast cells have primarily been associated with mediating the pathological secondary responses to allergens in sensitized hosts. In view of the recent evidence for a mast cell role in modulating primary immune responses to pathogens, the likelihood for a role of mast cells in influencing primary immune response to allergens has grown. New evidence suggests that mast cells drive the development of Th2 responses to allergens, particularly when allergen exposure occurs concomitantly with exposure...

  6. Role of Kupffer Cells in Thioacetamide-Induced Cell Cycle Dysfunction

    Directory of Open Access Journals (Sweden)

    Mirandeli Bautista

    2011-09-01

    Full Text Available It is well known that gadolinium chloride (GD attenuates drug-induced hepatotoxicity by selectively inactivating Kupffer cells. In the present study the effect of GD in reference to cell cycle and postnecrotic liver regeneration induced by thioacetamide (TA in rats was studied. Two months male rats, intraveously pretreated with a single dose of GD (0.1 mmol/Kg, were intraperitoneally injected with TA (6.6 mmol/Kg. Samples of blood and liver were obtained from rats at 0, 12, 24, 48, 72 and 96 h following TA intoxication. Parameters related to liver damage were determined in blood. In order to evaluate the mechanisms involved in the post-necrotic regenerative state, the levels of cyclin D and cyclin E as well as protein p27 and Proliferating Cell Nuclear Antigen (PCNA were determined in liver extracts because of their roles in the control of cell cycle check-points. The results showed that GD significantly reduced the extent of necrosis. Noticeable changes were detected in the levels of cyclin D1, cyclin E, p27 and PCNA when compared to those induced by thioacetamide. Thus GD pre-treatment reduced TA-induced liver injury and accelerated the postnecrotic liver regeneration. These results demonstrate that Kupffer cells are involved in TA-induced liver and also in the postnecrotic proliferative liver states.

  7. Post-mitotic role of nucleostemin as a promoter of skeletal muscle cell differentiation

    OpenAIRE

    Hirai, Hiroyuki; Romanova, Liudmila; Kellner, Steven; Verma, Mayank; Rayner, Samuel; Asakura, Atsushi; Kikyo, Nobuaki

    2009-01-01

    Nucleostemin (NS) is a nucleolar protein abundantly expressed in a variety of proliferating cells and undifferentiated cells. Its known functions include cell cycle regulation and the control of pre-rRNA processing. It also has been proposed that NS has an additional role in undifferentiated cells due to its downregulation during stem cell differentiation and its upregulation during tissue regeneration. Here, however, we demonstrate that skeletal muscle cell differentiation has a unique expre...

  8. Spectroscopic study on the role of TiO2 in the adsorption of Eu(III) and U(VI) on silica surfaces in aqueous solutions

    International Nuclear Information System (INIS)

    Highlights: • Enhanced adsorption of Eu(III) and U(VI) onto TiO2-coated silica. • Enhanced Eu(III) luminescence and lifetime on TiO2-coated silica. • Energy transfer from TiO2 of TiO2-coated silica to Eu(III) in solutions. - Abstract: To determine the effects of TiO2 on the adsorption of actinides onto mineral surfaces in groundwater, silica was partially coated with TiO2, and Eu(III) and U(VI) were individually adsorbed from separate 0.1 mM concentration solutions. The TiO2-coated silica showed higher Eu(III) and U(VI) adsorption capacities for increasing amounts of TiO2 coated on the silica surfaces, and thus the existence of TiO2 can decrease the mobility of Eu(III) and U(VI) contaminants. In luminescence studies, it was found that TiO2 considerably enhanced the luminescence of the adsorbed Eu(III) indicating that TiO2–Eu(III) forms surface complexes which may decrease the number of water molecules at the inner sphere of Eu(III), but this was not observed for U(VI). An energy transfer from the TiO2 to the Eu(III) was confirmed in this case of amorphous TiO2-coated silica in Eu(III) solutions, and an increase of the luminescence lifetime of Eu(III) for increasing concentrations of coated TiO2 was also observed

  9. Role of Pin1 in UVA-induced cell proliferation and malignant transformation in epidermal cells

    International Nuclear Information System (INIS)

    Highlights: → Pin1 expression is enhanced by low energy UVA irradiation in both skin tissues of hairless mice and JB6 C141 epidermal cells. → UVA irradiation increases activator protein-1 activity and cyclin D1 in a Pin1-dependent manner. → UVA potentiates EGF-inducible, anchorage-independent growth of epidermal cells, and this is suppressed by Pin1 inhibition or by anti-oxidant. -- Abstract: Ultraviolet A (UVA) radiation (λ = 320-400 nm) is considered a major cause of human skin cancer. Pin1, a peptidyl prolyl isomerase, is overexpressed in most types of cancer tissues and plays an important role in cell proliferation and transformation. Here, we demonstrated that Pin1 expression was enhanced by low energy UVA (300-900 mJ/cm2) irradiation in both skin tissues of hairless mice and JB6 C141 epidermal cells. Exposure of epidermal cells to UVA radiation increased cell proliferation and cyclin D1 expression, and these changes were blocked by Pin1 inhibition. UVA irradiation also increased activator protein-1 (AP-1) minimal reporter activity and nuclear levels of c-Jun, but not c-Fos, in a Pin1-dependent manner. The increases in Pin1 expression and in AP-1 reporter activity in response to UVA were abolished by N-acetylcysteine (NAC) treatment. Finally, we found that pre-exposure of JB6 C141 cells to UVA potentiated EGF-inducible, anchorage-independent growth, and this effect was significantly suppressed by Pin1inhibition or by NAC.

  10. Role of glial cells in innate immunity and their role in CNS demyelination.

    Science.gov (United States)

    Sriram, Subramaniam

    2011-10-28

    The adaptive and innate arms of the immune system are the two pillars of host defense against environmental pathogens. Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS which is considered to be autoimmune and is thought to result from breakdown in the usual checks and balances of the adaptive immune response. The major pathological outcome of the disease is "the MS plaque" a unique feature of CNS demyelination characterized by the destruction of oligodendrocytes with loss of myelin and underlying axons. The MS plaque is not seen in other inflammatory disorders of the CNS. The prevailing opinion suggests that MS is mediated by the activation of an adaptive immune response which targets neural antigens. Currently, the role of an innate immune in the development of the lesions in MS has remained unclear. We explore the potential cellular elements of the innate immune system and in particular glial cells, which are likely candidates in inducing the specific pathological picture that is evident in MS. Activated microglia and the release of molecules which are detrimental to oligodendrocyte have been suggested as mechanisms by which innate immunity causes demyelination in MS. However a microglia/macrophage centric model does not explain the specificity of lesion development in MS. We propose that activation pathways of receptors of the innate immune system present on oligodendrocytes and astrocytes rather than microglia are central to the pathogenesis of demyelination seen in MS. PMID:21907419

  11. Role of Heat Shock Proteins in Stem Cell Behavior

    OpenAIRE

    Fan, Guo-Chang

    2012-01-01

    Stress response is well appreciated to induce the expression of heat shock proteins (Hsps) in the cell. Numerous studies have demonstrated that Hsps function as molecular chaperones in the stabilization of intracellular proteins, repairing damaged proteins, and assisting in protein translocation. Various kinds of stem cells (embryonic stem cells, adult stem cells, or induced pluripotent stem cells) have to maintain their stemness and, under certain circumstances, undergo stress. Therefore, Hs...

  12. Immunoregulatory Role of Myeloid-derived Cells in Inflammatory Bowel Disease.

    Science.gov (United States)

    Leal, Marcelo Cerf; Däbritz, Jan

    2015-12-01

    As the frontiers of immunological research expand, new insights into the pathogenesis of long poorly understood diseases, such as inflammatory bowel disease (IBD), are opening up new possible avenues for treatment. Myeloid-derived cells (i.e., monocytes, macrophages, neutrophils, and dendritic cells), long believed to be effector cells driving the initiation of inflammation, have been increasingly shown to have immunoregulatory effects previously underappreciated. Dysfunction in the immunoregulatory roles of these cells may play a part in the pathogenesis of a subset of patients with IBD. The role of myeloid-derived suppressor cells, initially described in cancer, have been shown to play an important role in the balancing of effector and regulatory T cells in inflammation as well, and their role in IBD is also explored. The potential for future cell-based therapies for IBD is enhanced by the advances being made in the understanding of the innate immune system in the intestine. PMID:26244650

  13. Profilin Plays a Role in Cell Elongation, Cell Shape Maintenance, and Flowering in Arabidopsis

    DEFF Research Database (Denmark)

    Ramachandran, S.; Christensen, Hans Erik Mølager; Ishimaru, Y.;

    2000-01-01

    Profilin (PFN) is an ubiquitous, low-M-r, actin-binding protein involved in the organization of the cytoskeleton of eukaryotes including higher plants. PFNs are encoded by a multigene family in Arabidopsis. We have analyzed in vivo functions of Arabidopsis PFN by generating transgenic plants...... carrying a 35S-PFN-1 or 35S-antisense PFN-1 transgene. Etiolated seedlings underexpressing PFN (PFN-U) displayed an overall dwarf phenotype with short hypocotyls whose lengths were 20% to 25% that of wild type (WT) at low temperatures. Light-grown PFN-U plants were smaller in stature and flowered early...... expressed in the vascular bundles of cotyledons and leaves. Our results show that Arabidopsis PFNs play a role in cell elongation, cell shape maintenance, polarized growth of root hair, and unexpectedly, in determination of flowering time....

  14. Apolipophorin-III mediates antiplasmodial epithelial responses in Anopheles gambiae (G3 mosquitoes.

    Directory of Open Access Journals (Sweden)

    Lalita Gupta

    Full Text Available BACKGROUND: Apolipophorin-III (ApoLp-III is known to play an important role in lipid transport and innate immunity in lepidopteran insects. However, there is no evidence of involvement of ApoLp-IIIs in the immune responses of dipteran insects such as Drosophila and mosquitoes. METHODOLOGY/PRINCIPAL FINDINGS: We report the molecular and functional characterization of An. gambiae apolipophorin-III (AgApoLp-III. Mosquito ApoLp-IIIs have diverged extensively from those of lepidopteran insects; however, the predicted tertiary structure of AgApoLp-III is similar to that of Manduca sexta (tobacco hornworm. We found that AgApoLp-III mRNA expression is strongly induced in the midgut of An. gambiae (G3 strain mosquitoes in response to Plasmodium berghei infection. Furthermore, immunofluorescence stainings revealed that high levels of AgApoLp-III protein accumulate in the cytoplasm of Plasmodium-invaded cells and AgApoLp-III silencing increases the intensity of P. berghei infection by five fold. CONCLUSION: There are broad differences in the midgut epithelial responses to Plasmodium invasion between An. gambiae strains. In the G3 strain of An. gambiae AgApoLp-III participates in midgut epithelial defense responses that limit Plasmodium infection.

  15. Apolipophorin-III Mediates Antiplasmodial Epithelial Responses in Anopheles gambiae (G3) Mosquitoes

    Science.gov (United States)

    Jo, Yong Hun; Oh, Seung Han; Kumar, Sanjeev; Noh, Mi Young; Lee, Yong Seok; Cha, Sung-Jae; Seo, Sook Jae; Kim, Iksoo; Han, Yeon Soo; Barillas-Mury, Carolina

    2010-01-01

    Background Apolipophorin-III (ApoLp-III) is known to play an important role in lipid transport and innate immunity in lepidopteran insects. However, there is no evidence of involvement of ApoLp-IIIs in the immune responses of dipteran insects such as Drosophila and mosquitoes. Methodology/Principal Findings We report the molecular and functional characterization of An. gambiae apolipophorin-III (AgApoLp-III). Mosquito ApoLp-IIIs have diverged extensively from those of lepidopteran insects; however, the predicted tertiary structure of AgApoLp-III is similar to that of Manduca sexta (tobacco hornworm). We found that AgApoLp-III mRNA expression is strongly induced in the midgut of An. gambiae (G3 strain) mosquitoes in response to Plasmodium berghei infection. Furthermore, immunofluorescence stainings revealed that high levels of AgApoLp-III protein accumulate in the cytoplasm of Plasmodium-invaded cells and AgApoLp-III silencing increases the intensity of P. berghei infection by five fold. Conclusion There are broad differences in the midgut epithelial responses to Plasmodium invasion between An. gambiae strains. In the G3 strain of An. gambiae AgApoLp-III participates in midgut epithelial defense responses that limit Plasmodium infection. PMID:21072214

  16. Association of MiR-155 Expression with Prognosis in Resected 
Stage III Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yi GAO

    2014-05-01

    Full Text Available Background and objective Despite undergoing curative resection, the 5-year survival rate for stage III non-small cell lung cancer (NSCLC patients is less than 25%. There is a need for biomarkers for prediction of survival and guiding individual therapy. MiR-155 is one of most commonly upregulated miRNAs in malignancies, and regulates multiple pro-oncogenic pathways. We aimed to investigate the prognostic impact of miR-155 in resected stage III NSCLC patients. Methods Tumor formalin-fixed, paraffin-embedded (FFPE from 162 resected stage III NSCLC patients were collected. Total RNA including miRNA was extracted, and qRT-PCR was used to determine the expression of miR-155. Results Spearman rank correlation test showed a positive correlation between miR-155 expression and nodal status (r=0.169, P=0.032. MiR-155 expression had a significant prognostic impact in the total cohort (P<0.001, in squamous cell carcinomas (P=0.002 and in adenocarcinomas (P=0.003. In N0-1 subgroup, miR-155 expression did not have a significant prognostic on overall survival in univariate analysis (P=0.319. In N2 subgroup, miR-155 had a negative prognostic effect on OS in univariate analysis (P<0.001. Cox regression analysis revealed that miR-155 expression was unfavorable prognostic factors of OS (RR=2.311, 95%CI: 1.479-3.611, P<0.001. Conclusion High expression of miR-155 represents a valuable marker of poor clinical outcomes in patients with stage III NSCLC.

  17. UFT plus cisplatin with concurrent radiotherapy in unresectable stage III non-small cell lung cancer. Its application to outpatient practice

    International Nuclear Information System (INIS)

    Combination chemotherapy with tegafur-uracil (UFT) and cisplatin is active and less toxic for advanced non-small cell lung cancer. This treatment is likely to be applied to concurrent chemoradiotherapy for locally advanced non-small cell lung cancer, especially in the outpatient setting. Ten patients with unresectable stage III non-small cell lung cancer received the UFT plus cisplatin treatment combined with concurrent radiotherapy. The chemotherapeutic regimen consisted of oral administration of UFT 400 mg/m2 daily and venous infusion of cisplatin 20-25 mg/m2 on days 8-10. The administration of cisplatin was repeated every 3-4 weeks. Thoracic radiation started on day 8, and was completed to a total dose of 60-70 Gy. Adverse events (grade 3 or 4) occurred in 2 patients (esophagitis 2, leukopenia/neutropenia 1) with no treatment-related death. There were 7 partial responses (response rate 70.0%; 95% confidence interval (C.I.), 41.6-98.4%). The median survival time was 18.7 months with a 1-year survival rate of 77.8%. Two patients uneventfully received the treatment in an outpatient setting. With regard to the quality of life of patients, UFT plus cisplatin with concurrent radiotherapy might be the treatment of choice for unresectable stage III non-small cell lung cancer. (author)

  18. The role of fuel cells and electrolysers in future efficient energy systems

    DEFF Research Database (Denmark)

    Hendriksen, Peter Vang; Mathiesen, Brian Vad; Pedersen, Allan S.;

    2012-01-01

    Fuel cells can increase the efficiency of the energy system and electrolysers can help enable a de-carbonisation of the energy supply. In this chapter we explain the role of fuel cells in future energy systems together with the role of electrolysers in smart energy systems with increasing...

  19. Extraction and identification of exosomes from drug-resistant breast cancer cells and their potential role in cell-to-cell drug-resistance transfer

    Institute of Scientific and Technical Information of China (English)

    许金金

    2014-01-01

    Objective To explore whether docetaxel-resistant cells(MCF-7/Doc)and doxorubicin-resistant cells(MCF-7/ADM)can secrete Exosomes and their potential role in cell-cell drug-resistance transfer.Methods Exosomes were extracted from the cell culture supernatants of MCF-7/Doc and MCF-7/ADM cells by fractionation ultracentrifugation,and were identified by transmission

  20. Repeated administrations of human umbilical cord blood cells improve disease outcomes in a mouse model of Sanfilippo syndrome type III B.

    Science.gov (United States)

    Willing, Alison E; Garbuzova-Davis, Svitlana N; Zayko, Olga; Derasari, Hiranya M; Rawls, Ashley E; James, Chris R; Mervis, Ron F; Sanberg, Cyndy D; Kuzmin-Nichols, Nicole; Sanberg, Paul R

    2014-01-01

    Sanfilippo syndrome type III B (MPS III B) is an inherited disorder characterized by a deficiency of α-N-acetylglucosaminidase (Naglu) enzyme leading to accumulation of heparan sulfate in lysosomes and severe neurological deficits. We have previously shown that a single administration of human umbilical cord mononuclear cells (hUCB MNCs) into Naglu knockout mice decreased behavioral abnormalities and tissue pathology. In this study, we tested whether repeated doses of hUCB MNCs would be more beneficial than a single dose of cells. Naglu mice at 3 months of age were randomly assigned to either a Media-only group or one of three hUCB MNC treatment groups--single low dose (3 × 10(6) cells), single high dose (1.8 × 10(7) cells), or multiple doses (3 × 10(6) cells monthly for 6 months) delivered intravenously; cyclosporine was injected intraperitoneally to immune suppress the mice for the duration of the study. An additional control group of wild-type mice was also used. We measured anxiety in an open field test and cognition in an active avoidance test prior to treatment and then at monthly intervals for 6 months. hUCB MNCs restored normal anxiety-like behavior in these mice (p < 0.001). The repeated cell administrations also restored hippocampal cytoarchitecture, protected the dendritic tree, decreased GM3 ganglioside accumulation, and decreased microglial activation, particularly in the hippocampus and cortex. These data suggest that the neuroprotective effect of hUCB MNCs can be enhanced by repeated cell administrations. PMID:25565636