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Sample records for oncogene n-myc le

  1. Role of trace metals in cell proliferation in the human neuroblastoma: relations with the oncogene N-myc; Le role des metaux trace dans la proliferation des cellules de neuroblastome humaine: relations avec l`oncogene N-myc

    Energy Technology Data Exchange (ETDEWEB)

    Moretto, Ph.; Michelet, C. [Centre d`Etudes Nucleaires, Bordeaux-1 Univ., 33 Gradignan (France); Gouget, B.; Ortega, R.; Sergiant, C.; Llabador, Y.; Simonoff, M. [URA 451, Gradignan (France); Benard, J. [Laboratoire de Pharmacologie Clinique et Moleculaire, Institut Gustave Roussy, 94 - Villejuif (France)

    1997-06-01

    Neuroblastoma is one of the most common tumors in young children. Iron is known to be necessary for cellular proliferation. Several studies have suggested that neuroblastoma cells appear to be relatively sensitive to growth inhibition by specific Fe chelators, in vitro. In addition, it appeared that an increased serum ferritin level at diagnosis was associated with a poorer outcome than a normal level. On the other hand it was reported that untreated primary neuroblastoma had multiple copies of the N-myc oncogene. A significant association between genomic amplification and rapid tumor progression after diagnosis has been demonstrated. In order to study the relationship between iron N-myc amplification, we propose to determine the trace metal content of neuroblastoma cells. Preliminary results obtained with two distinct cell lines: SK-N-SH, a neuroblastoma cell line with a single copy of N-myc and IGR-N-91, a metastatic cell line exhibiting 60 copies of N-myc are presented. (authors) 8 refs.

  2. Loss of the N-myc oncogene in a patient with a small interstitial deletion of the short arm of chromosome 2

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    Saal, H.M. [Children`s Hospital Medical Center, Cincinnati, OH (United States); Johnson, R.C.; Carr, A.G.; Samango-Sprouse, C. [George Washington Univ. School of Medicine, Washington, DC (United States)] [and others

    1996-12-30

    To our knowledge, only four previous cases of distal chromosome 2p deletions exist in the literature. We present a patient with minor facial anomalies who had a distal interstitial deletion of the short arm of chromosome 2, del(2)(p24.2p25.1). This patient had many features seen in other patients with distal 2p deletion including short stature, {open_quotes}rectangular{close_quotes} facies, microcephaly, hypotonia, and mental retardation. This patient also has sensorineural hearing loss which has been described in one other patient with a similar deletion. The N-myc oncogene has been mapped to 2p24. By fluorescence in situ hybridization using a cDNA probe for the N-myc oncogene, this patient was found to have a deletion of the N-myc oncogene. This confirms the previous map location for N-myc. 17 refs., 3 figs., 1 tab.

  3. Radiosensitivity of small-cell lung cancer xenografts compared with activity of c-myc, N-myc, L-myc, c-raf-1 and K-ras proto-oncogenes

    DEFF Research Database (Denmark)

    Rygaard, K; Slebos, R J; Spang-Thomsen, M

    1991-01-01

    than CPH-54B, while, with respect to the 3 GLC tumours examined, GLC-16 was most sensitive, followed by GLC-14 and GLC-19. The CPH tumours expressed similar amounts of c-myc and c-raf-1 mRNA, and neither expressed N-myc or L-myc. GLC-14 expressed N-myc and c-raf-1 mRNA but no c-myc. GLC-16 and GLC-19...... expressed identical amounts of c-raf-1 and high levels of c-myc mRNA, but neither expressed N-myc or L-myc. None of the tumours was mutated at codon 12 or K-ras. Our results show that SCLC xenografts with different radiosensitivity may express identical amounts of some of the proto-oncogenes reported...... regrowth after single-dose irradiation. No long-term difference in expression of c-raf-1 or c-myc mRNA was detected between control tumours and tumours irradiated with 5 or 10 Gy....

  4. Progressive effects of N-myc deficiency on proliferation, neurogenesis, and morphogenesis in the olfactory epithelium.

    Science.gov (United States)

    Wittmann, Walter; Schimmang, Thomas; Gunhaga, Lena

    2014-06-01

    N-myc belongs to the myc proto-oncogene family, which is involved in numerous cellular processes such as proliferation, growth, apoptosis, and differentiation. Conditional deletion of N-myc in the mouse nervous system disrupted brain development, indicating that N-myc plays an essential role during neural development. How the development of the olfactory epithelium and neurogenesis within are affected by the loss of N-myc has, however, not been determined. To address these issues, we examined an N-myc(Foxg1Cre) conditional mouse line, in which N-myc is depleted in the olfactory epithelium. First changes in N-myc mutants were detected at E11.5, with reduced proliferation and neurogenesis in a slightly smaller olfactory epithelium. The phenotype was more pronounced at E13.5, with a complete lack of Hes5-positive progenitor cells, decreased proliferation, and neurogenesis. In addition, stereological analyses revealed reduced cell size of post-mitotic neurons in the olfactory epithelium, which contributed to a smaller olfactory pit. Furthermore, we observed diminished proliferation and neurogenesis also in the vomeronasal organ, which likewise was reduced in size. In addition, the generation of gonadotropin-releasing hormone neurons was severely reduced in N-myc mutants. Thus, diminished neurogenesis and proliferation in combination with smaller neurons might explain the morphological defects in the N-myc depleted olfactory structures. Moreover, our results suggest an important role for N-myc in regulating ongoing neurogenesis, in part by maintaining the Hes5-positive progenitor pool. In summary, our results provide evidence that N-myc deficiency in the olfactory epithelium progressively diminishes proliferation and neurogenesis with negative consequences at structural and cellular levels.

  5. N-myc regulates growth and fiber cell differentiation in lens development

    Science.gov (United States)

    Cavalheiro, Gabriel R.; Matos-Rodrigues, Gabriel E.; Zhao, Yilin; Gomes, Anielle L.; Anand, Deepti; Predes, Danilo; de Lima, Silmara; Abreu, Jose G.; Zheng, Deyou; Lachke, Salil A.; Cvekl, Ales; Martins, Rodrigo A. P.

    2017-01-01

    Myc proto-oncogenes regulate diverse cellular processes during development, but their roles during morphogenesis of specific tissues are not fully understood. We found that c-myc regulates cell proliferation in mouse lens development and previous genome-wide studies suggested functional roles for N-myc in developing lens. Here, we examined the role of N-myc in mouse lens development. Genetic inactivation of N-myc in the surface ectoderm or lens vesicle impaired eye and lens growth, while "late" inactivation in lens fibers had no effect. Unexpectedly, defective growth of N-myc--deficient lenses was not associated with alterations in lens progenitor cell proliferation or survival. Notably, N-myc-deficient lens exhibited a delay in degradation of DNA in terminally differentiating lens fiber cells. RNA-sequencing analysis of N-myc--deficient lenses identified a cohort of down-regulated genes associated with fiber cell differentiation that included DNaseIIβ. Further, an integrated analysis of differentially expressed genes in N-myc-deficient lens using normal lens expression patterns of iSyTE, N-myc-binding motif analysis and molecular interaction data from the String database led to the derivation of an N-myc-based gene regulatory network in the lens. Finally, analysis of N-myc and c-myc double-deficient lens demonstrated that these Myc genes cooperate to drive lens growth prior to lens vesicle stage. Together, these findings provide evidence for exclusive and cooperative functions of Myc transcription factors in mouse lens development and identify novel mechanisms by which N-myc regulates cell differentiation during eye morphogenesis. PMID:28716713

  6. Mechanism of endogenous myc gene down-regulation in E mu-N-myc tumors.

    OpenAIRE

    Ma, A; Smith, R. K.; Tesfaye, A.; Achacoso, P; Dildrop, R; Rosenberg, N; Alt, F W

    1991-01-01

    Transgenic mouse lines carrying the N-myc oncogene deregulated by the immunoglobulin heavy-chain enhancer spontaneously develop B-lymphoid tumors (R. Dildrop, A. Ma, K. Zimmerman, E. Hsu, A. Tesfaye, R. DePinho, and F. W. Alt, EMBO J. 8:1121-1128, 1989; H. Rosenbaum, E. Webb, J. M. Adams, S. Cory, and A. W. Harris, EMBO J. 8:749-755). Permanent cell lines derived from these tumors (E mu-N-myc cell lines) express extremely high levels of the N-myc transgene but little or no detectable endogeno...

  7. N-Myc Differentially Regulates Expression of MXI1 Isoforms in Neuroblastoma

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    Michael B. Armstrong

    2013-12-01

    Full Text Available Amplification of the MYCN proto-oncogene is associated with a poor prognosis in patients with metastatic neuroblastoma (NB. MYCN encodes the N-Myc protein, a transcriptional regulator that dimerizes with the Max transcription factor, binds to E-box DNA sequences, and regulates genes involved in cell growth and apoptosis. Overexpression of N-Myc leads to transcriptional activation and an increase in NB cell proliferation. Mxi1, a member of the Myc family of transcriptional regulators, also binds to Max. However, Mxi1 is a transcriptional repressor and inhibits proliferation of NB cells, suggesting that Mxi1 functions as an N-Myc antagonist. Our laboratory previously identified Mxi1-0, an alternatively transcribed Mxi1 isoform. Mxi1-0 has properties distinct from those of Mxi1; in contrast to Mxi1, Mxi1-0 is unable to suppress c-Myc-dependent transcription. We now show that Mxi1-0 expression increases in response to MYCN overexpression in NB cells, with a positive correlation between MYCN and MXI1-0 RNA levels. We also show that N-Myc expression differentially regulates the MXI1 and MXI1-0 promoters: Increased MYCN expression suppresses MXI1 promoter activity while enhancing transcription through the MXI1-0 promoter. Finally, induction of Mxi1-0 leads to increased proliferation, whereas expression of Mxi1 inhibits cell growth, indicating differential roles for these two proteins. These data suggest that N-Myc differentially regulates the expression of MXI1 and MXI1-0 and can alter the balance between the two transcription factors. Furthermore, MXI1-0 appears to be a downstream target of MYCN-dependent signaling pathways and may contribute to N-Myc-dependent cell growth and proliferation.

  8. Bcl-2 and N-Myc Coexpression Increases IGF-IR and Features of Malignant Growth in Neuroblastoma Cell Lines

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    Rama Jasty

    2001-01-01

    Full Text Available The bcl-2 and c-myc oncogenes cooperate to transform multiple cell types. In the pediatric malignancy NB2, Bcl2 is highly expressed. In tumors with a poor prognosis, N-Myc, a protein homologous to c-Myc, is overexpressed as a result of gene amplification. The present study was designed to determine whether Bcl-2 cooperates with N-Myc to bestow a tumorigenic phenotype to neuroblastoma (NB cells. NB cell lines that at baseline express neither Bcl-2 nor N-Myc were stably transfected to express these gene products. In this model, we found Bcl-2 rescues N-Myc-expressing cells from apoptosis induced by serum withdrawal. Coexpression of Bcl-2 and N-Myc supports growth in low serum conditions and anchorage-independent growth in soft agar. Similarly, in vivo tumorigenic and angiogenic activity was dependent on coexpression. Our data further suggests that the mechanism underlying these changes involves the receptor for insulin growth factor type I (IGF-IR.

  9. Nifurtimox reduces N-Myc expression and aerobic glycolysis in neuroblastoma.

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    Cabanillas Stanchi, Karin Melanie; Bruchelt, Gernot; Handgretinger, Rupert; Holzer, Ursula

    2015-01-01

    Neuroblastoma is one of the most common solid tumors in childhood and usually accompanied with poor prognosis and rapid tumor progression when diagnosed with amplification of the proto-oncogene N-Myc. The amplification of N-Myc has major influence on the maintenance of aerobic glycolysis, also known as the Warburg effect. This specific switch in the conversion of pyruvate to lactate instead of the conversion of pyruvate to acetyl-coenzyme A even in the presence of oxygen has important benefits for the tumor, e.g. increased production of enzymes and enzyme substrates that are involved in tumor progression, angiogenesis and inhibition of apoptosis. The antiprotozoal drug nifurtimox, which is generally used for the treatment of infections with the parasitic protozoan Trypanosoma cruzi, has been reported to have cytotoxic properties in the therapy of neuroblastoma. However, its action of mechanism has not been described in detail yet. The presented in vitro study on the neuroblastoma cell lines LA-N-1, IMR-32, LS and SK-N-SH shows an increased production of oxidative stress, a reduced lactate dehydrogenase enzyme activity and reduced lactate production after nifurtimox treatment. Furthermore, nifurtimox leads to reduced mRNA and protein levels of the proto-oncogene protein N-Myc. Thus, the current work gives new insights into the effect of nifurtimox on tumor metabolism revealing a shifted glucose metabolism from production of lactate to oxidative phosphorylation and a reduced expression of the major molecular prognostic factor in neuroblastoma N-Myc, presenting nifurtimox as a possible adjuvant therapeutic agent against (high risk) neuroblastoma.

  10. N-myc disrupts protein kinase C-mediated signal transduction in neuroblastoma

    NARCIS (Netherlands)

    Bernards, R.A.

    1991-01-01

    In neuroblastoma, amplification of the N-myc gene is closely correlated with increased metastatic ability. The mechanism by which N-myc acts to increase neuroblastoma malignancy is poorly understood as yet. It is shown here that transfection of N-myc in a neuroblastoma cell line causes suppression o

  11. SIRT1 Promotes N-Myc Oncogenesis through a Positive Feedback Loop Involving the Effects of MKP3 and ERK on N-Myc Protein Stability

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    Gherardi, Samuele; Scarlett, Christopher J.; Bedalov, Antonio; Xu, Ning; Iraci, Nuncio; Valli, Emanuele; Ling, Dora; Thomas, Wayne; van Bekkum, Margo; Sekyere, Eric; Jankowski, Kacper; Trahair, Toby; MacKenzie, Karen L.; Haber, Michelle; Norris, Murray D.; Biankin, Andrew V.; Perini, Giovanni; Liu, Tao

    2011-01-01

    The N-Myc oncoprotein is a critical factor in neuroblastoma tumorigenesis which requires additional mechanisms converting a low-level to a high-level N-Myc expression. N-Myc protein is stabilized when phosphorylated at Serine 62 by phosphorylated ERK protein. Here we describe a novel positive feedback loop whereby N-Myc directly induced the transcription of the class III histone deacetylase SIRT1, which in turn increased N-Myc protein stability. SIRT1 binds to Myc Box I domain of N-Myc protein to form a novel transcriptional repressor complex at gene promoter of mitogen-activated protein kinase phosphatase 3 (MKP3), leading to transcriptional repression of MKP3, ERK protein phosphorylation, N-Myc protein phosphorylation at Serine 62, and N-Myc protein stabilization. Importantly, SIRT1 was up-regulated, MKP3 down-regulated, in pre-cancerous cells, and preventative treatment with the SIRT1 inhibitor Cambinol reduced tumorigenesis in TH-MYCN transgenic mice. Our data demonstrate the important roles of SIRT1 in N-Myc oncogenesis and SIRT1 inhibitors in the prevention and therapy of N-Myc–induced neuroblastoma. PMID:21698133

  12. Sonic hedgehog elevates N-myc gene expression in neural stem cells.

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    Liu, Dongsheng; Wang, Shouyu; Cui, Yan; Shen, Lun; Du, Yanping; Li, Guilin; Zhang, Bo; Wang, Renzhi

    2012-08-05

    Proliferation of neural stem cells is regulated by the secreted signaling molecule sonic hedgehog. In this study, neural stem cells were infected with recombinant adeno-associated virus expressing sonic hedgehog-N-enhanced green fluorescent protein. The results showed that overexpression of sonic hedgehog in neural stem cells induced the increased expression of Gli1 and N-myc, a target gene of sonic hedgehog. These findings suggest that N-myc is a direct downstream target of the sonic hedgehog signal pathway in neural stem cells. Sonic hedgehog and N-myc are important mediators of sonic hedgehog-induced proliferation of neural stem cells.

  13. Sonic hedgehog elevates N-myc gene expression in neural stem cells★

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    Liu, Dongsheng; Wang, Shouyu; Cui, Yan; Shen, Lun; Du, Yanping; Li, Guilin; Zhang, Bo; Wang, Renzhi

    2012-01-01

    Proliferation of neural stem cells is regulated by the secreted signaling molecule sonic hedgehog. In this study, neural stem cells were infected with recombinant adeno-associated virus expressing sonic hedgehog-N-enhanced green fluorescent protein. The results showed that overexpression of sonic hedgehog in neural stem cells induced the increased expression of Gli1 and N-myc, a target gene of sonic hedgehog. These findings suggest that N-myc is a direct downstream target of the sonic hedgeho...

  14. N-myc Downstream Regulated Gene 1 (NDRG1 Is Fused to ERG in Prostate Cancer

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    Dorothee Pflueger

    2009-08-01

    Full Text Available A step toward the molecular classification of prostate cancer was the discovery of recurrent erythroblast transformation. specific rearrangements, most commonly fusing the androgen-regulated TMPRSS2 promoter to ERG. The TMPRSS2-ERG fusion is observed in around 90% of tumors that overexpress the oncogene ERG. The goal of the current study was to complete the characterization of these ERG-overexpressing prostate cancers. Using fluorescence in situ hybridization and reverse transcription.polymerase chain reaction assays, we screened 101 prostate cancers, identifying 34 cases (34% with the TMPRSS2-ERG fusion. Seven cases demonstrated ERG rearrangement by fluorescence in situ hybridization without the presence of TMPRSS2-ERG fusion messenger RNA transcripts. Screening for known 5' partners, we determined that three cases harbored the SLC45A3-ERG fusion. To discover novel 5' partners in these ERG-overexpressing and ERG-rearranged cases, we used paired-end RNA sequencing. We first confirmed the utility of this approach by identifying the TMPRSS2-ERG fusion in a known positive prostate cancer case and then discovered a novel fusion involving the androgen-inducible tumor suppressor, NDRG1 (N-myc downstream regulated gene 1, and ERG in two cases. Unlike TMPRSS2-ERG and SCL45A3-ERG fusions, the NDRG1-ERG fusion is predicted to encode a chimeric protein. Like TMPRSS2, SCL45A3 and NDRG1 are inducible not only by androgen but also by estrogen. This study demonstrates that most ERG-overexpressing prostate cancers harbor hormonally regulated TMPRSS2-ERG, SLC45A3-ERG, or NDRG1-ERG fusions. Broader implications of this study support the use of RNA sequencing to discover novel cancer translocations.

  15. N-Myc and GCN5 regulate significantly overlapping transcriptional programs in neural stem cells.

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    Verónica Martínez-Cerdeño

    Full Text Available Here we examine the functions of the Myc cofactor and histone acetyltransferase, GCN5/KAT2A, in neural stem and precursor cells (NSC using a conditional knockout approach driven by nestin-cre. Mice with GCN5-deficient NSC exhibit a 25% reduction in brain mass with a microcephaly phenotype similar to that observed in nestin-cre driven knockouts of c- or N-myc. In addition, the loss of GCN5 inhibits precursor cell proliferation and reduces their populations in vivo, as does loss of N-myc. Gene expression analysis indicates that about one-sixth of genes whose expression is affected by loss of GCN5 are also affected in the same manner by loss of N-myc. These findings strongly support the notion that GCN5 protein is a key N-Myc transcriptional cofactor in NSC, but are also consistent with recruitment of GCN5 by other transcription factors and the use by N-Myc of other histone acetyltransferases. Putative N-Myc/GCN5 coregulated transcriptional pathways include cell metabolism, cell cycle, chromatin, and neuron projection morphogenesis genes. GCN5 is also required for maintenance of histone acetylation both at its putative specific target genes and at Myc targets. Thus, we have defined an important role for GCN5 in NSC and provided evidence that GCN5 is an important Myc transcriptional cofactor in vivo.

  16. THE MYC FAMILY OF ONCOGENES AND THEIR PRESENCE AND IMPORTANCE IN SMALL-CELL LUNG-CARCINOMA AND OTHER TUMOR TYPES

    NARCIS (Netherlands)

    DEVRIES, EGE; MULDER, NH

    1993-01-01

    The myc family of cellular oncogenes, c - myr, N - myc, encodes three highly related, cell cycle specific, nuclear phosphoproteins. All are able to transform primary rat embryo fibroblasts when cotransfected with the c - ras oncogene. Myc family genes am differentially expressed with respect to tiss

  17. Sparstolonin B, a novel plant derived compound, arrests cell cycle and induces apoptosis in N-myc amplified and N-myc nonamplified neuroblastoma cells.

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    Ambrish Kumar

    Full Text Available Neuroblastoma is one of the most common solid tumors and accounts for ∼ 15% of all the cancer related deaths in the children. Despite the standard therapy for advanced disease including chemotherapy, surgery, and radiation, the mortality rate remains high for these patients. Hence, novel therapeutic agents are desperately needed. Here we examined the anticancer activity of a novel plant-derived compound, sparstolonin B (SsnB; 8,5'-dihydroxy-4-phenyl-5,2'-oxidoisocoumarin using neuroblastoma cell lines of different genetics. SsnB was recently isolated from an aquatic Chinese herb, Sparganium stoloniferum, and tubers of this herb have been used in traditional Chinese medicine for the treatment of several inflammatory diseases and cancers. Our cell viability and morphological analysis indicated that SsnB at 10 µM concentration significantly inhibited the growth of both N-myc amplified (SK-N-BE(2, NGP, and IMR-32 cells and N-myc nonamplified (SH-SY5Y and SKNF-1 cells neuroblastoma cells. The flow cytometric analyses suggested that SsnB arrests the cell cycle progression at G2-M phase in all neuroblastoma cell lines tested. Exposure of SsnB inhibited the compact spheroid formation and reduced the tumorigenicity of SH-SY5Y cells and SK-N-BE(2 cells in in vitro 3-D cell culture assays (anchorage-independent colony formation assay and hanging drop assay. SsnB lowers the cellular level of glutathione (GSH, increases generation of reactive oxygen species and activates the cleavage of caspase-3 whereas co-incubation of a GSH precursor, N-acetylcysteine, along with SsnB attenuates the inhibitory effects of SsnB and increases the neuroblastoma cell viability. Our results for the first time demonstrate that SsnB possesses anticancer activity indicating that SsnB-induced reactive oxygen species generation promotes apoptotic cell death in neuroblastoma cells of different genetic background. Thus these data suggest that SsnB can be a promising drug candidate

  18. WDR5 Supports an N-Myc Transcriptional Complex That Drives a Protumorigenic Gene Expression Signature in Neuroblastoma.

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    Sun, Yuting; Bell, Jessica L; Carter, Daniel; Gherardi, Samuele; Poulos, Rebecca C; Milazzo, Giorgio; Wong, Jason W H; Al-Awar, Rima; Tee, Andrew E; Liu, Pei Y; Liu, Bing; Atmadibrata, Bernard; Wong, Matthew; Trahair, Toby; Zhao, Quan; Shohet, Jason M; Haupt, Ygal; Schulte, Johannes H; Brown, Peter J; Arrowsmith, Cheryl H; Vedadi, Masoud; MacKenzie, Karen L; Hüttelmaier, Stefan; Perini, Giovanni; Marshall, Glenn M; Braithwaite, Antony; Liu, Tao

    2015-12-01

    MYCN gene amplification in neuroblastoma drives a gene expression program that correlates strongly with aggressive disease. Mechanistically, trimethylation of histone H3 lysine 4 (H3K4) at target gene promoters is a strict prerequisite for this transcriptional program to be enacted. WDR5 is a histone H3K4 presenter that has been found to have an essential role in H3K4 trimethylation. For this reason, in this study, we investigated the relationship between WDR5-mediated H3K4 trimethylation and N-Myc transcriptional programs in neuroblastoma cells. N-Myc upregulated WDR5 expression in neuroblastoma cells. Gene expression analysis revealed that WDR5 target genes included those with MYC-binding elements at promoters such as MDM2. We showed that WDR5 could form a protein complex at the MDM2 promoter with N-Myc, but not p53, leading to histone H3K4 trimethylation and activation of MDM2 transcription. RNAi-mediated attenuation of WDR5 upregulated expression of wild-type but not mutant p53, an effect associated with growth inhibition and apoptosis. Similarly, a small-molecule antagonist of WDR5 reduced N-Myc/WDR5 complex formation, N-Myc target gene expression, and cell growth in neuroblastoma cells. In MYCN-transgenic mice, WDR5 was overexpressed in precancerous ganglion and neuroblastoma cells compared with normal ganglion cells. Clinically, elevated levels of WDR5 in neuroblastoma specimens were an independent predictor of poor overall survival. Overall, our results identify WDR5 as a key cofactor for N-Myc-regulated transcriptional activation and tumorigenesis and as a novel therapeutic target for MYCN-amplified neuroblastomas.

  19. The expression and localization of N-myc downstream-regulated gene 1 in human trophoblasts.

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    Xiao-Hua Shi

    Full Text Available The protein N-Myc downstream-regulated gene 1 (NDRG1 is implicated in the regulation of cell proliferation, differentiation, and cellular stress response. NDRG1 is expressed in primary human trophoblasts, where it promotes cell viability and resistance to hypoxic injury. The mechanism of action of NDRG1 remains unknown. To gain further insight into the intracellular action of NDRG1, we analyzed the expression pattern and cellular localization of endogenous NDRG1 and transfected Myc-tagged NDRG1 in human trophoblasts exposed to diverse injuries. In standard conditions, NDRG1 was diffusely expressed in the cytoplasm at a low level. Hypoxia or the hypoxia mimetic cobalt chloride, but not serum deprivation, ultraviolet (UV light, or ionizing radiation, induced the expression of NDRG1 in human trophoblasts and the redistribution of NDRG1 into the nucleus and cytoplasmic membranes associated with the endoplasmic reticulum (ER and microtubules. Mutation of the phosphopantetheine attachment site (PPAS within NDRG1 abrogated this pattern of redistribution. Our results shed new light on the impact of cell injury on NDRG1 expression patterns, and suggest that the PPAS domain plays a key role in NDRG1's subcellular distribution.

  20. c-myc and N-myc promote active stem cell metabolism and cycling as architects of the developing brain.

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    Wey, Alice; Knoepfler, Paul S

    2010-06-01

    myc genes are associated with a wide variety of human cancers including most types of nervous system tumors. While the mechanisms by which myc overexpression causes tumorigenesis are multifaceted and have yet to be clearly elucidated, they are at least in part related to endogenous myc function in normal cells. Knockout (KO) of either c-myc or N-myc genes in neural stem and precursor cells (NSC) driven by nestin-cre impairs mouse brain growth and mutation of N-myc also causes microcephaly in humans in Feingold Syndrome. To further define myc function in NSC and nervous system development, we created a double KO (DKO) for c- and N-myc using nestin-cre. The DKO mice display profoundly impaired overall brain growth associated with decreased cell cycling and migration of NSC, which are strikingly decreased in number. The DKO brain also exhibits specific changes in gene expression including downregulation of genes involved in protein and nucleotide metabolism, mitosis, and chromatin structure as well as upregulation of genes associated with differentiation. Together these data support a model of nervous system tumorigenesis in which excess myc aberrantly locks in a developmentally active chromatin state characterized by overactive cell cycling, and metabolism as well as blocked differentiation.

  1. Reduced expression of N-Myc downstream-regulated gene 2 in human thyroid cancer

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    Ma Jianjun

    2008-10-01

    Full Text Available Abstract Background NDRG2 (N-Myc downstream-regulated gene 2 was initially cloned in our laboratory. Previous results have shown that NDRG2 expressed differentially in normal and cancer tissues. Specifically, NDRG2 mRNA was down-regulated or undetectable in several human cancers, and over-expression of NDRG2 inhibited the proliferation of cancer cells. NDRG2 also exerts important functions in cell differentiation and tumor suppression. However, it remains unclear whether NDRG2 participates in carcinogenesis of the thyroid. Methods In this study, we investigated the expression profile of human NDRG2 in thyroid adenomas and carcinomas, by examining tissues from individuals with thyroid adenomas (n = 40 and carcinomas (n = 35, along with corresponding normal tissues. Immunohistochemistry, quantitative RT-PCR and western blot methods were utilized to determine both the protein and mRNA expression status of Ndrg2 and c-Myc. Results The immunostaining analysis revealed a decrease of Ndrg2 expression in thyroid carcinomas. When comparing adenomas or carcinomas with adjacent normal tissue from the same individual, the mRNA expression level of NDRG2 was significantly decreased in thyroid carcinoma tissues, while there was little difference in adenoma tissues. This differential expression was confirmed at the protein level by western blotting. However, there were no significant correlations of NDRG2 expression with gender, age, different histotypes of thyroid cancers or distant metastases. Conclusion Our data indicates that NDRG2 may participate in thyroid carcinogenesis. This finding provides novel insight into the important role of NDRG2 in the development of thyroid carcinomas. Future studies are needed to address whether the down-regulation of NDRG2 is a cause or a consequence of the progression from a normal thyroid to a carcinoma.

  2. Severe acute respiratory syndrome coronavirus protein 6 mediates ubiquitin-dependent proteosomal degradation of N-Myc(and STAT) interactor

    Institute of Scientific and Technical Information of China (English)

    Weijia; Cheng; Shiyou; Chen; Ruiling; Li; Yu; Chen; Min; Wang; Deyin; Guo

    2015-01-01

    Severe acute respiratory syndrome coronavirus(SARS-Co V) encodes eight accessory proteins, the functions of which are not yet fully understood. SARS-Co V protein 6(P6) is one of the previously studied accessory proteins that have been documented to enhance viral replication and suppress host interferon(IFN) signaling pathways. Through yeast two-hybrid screening, we identified eight potential cellular P6-interacting proteins from a human spleen c DNA library. For further investigation, we targeted the IFN signaling pathway-mediating protein, N-Myc(and STAT) interactor(Nmi). Its interaction with P6 was confirmed within cells. The results showed that P6 can promote the ubiquitin-dependent proteosomal degradation of Nmi. This study revealed a new mechanism of SARS-Co V P6 in limiting the IFN signaling to promote SARS-Co V survival in host cells.

  3. Amino-terminal domains of c-myc and N-myc proteins mediate binding to the retinoblastoma gene product

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    Rustgi, Anil K.; Dyson, Nicholas; Bernards, Rene

    1991-08-01

    THE proteins encoded by the myc gene family are involved in the control of cell proliferation and differentiation, and aberrant expression of myc proteins has been implicated in the genesis of a variety of neoplasms1. In the carboxyl terminus, myc proteins have two domains that encode a basic domain/helix-loop-helix and a leucine zipper motif, respectively. These motifs are involved both in DNA binding and in protein dimerization2-5. In addition, myc protein family members share several regions of highly conserved amino acids in their amino termini that are essential for transformation6,7. We report here that an N-terminal domain present in both the c-myc and N-myc proteins mediates binding to the retinoblastoma gene product, pRb. We show that the human papilloma virus E7 protein competes with c-myc for binding to pRb, indicating that these proteins share overlapping binding sites on pRb. Furthermore, a mutant Rb protein from a human tumour cell line that carried a 35-amino-acid deletion in its C terminus failed to bind to c-myc. Our results suggest that c-myc and pRb cooperate through direct binding to control cell proliferation.

  4. Correlation of N-myc downstream-regulated gene 1 overexpression with progressive growth of colorectal neoplasm

    Institute of Scientific and Technical Information of China (English)

    Zhen Wang; Fang Wang; Wei-Qi Wang; Qian Gao; Wan-Li Wei; Yun Yang; Guo-Ying Wang

    2004-01-01

    AIM: To study the function of N-myc downstream-regulated gene 1 (NDRG1) in colorectal carcinogenesis and its correlation with tumor lymph node metastasis.METHODS: NDRG1 was detected at its protein level by immunohistochemistry (IHC) and image analysis (IA), and NDRG1 mRNA was detected by in situ hybridization (ISH)in formalin-fixed and paraffin-embedded sections with a total of 190 specimens including 38 normal colorectal mucosae, 31 colorectal adenomas, 45 non-metastatic colorectal carcinomas (CRCs), 38 metastatic primary CRC and subsequently regional lymph nodes respectively. At the same time, the correlations of NDRG1 with sex, age of patients and histological types of colorectal carcinomas were observed.RESULTS: NDRG1 proteins were gradually increased in colorectal carcinogenesis (P<0.05 or P<0.01). There was a significant difference in the expression of NDRG1 between non-metastatic and metastatic CRCs (P<0.05), and the correlation was positive (P<0.01, rs=0.329). However, there was no obvious difference in the expression of NDRG1 between the primary sites of CRCs and that in the metastatic sites of corresponding regional lymph nodes, nor was there an apparent difference in sex, age, and histological types.The expression of NDRG1 mRNA was generally in concordance with that of NDRG1 protein.CONCLUSION: NDRG1 gene may play an important role in colorectal carcinogenesis. In addition, NDRG1 may be a putative tumor metastasis promoter gene and is regarded as one of the molecular biological markers that can forecast early metastasis of CRCs. NDRG1 gene in the metastatic sites of regional lymph nodes may preserve its expression characteristics in the primary sites of CRCs to some extent.The expression of NDRG1 is not affected by sex, age and histological types. The role of NDRG1 in tumor metastatic process can be demonstrated byin vivo and in vitro.

  5. N-MYC down-regulated-like proteins regulate meristem initiation by modulating auxin transport and MAX2 expression.

    Directory of Open Access Journals (Sweden)

    Yashwanti Mudgil

    Full Text Available BACKGROUND: N-MYC down-regulated-like (NDL proteins interact with the Gβ subunit (AGB1 of the heterotrimeric G protein complex and play an important role in AGB1-dependent regulation of lateral root formation by affecting root auxin transport, auxin gradients and the steady-state levels of mRNA encoding the PIN-FORMED 2 and AUXIN 1 auxin transport facilitators. Auxin transport in aerial tissue follows different paths and utilizes different transporters than in roots; therefore, in the present study, we analyzed whether NDL proteins play an important role in AGB1-dependent, auxin-mediated meristem development. METHODOLOGY/PRINCIPAL FINDINGS: Expression levels of NDL gene family members need to be tightly regulated, and altered expression (both over-expression and down-regulation confers ectopic growth. Over-expression of NDL1 disrupts vegetative and reproductive organ development. Reduced expression of the NDL gene family members results in asymmetric leaf emergence, twinning of rosette leaves, defects in leaf formation, and abnormal silique distribution. Reduced expression of the NDL genes in the agb1-2 (null allele mutant rescues some of the abnormal phenotypes, such as silique morphology, silique distribution, and peduncle angle, suggesting that proper levels of NDL proteins are maintained by AGB1. We found that all of these abnormal aerial phenotypes due to altered NDL expression were associated with increases in basipetal auxin transport, altered auxin maxima and altered MAX2 expression within the inflorescence stem. CONCLUSION/SIGNIFICANCE: NDL proteins, together with AGB1, act as positive regulators of meristem initiation and branching. AGB1 and NDL1 positively regulate basipetal inflorescence auxin transport and modulate MAX2 expression in shoots, which in turn regulates organ and lateral meristem formation by the establishment and maintenance of auxin gradients.

  6. Oncogenic viruses and cancer

    Institute of Scientific and Technical Information of China (English)

    Guangxiang; George; Luo; Jing-hsiung; James; Ou

    2015-01-01

    <正>This special issue of the journal is dedicated to the important topic of oncogenic viruses and cancer.It contains seven review articles covering all known oncogenic viruses except for human T-lymphotropic virus type1(HTLV-1).These review articles are contributed by experts on specific viruses and their associated human cancers.Viruses account for about 20%of total human cancer cases.Although many viruses can cause various tumors in animals,only seven of them

  7. Imaging oncogene expression

    Energy Technology Data Exchange (ETDEWEB)

    Mukherjee, Archana [Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107 (United States)], E-mail: Archana.Mukherjee@jefferson.edu; Wickstrom, Eric [Department of Biochemistry and Molecular Biology, Thomas Jefferson University, 233S, 10th street, Philadelphia, PA 19107 (United States)], E-mail: eric@tesla.jci.tju.edu; Thakur, Mathew L. [Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107 (United States)], E-mail: Mathew.Thakur@jefferson.edu

    2009-05-15

    This review briefly outlines the importance of molecular imaging, particularly imaging of endogenous gene expression for noninvasive genetic analysis of radiographic masses. The concept of antisense imaging agents and the advantages and challenges in the development of hybridization probes for in vivo imaging are described. An overview of the investigations on oncogene expression imaging is given. Finally, the need for further improvement in antisense-based imaging agents and directions to improve oncogene mRNA targeting is stated.

  8. Lack of Rb and p53 delays cerebellar development and predisposes to large cell anaplastic medulloblastoma through amplification of N-Myc and Ptch2.

    Science.gov (United States)

    Shakhova, Olga; Leung, Carly; van Montfort, Erwin; Berns, Anton; Marino, Silvia

    2006-05-15

    Medulloblastomas are among the most common malignant brain tumors in childhood. They typically arise from neoplastic transformation of granule cell precursors in the cerebellum via deregulation of molecular pathways involved in normal cerebellar development. In a mouse model, we show here that impairment of the balance between proliferation and differentiation of granule cell precursors in the external granular layer of the developing cerebellum predisposes but is not sufficient to induce neoplastic transformation of these progenitor cells. Using array-based chromosomal comparative genomic hybridization, we show that genetic instability resulting from inactivation of the p53 pathway together with deregulation of proliferation induced by Rb loss eventually leads to neoplastic transformation of these cells by acquiring additional genetic mutations, mainly affecting N-Myc and Ptch2 genes. Moreover, we show that p53 loss influences molecular mechanisms that cannot be mimicked by the loss of either p19(ARF), p21, or ATM.

  9. Relation Among DNA Content, N-myc Gene Amplification and the Clinical Prognosis%小儿神经母细胞瘤DNA含量、N-myc基因扩增与临床预后的关系

    Institute of Scientific and Technical Information of China (English)

    刘获; 吴建新; 呼守生; 马汝柏; 林久治

    1995-01-01

    本文比较分析了18例神经母细胞瘤的DNA含量、N-myc基因扩增、临床分期、原发部位等因素与预后的关系.结果表明,有N-myc基因扩增的死亡率(7/10)明显高于无扩增的(1/8);DNA含量增高与肿瘤的恶性度成正比;临床分期与N-myc基因扩增情况相结合与病死率的关系极为密切.%In this study, 18 children with neuroblastoma were analysed on the relation among DNA content, N-myc gene amplification and the clinical staging. The results reveal; the mortality of patients with N-myc gene amplification (7/10) was higher than those without N-myc gene amplification (1/8); DNA content was related to malignancy of the tumor, combination of N-myc gene amplification and the clinical staging kept close link with the prognosis.

  10. Pesticides and oncogenic modulation.

    Science.gov (United States)

    Vakonaki, Elena; Androutsopoulos, Vasilis P; Liesivuori, Jyrki; Tsatsakis, Aristidis M; Spandidos, Demetrios A

    2013-05-10

    Pesticides constitute a diverse class of chemicals used for the protection of agricultural products. Several lines of evidence demonstrate that organochlorine and organophosphate pesticides can cause malignant transformation of cells in in vitro and in vivo models. In the current minireview a comprehensive summary of recent in vitro findings is presented along with data reported from human population studies, regarding the impact of pesticide exposure on activation or dysregulation of oncogenes and tumor suppressor genes. Substantial mechanistic work suggests that pesticides are capable of inducing mutations in oncogenes and increase their transcriptional expression in vitro, whereas human population studies indicate associations between pesticide exposure levels and mutation occurrence in cancer-related genes. Further work is required to fully explore the exact mechanisms by which pesticide exposure affects the integrity and normal function of oncogenes and tumor suppressor genes in human populations.

  11. N-myc downstream regulated gene 1 (NDRG1 promotes metastasis of human scirrhous gastric cancer cells through epithelial mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    Hiroki Ureshino

    Full Text Available Our recent study demonstrated that higher expression of N-myc downregulated gene 1 (NDRG1 is closely correlated with poor prognosis in gastric cancer patients. In this study, we asked whether NDRG1 has pivotal roles in malignant progression including metastasis of gastric cancer cells. By gene expression microarray analysis expression of NDRG1 showed the higher increase among a total of 3691 up-regulated genes in a highly metastatic gastric cancer cell line (58As1 than their parental low metastatic counterpart (HSC-58. The highly metastatic cell lines showed decreased expression of E-cadherin, together with enhanced expression of vimentin and Snail. This decreased expression of E-cadherin was restored by Snail knockdown in highly metastatic cell lines. We next established stable NDRG1 knockdown cell lines (As1/Sic50 and As1/Sic54 from the highly metastatic cell line, and both of these cell lines showed enhanced expression of E-cadherin and decreased expression of vimentin and Snail. And also, E-cadherin promoter-driven luciferase activity was found to be increased by NDRG1 knockdown in the highly metastatic cell line. NDRG1 knockdown in gastric cancer cell showed suppressed invasion of cancer cells into surround tissues, suppressed metastasis to the peritoneum and decreased ascites accumulation in mice with significantly improved survival rates. This is the first study to demonstrate that NDRG1 plays its pivotal role in the malignant progression of gastric cancer through epithelial mesenchymal transition.

  12. Correlation of N-myc downstream-regulated gene 1 expression with clinical outcomes of colorectal cancer patients of different race/ethnicity

    Institute of Scientific and Technical Information of China (English)

    Minori Koshiji; Thérèse Commes; David Piquemal; Curtis C Harris; Kam-Meng Tchou-Wong; Kensuke Kumamoto; Keiichirou Morimura; Yasufumi Utsumi; Michiko Aizawa; Masami Hoshino; Shinji Ohki; Seiichi Takenoshita; Max Costa

    2007-01-01

    AIM:To evaluate the role of N-myc downstreamregulated gene 1 (NDRG1) expression in prognosis and survival of colorectal cancer patients with different ethnic backgrounds.METHODS: Because NDRG1 is a downstream target of p53 and hypoxia inducible factor-1α (HIF-1α), we examined NDRG1 expression together with p53 and HIF1α by immunohistochemistry. A total of 157 colorectal cancer specimens including 80 from Japanese patients and 77 from US patients were examined. The correlation between protein expression with clinicopathological features and survival after surgery was analyzed.RESULTS: NDRG1 protein was significantly increased in colorectal tumor compared with normal epithelium in both Japanese and US patient groups. Expression of NDRG1 protein was significantly correlated with lymphatic invasion, venous invasion, depth of invasion,histopathological type, and Dukes'stage in Japanese colorectal cancer patients. NDRG1 expression was correlated to histopathological type, Dukes'stage and HIF-1α expression in US-Caucasian patients but not in US-African American patients. Interestingly, Kaplan-Meier survival analysis demonstrated that NDRG1 expression correlated significantly with poorer survival in US-African American patients but not in other patient groups.However, in p53-positive US cases, NDRG1 positivity correlated significantly with better survival. In addition,NDRG1 expression also correlated significantly with improved survival in US patients with stages Ⅲ and Ⅳtumors without chemotherapy. In Japanese patients with stages Ⅱ and Ⅲ tumors, strong NDRG1 staining in p53-positive tumors correlated significantly with improved survival but negatively in patients without chemotherapy.CONCLUSION: NDRG1 expression was correlated with various clinicopathological features and clinical outcomes in colorectal cancer depending on the race/ethnicity of the patients. NDRG1 may serve as a biological basis for the disparity of clinical outcomes of colorectal cancer

  13. Oncogenes in melanoma: an update.

    Science.gov (United States)

    Kunz, Manfred

    2014-01-01

    Melanoma is a highly aggressive tumour with poor prognosis in the metastatic stage. BRAF, NRAS, and KIT are three well-known oncogenes involved in melanoma pathogenesis. Targeting of mutated BRAF kinase has recently been shown to significantly improve overall survival of metastatic melanoma patients, underscoring the particular role of this oncogene in melanoma biology. However, recurrences regularly occur within several months, which supposedly involve further oncogenes. Moreover, oncogenic driver mutations have not been described for up to 30% of all melanomas. In order to obtain a more complete picture of the mutational landscape of melanoma, more recent studies used high-throughput DNA sequencing technologies. A number of new oncogene candidates such as MAPK1/2, ERBB4, GRIN2A, GRM3, RAC1, and PREX2 were identified. Their particular role in melanoma biology is currently under investigation. Evidence for the functional relevance of some of these new oncogene candidates has been provided in in vitro and in vivo experiments. However, these findings await further validation in clinical studies. This review provides an overview on well-known melanoma oncogenes and new oncogene candidates, based on recent high-throughput sequencing studies. The list of genes discussed herein is of course not complete but highlights some of the most significant of recent findings in this area. The new candidates may support more individualized treatment approaches for metastatic melanoma patients in the future.

  14. Foxm1 transcription factor is required for the initiation of lung tumorigenesis by oncogenic Kras(G12D.).

    Science.gov (United States)

    Wang, I-C; Ustiyan, V; Zhang, Y; Cai, Y; Kalin, T V; Kalinichenko, V V

    2014-11-13

    Lung cancer is the leading cause of deaths in cancer patients in the United States. Identification of new molecular targets is clearly needed to improve therapeutic outcomes of this devastating human disease. Activating mutations in K-Ras oncogene and increased expression of FOXM1 protein are associated with poor prognosis in patients with non-small-cell lung cancer. Transgenic expression of activated Kras(G12D) in mouse respiratory epithelium is sufficient to induce lung adenocarcinomas; however, transcriptional mechanisms regulated by K-Ras during the initiation of lung cancer remain poorly understood. Foxm1 transcription factor, a downstream target of K-Ras, stimulates cellular proliferation during embryogenesis, organ repair and tumor growth, but its role in tumor initiation is unknown. In the present study, we used transgenic mice expressing Kras(G12D) under control of Sftpc promoter to demonstrate that Foxm1 was induced in type II epithelial cells before the formation of lung tumors. Conditional deletion of Foxm1 from Kras(G12D)-expressing respiratory epithelium prevented the initiation of lung tumors in vivo. The loss of Foxm1 inhibited expression of K-Ras target genes critical for the nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathways, including Ikbkb, Nfkb1, Nfkb2, Rela, Jnk1, N-Myc, Pttg1 and Cdkn2a. Transgenic overexpression of activated FOXM1 mutant was sufficient to induce expression of these genes in alveolar type II cells. FOXM1 directly bound to promoter regions of Ikbkb, Nfkb2, N-Myc, Pttg1 and Cdkn2a, indicating that these genes are direct FOXM1 targets. FOXM1 is required for K-Ras-mediated lung tumorigenesis by activating genes critical for the NF-κB and JNK pathways.

  15. Le funambule et le parergon

    Directory of Open Access Journals (Sweden)

    Xavier Jeudon

    2015-09-01

    Full Text Available Loin de la fascination qu’exerce la chute, promesse de renouveau pour Baudelaire et de plaisir pour Adorno, le funambule fait quotidiennement l’expérience d’une prise et d’une maîtrise du risque. Faisant du risque un spectacle, le funambule évolue sur un fil, nous renvoyant aux premières sensations de la marche, mal assurée, hésitante et tellement audacieuse. Le funambule travaillant au quotidien son équilibre se doit donc de prendre des risques, mais aussi de donner l’illusion d’une première fois : simuler le danger là où il est pourtant. C’est en jouant sur le moment de la rupture, de la chute que le funambule capte l’attention. Il donne un corps à cette question de la limite et semble nous proposer une adaptation douce au risque, là où le dompteur parait s’y opposer plus frontalement.

  16. Le Comique

    OpenAIRE

    Pasquier, Renaud

    2011-01-01

    J’ai pris un trait d’un côté et un trait d’un autre ; et de ces divers traitsqui pouvaient convenir à une même personne, j’en ai fait des peinturesvraisemblables, cherchant moins à réjouir les lecteurs par le caractère,ou comme le disent les mécontents, par la satire de quelqu’un, qu’à leurproposer des défauts à éviter et des modèles à suivre.Jean de La Bruyère, Discours de réception à l’Académie française, 1693. Le spectacle s’achève après deux rappels sous les applaudissements d’un public c...

  17. Le Japon

    OpenAIRE

    Aveline, Natacha

    2004-01-01

    Ouvrage général de géographie et d'économie du Japon comportant de nombreuses illlustrations, une bibliographie commentée et des sujets pour les examens de géographie.; Cet ouvrage examine l'organisation spatiale du modèle de croissance japonais à toutes ses étapes, de ses origines (de l'époque Meiji à la fin du XIXe siècle) à la crise de Heisei (de 1991 à nos jours). Il fait état de la diversité des défis auxquels est confronté l'archipel dans le nouveau contexte mondialisé. Le regard se por...

  18. Oncogenic cancer/testis antigens

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Andersen, Mads H; Ditzel, Henrik J

    2015-01-01

    Recent developments have set the stage for immunotherapy as a supplement to conventional cancer treatment. Consequently, a significant effort is required to further improve efficacy and specificity, particularly the identification of optimal therapeutic targets for clinical testing. Cancer....../testis antigens are immunogenic, highly cancer-specific, and frequently expressed in various types of cancer, which make them promising candidate targets for cancer immunotherapy, including cancer vaccination and adoptive T-cell transfer with chimeric T-cell receptors. Our current understanding of tumor...... immunology and immune escape suggests that targeting oncogenic antigens may be beneficial, meaning that identification of cancer/testis antigens with oncogenic properties is of high priority. Recent work from our lab and others provide evidence that many cancer/testis antigens, in fact, have oncogenic...

  19. Le Tissu et le texte

    OpenAIRE

    Jean-Marie Lassus

    2010-01-01

    Le premier chapitre de La tumba del relámpago (1978) de l’écrivain péruvien Manuel Scorza synthétise une grande partie de la problématique de La guerra silenciosa, sa fresque de cinq romans racontant la lutte interminable des comuneros des Andes Centrales dans leur quête de justice et de reconnaissance, à partir de faits réels survenus dans le Pérou de la fin des années cinquante. Dans ce chapitre, la lecture du tissu de Doña Añada par Remigio Villena amène ce dernier à interpréter le dilemme...

  20. Le Sanskrit

    CERN Document Server

    Balbir, Nalini

    2013-01-01

    Cet ouvrage est destiné à tous ceux qui souhaitent se mettre ou se remettre à l'étude du sanskrit et ne peuvent y consacrer que quelques minutes par jour. En suivant le principe de la méthode quotidienne Assimil, vous acquerrez progressivement le vocabulaire et la grammaire de base qui sont nécessaires à la lecture des textes de la littérature sanskrite classique. Vous trouverez dans cette méthode une approche vivante de la langue et de la culture sanskrite classique à travers des textes d'abord adaptés pour le débutant puis authentiques. En quelques mois, vous manierez la langue sans efforts ni hésitation, de manière très naturelle. Les enregistrements reprennent l'intégralité des textes en sanskrit des leçons et des exercices de traduction du livre. Ils sont interprétés, à un rythme progressif, par des locuteurs natifs professionnels.

  1. Le vieillard et le chevalier

    Directory of Open Access Journals (Sweden)

    Mélanie JECKER

    2008-04-01

    Full Text Available Éléments introductifs Ces réflexions initiales n’auront pas pour point de départ le rappel du problème posé par la présence de vieillards toujours plus nombreux au sein de nos sociétés contemporaines. Je ne nie pas l’importance ni l’intérêt du phénomène relativement récent du vieillissement de la population en Occident, mais ce constat ne fut pas à l’origine de mon travail. Ce qui a porté ma curiosité vers le thème des âges de la vie n’est pas mon propre présent mais l’attrait et même, oserai...

  2. N-myc downstream-regulated gene 2 (NDRG2) suppresses the epithelial-mesenchymal transition (EMT) in breast cancer cells via STAT3/Snail signaling.

    Science.gov (United States)

    Kim, Myung-Jin; Lim, Jihyun; Yang, Young; Lee, Myeong-Sok; Lim, Jong-Seok

    2014-11-01

    Although NDRG2 has recently been found to be a candidate tumor suppressor, its precise role in the epithelial-mesenchymal transition (EMT) is not well understood. In the present study, we demonstrated that NDRG2 overexpression in MDA-MB-231 cells down-regulated the expression of Snail, a transcriptional repressor of E-cadherin and a key regulator of EMT, as well as the phosphorylation of signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor that is activated in many human malignancies including breast cancer. In addition, we confirmed that the expression of Snail and phospho-STAT3 was recovered when NDRG2 was knocked down by siRNA in MCF7 cells in which NDRG2 is endogenously expressed. Interestingly, MDA-MB-231-NDRG2 cells showed remarkably decreased Snail expression after treatment with JSI-124 (also known as cucurbitacin I) or Stattic, STAT3 inhibitors, compared to MDA-MB-231-mock cells. Moreover, STAT3 activation by EGF treatment induced higher Snail expression, and NDRG2 overexpression resulted in the inhibition of Snail expression in MDA-MB-231 cells stimulated by EGF in the absence or presence of STAT3 inhibitor. Treatment of MDA-MB-231 cells with STAT3 inhibitor led to a moderate decrease in wound healing and migration capacity, whereas STAT3 inhibitor treatment of MDA-MB-231-NDRG2 cells resulted in a significant attenuation of migration in both resting and EGF-stimulated cells. Collectively, our data demonstrate that the inhibition of STAT3 signaling by NDRG2 suppresses EMT progression of EMT via the down-regulation of Snail expression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Oncogenicity of human N-ras oncogene and proto-oncogene introduced into retroviral vectors

    Energy Technology Data Exchange (ETDEWEB)

    Souyri, M.; Vigon, I.; Charon, M.; Tambourin, P. (Hopital Cochin, Paris (France))

    1989-09-01

    The N-ras gene is the only member of the ras family which has never been naturally transduced into a retrovirus. In order to study the in vitro and in vivo oncogenicity of N-ras and to compare its pathogenicity to that of H-ras, the authors have inserted an activated or a normal form of human N-ras cDNA into a slightly modified Harvey murine sarcoma virus-derived vector in which the H-ras p21 coding region had been deleted. The resulting constructions were transfected into NIH 3T3 cells. The activated N-ras-containing construct (HSN) induced 10{sup 4} foci per {mu}g of DNA and was found to be as transforming as H-ras was. After infection of the transfected cells by either the ecotropic Moloney murine leukemia virus or the amphotropic 4070A helper viruses, rescued transforming viruses were injected into newborn mice. Both pseudotypes of HSN virus containing activated N-ras induced the typical Harvey disease with similar latency. However, they found that the virus which contained normal N-ras p21 (HSn) was also pathogenic and induced splenomegaly, lymphadenopathies, and sarcoma in mice after a latency of 3 to 7 weeks. In addition, Moloney murine leukemia virus pseudotypes of N-ras caused neurological disorders in 30% of the infected animals. These results differed markedly from those of previous experiments in which the authors had inserted the activated form of N-ras in the pSV(X) vector: the resulting SVN-ras virus was transforming on NIH 3T3 cells but was poorly oncogenic in vivo. Altogether, these data demonstrated unequivocally that N-ras is potentially as oncogenic as H-ras and that such oncogenic effect could depend on the vector environment.

  4. Oncogenic Brain Metazoan Parasite Infection

    Directory of Open Access Journals (Sweden)

    Angela N. Spurgeon

    2013-01-01

    Full Text Available Multiple observations suggest that certain parasitic infections can be oncogenic. Among these, neurocysticercosis is associated with increased risk for gliomas and hematologic malignancies. We report the case of a 71-year-old woman with colocalization of a metazoan parasite, possibly cysticercosis, and a WHO grade IV neuroepithelial tumor with exclusively neuronal differentiation by immunohistochemical stains (immunopositive for synaptophysin, neurofilament protein, and Neu-N and not for GFAP, vimentin, or S100. The colocalization and temporal relationship of these two entities suggest a causal relationship.

  5. RU486 (mifepristone) ameliorates cognitive dysfunction and reverses the down-regulation of astrocytic N-myc downstream-regulated gene 2 in streptozotocin-induced type-1 diabetic rats.

    Science.gov (United States)

    Zuo, Z-F; Wang, W; Niu, L; Kou, Z-Z; Zhu, C; Wang, W; Zhao, X-H; Luo, D-S; Zhang, T; Zhang, F-X; Liu, X-Z; Wu, S-X; Li, Y-Q

    2011-09-08

    Diabetic cognitive dysfunction (DCD), usually accompanied with chronically elevated glucocorticoids and hippocampal astrocytic alterations, is one of the most serious complications in patients with type-1 diabetes. However, the role for chronically elevated glucocorticoids and hippocampal astrocytic activations in DCD remains to be elucidated, and it is not clear whether astrocytic N-myc downstream-regulated gene 2 (NDRG2, involved in cell differentiation and development) participated in DCD. In the present study, three months after streptozotocin (STZ)-induced type-1 diabetes onset, rats showed cognitive impairments in Morris water maze test as well as elevated corticosterone level. Diabetic rats also presented down-regulation of glial fibrillary acidic protein (GFAP, a key indicator of astrocytic reactivity) and NDRG2 in hippocampus revealed by immunohistochemistry staining, real-time PCR and Western blot. Moreover, the diabetic cognitive impairments were ameliorated by 9-day glucocorticoids receptor (GR) blockade with RU486, and the down-regulation of hippocampal NDRG2 and GFAP in diabetic animals was also attenuated by 9-day GR blockade. These results suggest that glucocorticoids-GR system is crucial for DCD, and that astrocytic reactivity and NDRG2 are involved in these processes. Thus, inhibiting GR activation in the hippocampus may be a novel therapeutic strategy for treating DCD.

  6. Le savant et le politique

    Directory of Open Access Journals (Sweden)

    Philippe Corcuff

    2011-07-01

    Full Text Available L’article s’efforce de reproblématiser de manière équilibrée la question épistémologique du rapport entre le savant et le politique, en trois étapes. Tout d’abord, il revient sur les complications weberiennes concernant « la neutralité axiologique », en ce qu’elles sont éloignées du neutralisme unilatéral défendu par Nathalie Heinich. Ensuite, il va puiser dans des ressources philosophiques chez Maurice Merleau-Ponty et dans des ressources sociologiques chez Norbert Elias afin de traiter de manière nuancée les relations distanciation/engagement dans la perspective d’une distanciation compréhensive. Enfin, il termine par quatre propositions épistémologiques synthétiques valorisant une autonomie de l’activité scientifique émancipée du scientisme.The scientist and the politicsThis article attempts to problematize in a balanced way the epistemological question of the relationship between the scientist and the politics in three steps. At first, it will discuss the weberian complications regarding “axiological neutrality” in its remoteness to the unilateral neutralism defended by Nathalie Heinich. Then, it will seek within Maurice Merleau-Ponty’s philosophical resources and Norbert Elias’ sociological resources in order to treat with nuance the distanciation/engagement relationship from a comprehensive distancing perspective. At last, it will end with four synthetic epistemological proposals valuing autonomous scientific activity, emancipated from scientism.El intelectual y el políticoEl articulo hace hincapié en la necesidad de plantear de manera equilibrada el tema epistemológico de la relación entre el intelectual y el político. Puede efectuarse en tres etapas. En primer lugar el autor subraya la preocupación weberiana por la « neutralidad axiológica » en la medida en que es opuesta a la neutralidad unilateral de Nathalie Heinich. Seguidamente se apoya en los recursos filosóficos de Merleau

  7. 40 CFR 798.3300 - Oncogenicity.

    Science.gov (United States)

    2010-07-01

    ... Species of Experimental Animals for Inhalation Carcinogenicity Studies” Paper presented at Conference on...) HEALTH EFFECTS TESTING GUIDELINES Chronic Exposure § 798.3300 Oncogenicity. (a) Purpose. The objective of a long-term oncogenicity study is to observe test animals for a major portion of their life span for...

  8. Le vieillard et le chevalier

    Directory of Open Access Journals (Sweden)

    Mélanie JECKER

    2010-05-01

    Full Text Available La fin du Moyen Âge fascine. Deux facteurs principaux expliquent l’attraction qu’exerce cette période : elle apparaît d’une part comme un moment historique riche car double, phase de transition entre le Moyen Âge et la Renaissance, où se mêlent des cadres de représentation anciens et nouveaux. L’insinuation d’une pensée humaniste balbutiante s’y traduirait notamment par l’émergence de la notion d’individu, qui constitue l’un des objets de ce travail. Il faut invoquer, d’autre part, l’image macabre d’un bas Moyen Âge hanté par l’idée de la maladie et de la mort depuis l’épidémie de peste noire de 1348, obsédé par la brièveté de la vie humaine. Ces deux facettes de « l’automne du Moyen Âge » tel que l’évoque avec poésie Joan Huizinga sont-elles autre chose qu’une plaisante image d’Epinal? Cette étude cherche précisément à déterminer le degré de validité de ces deux topiques, à travers l’analyse de la représentation des âges de la vie dans un corpus bien défini, celui de la biographie chevaleresque castillane du XVe siècle. L’intérêt porté à l’individu, la conscience de la singularité impliquent en effet celle du caractère mouvant de la personne, or quel thème mieux que celui des âges permet de confirmer ou d’infirmer l’hypothèse du surgissement d’une nouvelle manière de concevoir l’homme, proprement « renaissante », en ce siècle de transition , La nature même du corpus retenu – des récits biographiques – suggère en effet une mutation dans l’appréhension de la personne, une attention prêtée à sa progressive transformation. L’étude de la représentation de la vieillesse, en particulier, révèle non seulement à quel point était alors réelle cette prétendue obsession de la déchéance physique et de la mortalité, mais aussi dans quelle mesure étaient soulignés et valorisés les changements individuels parallèles à l

  9. Le roi est mort!: Vive le roi?

    Directory of Open Access Journals (Sweden)

    Urias Arantes

    1992-12-01

    Full Text Available Ce texte examine critiquement les points d'appui et propos philosophiques du projet culturel néomoderne (Habermas, Roùanet, interroge le lien avoué entre modernité et néomodernisme, le débat de celui-ci avec les irrationalismes post-modernes, explicite préssuppositions et inconsistances du projet néomoderne ainsi que ce que le néomodernisme laisse dans l'ombre dans son rachat de la modernité et ce que par conséquent il ne peut pas penser. Sous le fil conducteur de la critique du néomodernisme, on a souligné une sorte de "fuite en avant" qui serait le destin commun des intellectuels brésiliens, la possibilité et la limite de leur existence sociale.

  10. Amplification of cellular oncogenes in solid tumors

    Directory of Open Access Journals (Sweden)

    Ozkan Bagci

    2015-01-01

    Full Text Available The term gene amplification refers to an increase in copy number of a gene. Upregulation of gene expression through amplification is a general mechanism to increase gene dosage. Oncogene amplifications have been shown in solid human cancers and they are often associated with progression of cancer. Defining oncogene amplification is useful since it is used as a prognostic marker in clinical oncology nowadays, especially v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (HER2 targeted agents are used in breast cancer patients with high level of HER2 overexpression as a therapeutic approach. However, patients without HER2 overexpression do not appear to benefit from these agents. We concluded that determination of oncogene amplification in solid tumors is an important factor in treatment of human cancers with many unknowns. We have referred to PubMed and some databases to prepare this article.

  11. Le Valais bilingue

    Directory of Open Access Journals (Sweden)

    Mathieu Petite

    2010-09-01

    Full Text Available Le Valais est l’un des trois cantons bilingues de la Suisse. 63 % de sa population parle le français dans la partie ouest du canton et 28 % l’allemand dans sa partie est. Ce « plurilinguisme de juxtaposition » (pour reprendre le terme d’André-Louis Sanguin dans sa Géographie politique de la Suisse soulève des questions politiques et sociales qu’ambitionne de traiter l’ouvrage des linguistes Iwar Werlen, Verena Tunger et Ursula Frei. Le constat auquel aboutit cette recherche sur le bilinguism...

  12. Le temps en images

    CERN Document Server

    Callender, Craig

    2014-01-01

    Qu'est-ce que le temps ? Le célèbre philosophe du Ve siècle, St Augustin, a dit qu'il savait ce qu'était le temps, tant que personne ne le lui demandait... Le temps est-il une quatrième dimension similaire à l'espace ou s'écoule-t-il dans un certain sens ? Et si le temps passe, est-il sensé de dire à quelle vitesse ? Est-ce que l'avenir existe ? Voyager dans le temps est-il possible ? Ce livre aborde ces questions et d'autres parmi les plus profondes et plus subtiles que l'on puisse se poser sur cette notion essentielle dans notre vie.

  13. Expression and distribution of N-myc downstream regulated gene 2 in pancreatic diseases%胰腺疾病组织N-myc下游调节基因2的表达与分布

    Institute of Scientific and Technical Information of China (English)

    贺菲菲; 焦凯; 刘新平; 沈岚

    2013-01-01

    The pancreatic tissues from patients with islet cell hyperplasia,insulinoma,and pancreatic adenocarcinoma,as well as normal pancreatic tissues were embedded with paraffin,serial sections were cut and mounted on glass slides.Immunohistochemical staining was carried out with N-myc down-stream regulated gene 2 (Ndrg2) monoclonal antibody by means of ABC method,and Western blotting was carried out to detect the expression and distribution of Ndrg2.The results showed that Ndrg2 positive immunoreactivity was mainly localized in the cytoplasm of islet cell,being similar to the localization of insulin positive immunoreactivity.The number and volume of pancreatic islets were increased in the patients with islet cell hyperplasia,and Ndrg2 expression was also increased.Western blotting results showed that the expression of Ndrg2 in the pancreas of patients with islet cell hyperplasia was increased compared with normal group.The above results suggest that Ndrg2 may play an important role in performing physiological function of islet cells.%分离胰岛细胞增生症患者、胰岛素瘤患者、胰尾高中分化腺癌患者和正常人胰腺组织,制成石蜡切片,用抗N-myc下游调节基因2(Ndrg2)单克隆抗体进行免疫组织化学染色(ABC法),用Western印迹法检测Ndrg2的表达与分布情况.结果显示,Ndrg2阳性反应物主要分布在胰岛细胞的胞浆,与胰岛素的阳性反应物分布与定位相似;胰岛细胞增生症患者胰岛数量增加,体积增大,且该疾病患者胰腺中Ndrg2表达增加;Western印迹实验结果显示胰岛细胞增生症患者胰腺组织中Ndrg2蛋白的表达量较正常组增高.提示Ndrg2基因可能在胰岛细胞中发挥重要的生理功能.

  14. Les gènes TWIST : cibles transcriptionnelles des gènes MYC dans le neuroblastome

    OpenAIRE

    Selmi, Abdelkader

    2009-01-01

    The N-MYC gene is amplified in 20-25 % of human neuroblastoma, and this amplification is associated with poor clinical outcome. We previously reported aconstant deregulation of TWIST1 in synergy with N-MYC in aggressive stage IVneuroblastoma harboring N-MYC amplification (Valsesia-Wittmann et al., 2004). We demonstrated here that specifically in neuroblastoma cells, TWIST1 and TWIST2 are negatively or positively regulated depending on Myc oncoproteins dosage, thus being a putative Myc transcr...

  15. Human genome: proto-oncogenes and proretroviruses.

    Science.gov (United States)

    Kisselev, L L; Chumakov, I M; Zabarovsky, E R; Prassolov, V S; Mett, V L; Berditchevsky, F B; Tret'yakov, L D

    1985-01-01

    A brief review of the studies undertaken at the Laboratory for Molecular Bases of Oncogenesis (Institute of Molecular Biology, Moscow) till middle of 1984 is presented. The human genome contains multiple dispersed nucleotide sequences related to the proto-oncogene mos and to proretroviral sequences in tight juxtaposition to each other. From sequencing appropriate cloned fragments of human DNA in phage and plasmid vectors it follows that one of these regions, NV-1, is a pseudogene of proto-mos with partial duplications and two Alu elements intervening its coding sequence, and the other, CL-1, seems to be also a mos-related gene with a deletion of the internal part of the structural gene. CL-1 is flanked by a proretroviral-like sequence including tRNAiMet binding site and U5 (part of the long terminal repeat). The proretroviral-like sequences are transcribed in 21-35S poly(A)+RNA abundant in normal and malignant human cells. Two hypotheses are proposed: endogenous retroviruses take part in amplification of at least some proto-oncogenes; proto-oncogenes are inactivated via insertion of movable genetic elements and conversion into pseudogenes. Potential oncogenicity of a normal human genome undergoes two controversial influences: it increases due to proto-oncogene amplification and decreases due to inactivation of some of them.

  16. HUMAN PAPILLOMA VIRUS — ONCOGENIC VIRUS

    Directory of Open Access Journals (Sweden)

    A.N. Mayansky

    2010-01-01

    Full Text Available The lecture is devoted to oncogenic viruses, particularly human papilloma virus. Papilloma viral infection is found in all parts of the globe and highly contagious. In addition to exhaustive current data on classification, specifics of papilloma viruses composition and epidemiology, the author describes in great detail the malignization mechanisms of papilloma viruses pockets. Also, issues of diagnostics and specific prevention and treatment of diseases caused by this virus are illustrated. Key words: oncogenic viruses, papilloma viruses, prevention, vaccination. (Pediatric Pharmacology. – 2010; 7(4:48-55

  17. Oncogene v-jun modulates DNA replication.

    Science.gov (United States)

    Wasylyk, C; Schneikert, J; Wasylyk, B

    1990-07-01

    Cell transformation leads to alterations in both transcription and DNA replication. Activation of transcription by the expression of a number of transforming oncogenes is mediated by the transcription factor AP1 (Herrlich & Ponta, 1989; Imler & Wasylyk, 1989). AP1 is a composite transcription factor, consisting of members of the jun and fos gene-families. c-jun and c-fos are progenitors of oncogenes, suggestion that an important transcriptional event in cell transformation is altered activity of AP1, which may arise either indirectly by oncogene expression or directly by structural modification of AP1. We report here that the v-jun oncogene and its progenitor c-jun, as fusion proteins with the lex-A-repressor DNA binding domain, can activate DNA replication from the Polyoma virus (Py) origin of replication, linked to the lex-A operator. The transcription-activation region of v-jun is required for activation of replication. When excess v-jun is expressed in the cell, replication is inhibited or 'squelched'. These results suggest that one consequence of deregulated jun activity could be altered DNA replication and that there are similarities in the way v-jun activates replication and transcription.

  18. DANS LE CONTEXTE IVOIRIEN

    African Journals Online (AJOL)

    LA RELATION "GENRE" ET SES IMPLICATIONS SOCIOLOGIQUES. DANS LE CONTEXTE IVOIRIEN ... de base et de la gestion des affaires publiques en milieu rural .... Les raisons économiques; du fait du faible pouvoir d'achat des parents face au ..... cause de rupture du contrat, toute femme a le droit de suspendre son.

  19. Avant le crime politique

    OpenAIRE

    Fell, Claude; Rutés, Sébastien

    2015-01-01

    La créativité récente dans le sous-genre policier au Mexique, que l’on appelle « néo-policier » favorise la mise en valeur des romans et nouvelles à caractère policier qui n’avaient pas dans ce pays le développement éditorial pris aux Etats-Unis. Le crime et l’enquête policière ont des composantes de fiction qui ne s’inscrivent pas dans le profil conventionnel du roman de détective. Des œuvres de plusieurs écrivains marquent cette évolution vers le néo-policier.Dans Ensayo de un crimen (1986)...

  20. Avant le crime politique

    OpenAIRE

    2015-01-01

    La créativité récente dans le sous-genre policier au Mexique, que l’on appelle « néo-policier » favorise la mise en valeur des romans et nouvelles à caractère policier qui n’avaient pas dans ce pays le développement éditorial pris aux Etats-Unis. Le crime et l’enquête policière ont des composantes de fiction qui ne s’inscrivent pas dans le profil conventionnel du roman de détective. Des œuvres de plusieurs écrivains marquent cette évolution vers le néo-policier.Dans Ensayo de un crimen (1986)...

  1. Oncogene mutational profile in nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang ZC

    2014-03-01

    Full Text Available Zi-Chen Zhang,1,* Sha Fu,1,* Fang Wang,1 Hai-Yun Wang,1 Yi-Xin Zeng,2 Jian-Yong Shao11Department of Molecular Diagnostics, 2Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People's Republic of China *These authors contributed equally to this work Abstract: Nasopharyngeal carcinoma (NPC is a common tumor in Southern China, but the oncogene mutational status of NPC patients has not been clarified. Using time-of-flight mass spectrometry, 238 mutation hotspots in 19 oncogenes were examined in 123 NPC patients. The relationships between mutational status and clinical data were assessed with a χ2 or Fisher's exact test. Survival analysis was performed using the Kaplan–Meier method with the log-rank test. In 123 patients, 21 (17.1% NPC tumors were positive for mutations in eight oncogenes: six patients had PIK3CA mutations (4.9%, five NRAS mutations (4.1%, four KIT mutations (3.3%, two PDGFRA mutations (1.6%, two ABL mutations (1.6%, and one with simultaneous mutations in HRAS, EGFR, and BRAF (1%. Patients with mutations were more likely to relapse or develop metastasis than those with wild-type alleles (P=0.019. No differences or correlations were found in other clinical characteristics or in patient survival. No mutations were detected in oncogenes AKT1, AKT2, CDK, ERBB2, FGFR1, FGFR3, FLT3, JAK2, KRAS, MET, and RET. These results demonstrate an association between NPC and mutations in NRAS, KIT, PIK3CA, PDGFRA, and ABL, which are associated with patient relapse and metastasis. Keywords: NPC, oncogene, mutation

  2. Multiple oncogenic mutations related to targeted therapy in nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jian-Wei Zhang; Hong-Yuan Zhao; Yu-Xiang Ma; Zhi-Huang Hu; Pei-Yu Huang; Li Zhang; Tao Qin; Shao-Dong Hong; Jing Zhang; Wen-Feng Fang; Yuan-Yuan Zhao; Yun-Peng Yang; Cong Xue; Yan Huang

    2015-01-01

    Introduction:An increasing number of targeted drugs have been tested for the treatment of nasopharyngeal carcinoma (NPC). However, targeted therapy-related oncogenic mutations have not been fully evaluated. This study aimed to detect targeted therapy-related oncogenic mutations in NPC and to determine which targeted therapy might be potentially effective in treating NPC. Methods:By using the SNaPshot assay, a rapid detection method, 19 mutation hotspots in 6 targeted therapy-related oncogenes were examined in 70 NPC patients. The associations between oncogenic mutations and clinicopathologic factors were analyzed. Results:Among 70 patients, 12 (17.1%) had mutations in 5 oncogenes:7 (10.0%) had v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) mutation, 2 (2.8%) had epidermal growth factor receptor (EGFR) mutation, 1 (1.4%) had phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation, 1 (1.4%) had Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and 1 (1.4%) had simultaneous EGFR and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations. No significant differences were observed between oncogenic mutations and clinicopathologic characteristics. Additionally, these oncogenic mutations were not associated with tumor recurrence and metastasis. Conclusions:Oncogenic mutations are present in NPC patients. The efficacy of targeted drugs on patients with the related oncogenic mutations requires further validation.

  3. Le dernier Wittgenstein et le dernier Husserl sur le langage

    Directory of Open Access Journals (Sweden)

    Paul Ricoeur

    2014-07-01

    Full Text Available This article presents an edited version of lectures given by Paul Ricœur at Johns Hopkins University in April 1966. Ricœur offers a comparative analysis of Wittgenstein’s and Husserl’s late works, taking the problem of language as the common ground of investigation for these two central figures of phenomenology and analytic philosophy. Ricœur develops his study in two parts. The first part considers Husserl’s approach to language after the Logical Investigations and concentrates on Formal and Transcendental Logic; leaving a transcendental reflection on language behind it re-examines a phenomenological conception, according to which the sphere of logic is not separable from that of experience. The main focus of the second part is Wittgenstein’s later philosophy as it moved on from the conception of an isomorphic relation between language and the world, as set out in the picture theory in the Tractatus Logico-Philosophicus, to the more pragmatic notion of a language-game in the Philosophical Investigations. In order to get beyond the irrevocable differences between the two philosophies and the unresolved theoretical issues on both sides, Ricœur suggests turning to a semiological paradigm based on the Saussurean distinction between “language” and “speaking.” Keyword: Analytic Philosophy, Husserl, Phenomenology, Semiology, Wittgenstein.  Résumé Cet article est une version éditée de conférences données par Paul Ricœur à la Johns Hopkins University en avril 1966. Ricœur propose une analyse comparée des dernières œuvres de Wittgenstein et Husserl, avec le problème du langage comme sol commun d’investigations pour ces deux figures centrales de la phénoménologie et la philosophie analytique. Cette analyse de Ricœur se joue à travers deux parties. La première partie revient sur l'approche du langage chez Husserl depuis Recherches logiques avec une attention particulière aux développements de Logique formelle et

  4. Tumelo le Moruo

    OpenAIRE

    Vuyani S. Vellem

    2015-01-01

    Paleng ya rona batho ba batsho, tumelo ya boKreste e fihlile lefatsheng la rona la Afrika Borwa mmoho le dikgoka tsa ditjhaba tsa boPhirima. BoKreste bo fihlile ka nako ya dintwa tseo mohopolo wa tsona e neng e le ho hapa lefatshe la, batho ba batsho. Ka mantswe amang, rona batho ba batsho, re ile ra qetella re le setjhaba se ileng sa hlolwa, mme lefatshe la rona la nkuwa ka dikgoka. Ka hare ho dikgoka tsena, ho ne ho dutse tumelo ya boKreste. Makgowa a ile are: �A re kwaleng mahlo re rapelen...

  5. Le genre et le logiciel libre

    OpenAIRE

    Archambault, Jean-Pierre; Sedooka, Ayuko; Baron, Georges-Louis

    2010-01-01

    Le texte qui suit est fondé sur l'expérience d'une recherche menée sur les femmes et le logiciel libre depuis la fin 2009 auprès de la communauté des acteurs du libre en France. Il ne s'agit pas d'un texte scientifique à proprement parler mais d'une réflexion étayée par une série de contacts et de discussions avec des militants et des praticiens, qui vise à inciter à la discussion et au débat. Il est également fondé sur les résultats d'une enquête quantitative du projet européen PREDIL, port...

  6. Le rythme du silence

    OpenAIRE

    Meschonnic, Henri

    2017-01-01

    1. Pour rompre le silence Dire « rythme du silence », c’est non seulement penser le silence comme langage, et parfois la réalisation maximale du langage, mais aussi parcourir les acceptions de la notion de silence. De ce qui n’est pas dit, ou qu’on est incapable de dire à ce que les mots ne peuvent pas dire, le fameux indicible, mais aussi l’innommable, et la censure, faire silence sur, jusqu’au problème poétique. Il y a aussi une langue de bois du silence. Et aussi le silence de ce qu’on ent...

  7. Le corps chinois

    OpenAIRE

    2016-01-01

    Pour le xviiie siècle, le corps est encore une machine harmonique. Cette harmonie, c’est tout à la fois la marque divine à l’intérieur du corps, une loi de nature qui permet d’atteindre au bonheur, et une manière de définir l’état de santé. Le corps semble un appareillage soumis à des lois physiques : l’horloge, la fontaine et particulièrement l’instrument de musique. On trouve cette dernière image dans Bacon, en 1639, pour qui la Nature donne des tempéraments pour le corps, « comme la parfai...

  8. Le Jardin de Fleur

    Index Scriptorium Estoniae

    2008-01-01

    Ettevõtja Martin Reinsalu osalusel Marokosse kerkiv kuurortide kompleks Le Jardin de Fleur tunnistati CNBC Araabiamaade kinnisvaraarendusprojektide seas Maroko parimaks arendusprojektiks ning parimaks golfiarenduskeskuseks. Projekt toetub araabia arhitektuurile, mida on kombineeritud kaasaegse maroko disainiga

  9. Le Jardin de Fleur

    Index Scriptorium Estoniae

    2008-01-01

    Ettevõtja Martin Reinsalu osalusel Marokosse kerkiv kuurortide kompleks Le Jardin de Fleur tunnistati CNBC Araabiamaade kinnisvaraarendusprojektide seas Maroko parimaks arendusprojektiks ning parimaks golfiarenduskeskuseks. Projekt toetub araabia arhitektuurile, mida on kombineeritud kaasaegse maroko disainiga

  10. Le pique-nique

    Directory of Open Access Journals (Sweden)

    2009-04-01

    Full Text Available Cet ouvrage collectif dirigé par Francine Barthe-Deloizy est le résultat d’une démarche collective (24 auteurs associant des apports impromptus (appelés ici florilèges à un corpus thématique, fruit d’une recherche entreprise dans le cadre d’un atelier organisé par l’Institut Français des Recherches Iraniennes (IFRI, les services d’actions culturelles de l’ambassade de France en Iran et le laboratoire ENEC de l’Université Paris 4 Sorbonne. Le livre entreprend la généalogie d’une pratique qu...

  11. Storicizzare le teorie psicocritiche

    OpenAIRE

    Roberto Talamo

    2015-01-01

    Le teorie psicoanalitiche della letteratura, dopo una fase di alterne fortune, sono oggi praticate da una cerchia di adepti sempre più ristretta. Le nuove koinè critico-teoriche tendono infatti a relegare la dottrina freudiana all’interno di un sapere letterario (e non interpretativo) o a sostituire ad essa strumenti ritenuti più efficaci nella descrizione della sfera del mentale in letteratura (neuroestetica e neuronarratologia). La proposta storiografica che qui si avanza non vuole prendere...

  12. Radiosensitivity of tumor cells. Oncogenes and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Peltenburg, L. T. C. [Leiden Univ., Leiden (Netherlands). Dept. of Clinical Oncology

    2000-12-01

    The success of treatment of cancer patients by radiotherapy largely depends on tumor radiosensitivity. Several molecular factors that determine the sensitivity of tumor cells to ionizing radiation have been identified during the last couple of years. Some of these factors are known as oncogenes and tumor suppressor genes. This review focuses on the influence of some of these molecular factors on a major determinant of radiosensitivity: i. e. programmed cell death or apoptosis. The crucial molecular step in ionizing radiation-induced apoptosis is the release of mitochondrial cytochrome c into the cell's cytosol. The ways the tumor suppressor protein p53, as well as the oncogenes ras and raf, c-myc and Bcl-2 can influence this process at different stages are presented. As will be discussed, the result of activation of an oncoprotein on tumor radiosensitivity depends on its mechanism of action and on the presence of other (oncogenic) factors, since complex interactions among many molecular factors determine the delicate balance between cell proliferation and cell death. The ongoing identification and characterization of factors influencing apoptosis will eventually make it possible to predict tumor radiosensitivity and thereby improve cancer treatment.

  13. Le faussaire roman

    CERN Document Server

    D'Anna, Gianfranco

    2016-01-01

    À l'aube du XXIe siècle, le monde de la science est sur le point de vivre une révolution. Le jeune physicien allemand Albert Hendrick Thebell, des célèbres laboratoires de recherche B-Labs, à Summit, dans le New Jersey, publie, dans les plus grandes revues scientifiques internationales, une série d'articles dans lesquels il prétend avoir obtenu des résultats extraordinaires qui pourraient révolutionner les bases mêmes de la technologie. Rapidement, la communauté scientifique puis les médias saluent en lui un futur prix Nobel; on compare même son génie à celui d'Albert Einstein. Le progrès scientifique semble avoir franchi une étape décisive, susceptible d'amener un futur meilleur. Mais ces découvertes sont-elles authentiques ? Car pendant ce temps, dans les mêmeslaboratoires, des voix s'élèvent pour contester non seulement les théories de Thebell mais aussi la légitimité même de ses expériences ; certains le soupçonnent d'avoir combiné la plus grande fraude scientifique de tous l...

  14. LE RAPPORT JURIDIQUE

    Directory of Open Access Journals (Sweden)

    Nicolae Popa

    2008-01-01

    Full Text Available Lele du droit en tant qu’organisateur de la vie sociale, dans ses principales relations, ayant comme but de discipliner la conduite des hommes dans leur intersection quotidienne, est tout d’abord relevé – sur le plan abstrait et théorique – par les traits du mécanisme de la réglementation juridique, mécanisme dont le contour est tracé par l’existence du systčme normatif juridique, partie composante (sous-systčme du systčme normatif social. Le mécanisme de la réglementation de la vie sociale par des normes juridiques met en lumičre des aspects des plus variés, marquant l’influence du droit sur la société – aspects surtout juridiques, psychologiques etc. En męme temps, toutefois, lele du droit ne peut pas ętre limité tout simplement ŕ cette influence théorique. Dans sa derničre essence, le droit signifie vie, il offre un cadre spécifique ŕ la vie sociale, étant, dans cette lumičre, le résultat de la traduction, dans un langage technique, des formes et des structures de la vie sociale1. En tant qu’expression de certaines tendances, d’un certain systčme de valeurs, la loi garantit l’ordre, la stabilité sociale, la sécurité juridique. En pénétrant dans le tissu des rapports interhumains, les aspects sociologiques du mécanisme de la réglementation juridique ne peuvent pas échapper ŕ l’analyse. L’étude des rapports juridiques souligne tout justement ces aspects sociologiques, les rapports de droit étant, avant tout, des rapports sociaux, dans lesquels les hommes entrent afin de satisfaire leurs besoins variés, des rapports de coopération et de coexistence.

  15. Le modèle basque

    Directory of Open Access Journals (Sweden)

    Juan-Angel PORTUGAL

    1986-12-01

    Full Text Available À l'intérieur du quadrilatère basque se dessine un sous-espace triangulaire dont les sommets sont les capitales provinciales; les côtés délimitent une aire prospère. La localisation de ces trois noyaux résulte d'une décision politico-économique et d'une diffusion de l'industrialisation. Ce triangle est un espace dynamique et attractif, autant dans le domaine de la démographie que du développement économique et industriel.

  16. Tumelo le Moruo

    Directory of Open Access Journals (Sweden)

    Vuyani S. Vellem

    2015-03-01

    Full Text Available Paleng ya rona batho ba batsho, tumelo ya boKreste e fihlile lefatsheng la rona la Afrika Borwa mmoho le dikgoka tsa ditjhaba tsa boPhirima. BoKreste bo fihlile ka nako ya dintwa tseo mohopolo wa tsona e neng e le ho hapa lefatshe la, batho ba batsho. Ka mantswe amang, rona batho ba batsho, re ile ra qetella re le setjhaba se ileng sa hlolwa, mme lefatshe la rona la nkuwa ka dikgoka. Ka hare ho dikgoka tsena, ho ne ho dutse tumelo ya boKreste. Makgowa a ile are: �A re kwaleng mahlo re rapeleng, rona ra kwala mahlo, mme ha re qeta hore Amen, re bula mahlo, ra fumana lefatshe le nkuwe matsohong a rona ho setse Bibele.� Re ile ra sala le Bibele eo ka yona re lekileng dilemong tse fitileng ho lwana ntwa ya topollo, kapa tokoloho hofihlela selemong sa 1994. Le ha re ile ra fumana tokoloho ka selemo seo, hare so ka re lokoloha ho tsa moruo. E kaba sena se bolela eng mabapi le tumelo ya rona ya boKreste? Segolweng sena re leka ho araba potso ena. Tumelo ke eng ho batho ba sa lokolohang moruong wa naha ya bona? Re lekola pale ya boKreste, tumelo ya batho le maemo a kereke ntlheng ya ho tadimana le tokoloho ka tumelo.Faith and economics. In our history from a black perspective, Christianity arrived through violent conquest from the west. Evidentially, this faith coincided with wars of dispossession and the ultimate defeat of black Africans. It is difficult to separate the violent defeat of black Africans from the arrival of Christian faith. This well-known statement within the circles of black Theology of liberation: When the white man arrived in our land he said, �let us pray and after prayer, when we opened our eyes, our land was taken and only the Bible was left in our hands,� captures the black sentiment of this history. Ironically, it was this Bible that black Africans used to wage their struggle for liberation up to the demise of apartheid in 1994.Nonetheless, political liberation is not enough as the struggle for economic liberation

  17. Le vernis des apparences

    Directory of Open Access Journals (Sweden)

    Grazia Nicosia

    2010-04-01

    Full Text Available Le but de cet article est de comprendre l’incidence sémiotique du nettoyage d’un tableau ainsi que la résultante cognitive induite sur l’observateur. Cette étude confronte l’analyse des phénomènes visuels engendrés par le jaunissement du vernis et son retrait, à des entretiens réalisés à dessein. Le retrait d’un vernis jauni change considérablement l’image. L’heure, le climat, la saison et l’activité même des personnages s’en trouvent ainsi modifié. La patine peut être perçue, soit comme un obstacle à l’exploration, soit pour ceux qui l’apprécient, comme le medium d’une relation plus intime entre l’œuvre et l’observateur.The purpose of this article is to understand the semiotic impact of the cleaning of a painting and the cognitive effects induced on the observer. This study analyses conjointly the visual phenomenon generated by yellowing varnish and its removal and controlled interviews of observers.The removal of yellowing varnish modifies considerably the perception of the picture. Daytime, climate, season and characters activities are modified. The patina may be perceived either as an obstacle to the painting exploration, or, for those who appreciate it, as a medium for a closer relationship between the painting and the observer.

  18. Le collisionneur du futur?

    CERN Multimedia

    CERN Audiovisual Service

    2009-01-01

    Pourquoi deux études parallèles pour un même collisionneur linéaire ? Loin d’être un double effort et un gaspillage de ressources, ces deux études s’inscrivent dans une stratégie de complémentarité afin de fournir la meilleure technologie requise par la physique du futur. Vendredi 12 juin a eu lieu au CERN la première réunion conjointe CLIC et ILC. Elle n’a pas été avare de bons résultats et d’importantes décisions. Le Collisionneur Linéaire International (ILC) et le Collisionneur Linéaire Compact (CLIC) sont deux études qui font, tous deux, appel à des technologies de pointe. A première vue en compétition, les deux études sont en réalité complémentaires et elles ont un objectif commun : proposer dans les plus brefs délais et au moindre coût, l‘accélérateur linéaire le mieux adapté pour prendre le relais de la physique des très hautes énergies après le LHC.

  19. Activation of proto-oncogenes by disruption of chromosome neighborhoods.

    Science.gov (United States)

    Hnisz, Denes; Weintraub, Abraham S; Day, Daniel S; Valton, Anne-Laure; Bak, Rasmus O; Li, Charles H; Goldmann, Johanna; Lajoie, Bryan R; Fan, Zi Peng; Sigova, Alla A; Reddy, Jessica; Borges-Rivera, Diego; Lee, Tong Ihn; Jaenisch, Rudolf; Porteus, Matthew H; Dekker, Job; Young, Richard A

    2016-03-25

    Oncogenes are activated through well-known chromosomal alterations such as gene fusion, translocation, and focal amplification. In light of recent evidence that the control of key genes depends on chromosome structures called insulated neighborhoods, we investigated whether proto-oncogenes occur within these structures and whether oncogene activation can occur via disruption of insulated neighborhood boundaries in cancer cells. We mapped insulated neighborhoods in T cell acute lymphoblastic leukemia (T-ALL) and found that tumor cell genomes contain recurrent microdeletions that eliminate the boundary sites of insulated neighborhoods containing prominent T-ALL proto-oncogenes. Perturbation of such boundaries in nonmalignant cells was sufficient to activate proto-oncogenes. Mutations affecting chromosome neighborhood boundaries were found in many types of cancer. Thus, oncogene activation can occur via genetic alterations that disrupt insulated neighborhoods in malignant cells.

  20. Oncogenic extracellular vesicles in brain tumour progression

    Directory of Open Access Journals (Sweden)

    Esterina eD'Asti

    2012-07-01

    Full Text Available The brain is a frequent site of neoplastic growth, including both primary and metastatic tumours. The clinical intractability of many brain tumours and their distinct biology are implicitly linked to the unique microenvironment of the central nervous system (CNS and cellular interactions within. Among the most intriguing forms of cellular interactions is that mediated by membrane-derived extracellular vesicles (EVs. Their biogenesis (vesiculation and uptake by recipient cells serves as a unique mechanism of intercellular trafficking of complex biological messages including the exchange of molecules that cannot be released through classical secretory pathways, or that are prone to extracellular degradation. Tumour cells produce EVs containing molecular effectors of several cancer-related processes such as growth, invasion, drug resistance, angiogenesis, and coagulopathy. Notably, tumour-derived EVs (oncosomes also contain oncogenic proteins, transcripts, DNA and microRNA (miR. Uptake of this material may change properties of the recipient cells and impact the tumour microenvironment. Examples of transformation-related molecules found in the cargo of tumour-derived EVs include the oncogenic epidermal growth factor receptor (EGFRvIII, tumour suppressors (PTEN and oncomirs (miR-520g. It is postulated that EVs circulating in blood or cerebrospinal fluid (CSF of brain tumour patients may be used to decipher molecular features (mutations of the underlying malignancy, reflect responses to therapy or molecular subtypes of primary brain tumours (e.g. glioma or medulloblastoma. It is possible that metastases to the brain may also emit EVs with clinically relevant oncogenic signatures. Thus EVs emerge as a novel and functionally important vehicle of intercellular communication that can mediate multiple biological effects. In addition, they provide a unique platform to develop molecular biomarkers in brain malignancies.

  1. Le corps des anges

    OpenAIRE

    Margel,Serge

    2017-01-01

    Ce séminaire fait suite à un cycle de conférences données en 2014 sur la notion de corps de chair dans le premier christianisme. Cette année la recherche a porté sur le corps spécifique des anges dans la patristique grecque et latine. Sur la base d’un corpus de textes délimité, j’ai essayé de montrer deux choses principales : d’un côté, on ne peut pas comprendre la spécificité du corps des anges sans l’inscrire dans le champ de l’angélologie chrétienne, qui assimile l’ange et l’âme, et d’un a...

  2. Storicizzare le teorie psicocritiche

    Directory of Open Access Journals (Sweden)

    Roberto Talamo

    2015-07-01

    Full Text Available Le teorie psicoanalitiche della letteratura, dopo una fase di alterne fortune, sono oggi praticate da una cerchia di adepti sempre più ristretta. Le nuove koinè critico-teoriche tendono infatti a relegare la dottrina freudiana all’interno di un sapere letterario (e non interpretativo o a sostituire ad essa strumenti ritenuti più efficaci nella descrizione della sfera del mentale in letteratura (neuroestetica e neuronarratologia. La proposta storiografica che qui si avanza non vuole prendere parte in questo dibattito pro o contro la psicocritica, ma vuole leggere le proposte di teoria psicoanalitica della letteratura alla luce di una riflessione sul concetto di ibridazione, concetto sul quale queste teorie hanno costruito il loro confronto con i paradigmi teorici di volta in volta egemoni.

  3. Le Nouveau Monde

    Directory of Open Access Journals (Sweden)

    Alain Musset

    2006-04-01

    Full Text Available L’histoire de la conquête du Nouveau Monde par les Européens semble devoir se résumer au destin de deux femmes chargées d’assurer le truchement entre les deux mondes et de jouer lele d’intermédiaire amoureuse ou de grande traîtresse : au Nord, Pocahontas, au Sud, La Malinche. Quand Cortés débarque en 1519 sur les côtes du Tabasco, un cacique désireux de lui plaire lui offre vingt femmes dont une superbe jeune fille, Malintzin (la Malinche, rebaptisée Marina. Celle-ci deviendra sa maîtres...

  4. Melanoma: oncogenic drivers and the immune system

    Science.gov (United States)

    Karachaliou, Niki; Pilotto, Sara; Teixidó, Cristina; Viteri, Santiago; González-Cao, María; Riso, Aldo; Morales-Espinosa, Daniela; Molina, Miguel Angel; Chaib, Imane; Santarpia, Mariacarmela; Richardet, Eduardo; Bria, Emilio

    2015-01-01

    Advances and in-depth understanding of the biology of melanoma over the past 30 years have contributed to a change in the consideration of melanoma as one of the most therapy-resistant malignancies. The finding that oncogenic BRAF mutations drive tumor growth in up to 50% of melanomas led to a molecular therapy revolution for unresectable and metastatic disease. Moving beyond BRAF, inactivation of immune regulatory checkpoints that limit T cell responses to melanoma has provided targets for cancer immunotherapy. In this review, we discuss the molecular biology of melanoma and we focus on the recent advances of molecularly targeted and immunotherapeutic approaches. PMID:26605311

  5. Le blue-jean

    OpenAIRE

    Miller, Daniel

    2012-01-01

    Le Blue-jean: pourquoi la technologie vient en dernier. La plupart des personnes pensent que la technique (ou la technologie) correspond à ce qui vient en amont du produit. Dans cet article, Daniel Miller s’intéresse plutôt à des cas dans lesquels l’ordre de la séquence est renversé et où le produit précède, ou initie, en quelque sorte, la technique. L’auteur commence par décrire les techniques d’usure artificielle des blue jeans  : une technique qui vise à copier les effets du port des blue ...

  6. Intracortical osteoblastic osteosarcoma with oncogenic rickets

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, T.; Hirohashi, Setsuo [Pathology Division, National Cancer Center Research Institute, Tokyo (Japan); Shimoda, Tadakazu [Clinical Laboratory Division, National Cancer Center Hospital, Tokyo (Japan); Yokoyama, Ryohei; Beppu, Yasuo [Orthopedic Division, National Cancer Center Hospital, Tokyo (Japan); Maeda, Shotaro [Department of Pathology, Nippon Medical School Hospital, Tokyo (Japan)

    1999-01-01

    Intracortical osteosarcoma is the rarest variant of osteosarcoma, occurring within, and usually confined to, the cortical bone. Oncogenic osteomalacia, or rickets, is an unusual clinicopathologic entity in which vitamin D-resistant osteomalacia, or rickets, occurs in association with some tumors of soft tissue or bone. We present a case of oncogenic rickets associated with intracortical osteosarcoma of the tibia in a 9-year-old boy, whose roentgenographic abnormalities of rickets disappeared and pertinent laboratory data except for serum alkaline phosphatase became normal after surgical resection of the tumor. Histologically, the tumor was an osteosarcoma with a prominent osteoblastic pattern. An unusual microscopic feature was the presence of matrix mineralization showing rounded calcified structures (calcified spherules). Benign osteoblastic tumors, such as osteoid osteoma and osteoblastoma, must be considered in the differential diagnosis because of the relatively low cellular atypia and mitotic activity of this tumor. The infiltrating pattern with destruction or engulfment of normal bone is a major clue to the correct diagnosis of intracortical osteosarcoma. The co-existing radiographic changes of rickets were due to the intracortical osteosarcoma. (orig.) With 8 figs., 25 refs.

  7. Oncogenic activation of NF-kappaB.

    Science.gov (United States)

    Staudt, Louis M

    2010-06-01

    Recent genetic evidence has established a pathogenetic role for NF-kappaB signaling in cancer. NF-kappaB signaling is engaged transiently when normal B lymphocytes respond to antigens, but lymphomas derived from these cells accumulate genetic lesions that constitutively activate NF-kappaB signaling. Many genetic aberrations in lymphomas alter CARD11, MALT1, or BCL10, which constitute a signaling complex that is intermediate between the B-cell receptor and IkappaB kinase. The activated B-cell-like subtype of diffuse large B-cell lymphoma activates NF-kappaB by a variety of mechanisms including oncogenic mutations in CARD11 and a chronic active form of B-cell receptor signaling. Normal plasma cells activate NF-kappaB in response to ligands in the bone marrow microenvironment, but their malignant counterpart, multiple myeloma, sustains a variety of genetic hits that stabilize the kinase NIK, leading to constitutive activation of the classical and alternative NF-kappaB pathways. Various oncogenic abnormalities in epithelial cancers, including mutant K-ras, engage unconventional IkappaB kinases to activate NF-kappaB. Inhibition of constitutive NF-kappaB signaling in each of these cancer types induces apoptosis, providing a rationale for the development of NF-kappaB pathway inhibitors for the treatment of cancer.

  8. Candide et le physicien

    CERN Document Server

    Espagnat, Bernard d'

    2008-01-01

    Les avancées considérables de la physique d'après guerre n'ont - on le sait - été possibles qu'au prix d'une vraie rupture entre elle et la physique dite " classique ". A quels changements cette rupture nous contraint-elle en ce qui concerne des notions essentielles, telles celles d'espace, de temps, d'objet et d'objectivité ? Quelles en sont les incidences quant à la portée de la connaissance, au rôle de la conscience, aux relations entre science et ontologie ? Ce sont là des questions de fond, fort délicates, auxquelles les personnes de tendance quelque peu philosophique sont plus sensibles que ne le sont les physiciens. Malheureusement, les premières ne disposent normalement pas des connaissances de pointe qui seules permettent d'approfondir de tels problèmes sans trop risquer de s'égarer. Etant donné l'impact que, par ses applications, la science a sur nos vies, nombreux sont ceux qui souhaitent se former une idée plus juste de ce qu'elle implique vraiment. Le présent ouvrage prend la for...

  9. Higgs le boson manquant

    CERN Document Server

    Carroll, Sean; Evans, Lyn; Gagnon, Pauline; Bernet, Lison

    2013-01-01

    Ce livre conte l'histoire de la plus fascinante aventure scientifique de notre temps : la quête du "boson de Higgs". La découverte présumée de cette particule élémentaire en juillet 2012 a secoué le monde, tant pour son étrangeté que pour la démesure des moyens déployés. Qu'on en juge : un accélérateur de 27 km de circonférence sous la frontière franco-suisse - le LHC, la plus grande machine jamais construite par l'Homme-, une équipe de 6 000 chercheurs, techniciens, ingénieurs, informaticiens, etc., et un budget de plus de 9 milliards de $ ! L'auteur, cosmologiste et vulgarisateur de renom, nous révèle les enjeux de cette recherche ultime : le boson expliquerait ni plus ni moins pourquoi la matière qui nous entoure a une masse, et lèverait un coin du voile qui entoure la mystérieuse "matière noire". Il détaille surtout sa genèse et les rivalités, les doutes mais aussi les intuitions géniales des acteurs du projet. Cette galerie de personnages hors norme font de la lecture de ce li...

  10. Le rouleau de la guerre

    NARCIS (Netherlands)

    Jongeling, Bastiaan

    1962-01-01

    Le projet initial de notre etude etait de presenter un commentaire avec traduction, et d'y ajouter quelques chapitres sur le caractere du contenu du rouleau, sur sa langue, sa date, ses rapports avec l'Ancien Testament et avec la litterature juive post-blblique; mais, le commentaire s'elargissant de

  11. Mislocalized activation of oncogenic RTKs switches downstream signaling outcomes

    DEFF Research Database (Denmark)

    Choudhary, Chuna Ram; Olsen, Jesper V; Brandts, Christian

    2009-01-01

    Inappropriate activation of oncogenic kinases at intracellular locations is frequently observed in human cancers, but its effects on global signaling are incompletely understood. Here, we show that the oncogenic mutant of Flt3 (Flt3-ITD), when localized at the endoplasmic reticulum (ER), aberrant...

  12. Oncogenic Transformation of Human-Derived Gastric Organoids.

    Science.gov (United States)

    Bertaux-Skeirik, Nina; Centeno, Jomaris; Gao, Jian; Gabre, Joel; Zavros, Yana

    2016-08-19

    The culture of organoids has represented a significant advancement in the gastrointestinal research field. Previous research studies have described the oncogenic transformation of human intestinal and mouse gastric organoids. Here we detail the protocol for the oncogenic transformation and orthotopic transplantation of human-derived gastric organoids.

  13. Oncogenic pathways implicated in ovarian epithelial cancer.

    Science.gov (United States)

    Nicosia, Santo V; Bai, Wenlong; Cheng, Jin Q; Coppola, Domenico; Kruk, Patricia A

    2003-08-01

    Characterization of intracellular signaling pathways should lead to a better understanding of ovarian epithelial carcinogenesis and provide an opportunity to interfere with signal transduction targets involved in ovarian tumor cell growth, survival, and progression. Challenges toward such an effort are significant because many of these signals are part of cascades within an intricate and likely redundant intracellular signaling network (Fig.1). For instance, a given signal may activate a dual intracellular pathway (ie, MEK1-MAPK and PI3K/Akt required for fibronectin-dependent activation of matrix metalloproteinase 9). A single pathway also may transduce more than one biologic or oncogenic signal (ie, PI3K signaling in epithelial and endothelial cell growth and sprouting of neovessels). Despite these challenges, evidence for therapeutic targeting of signal transduction pathways is accumulating in human cancer. For instance, the EGF-specific tyrosine kinase inhibitor ZD 1839 (Iressa) may have a beneficial therapeutic effect on ovarian epithelial cancer. Therapy of this cancer may include inhibitors of PI kinase (quercetin), ezrin and PIP kinase (genistein). The G protein-coupled family of receptors, including LPA, also is an attractive target to drugs, although their frequent pleiotropic functions may be at times toxic and lack specificity. Because of the lack of notable toxicity, PI3K/Akt pathway inhibitors such as FTIs are a promising targeted therapy of ovarian epithelial cancer. Increasing insight into the oncogenic pathways involved in ovarian epithelial cancer also is helping clinicians to understand better the phenomenon of chemoresistance in this malignancy. Oncogenic activation of gamma-synuclein promotes cell survival and provides resistance to paclitaxel, but such a resistance is partially overcome by an MEK inhibitor that suppresses ERK activity. Ovarian epithelial cancer is a complex group of neoplasms with an overall poor prognosis. Comprehension of

  14. Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.

    Science.gov (United States)

    Northcott, Paul A; Lee, Catherine; Zichner, Thomas; Stütz, Adrian M; Erkek, Serap; Kawauchi, Daisuke; Shih, David J H; Hovestadt, Volker; Zapatka, Marc; Sturm, Dominik; Jones, David T W; Kool, Marcel; Remke, Marc; Cavalli, Florence M G; Zuyderduyn, Scott; Bader, Gary D; VandenBerg, Scott; Esparza, Lourdes Adriana; Ryzhova, Marina; Wang, Wei; Wittmann, Andrea; Stark, Sebastian; Sieber, Laura; Seker-Cin, Huriye; Linke, Linda; Kratochwil, Fabian; Jäger, Natalie; Buchhalter, Ivo; Imbusch, Charles D; Zipprich, Gideon; Raeder, Benjamin; Schmidt, Sabine; Diessl, Nicolle; Wolf, Stephan; Wiemann, Stefan; Brors, Benedikt; Lawerenz, Chris; Eils, Jürgen; Warnatz, Hans-Jörg; Risch, Thomas; Yaspo, Marie-Laure; Weber, Ursula D; Bartholomae, Cynthia C; von Kalle, Christof; Turányi, Eszter; Hauser, Peter; Sanden, Emma; Darabi, Anna; Siesjö, Peter; Sterba, Jaroslav; Zitterbart, Karel; Sumerauer, David; van Sluis, Peter; Versteeg, Rogier; Volckmann, Richard; Koster, Jan; Schuhmann, Martin U; Ebinger, Martin; Grimes, H Leighton; Robinson, Giles W; Gajjar, Amar; Mynarek, Martin; von Hoff, Katja; Rutkowski, Stefan; Pietsch, Torsten; Scheurlen, Wolfram; Felsberg, Jörg; Reifenberger, Guido; Kulozik, Andreas E; von Deimling, Andreas; Witt, Olaf; Eils, Roland; Gilbertson, Richard J; Korshunov, Andrey; Taylor, Michael D; Lichter, Peter; Korbel, Jan O; Wechsler-Reya, Robert J; Pfister, Stefan M

    2014-07-24

    Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.

  15. The Exceptional Oncogenicity of HTLV-1.

    Science.gov (United States)

    Tagaya, Yutaka; Gallo, Robert C

    2017-01-01

    Human T-cell leukemia virus-1 (HTLV-1) is the first pathogenic human retrovirus identified in 1979 by the Gallo group. HTLV-1 causes fatal T-cell leukemia (adult T cell leukemia) and a progressive myelopahy (HTLV-1-associated myelopathy/ tropical spastic paraparesis, HAM/TSP) and other disorders. Since the discovery of HTLV-1, several other microorganisms are demonstrated to cause cancer in humans. In this article, we investigated the oncogenic capacity of HTLV-1, in comparison with those of other oncoviruses and one oncobacterium (Helicobacter pylori, H. Pylori) based on published literature. We conclude here that HTLV-1 is one of the most and may be the most carcinogenic among them and arguably one of the most potent of the known human carcinogens. This fact has not been noted before and is particularly important to justify why we need to study HTLV-1 as an important model of human viral oncogenesis.

  16. Glycerophospholipid profile in oncogene-induced senescence.

    Science.gov (United States)

    Cadenas, Cristina; Vosbeck, Sonja; Hein, Eva-Maria; Hellwig, Birte; Langer, Alice; Hayen, Heiko; Franckenstein, Dennis; Büttner, Bettina; Hammad, Seddik; Marchan, Rosemarie; Hermes, Matthias; Selinski, Silvia; Rahnenführer, Jörg; Peksel, Begüm; Török, Zsolt; Vígh, László; Hengstler, Jan G

    2012-09-01

    Alterations in lipid metabolism and in the lipid composition of cellular membranes are linked to the pathology of numerous diseases including cancer. However, the influence of oncogene expression on cellular lipid profile is currently unknown. In this work we analyzed changes in lipid profiles that are induced in the course of ERBB2-expression mediated premature senescence. As a model system we used MCF-7 breast cancer cells with doxycycline-inducible expression of NeuT, an oncogenic ERBB2 variant. Affymetrix gene array data showed NeuT-induced alterations in the transcription of many enzymes involved in lipid metabolism, several of which (ACSL3, CHPT1, PLD1, LIPG, MGLL, LDL and NPC1) could be confirmed by quantitative realtime PCR. A study of the glycerophospholipid and lyso-glycerophospholipid profiles, obtained by high performance liquid chromatography coupled to Fourier-transform ion cyclotron resonance-mass spectrometry revealed senescence-associated changes in numerous lipid species, including mitochondrial lipids. The most prominent changes were found in PG(34:1), PG(36:1) (increased) and LPE(18:1), PG(40:7) and PI(36:1) (decreased). Statistical analysis revealed a general trend towards shortened phospholipid acyl chains in senescence and a significant trend to more saturated acyl chains in the class of phosphatidylglycerol. Additionally, the cellular cholesterol content was elevated and accumulated in vacuoles in senescent cells. These changes were accompanied by increased membrane fluidity. In mitochondria, loss of membrane potential along with altered intracellular distribution was observed. In conclusion, we present a comprehensive overview of altered cholesterol and glycerophospholipid patterns in senescence, showing that predominantly mitochondrial lipids are affected and lipid species less susceptible to peroxidation are increased.

  17. Le 11 novembre 1942

    OpenAIRE

    Isoard, Paul

    2004-01-01

    “Citoyens de la Zone Niçoise !” Fidèles à la parole donnée, nous n’avons jamais manqué aux accords réciproques d’armistice. Dans le but d’empêcher que le sol de France ne puisse devenir un nouveau théâtre de guerre, à cause de débarquements de forces militaires anglo-américaines, nous occupons temporairement la zone démilitarisée. Pas un de Vous ne doit penser à d’intentions hostiles de notre côté.” C’est par la lecture de ce texte imprimé sur des tracts, lancés à partir d’un avion italien a...

  18. Le forme del fondo

    Directory of Open Access Journals (Sweden)

    Michel Maffesoli

    2004-12-01

    Full Text Available Non è vero che la natura ha paura del vuoto. Forse addirittura si completa. Il vuoto è anche una modalità dell'essere. È possibile nidificarvisi, avvolgersi pigramente e, così, proteggersi dall'angoscia del tempo che passa. Il vuoto delle apparenze è, in alcuni momenti, una delle forme d'espressione della vita sociale. Oltretutto occorre saperle riconoscere. Certamente, abbiamo tutti un'esistenza personale, ma siamo, ugualmente, i rappresentanti, a volte anche le vittime, di uno "spirito comune", forse anche di un "inconscio collettivo" che si è costituito di secolo in secolo. E, molto spesso, quando crediamo di esprimere le nostre idee, siamo soltanto dei portavoce, comparse di un vasto "theatrum mundi" dalle dimensioni infinite.

  19. Le cru, le cuit et le pourri dans _Le vice-consul_ de Marguerite Duras

    Directory of Open Access Journals (Sweden)

    Hélène Caron

    2011-05-01

    Full Text Available Bien que plusieurs articles critiques aient déjà avancé de nouvelles perspectives sur le texte Le Vice-Consul (LVC de Marguerite Duras, l’analyse de la représentation de la nourriture dans ce roman n’a fait l’objet d’aucune étude. Cet article tente donc de combler cette lacune en proposant d’analyser les images du cru et du cuit, images qui se rejoignent sous les notions du pourri et de l’abject, tout en offrant quelques interprétations de l’un des passages critiques du roman où la folle mendiante croque la tête d’un poisson vivant.

  20. Le Brahmane du Komintern

    Directory of Open Access Journals (Sweden)

    Elizabeth Burgos

    2008-01-01

    Full Text Available Le Brahmane du Komintern, largometraje documental del realizador francés Vladimir León, constituye un ejercicio ejemplar de investigación histórica y  de lograda factura de realización. Y, pese a no haber contado con la ayuda de ninguno organismo público, se trata de un ambicioso proyecto que cubre una amplia extensión geográfica que abarca: Estados Unidos, México, Moscú, Berlín, y la India. Gira en torno a una figura que tuvo en su tiempo su hora de gloria. Un bengalí, hijo de braman, la c...

  1. Le monde quantique

    CERN Document Server

    Aspect, A; Bensaude-Vincent, B; Castiel, A; Chevalley, C; Darrigol, O; Deligeorges, S; D'Espagnat, B; Laloë, F; Lévy-Leblond, J-M; Messiah, A; Paty, M; Vuillemin, J; Wheaton, B R

    1984-01-01

    Le monde quantique La physique quantique, après trois quarts de siècle, n'en finit pas d'être moderne. Elle est présente quotidiennement dans les laboratoires où les physiciens étudient atomes, noyaux et particules. Elle est entrée dans l'industrie où lasers, transistors et supraconducteurs lui doivent d'exister. Et elle continue à alimenter le débat philosophique sur la nature de la réalité dont elle montre la non-séparabilité fondamentale. Ses concepts de base, son développement, ses applications, ses controverses sont ici présentés par une pléiade de physiciens, d'historiens et de philosophes.

  2. Le silence des agneaux

    Directory of Open Access Journals (Sweden)

    BERNARD ROY

    2012-01-01

    Full Text Available Ce texte est avant tout une réflexion sur la notion d'obéissance, initiée à partir de deux évènements impliquant étroitement des membres de la profession infirmière. L'auteur se réjouit de la prise de parole et de l'implication directe d'infirmières dans le contexte du printemps érable. Il estime que la posture de ces infirmières s'inscrit dans ce que l'éthicien Guy Durand, appelle une obéissance autonome qui peut, du coup, mener à la désobéissance civile, à l'objection de conscience. En prenant exemple sur le silence des infirmières dans le contexte de la fermeture de postes d'infirmières en Minganie, l'auteur estime que cette posture est marginale chez les infirmières qui, majoritairement, adoptent une position de soumission et d'obéissance hétéronome.

  3. The oncogenic action of ionizing radiation on rat skin

    Energy Technology Data Exchange (ETDEWEB)

    Burns, F.J.

    1991-01-01

    Progress has occurred in several areas corresponding to the specific aims of the proposal: (1) Progression and multiple events in radiation carcinogenesis of rat skin as a function of LET; (2) cell cycle kinetics of irradiated rat epidermis as determined by double labeling and double emulsion autoradiography; (3) oncogene activation detected by in situ hybridization in radiation-induced rat skin tumors; (4) amplification of the c-myc oncogene in radiation-induced rat skin tumors as a function of LET; and (5) transformation of rat skin keratinocytes by ionizing radiation in combination with c-Ki-ras and c-myc oncogenes. 111 refs., 13 figs., 12 tabs.

  4. Le regard anachronique

    Directory of Open Access Journals (Sweden)

    Jean-Paul Aubert

    2011-01-01

    Full Text Available Cet article a pour objet l’anachronisme dans le film historique. Il s’appuie sur l’étude du long métrage Goya à Bordeaux, réalisé en 1999 par le cinéaste espagnol Carlos Saura. Cette biographie filmée du peintre Francisco de Goya fait mieux que composer avec l’anachronisme inhérent à toute reconstitution historique. Il l’assume et le revendique. La mise en cause de la chronologie et l’effacement de l’Histoire prennent sens dans la perspective d’une réflexion originale sur l’Histoire de l’art conçue comme un dialogue entre les œuvres et entre les époques.Este artículo está dedicado al problema del anacronismo en las películas históricas. Se basa en el estudio de Goya en Burdeos, un largo metraje rodado en 1999 por el director de cine español Carlos Saura. Esta biografía de Goya no sólo se acomoda con el anacronismo propio de la reconstitución histórica sino que lo asume y lo reivindica. El cuestionamiento de la cronología y el desinterés por la Historia cobran un nuevo sentido en el marco de una reflexión original sobre la Historia del arte concebida como un diálogo entre las obras y entre las épocas.

  5. Le survivant sans le syndrome Schreber

    Directory of Open Access Journals (Sweden)

    Richard Figuier

    2006-09-01

    Full Text Available On a pensé la catastrophe, mais a-t-on suffisamment pensé la survivance et la figure du survivant ? Ce n'est pas un hasard si celle-ci est au centre de Masse et puissance, oeuvre dans laquelle Canetti interroge la « mauvaise » survivance responsable de la poursuite de la logique de guerre. Mais où trouver la « bonne » ? Revenir de la catastrophe ne suffit pas pour être un « survivant authentique », selon l'expression de Kafka. Il faut avoir dépassé, avec Primo Levi et Robert Antelme, l'opposition de la vie comme croissance continue et de la mort comme son horrible contraire, par le don, dans la pauvreté solidaire, de cette vie retrouvée.Hemos reflexionado acerca de la catástrofe, pero ¿hemos meditado lo suficiente sobre la supervivencia y el superviviente? No es una coincidencia si el superviviente es el tema principal de Masse et puissance, obra en la cual Canetti analiza la «mala» supervivencia responsable de la persistencia de la lógica de guerra ¿Dónde sin embargo podemos encontrar la «buena» supervivencia? Superar la catástrofe no es suficiente para ser un «auténtico superviviente», según Kafka. Es fundamental ir más allá, con Primo Levi y Robert Antelme, de la oposición entre la vida, como crecimiento continuo, y la muerte, como su espantoso contrario, mediante la donación de forma solidaria de esta vida reencontrada.Disaster is the theme of many studies, but what about survival and of the figure of the survivor? This issue is central in Mass and power, work in which Canetti questions the “bad” survival, responsible for the continuation of the logic of war. But is there any “good” survival? Coming back from the catastrophe is not enough to be an “authentic survivor”, according to Kafka’s expression. To achieve this, it is necessary to have exceeded, with PrimoLevi and Robert Antelme, the opposition of life as a continuous growth and of death as its horrible opposite, by the gift, in a

  6. La piraterie sur le web

    CERN Document Server

    2002-01-01

    Les échanges de toutes sortes sont facilités à l'extrême par le web: des forums, des vidéoconférences, le commerce à distance, ou tout simplement la célérité des courriers électroniques ou la convivialité des chats, tout cela participe de la société de communication. Une certaine partie du monde découvre le nouvel horizon des échanges quasi instantanés, mais... les transactions sur le web sont-elles vraiment s res?

  7. Le principe roman

    CERN Document Server

    Ferrari, Jérôme

    2015-01-01

    Fasciné par la figure du physicien allemand Werner Heisenberg (1901-1976), fondateur de la mécanique quantique, inventeur du célèbre "principe d'incertitude" et Prix Nobel de physique en 1932, un jeune aspirant-philosophe désenchanté s'efforce, à l'aube du XXIe siècle, de considérer l'incomplétude de sa propre existence à l'aune des travaux et de la destinée de cet exceptionnel homme de sciences qui incarne pour lui la rencontre du langage scientifique et de la poésie, lesquels, chacun à leur manière, en ouvrant la voie au scandale de l'inédit, dessillent les yeux sur le monde pour en révéler la mystérieuse beauté que ne cessent de confisquer le matérialisme à l'œuvre dans l'Histoire des hommes.

  8. Oncogenic osteomalacia associated with soft tissue chondromyxoid fibroma

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Mi E-mail: jmpark@cmc.cuk.ac.kr; Woo, Young Kyun; Kang, Moo Il; Kang, Chang Suk; Hahn, Seong Tae

    2001-08-01

    Oncogenic osteomalacia is a rarely described clinical entity characterized by hypophosphatemia, phosphaturia, and a low concentration of 1,25-dihydroxyvitamin D{sub 3}. It is most often associated with benign mesenchymal tumor and can be cured with surgical removal of the tumor. In this paper, we present a case of oncogenic osteomalacia caused by chondromyxoid fibroma in the soft tissue of the sole of the foot in a 56-year-old woman.

  9. Identification of Novel Small Molecule Inhibitors of Oncogenic RET Kinase

    OpenAIRE

    Marialuisa Moccia; Qingsong Liu; Teresa Guida; Giorgia Federico; Annalisa Brescia; Zheng Zhao; Hwan Geun Choi; Xianming Deng; Li Tan; Jinhua Wang; Marc Billaud; Gray, Nathanael S.; Francesca Carlomagno; Massimo Santoro

    2015-01-01

    Oncogenic mutation of the RET receptor tyrosine kinase is observed in several human malignancies. Here, we describe three novel type II RET tyrosine kinase inhibitors (TKI), ALW-II-41-27, XMD15-44 and HG-6-63-01, that inhibit the cellular activity of oncogenic RET mutants at two digit nanomolar concentration. These three compounds shared a 3-trifluoromethyl-4-methylpiperazinephenyl pharmacophore that stabilizes the 'DFG-out' inactive conformation of RET activation loop. They blocked RET-media...

  10. Inhibition of Ras oncogenic activity by Ras protooncogenes.

    Science.gov (United States)

    Diaz, Roberto; Lue, Jeffrey; Mathews, Jeremy; Yoon, Andrew; Ahn, Daniel; Garcia-España, Antonio; Leonardi, Peter; Vargas, Marcelo P; Pellicer, Angel

    2005-01-10

    Point mutations in ras genes have been found in a large number and wide variety of human tumors. These oncogenic Ras mutants are locked in an active GTP-bound state that leads to a constitutive and deregulated activation of Ras function. The dogma that ras oncogenes are dominant, whereby the mutation of a single allele in a cell will predispose the host cell to transformation regardless of the presence of the normal allele, is being challenged. We have seen that increasing amounts of Ras protooncogenes are able to inhibit the activity of the N-Ras oncogene in the activation of Elk in NIH 3T3 cells and in the formation of foci. We have been able to determine that the inhibitory effect is by competition between Ras protooncogenes and the N-Ras oncogene that occurs first at the effector level at the membranes, then at the processing level and lastly at the effector level in the cytosol. In addition, coexpression of the N-Ras protooncogene in thymic lymphomas induced by the N-Ras oncogene is associated with increased levels of p107, p130 and cyclin A and decreased levels of Rb. In the present report, we have shown that the N-Ras oncogene is not truly dominant over Ras protooncogenes and their competing activities might be depending on cellular context.

  11. Relationship between the high-risk HPV infection and the expression of oncogenes, anti-oncogenes in cervical dysplasia

    Institute of Scientific and Technical Information of China (English)

    Li-Ping Shi; Xiu-Jie Sheng

    2017-01-01

    Objective:To study the relationship between the infection of high-risk HPV in cervical precancerous lesion and the expression of oncogene, anti-oncogene.Methods:218 cases ofcervical intraepithelial neoplasia patients in our hospital during May 2014–May 2016 were chosed and divided into high-risk HPV group (n=107), low-risk HPV group (n=111) according to cervical tissue HPV test; another 100 cases of patients received cervical biopsy and confirmed as benign lesions were enrolled in the control group. RT-PCR method was used to detect the mRNA expression of proto-oncogene and anti-oncogene in three groups, Western-blot method was used to detect the protein expression of Sox-2 and Wnt/β-catenin signal pathway.Results: mRNA expression of oncogene DEK, Bmi-1, c-fos, K-ras, Prdx4 in high-risk HPV group were higher than low-risk HPV group and control group (P<0.05); mRNA expression of anti-oncogene P27, P16, DAPK, PTEN, eIF4E3 in high-risk HPV group were lower than low-risk HPV group and control group (P<0.05); expression of Sox-2 and Wnt/β-catenin signaling pathway protein Sox-2,β-catenin, wnt-1, wnt-3a in high-risk HPV group were higher than low-risk HPV group and control group (P<0.05).Conclusions:High-risk HPV infection can increase the expression of oncogenes and reduce the expression of anti-oncogenes in cervical dysplasia tissues on Sox-2- and Wnt/β-catenin signaling pathway manners.

  12. Equazioni: le icone del sapere

    NARCIS (Netherlands)

    S. Bais

    2009-01-01

    Il mistero del cosmo è scritto nel linguaggio della matematica, e le equazioni sono le frasi che ne esprimono la bellezza e la profondità. Cercare di spiegare la scienza senza equazioni è come cercare di spiegare l’arte senza illustrazioni: partendo da questo presupposto, Sander Bais presenta una ga

  13. Le crime fantastique dans _Le grand saigneur_ de Rachilde

    Directory of Open Access Journals (Sweden)

    Vicky Gauthier

    2011-11-01

    Full Text Available Marguerite Eymery-Vallette (1860-1953 – plus connue sous son pseudonyme d’homme de lettres Rachilde et davantage encore pour la controverse qu’elle a créée avec la parution de sa troisième œuvre, Monsieur Vénus, roman matérialiste (1884 – a énormément publié tout au long de sa carrière littéraire (on dénombre plus d’une soixantaine d’œuvres : romans, nouvelles, contes, pièces de théâtre, etc.. Écrivant à une époque dite décadente, Rachilde y brille par ses œuvres subversives, abordant entre autres les pratiques sexuelles dépravées (sadomasochisme, nécrophilie, zoophilie, etc., mais surtout le crime (qu’il soit question de meurtre, de viol, de suicide, etc.. Ainsi, son personnage de prédilection est le marginal, le criminel dénué de morale. Cet article portera donc sur la façon dont le crime (et donc le criminel chez Rachilde verse dans le fantastique, plus spécifiquement dans un fantastique du monstrueux moral que je définirai dans un premier temps. Le roman de Rachilde, Le Grand Saigneur (1922, servira ensuite d’exemple significatif de ce monstrueux moral, notamment par l’étude du personnage éponyme de l’œuvre, soit le marquis Yves de Pontcroix, qui incarne ce criminel arborant les traces tant morales (tempérament sauvage et étrange que physiques (force hors du commun, pâleur de la peau, etc. de sa monstruosité. C’est donc dire que face au(x crime(x (ou au criminel le fantastique semble s’imposer de lui-même en guise d’explication : le genre humain ne peut vraisemblablement avoir quelque chose en commun avec cette monstruosité (ou ce monstre moral, pour reprendre les mots de Michel Foucault dans Les Anormaux. En somme, cet article se penchera sur la spécificité de l’écriture rachildienne, qui, dans le cas du roman Le Grand Saigneur, attribue une dimension fantastique au personnage criminel, renforçant d’autant plus la preuve de sa difformité (monstruosité et de sa

  14. Le Baratze (ou

    Directory of Open Access Journals (Sweden)

    Jacques Blot

    1998-01-01

    Full Text Available El círculo de piedras Mendizabal 7, de 8 metros de diámetro,   presenta una corona externa constituida de grandes bloques   hincados en la tierra, y otra interna y tangente, de elementos idénticos sólo puestos en el suelo. El cajón central está compuesto de cuatro losas y una tapa. No hay depósito de huesos ni de carbón de leña ; sólo se encuentran dos herraduras, entre las cuales una completa de tipo medieval, que podrían permitir de pensar en una construcción del círculo en el periodo histórico.

  15. Le Milton de Toland

    Directory of Open Access Journals (Sweden)

    James C. BROWN

    2003-10-01

    Full Text Available Alors que l’œuvre de John Milton suscite encore de nombreuses critiques et interprétations, je vous propose un retour en arrière afin d’étudier l’un des premiers écrits biographiques dédié à la vie et à l’œuvre du poète anglais signé par le philosophe irlandais John Toland. Paru en 1698, Life of John Milton dresse un portrait plus complet que ceux que l’on trouve dans les précédentes biographies du poète anglais (Darbishire xxix. Ayant été l’un des premiers biographes de Milton, Toland a pub...

  16. Le citoyen rieur

    Directory of Open Access Journals (Sweden)

    Anna Rycman

    2009-11-01

    Full Text Available Dans la Pologne d’aujourd’hui, l’évolution des modèles d’engagement civique et politique s’opère plus particulièrement auprès des jeunes générations. Parmi les expériences nouvelles de participation politique, les nouvelles technologies de l’information et de la communication offrent des opportunités radicales de reconfigurer l’espace public. La jeunesse polonaise investit en masse le Web. Dans le flux de paroles affranchies circulant et dialoguant dans le cyberespace, nous nous intéressons ici au développement d’un discours qui emprunte au registre de la dérision et de la satire politiques. Une multitude de sites critiques, de nature apparemment contestataire, des sites d’opposition fondés sur le genre satirique, ont émergé comme réponse apportée à la situation politique. Cet espace public électronique représente une forme moderne de « folklore politique », contribuant au processus de socialisation des jeunes citoyens polonais.The laughing citizen. A modern form of civic commitment in democratic Poland?In present day Poland, the evolution of civic and political commitment models is above all the affaire of the younger generations. Among the current opportunities for political participation, the new information and communication technologies offer radical opportunities to reconfigure the public arena. Polish youth are flocking to the Web. Amongst the flux of frank points of views circulating and dialoguing in cyberspace, our interest here is the development of a discourse inspired by political and satirical derision. A multitude of critical, apparently anti-establishment, sites and general opposition sites using the satirical style have emerged as a response to the political situation. This public electronic space represents a modern form of « political folklore », contributing to the socialising processes of young polish citizens.El ciudadano que rie. ¿Nueva forma del compromiso cívico en la

  17. Le temps des saints

    OpenAIRE

    Alberola Romá, Armando; Armogathe,Jean-Robert; Blanco, Emilio; Caillavet, Chantal; Cantarino, Elena; Cárceles de Gea, Beatriz; Cavillac, Michel; Chastagnaret, Gérard; Corcuera Atienza, Javier; Croizat-Viallet, Jean; Edouard, Sylvène; Goffaux, Bertrand; González Calleja, Eduardo; Huard, Raymond; Lacomba, Marta

    2006-01-01

    Les contributeurs de ce dossier — historiens, spécialistes de la littérature et de l’iconographie — ont souhaité montrer comment se «fabriquent», au sens noble du terme, les saints dans l’Église catholique espagnole. Par l’écrit ou la parole, par les textes et les images, la sainteté est au Siècle d’or le centre d’une production culturelle intense ainsi qu’un enjeu idéologique: il s’agit, d’une part, de réaffirmer un culte très contesté par la Réforme et de souligner la prééminence de l’Espag...

  18. Conaissez vous le roumain?

    Directory of Open Access Journals (Sweden)

    Montes Giraldo José Joaquín

    2003-06-01

    Full Text Available

    Mioara AVRAM, Marius SALA, Conaissez vous le roumain?, Bucarest, Unión Latina, 2001. El libro de Avram y Sala es en parte una condensación del libro de Sala. Presenta en su primer capítulo lo esencial de la historia externa del rumano: nombres, localización, hablantes, clasificación genealógica, tipo, orígenes, dialectos, contactos lingüísticos antiguos y modernos, escritura, normalización, lengua literaria, etc. Esto acompañado de indicaciones bibliográficas y sobre el estudio del rumano en universidades extranjeras.

     

  19. Le grand inventaire

    Directory of Open Access Journals (Sweden)

    Michel Melot

    2012-05-01

    Full Text Available Depuis quarante ans qu’il existe, l’Inventaire général des monuments et des richesses artistiques de la France n’a pas seulement progressé, couvrant près de dix mille communes, documentant plus de vingt mille dans cinq millions de pages, trois millions de photographies, et cent mille dessins. Il est devenu ce que ses fondateurs désiraient qu’il fût. Il n’est pas une liste d’objets plus ou moins singuliers qu’on aurait oubliés, mais l’observation méthodique de l’émergence dans le monde de l’ar...

  20. Le fonds Thomas Owen

    OpenAIRE

    Stippen, Philippe Van

    2016-01-01

    Les documents et les objets du Fonds Thomas Owen, acquis par les Archives et Musée de la Littérature en mars 2014, par l’intermédiaire du collectionneur, antiquaire et peintre Jean Bertot (le fils de Thomas Owen), sont à présent inventoriés et encodés dans la base de données de l’institution. Il s’agit d’un fonds représentatif de la triple vie de Thomas Owen, lequel, parallèlement à son activité d’écrivain reconnu, était aussi un industriel prospère sous son vrai nom de Gérald Bertot et un cr...

  1. Identification of Novel Small Molecule Inhibitors of Oncogenic RET Kinase.

    Directory of Open Access Journals (Sweden)

    Marialuisa Moccia

    Full Text Available Oncogenic mutation of the RET receptor tyrosine kinase is observed in several human malignancies. Here, we describe three novel type II RET tyrosine kinase inhibitors (TKI, ALW-II-41-27, XMD15-44 and HG-6-63-01, that inhibit the cellular activity of oncogenic RET mutants at two digit nanomolar concentration. These three compounds shared a 3-trifluoromethyl-4-methylpiperazinephenyl pharmacophore that stabilizes the 'DFG-out' inactive conformation of RET activation loop. They blocked RET-mediated signaling and proliferation with an IC50 in the nM range in fibroblasts transformed by the RET/C634R and RET/M918T oncogenes. They also inhibited autophosphorylation of several additional oncogenic RET-derived point mutants and chimeric oncogenes. At a concentration of 10 nM, ALW-II-41-27, XMD15-44 and HG-6-63-01 inhibited RET kinase and signaling in human thyroid cancer cell lines carrying oncogenic RET alleles; they also inhibited proliferation of cancer, but not non-tumoral Nthy-ori-3-1, thyroid cells, with an IC50 in the nM range. The three compounds were capable of inhibiting the 'gatekeeper' V804M mutant which confers substantial resistance to established RET inhibitors. In conclusion, we have identified a type II TKI scaffold, shared by ALW-II-41-27, XMD15-44 and HG-6-63-01, that may be used as novel lead for the development of novel agents for the treatment of cancers harboring oncogenic activation of RET.

  2. Identification of Novel Small Molecule Inhibitors of Oncogenic RET Kinase.

    Science.gov (United States)

    Moccia, Marialuisa; Liu, Qingsong; Guida, Teresa; Federico, Giorgia; Brescia, Annalisa; Zhao, Zheng; Choi, Hwan Geun; Deng, Xianming; Tan, Li; Wang, Jinhua; Billaud, Marc; Gray, Nathanael S; Carlomagno, Francesca; Santoro, Massimo

    2015-01-01

    Oncogenic mutation of the RET receptor tyrosine kinase is observed in several human malignancies. Here, we describe three novel type II RET tyrosine kinase inhibitors (TKI), ALW-II-41-27, XMD15-44 and HG-6-63-01, that inhibit the cellular activity of oncogenic RET mutants at two digit nanomolar concentration. These three compounds shared a 3-trifluoromethyl-4-methylpiperazinephenyl pharmacophore that stabilizes the 'DFG-out' inactive conformation of RET activation loop. They blocked RET-mediated signaling and proliferation with an IC50 in the nM range in fibroblasts transformed by the RET/C634R and RET/M918T oncogenes. They also inhibited autophosphorylation of several additional oncogenic RET-derived point mutants and chimeric oncogenes. At a concentration of 10 nM, ALW-II-41-27, XMD15-44 and HG-6-63-01 inhibited RET kinase and signaling in human thyroid cancer cell lines carrying oncogenic RET alleles; they also inhibited proliferation of cancer, but not non-tumoral Nthy-ori-3-1, thyroid cells, with an IC50 in the nM range. The three compounds were capable of inhibiting the 'gatekeeper' V804M mutant which confers substantial resistance to established RET inhibitors. In conclusion, we have identified a type II TKI scaffold, shared by ALW-II-41-27, XMD15-44 and HG-6-63-01, that may be used as novel lead for the development of novel agents for the treatment of cancers harboring oncogenic activation of RET.

  3. Dans le tourbillon des particules

    CERN Document Server

    Zito, Marco

    2015-01-01

    Accélérateurs géants, détecteurs complexes, particules énigmatiques... La physique subatomique peut sembler bien intimidante pour le novice. Et pourtant, qui n a jamais entendu parler du boson de Higgs et du CERN, le laboratoire européen où il a été découvert en 2012 ? Nul besoin d être un spécialiste pour comprendre de quoi il s agit. Aujourd hui, une théorie extraordinairement élégante, le Modèle Standard, décrit tous les résultats des expériences dans le domaine. Trente-sept particules élémentaires et quatre forces fondamentales : c est tout ce dont nous avons besoin pour expliquer la matière et l Univers ! Ce livre, destiné à un large public, raconte sans équations le long parcours qui a abouti au Modèle Standard. Ce parcours, parfois sinueux, a été entamé lorsque les Grecs anciens, et peut-être d autres avant eux, ont imaginé que la matière est composée de petites « billes ». Il faudra attendre plusieurs siècles pour qu on réalise que la matière, à l échelle micros...

  4. Stable oncogenic transformation induced by microcell-mediated gene transfer

    Institute of Scientific and Technical Information of China (English)

    吕有勇; Donald G.Blair

    1995-01-01

    Oncogenes have been identified using DNA-mediated transfection, but the size of the transferable and unrearranged DNA, gene rearrangement and amplification which occur during the transfection process limit the use of the techniques. We have evaluated microcell-mediated gene transfer techniques for the transfer and analysis of dominant oncogenes. MNNG-HOS, a transformed human cell line which contained the met oncogene mapping to human chromosome 7 was infected with retroviruses carrying drug resistance markers and used to optimize microcell preparation and transfer. Stable and drug-resistant hybrids containing single human chromosomes as well as the foci of the transformed cells containing the activated met oncogene and intact hitman chromosomes were obtained. Hybridization analysis with probes (i.e. collA2, pJ3.11) mapping up to 1 Mb away from met shows that the cells from the individual focr contain different amounts of apparently unrearranged human DNA associated with the oncogene, and the microcell-g

  5. Oncogenes and RNA splicing of human tumor viruses.

    Science.gov (United States)

    Ajiro, Masahiko; Zheng, Zhi-Ming

    2014-09-01

    Approximately 10.8% of human cancers are associated with infection by an oncogenic virus. These viruses include human papillomavirus (HPV), Epstein-Barr virus (EBV), Merkel cell polyomavirus (MCV), human T-cell leukemia virus 1 (HTLV-1), Kaposi's sarcoma-associated herpesvirus (KSHV), hepatitis C virus (HCV) and hepatitis B virus (HBV). These oncogenic viruses, with the exception of HCV, require the host RNA splicing machinery in order to exercise their oncogenic activities, a strategy that allows the viruses to efficiently export and stabilize viral RNA and to produce spliced RNA isoforms from a bicistronic or polycistronic RNA transcript for efficient protein translation. Infection with a tumor virus affects the expression of host genes, including host RNA splicing factors, which play a key role in regulating viral RNA splicing of oncogene transcripts. A current prospective focus is to explore how alternative RNA splicing and the expression of viral oncogenes take place in a cell- or tissue-specific manner in virus-induced human carcinogenesis.

  6. Le sentiment religieux dans le Jeu de Saint Nicolas

    OpenAIRE

    Rey-Flaud, Henri

    2014-01-01

    Le Jeu de saint Nicolas est un miracle, c'est même le premier miracle dramatisé en français. Il appartient donc de fait au théâtre religieux, au théâtre qui "relie" les hommes entre eux, les hommes au groupe, les hommes à la divinité. La religion dans le Jeu de saint Nicolas, ce sont d'abord les dieux païens, incarnés par Tervagan qui sont comme une caricature de la divinité selon Bodel. Le dieu païen est coupé des hommes. Il s'adresse à eux par l'oracle ambigu au Roi (v. 183). D'emblée, il n...

  7. Le bal du loup

    CERN Multimedia

    Happy Children's Home

    2013-01-01

    The Bord'eau amateur theatre group will graciously perform a play of their creation Le bal du loup Saturday 19 October 2013 at 20:00 Sunday 20 October at 17:00 in the Théâtre des Grottes Rue Louis Favre 43, 1201 Genève Children from age 12 upwards. Summary: The new-elected mayoress of a small village would like to clean up the town by prohibiting alcohol and getting rid of its prostitutes. Then along comes « Massimo Lupo » the pimp... The performances will be given to support the Happy Children's Home charity, which runs a foster-home in Pokhara for Nepali children:  http://www.happychildrenshome.org/ Admission : minimum charge of 10 CHF per person requested, to cover the cost of technical assistance and theatre rental. Any profit will be used solely for the foster-home. At the end of each performance members of the HCH charity will be happy to answer any questions you may have. The theatre has 86 seats, thank you for reserv...

  8. Le parfum et la chair

    OpenAIRE

    Guérer, Annick Le

    2010-01-01

    De l’Antiquité jusqu’à l’orée du xixe siècle, le parfum reste profondément marqué par ses relations étroites avec la chair. Son histoire est celle d’une désincarnation qui a conduit à en faire un produit abstrait et un objet marketing. Cette désincarnation, au sens le plus propre du terme, touche le parfum lui-même lorsqu’il abandonne les produits animaux utilisés pour sa composition. Mais c’est aussi une désincarnation « fonctionnelle » dans la mesure où s’efface son rôle primordial dans la ...

  9. Oncogene-mediated transformation of fetal rat colon in vitro.

    Science.gov (United States)

    Pories, S; Jaros, K; Steele, G; Pauley, A; Summerhayes, I C

    1992-05-01

    Short-term maintenance of fetal rat colonic tissue in vitro has been demonstrated using a collagen matrix organ culture system. The introduction of single (v-myc, v-rasH, v-src) oncogenes or combinations of oncogenes (v-myc/rasH, v-myc/src) into normal colon mucosal elements was established using retroviral vectors, resulting in enhanced proliferation and migration of epithelial cells from the lumen of tissue implants. Expression of a single oncogene in normal colon epithelium did not result in the establishment of cell lines. In contrast, expression of cooperating oncogenic elements resulted in cell lines in greater than 80% of experiments, revealing different morphological characteristics dependent upon the oncogene combination used. Confirmation of the expression of viral transcripts was determined using Northern blot analysis and viral oncoprotein expression using Western blot analysis (p21) and an immunoprecipitation kinase assay (src). Expression of keratin filaments was lost following passaging of cell lines but could be induced by the myc/ras transformants by growth on Rat-1 feeder layers. This induction phenomenon was not observed with myc/src lines, and although these expressed high levels of sucrase isomaltase the epithelial origin of these cells is unclear. Karyotypic analysis performed on three myc/ras-transformed cell lines revealed a normal chromosome complement associated with transformation. In this report we describe a novel in vitro transformation system for normal rat colonic epithelium mediated by the introduction of oncogene elements using different retroviral vector constructs. The potential to generate cell lines representing different stages of neoplastic progression using relevant genetic components presents significant advantages for the study of cellular and molecular interactions underlying colon neoplastic progression.

  10. Le bégaiement

    Science.gov (United States)

    Perez, Hector R.; Stoeckle, James H.

    2016-01-01

    Résumé Objectif Fournir une mise à jour sur l’épidémiologie, l’hérédité, la physiopathologie, le diagnostic et le traitement du bégaiement développemental. Qualité des données Une recherche d’études récentes ou non portant sur l’épidémiologie, l’hérédité, la physiopathologie, le diagnostic et le traitement du bégaiement développemental a été effectuée dans les bases de données MEDLINE et Cochrane. La plupart des recommandations s’appuient sur des études de petite envergure, des données probantes de qualité limitée ou des consensus. Message principal Le bégaiement est un trouble d’élocution fréquent chez les personnes de tous âges, il altère la fluidité verbale normale et l’enchaînement du discours. Le bégaiement a été lié à des différences de l’anatomie, du fonctionnement et de la régulation dopaminergique du cerveau qui seraient de source génétique. Il importe de poser le diagnostic avec attention et de faire les recommandations qui conviennent chez les enfants, car de plus en plus, le consensus veut que l’intervention précoce par un traitement d’orthophonie soit cruciale chez les enfants bègues. Chez les adultes, le bégaiement est lié à une morbidité psychosociale substantielle, dont l’anxiété sociale et une piètre qualité de vie. Les traitements pharmacologiques ont soulevé l’intérêt depuis quelques années, mais les données cliniques sont limitées. Le traitement des enfants et des adultes repose sur l’orthophonie. Conclusion De plus en plus de recherches ont tenté de lever le voile sur la physiopathologie du bégaiement. La meilleure solution pour les enfants et les adultes bègues demeure la recommandation à un traitement d’orthophonie.

  11. Un oiseau "sabote" le CERN

    CERN Multimedia

    Colson, Sébastien

    2009-01-01

    Un oiseau, un simple oiseau, est parvenu à bloquer à lui tout seul l'accélérateur à particules à 3,7 milliards d'euros. UNe histoire quasiment bulresque qui a toutefois impacté le fonctionnement de la machine durant près de cinq jours, puisque c'est le système de refroidissement qui a été affecté. (1 page)

  12. In Silico Analysis of Oncogenes for Renal Cancer

    Directory of Open Access Journals (Sweden)

    Sim-Hui Tee

    2012-01-01

    Full Text Available Computational tools and methods play a vital role in handling and analyzing a large volume of genomic data. In cancer research, in silico methods such as computational algorithm and protein databases are indispensable. In this paper, we adopted an in silico approach to analyze oncogenes that cause  renal cancer. Our objective is to identify and analyze the genes which are over expressed in the renal cancer tissues. The identification of oncogenes for renal cancer could provide directions and insights for molecular cancer treatment.

  13. Expression Study of LeGAPDH, LeACO1, LeACS1A, and LeACS2 in Tomato Fruit (Solanum lycopersicum

    Directory of Open Access Journals (Sweden)

    Pijar Riza Anugerah

    2015-10-01

    Full Text Available Tomato is a climacteric fruit, which is characterized by ripening-related increase of respiration and elevated ethylene synthesis. Ethylene is the key hormone in ripening process of climacteric fruits. The objective of this research is to study the expression of three ethylene synthesis genes: LeACO1, LeACS1A, LeACS2, and a housekeeping gene LeGAPDH in ripening tomato fruit. Specific primers have been designed to amplify complementary DNA fragment of LeGAPDH (143 bp, LeACO1 (240 bp, LeACS1A (169 bp, and LeACS2 (148 bp using polymerase chain reaction. Nucleotide BLAST results of the complementary DNA fragments show high similarity with LeGAPDH (NM_001247874.1, LeACO1 (NM_001247095.1, LeACS1A(NM_001246993.1, LeACS2 (NM_001247249.1, respectively. Expression study showed that LeACO1, LeACS1A, LeACS2, and LeGAPDH genes were expressed in ripening tomato fruit. Isolation methods, reference sequences, and primers used in this study can be used in future experiments to study expression of genes responsible for ethylene synthesis using quantitative polymerase chain reaction and to design better strategy for controlling fruit ripening in agroindustry.

  14. Le livre sur le livre traité de documentation

    CERN Document Server

    Otlet, Paul

    2015-01-01

    Paul Otlet est considéré comme le père des sciences de l'information. Ouvrage fondateur et fondamental, le Traité de documentation. Le livre sur le livre (1934) est l'aboutissement de son travail inlassable pour rassembler, classer et partager les connaissances. Otlet y propose une remarquable synthèse du savoir sur le livre et le document en même temps qu'il anticipe Internet et l'hypertexte. La réédition du Traité de documentation, 70 ans après la disparition de son auteur, coïncide avec la réouverture du Mundaneum à Mons, où le fabuleux héritage documentaire légué par Paul Otlet et Henri La Fontaine est conservé. « Ici, la table de travail n'est plus chargée d'aucun livre. À leur place se dresse un écran et à portée un téléphone. Là-bas, au loin, dans un édifice immense, sont tous les livres et tous les renseignements. De là, on fait apparaître sur l'écran la page à lire pour connaître la réponse aux questions posées par téléphone. » Préfaces de Benoît Peeters (éc...

  15. Le modèle spatial de la capitale allemande

    Directory of Open Access Journals (Sweden)

    Antoine Laporte

    2013-06-01

    Full Text Available En Allemagne, en 1999, le Chancelier fédéral et son gouvernement ont quitté Bonn pour Berlin. Ce transfert du pouvoir est accompagné de celui d’une grande partie de l’appareil d’État et de la haute administration, et des fonctions qui leur sont traditionnellement attribuées comme la presse, les lobbys ou encore la diplomatie. Le déplacement du statut de capitale effective de l’Allemagne de Bonn à Berlin est le résultat des évolutions géopolitiques d’un pays ayant recouvré son unité et sa pleine et entière souveraineté. Installer le pouvoir exécutif et législatif à Berlin était une démarche hautement symbolique, visant à normaliser la position de l’ancienne capitale de la RDA et du IIIe Reich comme véritable centre politique de l’Allemagne. Or le déplacement des institutions fédérales n’est pas qu’un acte symbolique. Il entraîne également à l’échelle intra-urbaine des dynamiques très concrètes sur le tissu urbain et participe à la mise en place de nouvelles centralités dans la ville. En effet, le statut de capitale d’État prédestine l’agglomération à la coprésence de nombreuses fonctions urbaines spécifiques plus ou moins directement liées à l’exercice ou à la symbolique du pouvoir.

  16. Le pompage optique naturel dans le milieu astrophysique

    Science.gov (United States)

    Pecker, J.-C.

    The title of this lecture abstracts only a part of it : the importance in astrophysics of the study of non-LTE situations has become considerable, as well in the stellar atmospheres as, still more, in the study of fortuitous coincidences as a mechanism of formation of emission line nebular spectra, or of molecular interstellar « masers ». Another part of this talk underlines the role of Kastler in his time, and describes his warm personality through his public reactions in front of the nuclear armement, of the Viet-Nam and Algerian wars, of the problems of political refugees... Kastler was a great scientist ; he was also a courageous humanist. 1976 : Les accords nucléaires du Brésil : allocution d'ouverture (19 mars). Colloque sur le sujet ci-dessus. 1976 : La promotion de la culture dans le nouvel ordre économique international, allocution à l'occasion d'une table ronde sur ce thème par l'UNESCO (23-27 juin 1976) ; « Sciences et Techniques », octobre 1976. 1979 : La bête immonde (avec J.-C. Pecker), « Le Matin », 20 mars. 1979 : Appel à nos ministres (avec J.-C. Pecker), « Le Monde », 13 décembre. 1979 : Le flou, le ténébreux, l'irrationnel (avec J.-C. Pecker), « Le Monde », 14 septembre. 1980 : Education à la paix, Préface, in : Publ. UNESCO. 1981 : Le vrai danger, « Le Monde », 6 août 1981. 1982 : Nucléaire civil et militaire, « Le Monde », 1er juin 1982. 1982 : Les scientifiques face à la perspective d'holocauste nucléaire (texte inédit). Le titre de cette communication en résume seulement une partie : l'importance prise en astrophysique par l'analyse des situations hors ETL est devenue considérable, qu'il s'agisse des atmosphères stellaires, ou plus encore, des coïncidences fortuites de la formation des spectres d'émission nébulaires, ou des « masers » moléculaires interstellaires. Une autre partie de cet exposé souligne lele de Kastler dans son époque, et décrit sa personnalité généreuse à travers ses r

  17. Le volcanisme dans le Sud-Ouest de Madagascar

    Science.gov (United States)

    Nicollet, Christian

    Le volcanisme dans le Sud-Ouest de Madagascar comprend: (1) des coulées turoniennes et campaniennes d'olivine-tholéiites et quartz-tholéiites typiques de marge continentale passive; elles sont contemporaines de la séparation Inde-Madagascar, (2) un systène filonien de tholéiites, de basaltes alcalins, de basanites et d'olivine-néphélinites (?); non daté, cet événement magmetique est-il à rattacher au déplacement du Nord vers le Sud de Madagascar au cours de la séparation de l'île avec l'Afrique,ou l'Afrique ou l'Antartique, entre 150 MA et 80-90 MA? Ou bien est-il contemporain des coulées tholéiitiques turoniennes et campaniennes ou encore postérieures à celles-ci? et (3) des necks et coulées à faible extention de laves alcalines post-pliocène (?) associés aux failles subsidentes qui ont fonctionné pendant tout le tertiaire.

  18. The mystery of oncogenic KRAS: Lessons from studying its wild-type counter part.

    Science.gov (United States)

    Chang, Yuan-I; Damnernsawad, Alisa; Kong, Guangyao; You, Xiaona; Wang, Demin; Zhang, Jing

    2016-07-22

    Using conditional knock-in mouse models, we and others have shown that despite the very high sequence identity between Nras and Kras proteins, oncogenic Kras displays a much stronger leukemogenic activity than oncogenic Nras in vivo. In this manuscript, we will summarize our recent work of characterizing wild-type Kras function in adult hematopoiesis and in oncogenic Kras-induced leukemogenesis. We attribute the strong leukemogenic activity of oncogenic Kras to 2 unique aspects of Kras signaling. First, Kras is required in mediating cell type- and cytokine-specific ERK1/2 signaling. Second, oncogenic Kras, but not oncogenic Nras, induces hyperactivation of wild-type Ras, which significantly enhances Ras signaling in vivo. We will also discuss a possible mechanism that mediates oncogenic Kras-evoked hyperactivation of wild-type Ras and a potential approach to down-regulate oncogenic Kras signaling.

  19. Role of ets Oncogenes in the Progression of Breast Cancer

    Science.gov (United States)

    1998-10-01

    Mazabraud A. (1988). Cancer Kato J, Matsuoka M, Polyak K, Massague J and Sherr CJ. Genet. Cytogenet., 32, 229-238. (1994). Cell, 79, 487-496. Vairo G...Francisco LV , Roach JC, Argonza R, D, Weber BL and EI-Deiryh WS. (1998). Oncogene, 16, King MC and Ostrander EA. (1996). Human Mol. Genet., 1713-1721. 5

  20. Targeting MET Amplification as a New Oncogenic Driver

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Hisato [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Okamoto, Isamu, E-mail: okamotoi@kokyu.med.kyushu-u.ac.jp [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Center for Clinical and Translational Research, Kyushu University Hospital, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582 (Japan); Okamoto, Wataru [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Division of Transrlational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577 (Japan); Tanizaki, Junko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, HIM223, 450 Brookline Avenue, Boston, MA 02215 (United States); Nakagawa, Kazuhiko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Nishio, Kazuto [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan)

    2014-07-22

    Certain genetically defined cancers are dependent on a single overactive oncogene for their proliferation and survival, a phenomenon known as “oncogene addiction”. A new generation of drugs that selectively target such “driver oncogenes” manifests a clinical efficacy greater than that of conventional chemotherapy in appropriate genetically defined patients. MET is a proto-oncogene that encodes a receptor tyrosine kinase, and aberrant activation of MET signaling occurs in a subset of advanced cancers as result of various genetic alterations including gene amplification, polysomy, and gene mutation. Our preclinical studies have shown that inhibition of MET signaling either with the small-molecule MET inhibitor crizotinib or by RNA interference targeted to MET mRNA resulted in marked antitumor effects in cancer cell lines with MET amplification both in vitro and in vivo. Furthermore, patients with non-small cell lung cancer or gastric cancer positive for MET amplification have shown a pronounced clinical response to crizotinib. Accumulating preclinical and clinical evidence thus suggests that MET amplification is an “oncogenic driver” and therefore a valid target for treatment. However, the prevalence of MET amplification has not been fully determined, possibly in part because of the difficulty in evaluating gene amplification. In this review, we provide a rationale for targeting this genetic alteration in cancer therapy.

  1. c-Abl antagonizes the YAP oncogenic function.

    Science.gov (United States)

    Keshet, R; Adler, J; Ricardo Lax, I; Shanzer, M; Porat, Z; Reuven, N; Shaul, Y

    2015-06-01

    YES-associated protein (YAP) is a central transcription coactivator that functions as an oncogene in a number of experimental systems. However, under DNA damage, YAP activates pro-apoptotic genes in conjunction with p73. This program switching is mediated by c-Abl (Abelson murine leukemia viral oncogene) via phosphorylation of YAP at the Y357 residue (pY357). YAP as an oncogene coactivates the TEAD (transcriptional enhancer activator domain) family transcription factors. Here we asked whether c-Abl regulates the YAP-TEAD functional module. We found that DNA damage, through c-Abl activation, specifically depressed YAP-TEAD-induced transcription. Remarkably, c-Abl counteracts YAP-induced transformation by interfering with the YAP-TEAD transcriptional program. c-Abl induced TEAD1 phosphorylation, but the YAP-TEAD complex remained unaffected. In contrast, TEAD coactivation was compromised by phosphomimetic YAP Y357E mutation but not Y357F, as demonstrated at the level of reporter genes and endogenous TEAD target genes. Furthermore, YAP Y357E also severely compromised the role of YAP in cell transformation, migration, anchorage-independent growth, and epithelial-to-mesenchymal transition (EMT) in human mammary MCF10A cells. These results suggest that YAP pY357 lost TEAD transcription activation function. Our results demonstrate that YAP pY357 inactivates YAP oncogenic function and establish a role for YAP Y357 phosphorylation in cell-fate decision.

  2. Targeting MET Amplification as a New Oncogenic Driver

    Directory of Open Access Journals (Sweden)

    Hisato Kawakami

    2014-07-01

    Full Text Available Certain genetically defined cancers are dependent on a single overactive oncogene for their proliferation and survival, a phenomenon known as “oncogene addiction”. A new generation of drugs that selectively target such “driver oncogenes” manifests a clinical efficacy greater than that of conventional chemotherapy in appropriate genetically defined patients. MET is a proto-oncogene that encodes a receptor tyrosine kinase, and aberrant activation of MET signaling occurs in a subset of advanced cancers as result of various genetic alterations including gene amplification, polysomy, and gene mutation. Our preclinical studies have shown that inhibition of MET signaling either with the small-molecule MET inhibitor crizotinib or by RNA interference targeted to MET mRNA resulted in marked antitumor effects in cancer cell lines with MET amplification both in vitro and in vivo. Furthermore, patients with non-small cell lung cancer or gastric cancer positive for MET amplification have shown a pronounced clinical response to crizotinib. Accumulating preclinical and clinical evidence thus suggests that MET amplification is an “oncogenic driver” and therefore a valid target for treatment. However, the prevalence of MET amplification has not been fully determined, possibly in part because of the difficulty in evaluating gene amplification. In this review, we provide a rationale for targeting this genetic alteration in cancer therapy.

  3. L’avion, le cerf-volant et le deuil

    Directory of Open Access Journals (Sweden)

    Jean Marie Théodat

    2009-07-01

    Full Text Available Le hasard de l’actualité nous fait publier ce neuvième numéro avec un Sur le Vif en résonance décalée par rapport à l’émoi planétaire suscité par la disparition brutale, le jeudi 25 juin, de Michael Jackson. Certes, la pop music n’est pas notre cœur de métier, mais une fois faite la part de l’ombre des coulisses d’une vie que l’on devine pleine de douleurs enfouies, et celle des paillettes qui illuminent la scène, demeure l’incontestable talent dont la ferveur planétaire justifie, dans ces co...

  4. Le sacré sauvage

    Directory of Open Access Journals (Sweden)

    Roger Bastide

    2010-09-01

    Full Text Available Conférence prononcée le 13 septembre 1973 dans le cadre des Rencontres Internationales de Genève qui avaient pour thème cette année-là « Le besoin religieux ». Cette conférence figure dans les Actes de cette rencontre (Le Besoin religieux, Éditions de la Baconnière, Neuchâtel, 1974, pp. 123-145. Elle a été republiée dans un ouvrage posthume dont elle est l’éponyme, ouvrage édité par Henri Desroche (Paris, éditions Stock, 1975. Nous reproduisons ici le texte intégral original, avec l’aimable autorisation des Rencontres Internationales de Genève auxquelles SociologieS adresse ses remerciements.The wild sacredText of a lecture taken on November the 13th 1973 during the Rencontres Internationales de Genève whom theme was "The religious need". This lecture was first published in: Le Besoin religieux (La Baconnière Editions, Neuchâtel, 1974, pp. 123-145, and published once again in a posthumous book: Le sacré sauvage ("The wild sacred" edited by Henri Desroche (Paris, Stock Editions, 1975. It is reproduced here with the kind authorization of the Rencontres Internationales de Genève. SociologieS gives them sincere thanks.Le Sacré sauvage (Lo sagrado en el mundo primitivoConferencia efectuada el 13 de septiembre de 1973 en el marco de las Rencontres Internationales de Genève (Encuentros Internacionales de Ginebra que tenia como tema general la necesidad de la experiencia religiosa (“Le besoin religieux”, Éditions de la Baconnière, Neuchâtel, 1974, pp. 123-145. Esta conferencia fue publicada de nuevo en un trabajo póstumo que lleva el mismo título, editado por Henri Desroche (Paris, Éditions Stock, 1975. Reproducimos aquí la integralidad del texto original con la amable autorización de las Rencontres Internationales de Genève, a las cuales la revista SociologieS expresa su agradecimiento.

  5. Le LHC, un tunnel cosmique

    CERN Document Server

    CERN. Geneva

    2009-01-01

    Et si la lumière au bout du tunnel du LHC était cosmique ? En d’autres termes, qu’est-ce que le LHC peut nous apporter dans la connaissance de l’Univers ? Car la montée en énergie des accélérateurs de particules nous permet de mieux appréhender l’univers primordial, chaud et dense. Mais dans quel sens dit-on que le LHC reproduit des conditions proches du Big bang ? Quelles informations nous apporte-t-il sur le contenu de l’Univers ? La matière noire est-elle détectable au LHC ? L’énergie noire ? Pourquoi l’antimatière accumulée au CERN est-elle si rare dans l’Univers ? Et si le CERN a bâti sa réputation sur l’exploration des forces faibles et fortes qui opèrent au sein des atomes et de leurs noyaux, est-ce que le LHC peut nous apporter des informations sur la force gravitationnelle qui gouverne l’évolution cosmique ? Depuis une trentaine d’années, notre compréhension de l’univers dans ses plus grandes dimensions et l’appréhension de son comportement aux plus peti...

  6. The DNA damage checkpoint precedes activation of ARF in response to escalating oncogenic stress during tumorigenesis

    DEFF Research Database (Denmark)

    Evangelou, K; Bartkova, J; Kotsinas, A

    2013-01-01

    to various oncogenes showed that the delayed upregulation of ARF reflected a requirement for a higher, transcriptionally based threshold of oncogenic stress, elicited by at least two oncogenic ‘hits’, compared with lower activation threshold for DDR. We propose that relative to DDR activation, ARF provides...

  7. Le Corbusier’s Dioramas

    Directory of Open Access Journals (Sweden)

    José Ramón Alonso Pereira

    2013-10-01

    Full Text Available AbstractLe Corbusier symbolizes the modern rational urbanism, whose rigorous effort of town planning demands a parallel effort of comprehension. It opposes to these contemporary urbanism that wish to perceive and to enjoy cities in a sensible way. Nevertheless, sentiment and reason are not adverses and Le Corbusier gives us at his  moment keys to intent a synthesis, joined them in a singular way by means of his ‘boîtes à miracles’ or ‘magic boxes’: those "architectural spectacles of synthesis" that he defined in 1951 Ciam. Here we try to approach to the first of those ‘spectacles’: the ‘diorama’, considering it as a corbusean strategy of mediation between rational and sensible in modern and contemporary city.Key wordsLe Corbusier, diorama, Ville Contemporaine, Plan Voisin, Plan Maciá

  8. Nietzsche, Deleuze et le sport

    OpenAIRE

    Leclercq, Stéfan

    2006-01-01

    Les philosophies de Nietzsche et Deleuze ont en commun que la pensée, comme la vie qu’elle recèle, n’est que mouvements. Mouvements rapides et hétérogènes parcourant les surfaces, comprenant l’être lui-même comme surface à traverser. Mouvements et surface organisent un jeu, celui de la pensée. Ce jeu, que Deleuze appellera « le jeu idéal », est à comparer par ses spécificités aux sports. Mais si la pensée, par son mouvement intempestif, saute toutes les limites, le sport ne peut trouver sa va...

  9. La pluie et le topoclimat

    OpenAIRE

    Van Hamme, T.

    1992-01-01

    Lorsqu'on étudie les potentialités agroéconomiques d'une région à relief accidenté, une question importante qui se pose est de savoir s'il y a des orientations et des inclinaisons privilégiées au point de vue pluviosité. De plus, il est aussi important de comparer l'action érosive de l'eau, d'un versant à un autre, en fonction de l'inclinaison et de l'orientation. Dans le cadre de cet article, on propose un modèle original permettant de répondre à ces questions. Ce modèle est particulièrement...

  10. Nietzsche, Darwin et le darwinisme

    OpenAIRE

    Merlio, Gilbert

    2012-01-01

    Le darwinisme a été pour Nietzsche un auxiliaire précieux dans son combat contre le dualisme platonicien et chrétien. Nietzsche adhère aux deux idées qui le fondent : l’idée de lutte pour la vie et l’idée d’évolution. On ne peut comprendre l’homme en faisant abstraction de son origine animale, de ses instincts et de ses affects. La généalogie a pour tâche de les mettre au jour. Nietzsche critique cependant l’aspect mécanique et utilitaire de la sélection naturelle darwinienne qui n’envisage q...

  11. le programme SET-Routes

    CERN Multimedia

    CERN Audiovisual Service

    2009-01-01

    Les routes de la science sont plus escarpées pour les femmes Le programme SET-Routes, qui visait à sensibiliser les jeunes filles à l’intérêt des carrières scientifiques, a pris fin en avril. Porté par l’EMBL, l’EMBO et le CERN, il a mis en place un réseau de femmes scientifiques, des ambassadrices qui se sont rendues dans les établissements scolaires européens pour parler de leur parcours scientifique.

  12. The use of Gene Ontology terms and KEGG pathways for analysis and prediction of oncogenes.

    Science.gov (United States)

    Xing, Zhihao; Chu, Chen; Chen, Lei; Kong, Xiangyin

    2016-11-01

    Oncogenes are a type of genes that have the potential to cause cancer. Most normal cells undergo programmed cell death, namely apoptosis, but activated oncogenes can help cells avoid apoptosis and survive. Thus, studying oncogenes is helpful for obtaining a good understanding of the formation and development of various types of cancers. In this study, we proposed a computational method, called OPM, for investigating oncogenes from the view of Gene Ontology (GO) and biological pathways. All investigated genes, including validated oncogenes retrieved from some public databases and other genes that have not been reported to be oncogenes thus far, were encoded into numeric vectors according to the enrichment theory of GO terms and KEGG pathways. Some popular feature selection methods, minimum redundancy maximum relevance and incremental feature selection, and an advanced machine learning algorithm, random forest, were adopted to analyze the numeric vectors to extract key GO terms and KEGG pathways. Along with the oncogenes, GO terms and KEGG pathways were discussed in terms of their relevance in this study. Some important GO terms and KEGG pathways were extracted using feature selection methods and were confirmed to be highly related to oncogenes. Additionally, the importance of these terms and pathways in predicting oncogenes was further demonstrated by finding new putative oncogenes based on them. This study investigated oncogenes based on GO terms and KEGG pathways. Some important GO terms and KEGG pathways were confirmed to be highly related to oncogenes. We hope that these GO terms and KEGG pathways can provide new insight for the study of oncogenes, particularly for building more effective prediction models to identify novel oncogenes. The program is available upon request. We hope that the new findings listed in this study may provide a new insight for the investigation of oncogenes. This article is part of a Special Issue entitled "System Genetics" Guest Editor

  13. High Risk Alpha Papillomavirus Oncogenes Impair the Homologous Recombination Pathway.

    Science.gov (United States)

    Wallace, Nicholas A; Khanal, Sujita; Robinson, Kristin L; Wendel, Sebastian O; Messer, Joshua J; Galloway, Denise A

    2017-08-02

    Persistent high risk genus α human papillomavirus (HPV) infections cause nearly every cervical carcinoma and a subset of tumors in the oropharyngeal tract. During the decades required for HPV-associated tumorigenesis, the cellular genome becomes significantly destabilized. Our analysis of cervical tumors from 4 separate data sets found a significant upregulation of the homologous recombination (HR) pathway genes. The increased abundance of HR proteins can be replicated in primary cells by expression of the two HPV oncogenes (E6 and E7) required for HPV-associated transformation. HPV E6 and E7 also enhanced the ability of HR proteins to form repair foci, yet both E6 and E7 reduce the ability of the HR pathway to complete double strand break (DSB) repair by about 50%. The HPV oncogenes hinder HR by allowing the process to begin at points in the cell cycle when the lack of a sister chromatid to serve as a homologous template prevents completion of the repair. Further, HPV E6 attenuates repair by causing RAD51 to be mislocalized away from both transient and persistent DSBs, while HPV E7 is only capable of impairing RAD51 localization to transient lesions. Finally, we show that the inability to robustly repair DSBs causes some of these lesions to be more persistent, a phenotype that correlates with increased integration of episomal DNA. Together these data support our hypothesis that HPV oncogenes contribute to the genomic instability observed in HPV-associated malignancies by attenuating the repair of damaged DNA.IMPORTANCE: This work expands the understanding of HPV biology, establishing a direct role for both HPV E6 and E7 in the destabilization of the host genome by blocking the homologous repair of DSBs. To our knowledge, this is the first time that both viral oncogenes were shown to disrupt this DSB repair pathway. We show that HPV E6 and E7 allow HR to initiate at an inappropriate part of the cell cycle. The mislocalization of RAD51 away from DSBs in cells

  14. The ETS family of oncogenic transcription factors in solid tumours.

    Science.gov (United States)

    Sizemore, Gina M; Pitarresi, Jason R; Balakrishnan, Subhasree; Ostrowski, Michael C

    2017-06-01

    Findings over the past decade have identified aberrant activation of the ETS transcription factor family throughout all stages of tumorigenesis. Specifically in solid tumours, gene rearrangement and amplification, feed-forward growth factor signalling loops, formation of gain-of-function co-regulatory complexes and novel cis-acting mutations in ETS target gene promoters can result in increased ETS activity. In turn, pro-oncogenic ETS signalling enhances tumorigenesis through a broad mechanistic toolbox that includes lineage specification and self-renewal, DNA damage and genome instability, epigenetics and metabolism. This Review discusses these different mechanisms of ETS activation and subsequent oncogenic implications, as well as the clinical utility of ETS factors.

  15. Malignant transformation of diploid human fibroblasts by transfection of oncogenes

    Energy Technology Data Exchange (ETDEWEB)

    McCormick, J.J.

    1992-01-01

    This document consist of brief reports prepared by postdoctoral students supported by the project, each describing his accomplishments under the grant. Topics include (1) Malignant Transformation of MSU-1. 1 Cells by Gamma Radiation, (2) Correlation between Levels of ras Expression and Presence of Transformed Phenotypes Including Tumorigenicity, Using a Modulatable Promoter, (3) Relation between Specific rad Oncogene Expression, (4) Correlation of Genetic Changes in Fibroblastic Tumors with Malignancies, (5)Transformation of MSU-1.1 Cells by sis Oncogene, (6) Malignant Transformation of MSU-1.0 Cells, (7) Correlation of Urokinase Plasminogen Activation (mu-PA) with Malignant Phenotype, (8)Two Dimensional Gel Electrophoresis Studies of the Proteins of the Major Cell Strains of the MSU-1 Family of Cells, and (9) Correlation between Proteinase Activity Levels and Malignancy.

  16. Regulation of apoptosis by the papillomavirus E6 oncogene

    Institute of Scientific and Technical Information of China (English)

    Ting-Ting Li; Li-Na Zhao; Zhi-Guo Liu; Ying Han; Dai-Ming Fan

    2005-01-01

    Infection with human papillomaviruses is strongly associated with the development of multiple cancers including esophageal squamous cell carcinoma. The HPV E6 gene is essential for the oncogenic potential of HPV.The recgulation of apoptosis by oncogene has been relatel to carcinogenesis closely; therefore, the modulation of E6 on cellular apoptosis has become a hot research topic recently. Inactivation of the pro-apoptotic tumor suppressor p53 by E6 is an important mechanism by which E6promotes cell growth; it is expected that inactivation of p53 by E6 should lead to a reduction in cellular apoptosis,numerous studies showed that E6 could in fact sensitize cells to apoptosis. The molecular basis for apoptosis modulation by E6 is poorly understood. In this article, we will present an overview of observations and current understanding of molecular basis for E6-induced apoptosis.

  17. Oncogenic osteomalacia presenting as bilateral stress fractures of the tibia

    Energy Technology Data Exchange (ETDEWEB)

    Ohashi, Kenjirou; Ohnishi, Takeshi; Ishikawa, Tohru [Department of Radiology, St. Marianna University Hospital, Kanagawa (Japan); Tani, Haruo [Department of Internal Medicine III, St. Marianna University Hospital, Kawasaki City, Kanagawa (Japan); Uesugi, Keisuke [Department of Otolaryngology, St. Marianna University Hospital, Kawasaki City, Kanagawa (Japan); Takagi, Masayuki [Department of Pathology, St. Marianna University Hospital, Kawasaki City, Kanagawa (Japan)

    1999-01-01

    We report on a patient with bilateral stress fractures of the tibia who subsequently showed classic biochemical features of oncogenic osteomalacia. Conventional radiographs were normal. MR imaging revealed symmetric, bilateral, band-like low-signal lesions perpendicular to the medial cortex of the tibiae and corresponding to the only lesions subsequently seen on the bone scan. A maxillary sinus lesion was subsequently detected and surgically removed resulting in prompt alleviation of symptoms and normalization of hypophosphatemia and low 1,25-(OH){sub 2} vitamin D{sub 3}. The lesion was pathologically diagnosed as a hemangiopericytoma-like tumor. Patients with oncogenic osteomalacia may present with stress fractures limited to the tibia, as seen in athletes. The clue to the real diagnosis lies in paying close attention to the serum phosphate levels, especially in patients suffering generalized symptoms of weakness and not given to unusual physical activity. (orig.) With 4 figs., 6 refs.

  18. Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences

    Science.gov (United States)

    Balaj, Leonora; Lessard, Ryan; Dai, Lixin; Cho, Yoon-Jae; Pomeroy, Scott L.; Breakefield, Xandra O.; Skog, Johan

    2011-01-01

    Tumour cells release an abundance of microvesicles containing a selected set of proteins and RNAs. Here, we show that tumour microvesicles also carry DNA, which reflects the genetic status of the tumour, including amplification of the oncogene c-Myc. We also find amplified c-Myc in serum microvesicles from tumour-bearing mice. Further, we find remarkably high levels of retrotransposon RNA transcripts, especially for some human endogenous retroviruses, such as LINE-1 and Alu retrotransposon elements, in tumour microvesicles and these transposable elements could be transferred to normal cells. These findings expand the nucleic acid content of tumour microvesicles to include: elevated levels of specific coding and non-coding RNA and DNA, mutated and amplified oncogene sequences and transposable elements. Thus, tumour microvesicles contain a repertoire of genetic information available for horizontal gene transfer and potential use as blood biomarkers for cancer. PMID:21285958

  19. Advances on Driver Oncogenes of Squamous Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Wei HONG

    2014-05-01

    Full Text Available Background and objective Lung cancer is the leading cause of cancer-related deaths worldwide. Next to adenocarcinoma, squamous cell carcinoma (SCC of the lung is the most frequent histologic subtype in non-small cell lung cancer. Several molecular alterations have been defined as "driver oncogenes" responsible for both the initiation and maintenance of the malignancy. The squamous cell carcinoma of the lung has recently shown peculiar molecular characteristics which relate with both carcinogenesis and response to targeted drugs. So far, about 40% of lung squamous cell carcinoma has been found harbouring driver oncogenes, in which fibroblast growth factor receptor 1 (FGFR1 plays important roles. In this review, we will report the mainly advances on some latest driver mutations of squamous cell lung cancer.

  20. Pharmacological strategies to target oncogenic KRAS signaling in pancreatic cancer.

    Science.gov (United States)

    Chuang, Hsiao-Ching; Huang, Po-Hsien; Kulp, Samuel K; Chen, Ching-Shih

    2017-03-01

    The clear importance of mutated KRAS as a therapeutic target has driven the investigation of multiple approaches to inhibit oncogenic KRAS signaling at different molecular levels. However, no KRAS-targeted therapy has reached the clinic to date, which underlies the intrinsic difficulty in developing effective, direct inhibitors of KRAS. Thus, this article provides an overview of the history and recent progress in the development of pharmacological strategies to target oncogenic KRAS with small molecule agents. Mechanistically, these KRAS-targeted agents can be classified into the following four categories. (1) Small-molecule RAS-binding ligands that prevent RAS activation by binding within or outside the nucleotide-binding motif. (2) Inhibitors of KRAS membrane anchorage. (3) Inhibitors that bind to RAS-binding domains of RAS-effector proteins. (4) Inhibitors of KRAS expression. The advantage and limitation of each type of these anti-KRAS agents are discussed.

  1. Annotating MYC oncogene status with 89Zr-transferrin imaging

    OpenAIRE

    Holland, Jason P.; Evans, Michael J.; Rice, Samuel L.; Wongvipat, John; Sawyers, Charles L.; Lewis, Jason S.

    2012-01-01

    A non-invasive technology that quantitatively measures the activity of oncogenic signaling pathways could broadly impact cancer diagnosis and treatment using targeted therapies. Here we describe the development of 89Zr-desferrioxamine transferrin (89Zr-Tf), a novel positron emission tomography (PET) radiotracer that binds the transferrin receptor 1 (TFRC, CD71) with high avidity. 89Zr-Tf produces high contrast PET images that quantitatively reflect treatment-induced changes in MYC-regulated T...

  2. Mutations in the RET proto-oncogene in sporadic pheochromocytomas

    Energy Technology Data Exchange (ETDEWEB)

    Thibodeau, S.N.; Lindor, N.M.; Honchel, R. [Mayo Clinic and Foundation, Rochester, MN (United States)] [and others

    1994-09-01

    Mutations in the RET proto-oncogene have recently been demonstrated in kindreds with Multiple Endocrine Neoplasia (MEN) types 2A and 2B. Both of these autosomal dominant disorders are characterized by the development of neoplasia in cell lines of neural crest origin, such as medullary throid carcinomas and pheochromocytomas. Individuals with MEN 2B have, in addition, ganglioneuromas of the lips, tongue and colon, a marfanoid habitus, and corneal nerve thickening. Approximately 90% of patients with MEN 2A have a germline mutation in exons 10 or 11, while 95% of patients with MEN 2B have a T{yields}C transition in codon 918 of exon 16. In this study, pheochromocytomas from 29 individuals who had no clinical evidence of MEN 2A or 2B (sporadic) were examined for the presence of either germline or somatic mutations in exons 10, 11, and 16 of the RET proto-oncogene. Of the 29 tumors examined, 3 (10%) were found to have a mutation in one of the three exons. One tumor had a G{yields}A transition in codon 609 (exon 10), another had a 6 bp deletion encompassing codons 632 & 633 (exon 11), and the final tumor had a T{yields}C transition in codon 918 (exon 16). These mutations were not found in the corresponding normal DNA from these individuals, indicating that the mutation were somatic in origin. Although we cannot exclude the possibility of mutations in other regions of the RET proto-oncogene, our data suggests that: (1) individuals presenting with apparently sporadic pheochromocytomas are not likely to have undiagnosed MEN 2A or 2B; and (2) somatic mutations in the RET proto-oncogene contribute to the process of tumorigenesis in a small percentage of sporadic pheochromocytomas.

  3. PKC Epsilon: A Novel Oncogenic Player in Prostate Cancer

    Science.gov (United States)

    2014-09-01

    Malik, A., Zaman, N., Sarfaraz, S., Siddiqui, I. A., Syed, D. N. et al (2007). Combined inhibitory effects of green tea polyphenols and selective...not only in prostate cancer but also in several other epithelial cancers including lung , breast, and thyroid cancer8, 13, 20-26. Studies from our...Cvarepsilon is required for non-small cell lung carcinoma growth and regulates the expression of apoptotic genes. Oncogene 31: 2593-2600. 23 Hafeez, B. B

  4. CERN: le Mondial de la particule

    CERN Multimedia

    Favier, R

    1998-01-01

    Avec le LEP (acc\\’{e}l\\’{e}rateur de particules), le CERN est devenu le v\\’{e}ritable phare de la science europ\\’{e}enne. Notamment pour la physique des particules. Riche de multiples exp\\’{e}riences r\\’{e}ussies, mais aussi de quelques prix Nobel, le CERN est en train de vivre une nouvelle aventure scientifique, en lan

  5. LE CORBUSIER: CONCURSOS Y PALACIOS / Le Corbusier: competitions and palaces

    Directory of Open Access Journals (Sweden)

    Fernando Zaparaín Hernández

    2012-11-01

    Full Text Available RESUMEN Cuando Le Corbusier ya había pasado de los cuarenta años se enfrentó a dos concursos internacionales: el Palacio de las Naciones en Ginebra (1926–31 y el Palacio de los Soviets en Moscú (1931–32 con los que intentaba acceder a grandes encargos de estado con mayor escala urbana en los que poner a prueba su ideario moderno sobre arquitectura y urbanismo. En ambos casos estuvo entre los vencedores pero por conveniencia e indecisión, los poderes políticos optaron por soluciones academicistas. Al conocer las decisiones definitivas, Le Corbusier y todos sus contactos del Movimiento Moderno orquestaron diversas polémicas ante los medios de comunicación y los gobernantes por entender que el progreso se veía lastrado por el triunfo de propuestas reaccionarias. Mediante el estudio de la correspondencia con personas particulares como Moser, Giedion, Colly o Stonorov, conservada en la Fundación Le Corbusier, se analizan las relaciones y el tono ideológico en torno a aquellas protestas. En esos textos quedan reflejados los principales rasgos que caracterizan la modernidad como su internacionalización, la seguridad en la propia misión, la defensa de lo nuevo o el método dialéctico.SUMMARY When Le Corbusier had already passed the age of forty he confronted two international competitions: the Palais des Nations in Geneva (1926–1931 and the Palace of the Soviets in Moscow (1931–32, with which he attempted to access large state commissions, with greater urban scale, in which to test his ideas about modern architecture and urbanism. In both cases he was among the winners, but through convenience and indecision the political powers opted for solutions from academicians. Upon knowing the final decisions, Le Corbusier and all his contacts in the Modern Movement orchestrated several controversies with the media, and the people in power, to convey that progress seemed burdened by the triumph of reactionary proposals. The relationships and

  6. Activation of oncogenes by radon progeny and x-rays

    Energy Technology Data Exchange (ETDEWEB)

    Ling, C.C.

    1990-01-01

    The overall goal of this proposal is to study the carcinogenic effect of both high and low LET radiation at the molecular level, utilizing techniques developed in molecular biology, cancer cell biology and radiation biology. The underlying assumption is that malignant transformation of normal cells is a multistep process requiring two or more molecular events in the genomic DNA. We hypothesize that radiation may induce such events in one or more steps of the multistep process. We will use in vitro models of transformation that reproduce the stepwise progression of normal cells toward the transformed phenotype and ask whether radiation can provide the necessary activating function at discrete steps along this path. Our strategy involves transfecting into normal primary cells a variety of cloned oncogenes that are known to supply only some of the functions necessary for full transformation. These partially transformed'' cells will be the targets for irradiation by x-rays and alpha particles. The results will provide the basis for assessing the ability of ionizing radiation to activate oncogenic functions that complement'' the oncogene already present in the transfected cells and produce the fully transformed phenotype. Progress is described. 121 refs.

  7. Phosphoglycerate Dehydrogenase: Potential Therapeutic Target and Putative Metabolic Oncogene

    Directory of Open Access Journals (Sweden)

    Cheryl K. Zogg

    2014-01-01

    Full Text Available Exemplified by cancer cells’ preference for glycolysis, for example, the Warburg effect, altered metabolism in tumorigenesis has emerged as an important aspect of cancer in the past 10–20 years. Whether due to changes in regulatory tumor suppressors/oncogenes or by acting as metabolic oncogenes themselves, enzymes involved in the complex network of metabolic pathways are being studied to understand their role and assess their utility as therapeutic targets. Conversion of glycolytic intermediate 3-phosphoglycerate into phosphohydroxypyruvate by the enzyme phosphoglycerate dehydrogenase (PHGDH—a rate-limiting step in the conversion of 3-phosphoglycerate to serine—represents one such mechanism. Forgotten since classic animal studies in the 1980s, the role of PHGDH as a potential therapeutic target and putative metabolic oncogene has recently reemerged following publication of two prominent papers near-simultaneously in 2011. Since that time, numerous studies and a host of metabolic explanations have been put forward in an attempt to understand the results observed. In this paper, I review the historic progression of our understanding of the role of PHGDH in cancer from the early work by Snell through its reemergence and rise to prominence, culminating in an assessment of subsequent work and what it means for the future of PHGDH.

  8. Oncogenic Kras initiates leukemia in hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Amit J Sabnis

    2009-03-01

    Full Text Available How oncogenes modulate the self-renewal properties of cancer-initiating cells is incompletely understood. Activating KRAS and NRAS mutations are among the most common oncogenic lesions detected in human cancer, and occur in myeloproliferative disorders (MPDs and leukemias. We investigated the effects of expressing oncogenic Kras(G12D from its endogenous locus on the proliferation and tumor-initiating properties of murine hematopoietic stem and progenitor cells. MPD could be initiated by Kras(G12D expression in a highly restricted population enriched for hematopoietic stem cells (HSCs, but not in common myeloid progenitors. Kras(G12D HSCs demonstrated a marked in vivo competitive advantage over wild-type cells. Kras(G12D expression also increased the fraction of proliferating HSCs and reduced the overall size of this compartment. Transplanted Kras(G12D HSCs efficiently initiated acute T-lineage leukemia/lymphoma, which was associated with secondary Notch1 mutations in thymocytes. We conclude that MPD-initiating activity is restricted to the HSC compartment in Kras(G12D mice, and that distinct self-renewing populations with cooperating mutations emerge during cancer progression.

  9. Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture.

    Science.gov (United States)

    Li, Xingnan; Nadauld, Lincoln; Ootani, Akifumi; Corney, David C; Pai, Reetesh K; Gevaert, Olivier; Cantrell, Michael A; Rack, Paul G; Neal, James T; Chan, Carol W-M; Yeung, Trevor; Gong, Xue; Yuan, Jenny; Wilhelmy, Julie; Robine, Sylvie; Attardi, Laura D; Plevritis, Sylvia K; Hung, Kenneth E; Chen, Chang-Zheng; Ji, Hanlee P; Kuo, Calvin J

    2014-07-01

    The application of primary organoid cultures containing epithelial and mesenchymal elements to cancer modeling holds promise for combining the accurate multilineage differentiation and physiology of in vivo systems with the facile in vitro manipulation of transformed cell lines. Here we used a single air-liquid interface culture method without modification to engineer oncogenic mutations into primary epithelial and mesenchymal organoids from mouse colon, stomach and pancreas. Pancreatic and gastric organoids exhibited dysplasia as a result of expression of Kras carrying the G12D mutation (Kras(G12D)), p53 loss or both and readily generated adenocarcinoma after in vivo transplantation. In contrast, primary colon organoids required combinatorial Apc, p53, Kras(G12D) and Smad4 mutations for progressive transformation to invasive adenocarcinoma-like histology in vitro and tumorigenicity in vivo, recapitulating multi-hit models of colorectal cancer (CRC), as compared to the more promiscuous transformation of small intestinal organoids. Colon organoid culture functionally validated the microRNA miR-483 as a dominant driver oncogene at the IGF2 (insulin-like growth factor-2) 11p15.5 CRC amplicon, inducing dysplasia in vitro and tumorigenicity in vivo. These studies demonstrate the general utility of a highly tractable primary organoid system for cancer modeling and driver oncogene validation in diverse gastrointestinal tissues.

  10. PRG3 induces Ras-dependent oncogenic cooperation in gliomas

    Science.gov (United States)

    Yakubov, Eduard; Chen, Daishi; Broggini, Thomas; Sehm, Tina; Majernik, Gökce Hatipoglu; Hock, Stefan W.; Schwarz, Marc; Engelhorn, Tobias; Doerfler, Arnd; Buchfelder, Michael; Eyupoglu, Ilker Y.; Savaskan, Nicolai E.

    2016-01-01

    Malignant gliomas are one of the most devastating cancers in humans. One characteristic hallmark of malignant gliomas is their cellular heterogeneity with frequent genetic lesions and disturbed gene expression levels conferring selective growth advantage. Here, we report on the neuronal-associated growth promoting gene PRG3 executing oncogenic cooperation in gliomas. We have identified perturbed PRG3 levels in human malignant brain tumors displaying either elevated or down-regulated PRG3 levels compared to non-transformed specimens. Further, imbalanced PRG3 levels in gliomas foster Ras-driven oncogenic amplification with increased proliferation and cell migration although angiogenesis was unaffected. Hence, PRG3 interacts with RasGEF1 (RasGRF1/CDC25), undergoes Ras-induced challenges, whereas deletion of the C-terminal domain of PRG3 (PRG3ΔCT) inhibits Ras. Moreover PRG3 silencing makes gliomas resistant to Ras inhibition. In vivo disequilibrated PRG3 gliomas show aggravated proliferation, invasion, and deteriorate clinical outcome. Thus, our data show that the interference with PRG3 homeostasis amplifies oncogenic properties and foster the malignancy potential in gliomas. PMID:27058420

  11. CRAF R391W is a melanoma driver oncogene

    Science.gov (United States)

    Atefi, Mohammad; Titz, Bjoern; Tsoi, Jennifer; Avramis, Earl; Le, Allison; Ng, Charles; Lomova, Anastasia; Lassen, Amanda; Friedman, Michael; Chmielowski, Bartosz; Ribas, Antoni; Graeber, Thomas G.

    2016-01-01

    Approximately 75% of melanomas have known driver oncogenic mutations in BRAF, NRAS, GNA11 or GNAQ, while the mutations providing constitutive oncogenic signaling in the remaining melanomas are not known. We established a melanoma cell line from a tumor with none of the common driver mutations. This cell line demonstrated a signaling profile similar to BRAF-mutants, but lacked sensitivity to the BRAF inhibitor vemurafenib. RNA-seq mutation data implicated CRAF R391W as the alternative driver mutation of this melanoma. CRAF R391W was homozygous and over expressed. These melanoma cells were highly sensitive to CRAF, but not BRAF knockdown. In reconstitution experiments, CRAF R391W, but not CRAF WT, transformed NIH3T3 cells in soft-agar colony formation assays, increased kinase activity in vitro, induced MAP kinase signaling and conferred vemurafenib resistance. MAP kinase inducing activity was dependent on CRAF dimerization. Thus, CRAF is a bona fide alternative oncogene for BRAF/NRAS/GNAQ/GNA11 wild type melanomas. PMID:27273450

  12. Le LHC, priorité absolue

    CERN Multimedia

    Huet, S

    2002-01-01

    Le LHC, sa mise en est repoussee a 2007 quand les physiciens esperaient 2006. Le CERN a sous-estime les couts, environ 11% pour les 1 200 aimants supraconducteurs. Les Etats membres n'augmenteront pas leurs subventions, il propose donc cette semaine un plan drastique : tout pour le LHC (1/2 page).

  13. Le CERN ouvre ses entrailles au public

    CERN Multimedia

    2004-01-01

    "Le CERN se lance dans une grande opération de relations publiques pour son cinquantième anniversaire. Le centre de recherche organisera une journée portes ouvertes le 16 octobre. Quelque 50 sites pourrant être visités" (1/2 page)

  14. Synonymous codon changes in the oncogenes of the cottontail rabbit papillomavirus lead to increased oncogenicity and immunogenicity of the virus

    Science.gov (United States)

    Cladel, Nancy M.; Budgeon, Lynn R.; Hu, Jiafen; Balogh, Karla K.; Christensen, Neil D.

    2013-01-01

    Papillomaviruses use rare codons with respect to the host. The reasons for this are incompletely understood but among the hypotheses is the concept that rare codons result in low protein production and this allows the virus to escape immune surveillance. We changed rare codons in the oncogenes E6 and E7 of the cottontail rabbit papillomavirus to make them more mammalian-like and tested the mutant genomes in our in vivo animal model. While the amino acid sequences of the proteins remained unchanged, the oncogenic potential of some of the altered genomes increased dramatically. In addition, increased immunogenicity, as measured by spontaneous regression, was observed as the numbers of codon changes increased. This work suggests that codon usage may modify protein production in ways that influence disease outcome and that evaluation of synonymous codons should be included in the analysis of genetic variants of infectious agents and their association with disease. PMID:23433866

  15. Le campus et le C.H.U de Bordeaux 1959-2005

    Directory of Open Access Journals (Sweden)

    Marc Saboya

    2012-04-01

    Full Text Available Première partie : Le campus et le CHU : 1959-1974Le campus, style « sévère »Le 23 juillet 1963, le plan masse du complexe universitaire prolongeant les premières réalisations de René-André Coulon est approuvé par le Conseil général des bâtiments de France. L’extension, programmée dès le départ mais impulsée par le recteur Babin, s’étire sur près de 250 ha. Le campus de Talence, Pessac et Gradignan est désormais un des plus grands d’Europe. Le plan, confié à l’architecte parisien Louis Sainsau...

  16. Le cosmos et le lotus confessions d'un astrophysicien

    CERN Document Server

    Trinh, Xuan Thuan

    2011-01-01

    Que nous dit vraiment la science sur la nature de l'univers, sur son origine et son avenir ? Par quel mystère le langage mathématique, pure création de l'esprit humain, se révèle-t-il aussi performant pour nous décrire les phénomènes physiques, de l'infiniment petit à l'infiniment grand ? S'il existe un ordre du monde, ce que nous en disent la physique quantique et la théorie de la relativité est-il compatible avec ce qu'enseigne le bouddhisme ? Et que peut-on en conclure concernant notre propre vie ? A ces questions passionnantes et à beaucoup d'autres, le célèbre astrophysicien Trinh Xuan Thuan répond ici d'une façon personnelle, en s'appuyant sur son expérience. Son itinéraire l'a placé d'emblée à la confluence de trois cultures : issu d'une famille de lettrés vietnamiens imprégnée de traditions bouddhiste et confucéenne, il a reçu une éducation à la française puis une formation scientifique à l'américaine. Une telle richesse de points de vue lui permet d'apporter, non pas de...

  17. Le contrôle de gestion des entreprises familiales : un contrôle non-financiarisé ?

    OpenAIRE

    Barbelivien, Dominique

    2016-01-01

    Nous examinons la tendance décrite dans la littérature quant à la financiarisation de la fonction de contrôle de gestion en nous appuyant sur le cas d’une entreprise de taille intermédiaire familiale. Nous constatons que le contrôle de gestion dans le cas étudié correspond à une rationalisation des décisions opérationnelles et développons les raisons qui peuvent expliquer la persistance d’un contrôle de gestion très opérationnel. Le contexte d’entreprise familiale dans laquelle il y a confusi...

  18. Le contrôle de gestion des entreprises familiales : un contrôle non-financiarisé ?

    OpenAIRE

    Barbelivien, Dominique

    2016-01-01

    Nous examinons la tendance décrite dans la littérature quant à la financiarisation de la fonction de contrôle de gestion en nous appuyant sur le cas d’une entreprise de taille intermédiaire familiale. Nous constatons que le contrôle de gestion dans le cas étudié correspond à une rationalisation des décisions opérationnelles et développons les raisons qui peuvent expliquer la persistance d’un contrôle de gestion très opérationnel. Le contexte d’entreprise familiale dans laquelle il y a confusi...

  19. Can plant oncogenes inhibit programmed cell death? The rolB oncogene reduces apoptosis-like symptoms in transformed plant cells.

    Science.gov (United States)

    Gorpenchenko, Tatiana Y; Aminin, Dmitry L; Vereshchagina, Yuliya V; Shkryl, Yuri N; Veremeichik, Galina N; Tchernoded, Galina K; Bulgakov, Victor P

    2012-09-01

    The rolB oncogene was previously identified as an important player in ROS metabolism in transformed plant cells. Numerous reports indicate a crucial role for animal oncogenes in apoptotic cell death. Whether plant oncogenes such as rolB can induce programmed cell death (PCD) in transformed plant cells is of particular importance. In this investigation, we used a single-cell assay based on confocal microscopy and fluorescent dyes capable of discriminating between apoptotic and necrotic cells. Our results indicate that the expression of rolB in plant cells was sufficient to decrease the proportion of apoptotic cells in steady-state conditions and diminish the rate of apoptotic cells during induced PCD. These data suggest that plant oncogenes, like animal oncogenes, may be involved in the processes mediating PCD.

  20. N-MYC下游调节基因-2蛋白在前列腺肿瘤组织中的表达%Analysis of the N-MYC down-stream regulate gene-2 protein expression in prostatic carcinoma tissues

    Institute of Scientific and Technical Information of China (English)

    孟强; 毕玉彪; 于新路; 曹丽佳; 孙明; 于垂恭

    2011-01-01

    [Objective] To study the expression of N-MYC down-stream regulated gene-2 (NDRG2), a new candidate tumor suppressor, in prostate cancer, and to investigate its clinical and pathological implications. [Methods] Formalin-fixed,paraffin-embedded tissue sections from 42 cases of prostatic carcinoma(PCa) and 9 cases of benign prostate hyperplasia (BPH) were analyzed retrospectively with immunohistochemistry ( S-P method). [Results] The NDRG2 gene was highly expressed in benign prostatic hyperplasia tissues, but not in carcinomatous ones. Positive expression of NDRG2 proteins was detected in 14 of the 17 (82.35%) benign tumor samples and accounted for 32.69% in prostatic carcinoma ones. Furthermore, positive expression of NDRG2 in prostatic carcinoma samples decreased significantly with the increasing of the gleason score (r = -0.5197) .However, positive expression of NDRG2 was not correlated with TN M tumor stages or the concentration of prostate-specific antigen (P SA)in blood serum(P > 0.05).[Conclusior] The NDRG2 expression level was lower in PCA than in BPH. NDRG2 may play an essential role in prostate carcinogenesis and in the progress of PCA.%[目的]N-MYC下游调节基因-2(NDRG2)在前列腺癌及前列腺增生中的表达与临床病理特征和生物学行为的关系[方法]前列腺肿瘤标本51例,其中前列腺增生标本9例,前列腺癌标本42例,均为存档石蜡切片,应用免疫组织化学(S-P法)研究NDRG2表达.[结果]NDRG2在前列腺增生组织表达为82.35%,在前列腺癌组织为32.69%,两者差异有统计学意义(P<0.01).NDRG2表达水平同Gleason评分呈负相关(r=-0.5197),在不同临床TNM分期间、在血清PSA浓度≤20 ng/ml与PSA浓度>20ng/ml组间差异无统计学意义(P>0.05).[结论]NDRG2表达在前列腺癌组织低于前列腺增生组织,且表达与Gleason评分呈负相关.表明NDRG2有可能参与了前列腺癌的发生及发展过程.

  1. Le sette meraviglie del cosmo

    CERN Document Server

    Narlikar, Jayant V

    2004-01-01

    Tra giganti, "nane" e stelle che esplodono in cielo, un vademecum per scoprire il cosmo e i misteri che lo abitano. Lasciati alle spalle i confini sicuri della Terra e del Sistema solare, assistiamo a un'esplosione continua di fenomeni inaspettati. L'universo si svela nel suo continuo mutamento, cresce in fascino e complessità via via che ci addentriamo nei suoi spazi profondi. Tramite esempi semplici, aneddoti umoristici e una prosa cristallina, Vishnu Narkilar racconta l'emozione di fronte alle sorprese del cosmo. Le "sette meraviglie" sono i fenomeni misteriosi che si nascondono dietro le stelle che punteggiano il cielo, una schiera di eventi spettacolari che per secoli hanno sfidato la curiosità umana ed eluso ogni spiegazione.

  2. Ce que permet le document

    OpenAIRE

    2012-01-01

    Avec l’archive, à laquelle il est souvent associé, le document occupe une place centrale dans les expositions comme dans les publications actuelles sur l’art contemporain. Les présents ouvrages n’ont pas pour objectif d’apporter un éclairage à ce vaste tournant mnémonique qui semble s’emparer des pratiques et des discours sur l’art depuis le début de ce troisième millénaire, même si les contributions de certains de leurs auteurs pointent des éléments conjoncturels (l’après 11 septembre) ou te...

  3. Le supplice tragique de Phyton

    OpenAIRE

    Chamoux, François

    2015-01-01

    Le siège et la prise de Rhégion par Denys l'Ancien représentent dans l'histoire du tyran un épisode d'une importance capitale. Diodore lui consacre un long développement qui dérive probablement de Timée, source principale de Diodore pour les affaires de Sicile. Le siège dura onze mois (387-386) et s'acheva par la reddition de la ville, réduite par la famine. Les efforts de Denys et les moyens considérables qu'il avait mis en œuvre pour emporter d'assaut les murailles n'avaient pu faire plier ...

  4. Noam Chomsky, Le bien commun

    OpenAIRE

    Ferrand, Laure

    2014-01-01

    Le bien commun regroupe une série d’entretiens réalisés par le journaliste américain David Barsamian avec Noam Chomsky. Ils traitent essentiellement de l’approche politique et critique de Chomsky à travers les différents écrits qu’il a publiés et les conférences qu’il a données. Ainsi, nous retrouvons dans cet ouvrage les questions principales qui irriguent la pensée de l’auteur : l’économie capitaliste est-elle synonyme de liberté ? Les États-Unis - et plus largement les pays se caractérisan...

  5. Le Yémen politique

    OpenAIRE

    Sylvaine Giraud

    2002-01-01

    Ouvrages 1999 ABÛ ISBAL (Bilqîs). An-nukhba as-siyâsîya al-hâkima fîl-Yaman 1978/1990. (L'élite politique au pouvoir au Yémen). Le Caire : Maktabat Madbûlî, 1999.  MERMIER (Franck), LEVEAU (Rémy) et STEINBACH (Udo), éds. Le Yémen contemporain. Paris : Karthala, 1999.  Al-mughtaribûn : Ar-râfid al-asâsî lit-tanmiya al-mustadâma. (Les émigrés : apport essentiel au développement durable). Sana'a : Al-Majlis al-Istishârî, Wizârat Shu'ûn al-Mughtaribîn, 1999.  1998 AL-AGHBARÎ (Ak...

  6. Le doigt d'Oreste

    OpenAIRE

    2014-01-01

    Quant aux liens du meurtrier et de sa victime, tout l'effort de la cité en Grèce ancienne sera de les effacer en instituant les tribunaux du sang et en posant la question abstraite des formes et des degrés de responsabilité de l'accusé d'homicide. C'est dans l'imaginaire autour d'Oreste entre le Ve et le VIe siècle avant notre ère que se rassemblent les représentations les plus vives liant la victime à son meurtrier, à son corps autant qu'à son être intime. With regard to the bonds linking...

  7. Le glaive de la parole

    Directory of Open Access Journals (Sweden)

    Luce Marchal-Albert

    2006-09-01

    Full Text Available Chacun sait, selon le mot de Pierre Viret, « en quelle confusion est la Chrestienté » au xvie siècle en Europe. C’est le deuxième quart du siècle qui nous intéressera ici, et en particulier l’année 1545, qui constitue une année charnière qui voit vaciller l’Église romaine, flamber et culminer la chasse aux hérétiques en même temps qu’elle voit la jeune Église réformée se renforcer et se positionner avec succès dans un champ religieux plus que chaotique. Les ouvrages polémiques réformés écrits...

  8. Louvre-Lens : le Louvre autrement

    OpenAIRE

    Audrey Bodéré

    2010-01-01

    ∙ Quels sont les enjeux du projet Louvre-Lens pour le Musée du Louvre ? Par ce projet, le Louvre participe tant à la politique de décentralisation qu’à une volonté de démocratisation culturelle, en allant à la rencontre de nouveaux publics. Mais le projet scientifique et culturel du Louvre-Lens (PSC) précise aussi que l'un des principaux défis est d'oser le « Louvre autrement ». La présentation des collections est donc repensée pour traduire le monde Louvre à Lens. Le lien entre le Louvre Par...

  9. Louvre-Lens : le Louvre autrement

    Directory of Open Access Journals (Sweden)

    Audrey Bodéré

    2010-04-01

    Full Text Available ∙ Quels sont les enjeux du projet Louvre-Lens pour le Musée du Louvre ? Par ce projet, le Louvre participe tant à la politique de décentralisation qu’à une volonté de démocratisation culturelle, en allant à la rencontre de nouveaux publics. Mais le projet scientifique et culturel du Louvre-Lens (PSC précise aussi que l'un des principaux défis est d'oser le « Louvre autrement ». La présentation des collections est donc repensée pour traduire le monde Louvre à Lens. Le lien entre le Louvre Par...

  10. Le Contrat de service public.

    OpenAIRE

    2009-01-01

    La Banque de France est concernée par le développement et la compétitivité des territoires, par l’amélioration de l’accès et de la qualité des services offerts aux publics, thèmes au coeur du Contrat de service public conclu, depuis 2003, avec l’État.

  11. Georges et le big bang

    CERN Document Server

    Hawking, Lucy; Parsons, Gary

    2011-01-01

    Georges et Annie, sa meilleure amie, sont sur le point d'assister à l'une des plus importantes expériences scientifiques de tous les temps : explorer les premiers instants de l'Univers, le Big Bang ! Grâce à Cosmos, leur super ordinateur, et au Grand Collisionneur de hadrons créé par Éric, le père d'Annie, ils vont enfin pouvoir répondre à cette question essentielle : pourquoi existons nous ? Mais Georges et Annie découvrent qu'un complot diabolique se trame. Pire, c'est toute la recherche scientifique qui est en péril ! Entraîné dans d'incroyables aventures, Georges ira jusqu'aux confins de la galaxie pour sauver ses amis...Une plongée passionnante au coeur du Big Bang. Les toutes dernières théories de Stephen Hawking et des plus grands scientifiques actuels.

  12. Oncogenic NRAS Primes Primary Acute Myeloid Leukemia Cells for Differentiation.

    Directory of Open Access Journals (Sweden)

    Cornelia Brendel

    Full Text Available RAS mutations are frequently found among acute myeloid leukemia patients (AML, generating a constitutively active signaling protein changing cellular proliferation, differentiation and apoptosis. We have previously shown that treatment of AML patients with high-dose cytarabine is preferentially beneficial for those harboring oncogenic RAS. On the basis of a murine AML cell culture model, we ascribed this effect to a RAS-driven, p53-dependent induction of differentiation. Hence, in this study we sought to confirm the correlation between RAS status and differentiation of primary blasts obtained from AML patients. The gene expression signature of AML blasts with oncogenic NRAS indeed corresponded to a more mature profile compared to blasts with wildtype RAS, as demonstrated by gene set enrichment analysis (GSEA and real-time PCR analysis of myeloid ecotropic viral integration site 1 homolog (MEIS1 in a unique cohort of AML patients. In addition, in vitro cell culture experiments with established cell lines and a second set of primary AML cells showed that oncogenic NRAS mutations predisposed cells to cytarabine (AraC driven differentiation. Taken together, our findings show that AML with inv(16 and NRAS mutation have a differentiation gene signature, supporting the notion that NRAS mutation may predispose leukemic cells to AraC induced differentiation. We therefore suggest that promotion of differentiation pathways by specific genetic alterations could explain the superior treatment outcome after therapy in some AML patient subgroups. Whether a differentiation gene expression status may generally predict for a superior treatment outcome in AML needs to be addressed in future studies.

  13. ERBB oncogene proteins as targets for monoclonal antibodies.

    Science.gov (United States)

    Polanovski, O L; Lebedenko, E N; Deyev, S M

    2012-03-01

    General properties of the family of tyrosine kinase ERBB receptors are considered in connection with their role in the generation of cascades of signal transduction in normal and tumor cells. Causes of acquisition of oncogene features by genes encoding these receptors and their role in tumorigenesis are analyzed. Anti-ERBB monoclonal antibodies approved for therapy are described in detail, and mechanisms of their antitumor activity and development of resistance to them are reviewed. The existing and the most promising strategies for creating and using monoclonal antibodies and their derivatives for therapy of cancer are discussed.

  14. Le Carême et le Ramadan : recréer le corps. Un cas libanais

    Directory of Open Access Journals (Sweden)

    Aïda Kanafani-Zahar

    2006-11-01

    Full Text Available Accorder son corps aux exigences du sacré afin d’accueillir une ferveur religieuse d’une grande intensité est l’objectif du Grand Carême et du Ramadan. Dès lors, de nouvelles normes sont élaborées. Elles puisent leur légitimité dans un corpus de symboles fondé, pour le Carême, sur la couleur et le goût des aliments, le désir de nature, les privations volontaires et, pour le Ramadan, sur le bouleversement du rythme alimentaire. Dans les jeûnes chrétien et musulman tels qu’ils sont vécus à Hsoun, un village du Mont Liban, le lien entre temps alimentaire et temps de l’adoration est au plus fort.

  15. le des medias dans le domaine scientifique

    CERN Document Server

    De Closets, F; Curien, Hubert; Meijers, H; Moosleitner, G P; Patermann, C; Rubbia, Carlo; CERN. Geneva; 2271246

    1993-01-01

    Promotion de la science dans les médias - création d'un réseau européen de sources scientifiques - Pourquoi la science a la presse qu'elle mérite. - Intégration des médias scientifiques de l'Europe de l'Est -Rôle des médias dans la stimulation de l'intérêt scientifique parmi la jeunesse européenne. Ouverture N.CALDER - Conférence F. de CLOSETS

  16. Le tennis dans le monde: état et prospective

    Directory of Open Access Journals (Sweden)

    Pierre DUMOLARD

    1989-06-01

    Full Text Available Le tennis est peu ou prou pratiqué dans tous les pays du monde, mais avec de considérables variations d'intensité. Actuellement, ses points d'ancrage se situent dans les pays développés occidentaux et dans l'ancienne sphère d'influence britannique. En tenant compte de l'évolution démographique et économique possible des nations, des projections de pénétration de ce sport sont établies pour l'horizon 2000.

  17. Retroviruses hijack chromatin loops to drive oncogene expression and highlight the chromatin architecture around proto-oncogenic loci.

    Directory of Open Access Journals (Sweden)

    Jillian M Pattison

    Full Text Available The majority of the genome consists of intergenic and non-coding DNA sequences shown to play a major role in different gene regulatory networks. However, the specific potency of these distal elements as well as how these regions exert function across large genomic distances remains unclear. To address these unresolved issues, we closely examined the chromatin architecture around proto-oncogenic loci in the mouse and human genomes to demonstrate a functional role for chromatin looping in distal gene regulation. Using cell culture models, we show that tumorigenic retroviral integration sites within the mouse genome occur near existing large chromatin loops and that this chromatin architecture is maintained within the human genome as well. Significantly, as mutagenesis screens are not feasible in humans, we demonstrate a way to leverage existing screens in mice to identify disease relevant human enhancers and expose novel disease mechanisms. For instance, we characterize the epigenetic landscape upstream of the human Cyclin D1 locus to find multiple distal interactions that contribute to the complex cis-regulation of this cell cycle gene. Furthermore, we characterize a novel distal interaction upstream of the Cyclin D1 gene which provides mechanistic evidence for the abundant overexpression of Cyclin D1 occurring in multiple myeloma cells harboring a pathogenic translocation event. Through use of mapped retroviral integrations and translocation breakpoints, our studies highlight the importance of chromatin looping in oncogene expression, elucidate the epigenetic mechanisms crucial for distal cis-regulation, and in one particular instance, explain how a translocation event drives tumorigenesis through upregulation of a proto-oncogene.

  18. Retroviruses Hijack Chromatin Loops to Drive Oncogene Expression and Highlight the Chromatin Architecture around Proto-Oncogenic Loci

    Science.gov (United States)

    Pattison, Jillian M.; Wright, Jason B.; Cole, Michael D.

    2015-01-01

    The majority of the genome consists of intergenic and non-coding DNA sequences shown to play a major role in different gene regulatory networks. However, the specific potency of these distal elements as well as how these regions exert function across large genomic distances remains unclear. To address these unresolved issues, we closely examined the chromatin architecture around proto-oncogenic loci in the mouse and human genomes to demonstrate a functional role for chromatin looping in distal gene regulation. Using cell culture models, we show that tumorigenic retroviral integration sites within the mouse genome occur near existing large chromatin loops and that this chromatin architecture is maintained within the human genome as well. Significantly, as mutagenesis screens are not feasible in humans, we demonstrate a way to leverage existing screens in mice to identify disease relevant human enhancers and expose novel disease mechanisms. For instance, we characterize the epigenetic landscape upstream of the human Cyclin D1 locus to find multiple distal interactions that contribute to the complex cis-regulation of this cell cycle gene. Furthermore, we characterize a novel distal interaction upstream of the Cyclin D1 gene which provides mechanistic evidence for the abundant overexpression of Cyclin D1 occurring in multiple myeloma cells harboring a pathogenic translocation event. Through use of mapped retroviral integrations and translocation breakpoints, our studies highlight the importance of chromatin looping in oncogene expression, elucidate the epigenetic mechanisms crucial for distal cis-regulation, and in one particular instance, explain how a translocation event drives tumorigenesis through upregulation of a proto-oncogene. PMID:25799187

  19. A novel putative tyrosine kinase receptor with oncogenic potential.

    Science.gov (United States)

    Janssen, J W; Schulz, A S; Steenvoorden, A C; Schmidberger, M; Strehl, S; Ambros, P F; Bartram, C R

    1991-11-01

    We have detected transforming activity by a tumorigenicity assay using NIH3T3 cells transfected with DNA from a chronic myeloproliferative disorder patient. Here, we report the cDNA cloning of the corresponding oncogene, designated UFO, in allusion to the as yet unidentified function of its protein. Nucleotide sequence analysis of a 3116bp cDNA clone revealed a 2682-bp-long open reading frame capable of directing the synthesis of a 894 amino acid polypeptide. The predicted UFO protein exhibits characteristic features of a transmembrane receptor with associated tyrosine kinase activity. The UFO proto-oncogene maps to human chromosome 19q13.1 and is transcribed into two 5.0 kb and 3.2 kb mRNAs in human bone marrow and human tumor cell lines. The UFO locus is evolutionarily conserved between vertebrate species. A 4.0 kb mRNA of the murine UFO homolog is expressed in a variety of different mouse tissues. We thus have identified a novel element of the complex signaling network involved in the control of cell proliferation and differentiation.

  20. Design of a small molecule against an oncogenic noncoding RNA.

    Science.gov (United States)

    Velagapudi, Sai Pradeep; Cameron, Michael D; Haga, Christopher L; Rosenberg, Laura H; Lafitte, Marie; Duckett, Derek R; Phinney, Donald G; Disney, Matthew D

    2016-05-24

    The design of precision, preclinical therapeutics from sequence is difficult, but advances in this area, particularly those focused on rational design, could quickly transform the sequence of disease-causing gene products into lead modalities. Herein, we describe the use of Inforna, a computational approach that enables the rational design of small molecules targeting RNA to quickly provide a potent modulator of oncogenic microRNA-96 (miR-96). We mined the secondary structure of primary microRNA-96 (pri-miR-96) hairpin precursor against a database of RNA motif-small molecule interactions, which identified modules that bound RNA motifs nearby and in the Drosha processing site. Precise linking of these modules together provided Targaprimir-96 (3), which selectively modulates miR-96 production in cancer cells and triggers apoptosis. Importantly, the compound is ineffective on healthy breast cells, and exogenous overexpression of pri-miR-96 reduced compound potency in breast cancer cells. Chemical Cross-Linking and Isolation by Pull-Down (Chem-CLIP), a small-molecule RNA target validation approach, shows that 3 directly engages pri-miR-96 in breast cancer cells. In vivo, 3 has a favorable pharmacokinetic profile and decreases tumor burden in a mouse model of triple-negative breast cancer. Thus, rational design can quickly produce precision, in vivo bioactive lead small molecules against hard-to-treat cancers by targeting oncogenic noncoding RNAs, advancing a disease-to-gene-to-drug paradigm.

  1. Oncogenic programmes and Notch activity: an 'organized crime'?

    Science.gov (United States)

    Dominguez, Maria

    2014-04-01

    The inappropriate Notch signalling can influence virtually all aspect of cancer, including tumour-cell growth, survival, apoptosis, angiogenesis, invasion and metastasis, although it does not do this alone. Hence, elucidating the partners of Notch that are active in cancer is now the focus of much intense research activity. The genetic toolkits available, coupled to the small size and short life of the fruit fly Drosophila melanogaster, makes this an inexpensive and effective animal model, suited to large-scale cancer gene discovery studies. The fly eye is not only a non-vital organ but its stereotyped size and disposition also means it is easy to screen for mutations that cause tumours and metastases and provides ample opportunities to test cancer theories and to unravel unanticipated nexus between Notch and other cancer genes, or to discover unforeseen Notch's partners in cancer. These studies suggest that Notch's oncogenic capacity is brought about not simply by increasing signal strength but through partnerships, whereby oncogenes gain more by cooperating than acting individually, as in a ring 'organized crime'.

  2. REST regulates oncogenic properties of glioblastoma stem cells

    Science.gov (United States)

    Kamal, Mohamed M.; Sathyan, Pratheesh; Singh, Sanjay K.; Zinn, Pascal O.; Marisetty, Anantha L.; Liang, Shoudan; Gumin, Joy; El-Mesallamy, Hala Osman; Suki, Dima; Colman, Howard; Fuller, Gregory N.; Lang, Frederick F.; Majumder, Sadhan

    2013-01-01

    Glioblastoma multiforme (GBM) tumors are the most common malignant primary brain tumors in adults. Although many GBM tumors are believed to be caused by self-renewing, glioblastoma-derived stem-like cells (GSCs), the mechanisms that regulate self-renewal and other oncogenic properties of GSCs are only now being unraveled. Here we showed that GSCs derived from GBM patient specimens express varying levels of the transcriptional repressor REST, suggesting heterogeneity across different GSC lines. Loss- and gain-of-function experiments indicated that REST maintains self-renewal of GSCs. High REST-expressing GSCs (HR-GSCs) produced tumors histopathologically distinct from those generated by low REST-expressing GSCs (LR-GSCs) in orthotopic mouse brain tumor models. Knockdown of REST in HR-GSCs resulted in increased survival in GSC-transplanted mice and produced tumors with higher apoptotic and lower invasive properties. Conversely, forced expression of exogenous REST in LR-GSCs produced decreased survival in mice and produced tumors with lower apoptotic and higher invasive properties, similar to HR-GSCs. Thus, based on our results, we propose that a novel function of REST is to maintain self-renewal and other oncogenic properties of GSCs and that REST can play a major role in mediating tumorigenicity in GBM. PMID:22228704

  3. Metastatic pancreatic cancer is dependent on oncogenic Kras in mice.

    Directory of Open Access Journals (Sweden)

    Meredith A Collins

    Full Text Available Pancreatic cancer is one of the deadliest human malignancies, and its prognosis has not improved over the past 40 years. Mouse models that spontaneously develop pancreatic adenocarcinoma and mimic the progression of the human disease are emerging as a new tool to investigate the basic biology of this disease and identify potential therapeutic targets. Here, we describe a new model of metastatic pancreatic adenocarcinoma based on pancreas-specific, inducible and reversible expression of an oncogenic form of Kras, together with pancreas-specific expression of a mutant form of the tumor suppressor p53. Using high-resolution magnetic resonance imaging to follow individual animals in longitudinal studies, we show that both primary and metastatic lesions depend on continuous Kras activity for their maintenance. However, re-activation of Kras* following prolonged inactivation leads to rapid tumor relapse, raising the concern that Kras*-resistance might eventually be acquired. Thus, our data identifies Kras* as a key oncogene in pancreatic cancer maintenance, but raises the possibility of acquired resistance should Kras inhibitors become available for use in pancreatic cancer.

  4. Oncogenes Activate an Autonomous Transcriptional Regulatory Circuit That Drives Glioblastoma

    Directory of Open Access Journals (Sweden)

    Dinesh K. Singh

    2017-01-01

    Full Text Available Efforts to identify and target glioblastoma (GBM drivers have primarily focused on receptor tyrosine kinases (RTKs. Clinical benefits, however, have been elusive. Here, we identify an SRY-related box 2 (SOX2 transcriptional regulatory network that is independent of upstream RTKs and capable of driving glioma-initiating cells. We identified oligodendrocyte lineage transcription factor 2 (OLIG2 and zinc-finger E-box binding homeobox 1 (ZEB1, which are frequently co-expressed irrespective of driver mutations, as potential SOX2 targets. In murine glioma models, we show that different combinations of tumor suppressor and oncogene mutations can activate Sox2, Olig2, and Zeb1 expression. We demonstrate that ectopic co-expression of the three transcription factors can transform tumor-suppressor-deficient astrocytes into glioma-initiating cells in the absence of an upstream RTK oncogene. Finally, we demonstrate that the transcriptional inhibitor mithramycin downregulates SOX2 and its target genes, resulting in markedly reduced proliferation of GBM cells in vivo.

  5. Oncogenes Activate an Autonomous Transcriptional Regulatory Circuit That Drives Glioblastoma.

    Science.gov (United States)

    Singh, Dinesh K; Kollipara, Rahul K; Vemireddy, Vamsidara; Yang, Xiao-Li; Sun, Yuxiao; Regmi, Nanda; Klingler, Stefan; Hatanpaa, Kimmo J; Raisanen, Jack; Cho, Steve K; Sirasanagandla, Shyam; Nannepaga, Suraj; Piccirillo, Sara; Mashimo, Tomoyuki; Wang, Shan; Humphries, Caroline G; Mickey, Bruce; Maher, Elizabeth A; Zheng, Hongwu; Kim, Ryung S; Kittler, Ralf; Bachoo, Robert M

    2017-01-24

    Efforts to identify and target glioblastoma (GBM) drivers have primarily focused on receptor tyrosine kinases (RTKs). Clinical benefits, however, have been elusive. Here, we identify an SRY-related box 2 (SOX2) transcriptional regulatory network that is independent of upstream RTKs and capable of driving glioma-initiating cells. We identified oligodendrocyte lineage transcription factor 2 (OLIG2) and zinc-finger E-box binding homeobox 1 (ZEB1), which are frequently co-expressed irrespective of driver mutations, as potential SOX2 targets. In murine glioma models, we show that different combinations of tumor suppressor and oncogene mutations can activate Sox2, Olig2, and Zeb1 expression. We demonstrate that ectopic co-expression of the three transcription factors can transform tumor-suppressor-deficient astrocytes into glioma-initiating cells in the absence of an upstream RTK oncogene. Finally, we demonstrate that the transcriptional inhibitor mithramycin downregulates SOX2 and its target genes, resulting in markedly reduced proliferation of GBM cells in vivo.

  6. Le nouvel Edito B1

    CERN Document Server

    Heu, Elodie; Pinson, Cécile

    2012-01-01

    - Une organisation des contenus plus segmentée. Chaque unité thématique se divise en 2 dossiers constituant un ensemble pédagogique complet : un travail croisé des compétences, des entraînements spécifiques à la grammaire, un enrichissement du vocabulaire ainsi qu'en alternance, des éclairages ciblés sur la France ou la francophonie et l'interculturel. - Des renvois réguliers vers le cahier d'exercices pour consolider les nouveaux éléments grammaticaux et lexicaux.

  7. LeFort I Osteotomy.

    Science.gov (United States)

    Buchanan, Edward P; Hyman, Charles H

    2013-08-01

    The LeFort I osteotomy is one of the most commonly used procedures to correct midface deformities. It allows for correction in three dimensions including advancement, retrusion, elongation, and shortening. It is indicated, often in conjunction with mandibular surgery, for class II and III malocclusion, facial asymmetry, obstructive sleep apnea, and maxillary atrophy. Before surgery, proper orthodontics and surgical planning should be undertaken to ensure adequate outcomes. Overall, the surgery is widely used due to its low complication profile and reliable long-term results.

  8. Le arene politiche del corpo

    Directory of Open Access Journals (Sweden)

    Mariella Pandolfi

    2013-07-01

    Full Text Available L’antropologia contemporanea ha da tempo costruito intorno alla categoria “corpo” una zona di riflessione particolarmente porosa a ogni contaminazione disciplinare e a una più attenta sensibilità verso i nuovi paradigmi identitari emersi dagli anni Ottanta in poi. In tutti i suoi settori di ricerca, dall’antropologia medica al femminismo, da quella giuridica allo spazio politico, dall’etnopsichiatria al post-strutturalismo, la voce “corpo” si è imposta come luogo privilegiato per cercare di abbattere o per lo meno di rendere meno radicali le querelle disciplinari.

  9. Prediction of oncogenic interactions and cancer-related signaling networks based on network topology.

    Science.gov (United States)

    Acencio, Marcio Luis; Bovolenta, Luiz Augusto; Camilo, Esther; Lemke, Ney

    2013-01-01

    Cancer has been increasingly recognized as a systems biology disease since many investigators have demonstrated that this malignant phenotype emerges from abnormal protein-protein, regulatory and metabolic interactions induced by simultaneous structural and regulatory changes in multiple genes and pathways. Therefore, the identification of oncogenic interactions and cancer-related signaling networks is crucial for better understanding cancer. As experimental techniques for determining such interactions and signaling networks are labor-intensive and time-consuming, the development of a computational approach capable to accomplish this task would be of great value. For this purpose, we present here a novel computational approach based on network topology and machine learning capable to predict oncogenic interactions and extract relevant cancer-related signaling subnetworks from an integrated network of human genes interactions (INHGI). This approach, called graph2sig, is twofold: first, it assigns oncogenic scores to all interactions in the INHGI and then these oncogenic scores are used as edge weights to extract oncogenic signaling subnetworks from INHGI. Regarding the prediction of oncogenic interactions, we showed that graph2sig is able to recover 89% of known oncogenic interactions with a precision of 77%. Moreover, the interactions that received high oncogenic scores are enriched in genes for which mutations have been causally implicated in cancer. We also demonstrated that graph2sig is potentially useful in extracting oncogenic signaling subnetworks: more than 80% of constructed subnetworks contain more than 50% of original interactions in their corresponding oncogenic linear pathways present in the KEGG PATHWAY database. In addition, the potential oncogenic signaling subnetworks discovered by graph2sig are supported by experimental evidence. Taken together, these results suggest that graph2sig can be a useful tool for investigators involved in cancer research

  10. Prediction of oncogenic interactions and cancer-related signaling networks based on network topology.

    Directory of Open Access Journals (Sweden)

    Marcio Luis Acencio

    Full Text Available Cancer has been increasingly recognized as a systems biology disease since many investigators have demonstrated that this malignant phenotype emerges from abnormal protein-protein, regulatory and metabolic interactions induced by simultaneous structural and regulatory changes in multiple genes and pathways. Therefore, the identification of oncogenic interactions and cancer-related signaling networks is crucial for better understanding cancer. As experimental techniques for determining such interactions and signaling networks are labor-intensive and time-consuming, the development of a computational approach capable to accomplish this task would be of great value. For this purpose, we present here a novel computational approach based on network topology and machine learning capable to predict oncogenic interactions and extract relevant cancer-related signaling subnetworks from an integrated network of human genes interactions (INHGI. This approach, called graph2sig, is twofold: first, it assigns oncogenic scores to all interactions in the INHGI and then these oncogenic scores are used as edge weights to extract oncogenic signaling subnetworks from INHGI. Regarding the prediction of oncogenic interactions, we showed that graph2sig is able to recover 89% of known oncogenic interactions with a precision of 77%. Moreover, the interactions that received high oncogenic scores are enriched in genes for which mutations have been causally implicated in cancer. We also demonstrated that graph2sig is potentially useful in extracting oncogenic signaling subnetworks: more than 80% of constructed subnetworks contain more than 50% of original interactions in their corresponding oncogenic linear pathways present in the KEGG PATHWAY database. In addition, the potential oncogenic signaling subnetworks discovered by graph2sig are supported by experimental evidence. Taken together, these results suggest that graph2sig can be a useful tool for investigators involved

  11. [Nature of cancer explored from the perspective of the functional evolution of proto-oncogenes].

    Science.gov (United States)

    Watari, Akihiro

    2012-01-01

    The products of proto-oncogene play critical roles in the development or maintenance of multicellular societies in animals via strict regulatory systems. When these regulatory systems are disrupted, proto-oncogenes can become oncogenes, and thereby induce cell transformation and carcinogenesis. To understand the molecular basis for development of the regulatory system of proto-oncogenes during evolution, we screened for ancestral proto-oncogenes from the unicellular choanoflagellate Monosiga ovata (M. ovata) by monitoring their transforming ability in mammalian cells; consequently, we isolated a Pak gene ortholog, which encodes a serine/threonine kinase as a 'primitive oncogene'. We also cloned Pak orthologs from fungi and the multicellular sponge Ephydatia fluviatilis, and compared their regulatory features with that of M. ovata Pak (MoPak). MoPak is constitutively active and induces cell transformation in mammalian cells. In contrast, Pak orthologs from multicellular animals are strictly regulated. Analyses of Pak mutants revealed that structural alterations in the auto-inhibitory domain (AID) are responsible for the enhanced kinase activity and the oncogenic activity of MoPak. Furthermore, we show that Rho family GTPases-mediated regulatory system of Pak kinase is conserved throughout the evolution from unicellular to multicellular animals, but the MoPak is more sensitive to the Rho family GTPases-mediated activation than multicellular Pak. These results show that maturation of AID function was required for the development of the strict regulatory system of the Pak proto-oncogene, and support the potential link between the development of the regulatory system of proto-oncogenes and the evolution of multicellularity. Further analysis of oncogenic functions of proto-oncogene orthologs in the unicellular genes would provide some insights into the mechanisms of the destruction of multicellular society in cancer.

  12. Le corps dans l'Antiquité

    Directory of Open Access Journals (Sweden)

    Sophie Lalanne

    2008-06-01

    Full Text Available Ouvrages générauxLaqueur Thomas, La fabrique du sexe. Essai sur le corps et le genre en Occident, trad. fr., Paris, Gallimard, 1992.Feher Michel, Naddaff Ramona, Tazi Nadia, Fragments for a History of the Human Body, 3 volumes, New York, Zone Books, 1989.Le Corps dans l’AntiquitéBodiou Lydie, Frère Dominique, Mehl Véronique dir., L’expression des corps. Gestes, attitudes, regards dans l’iconographie antique, Rennes, Presses Universitaires de Rennes, 2006.Bonnard Jean-Baptiste, Le complexe de ...

  13. Counselling sur le SIDA au Japon

    OpenAIRE

    大嶋, 美登子 

    2010-01-01

    Dans cet article, nous traitons le counselling sur le Sida au Japon. Nousexaminons tout d’abord, l’état actuel des situations qui entourent lesmalades du Sida et les contaminés par le virus du HIV. Ensuit, nous prenonsen considération l’aperçu histroique du counselling en leur faveur, sonintroduction, son système, son état actuel, en citant principalement les activitésréalisées dans le département d’OITA Enfin, nous présentons ce quiest indispensable et nécessaire au counselling pour les mala...

  14. Le principe d’inertie et le conatus du corps

    Directory of Open Access Journals (Sweden)

    Épaminondas Vamboulis

    2005-09-01

    Full Text Available Le principe d’inertie constitue la loi fondamentale qui a permis à la nouvelle physique du XVIIe siècle de construire son édifice en s’opposant aux explications scolastiques des phénomènes physiques. Tant Descartes que Spinoza ont proposé des démonstrations de cette loi physique en l’intégrant chacun dans son propre système philosophique. Spinoza dans ses Principes de la philosophie de Descartes propose même implicitement une critique de la démonstration cartésienne. Nous analysons cette critique dans la première partie de cet article et dans la suite nous proposons une lecture de la manière dont Spinoza déduit le principe d’inertie dans l’Éthique. Comme ce principe présente quant à son énoncé et quant à sa conceptualisation des affinités avec la théorie du conatus de la troisième partie de l’Éthique, cet article met en valeur la relation de ces deux parties du système et tire de leur confrontation quelques conclusions concernant le statut et la place de la physique dans la philosophie de Spinoza.The principle of inertia, despite the fact that it cannot be proven by any kind of experimental observation, is one of those principles that during the seventeenth century formed the foundations of a new physics. Both Descartes and Spinoza have tried however to demonstrate this principle and integrate it in their philosophical systems. Spinoza even proposes in his work Descartes’ Principles of Philosophy, while presenting Descartes’ view on that matter, a critical appraisal of some of the metaphysical presuppositions of the cartesian demonstration. An analysis of Spinoza’s arguments leads us to a study of the relation of the principle of inertia and the conatus theory of the Ethics, and subsequently to an interrogation concerning the status of Spinoza’s physics and the place that this science occupies in Spinoza’s philosophy.

  15. microRNA-181b promotes migration and invasion of osteosarcoma cells by targeting N-myc downstream regulated gene 2%miR-181b通过靶向调控N-myc下游调节基因2影响骨肉瘤细胞的迁移和侵袭

    Institute of Scientific and Technical Information of China (English)

    邵建立; 李志忠; 王亮; 焦根龙; 周志刚; 孙国栋

    2016-01-01

    Objective To investigate the effects of miR-181b on the migration and invasion of osteosarcoma cells. Methods Three cultured osteosarcoma cell lines and MG-63 cells transfected with miR-181b inhibitor were examined for miR-181b expression using qRT-PCR analysis. The cell migration and invasion of the transfected cells were assessed with Transwell assay. The targets of miR-181b were predicted using a miRNA target prediction software and the results were verified with luciferase reporter assay. The target protein expression in osteosarcoma cells lines was determined by Western blotting, and the cell migration and invasion changes following inhibition of miR-181b or its target protein were assessed using Transwell assay. Results All the 3 osteosarcoma cells lines showed significantly up-regulated miR-181b expression. Inhibition of miR-181b expression obviously suppressed the migration and invasion of MG-63 cells. Based on luciferase reporter assay, N-myc downstream regulated gene 2 (NDRG2) was identified as the direct target gene of miR-181b, and inhibition of NDRG2 expression significantly reversed the effect of miR-181b on cell migration and invasion in MG-63 cells. Conclusion miR-181b is over-expressed in osteosarcoma cells, and inhibition of miR-181b, which directly targets NDRG2, can suppress the migration and invasion of osteosarcoma cells.%目的:探讨miR-181b对骨肉瘤细胞迁移和侵袭的影响。方法培养骨肉瘤细胞,实时荧光定量PCR检测miR-181b在骨肉瘤细胞中的表达。抑制miR-181b的表达,Transwell检测对骨肉瘤迁移和侵袭的影响;生物信息学分析miR-181b靶基因并采用荧光素酶报告基因分析miR-181b和靶基因在骨肉瘤中是否直接作用,同时采用Western Blotting检测靶基因在骨肉瘤细胞中的表达以及Transwell检测靶基因对骨肉瘤迁移和侵袭的影响。结果实时荧光定量PCR结果表明miR-181b在骨肉瘤细胞中高表达。抑制miR-181b的表达

  16. Functional Analysis of the Proto-oncogenes Septin9 and Nras

    DEFF Research Database (Denmark)

    Lassen, Louise Berkhoudt

    regardless of genotype indicating an oncogenic role of SEPT9. Nras is a potent proto-oncogene involved in signaling through a number of proliferative pathways. Earlier detected retroviral integration sites resulting in B-cell lymphomas were used to create Nras knock in models harboring the LTR from...

  17. L’Association du personnel, le TREF, le Comité des Finances et le Conseil du CERN

    CERN Multimedia

    Staff Association

    2016-01-01

    L’Association du personnel, forte de son approche participative et consensuelle, recherche toujours le meilleur accord possible pour l’Organisation et son personnel. Pour ce faire, discussions et concertation avec la Direction, travail d’explication et de persuasion au TREF et ailleurs auprès des délégués des États membres sont nos principaux atouts. TREF (Tripartite Employment Conditions Forum), un Forum d’échanges, de discussions « L’objectif du Forum est d’améliorer le processus de prise de décision  en donnant aux personnes concernées la possibilité et le temps de comprendre pleinement la position de tous les participants. » (CERN/RTG/8) Le Forum tripartite sur les conditions d’emploi (TREF), créé par le Conseil du CERN en juin 1994, est composé de r...

  18. RET oncogene in MEN2, MEN2B, MTC and other forms of thyroid cancer.

    Science.gov (United States)

    Lodish, Maya B; Stratakis, Constantine A

    2008-04-01

    Hereditary medullary thyroid carcinoma (MTC) is caused by specific autosomal dominant gain-of-function mutations in the RET proto-oncogene. Genotype-phenotype correlations exist that help predict the presence of other associated endocrine neoplasms as well as the timing of thyroid cancer development. MTC represents a promising model for targeted cancer therapy, as the oncogenic event responsible for initiating malignancy has been well characterized. The RET proto-oncogene has become the target for molecularly designed drug therapy. Tyrosine kinase inhibitors targeting activated RET are currently in clinical trials for the treatment of patients with MTC. This review will provide a brief overview of MTC and the associated RET oncogenic mutations, and will summarize the therapies designed to strategically interfere with the pathologic activation of the RET oncogene.

  19. la lutte contre le SIDA au Cameroun

    African Journals Online (AJOL)

    Chantel

    gestion peu rigoureuse des affaires publiques ont conduit le pays à .... difficultés économiques que connaissent la plupart des malades et ..... reconsidère la relation homme/femme. ..... S'agissant de la répression de la contamination, le droit.

  20. L'astronomie dans le monde

    OpenAIRE

    Manfroid, Jean

    2004-01-01

    Le réveil d'Huygens; à la recherche du rayonnement le plus froid; Les vagues monstrueuses qui coulent des navires sont repérées par les satellites radar de l'ESA; Exoplanète poids plume; Sinfoni à  l'ESO; TrES 1; Cassiopée A

  1. Classical Oncogenes and Tumor Suppressor Genes: A Comparative Genomics Perspective

    Directory of Open Access Journals (Sweden)

    Oxana K. Pickeral

    2000-05-01

    Full Text Available We have curated a reference set of cancer-related genes and reanalyzed their sequences in the light of molecular information and resources that have become available since they were first cloned. Homology studies were carried out for human oncogenes and tumor suppressors, compared with the complete proteome of the nematode, Caenorhabditis elegans, and partial proteomes of mouse and rat and the fruit fly, Drosophila melanogaster. Our results demonstrate that simple, semi-automated bioinformatics approaches to identifying putative functionally equivalent gene products in different organisms may often be misleading. An electronic supplement to this article1 provides an integrated view of our comparative genomics analysis as well as mapping data, physical cDNA resources and links to published literature and reviews, thus creating a “window” into the genomes of humans and other organisms for cancer biology.

  2. Mutations of the KRAS oncogene in endometrial hyperplasia and carcinoma.

    Directory of Open Access Journals (Sweden)

    Wiesława Niklińska

    2009-05-01

    Full Text Available The aim of this study was to examine the prevalence and clinicopathological significance of KRAS point mutation in endometrial hyperplasia and carcinoma. We analysed KRAS in 11 cases of complex atypical hyperplasia and in 49 endometrial carcinomas using polymerase chain reaction associated with restriction fragment length polymorphism (PCR-RFPL. Point mutations at codon 12 of KRAS oncogene were identified in 7 of 49 (14,3% tumor specimens and in 2 of 11 (18,2% hyperplasias. No correlation was found between KRAS gene mutation and age at onset, histology, grade of differentiation and clinical stage. We conclude that KRAS mutation is a relatively common event in endometrial carcinogenesis, but with no prognostic value.

  3. Structural Effects of Oncogenic PI3K alpha Mutations

    Energy Technology Data Exchange (ETDEWEB)

    S Gabelli; C Huang; D Mandelker; O Schmidt-Kittler; B Vogelstein; L Amzel

    2011-12-31

    Physiological activation of PI3K{alpha} is brought about by the release of the inhibition by p85 when the nSH2 binds the phosphorylated tyrosine of activated receptors or their substrates. Oncogenic mutations of PI3K{alpha} result in a constitutively activated enzyme that triggers downstream pathways that increase tumor aggressiveness and survival. Structural information suggests that some mutations also activate the enzyme by releasing p85 inhibition. Other mutations work by different mechanisms. For example, the most common mutation, His1047Arg, causes a conformational change that increases membrane association resulting in greater accessibility to the substrate, an integral membrane component. These effects are examples of the subtle structural changes that result in increased activity. The structures of these and other mutants are providing the basis for the design of isozyme-specific, mutation-specific inhibitors for individualized cancer therapies.

  4. Oncogenes, protooncogenes, and tumor suppressor genes in acute myelogenous leukemia.

    Science.gov (United States)

    Hijiya, N; Gewirtz, A M

    1995-05-01

    In recent years, our understanding of normal human hematopoiesis has expanded greatly. We have increased our knowledge of regulatory growth factors, the receptors through which they act, and the secondary messengers involved in transducing the growth/differentiation signals from the cytoplasmic membrane to the nucleus. This knowledge has revealed potential mechanisms for inducing the neoplastic transformation of hematopoietic cells. This applies in particular to the role of viral oncogenes and cellular protooncogenes and, more recently, to the role of tumor suppressor genes. Protooncogenes are intimately involved in the processes of cell proliferation and differentiation. Therefore, any amplification, mutation, structural alteration, or change in transcriptional regulation of protooncogenes might lead to or be associated with induction of the malignant phenotype. Based on the importance of these genes in leukemogenesis and the maintenance of the malignant phenotype, it seems reasonable to hypothesize that targeted disruption of leukemogenic genes may be of therapeutic value.

  5. Terminal and progenitor lineage-survival oncogenes as cancer markers.

    Science.gov (United States)

    Vias, Maria; Ramos-Montoya, Antonio; Mills, Ian G

    2008-11-01

    Tumour classification has traditionally focused on differentiation and cellular morphology, and latterly on the application of genomic approaches. By combining chromatin immunoprecipitation with expression array, it has been possible to identify direct gene targets for transcription factors for nuclear hormone receptors. At the same time, there have been great strides in deriving stem and progenitor cells from tissues. It is therefore timely to propose that pairing the isolation of these cell subpopulations from tissues and tumours with these genomics approaches will reveal conserved gene targets for transcription factors. By focusing on transcription factors (lineage-survival oncogenes) with roles in both organogenesis and tumourigenesis at multiple organ sites, we suggest that this comparative genomics approach will enable developmental biology to be used more fully in relation to understanding tumour progression and will reveal new cancer markers. We focus here on neurogenesis and neuroendocrine differentiation in tumours.

  6. Use of glycolytic pathways for inhibiting or measuring oncogenic signaling

    Energy Technology Data Exchange (ETDEWEB)

    Onodera, Yasuhito; Bissell, Mina

    2017-06-27

    Disclosed are methods in which glucose metabolism is correlated to oncogenesis through certain specific pathways; inhibition of certain enzymes is shown to interfere with oncogenic signaling, and measurement of certain enzyme levels is correlated with patient survival. The present methods comprise measuring level of expression of at least one of the enzymes involved in glucose uptake or metabolism, wherein increased expression of the at least one of the enzymes relative to expression in a normal cell correlates with poor prognosis of disease in a patient. Preferably the genes whose expression level is measured include GLUT3, PFKP, GAPDH, ALDOC, LDHA and GFPT2. Also disclosed are embodiments directed towards downregulating the expression of some genes in glucose uptake and metabolism.

  7. Tumor-derived exosomes in oncogenic reprogramming and cancer progression.

    Science.gov (United States)

    Saleem, Sarmad N; Abdel-Mageed, Asim B

    2015-01-01

    In multicellular organisms, effective communication between cells is a crucial part of cellular and tissue homeostasis. This communication mainly involves direct cell-cell contact as well as the secretion of molecules that bind to receptors at the recipient cells. However, a more recently characterized mode of intercellular communication-the release of membrane vesicles known as exosomes-has been the subject of increasing interest and intensive research over the past decade. Following the discovery of the exosome-mediated immune activation, the pathophysiological roles of exosomes have been recognized in different diseases, including cancer. In this review, we describe the biogenesis and main physical characteristics that define exosomes as a specific population of secreted vesicles, with a special focus on their role in oncogenic transformation and cancer progression.

  8. Structural effects of oncogenic PI3Kα mutations.

    Science.gov (United States)

    Gabelli, Sandra B; Huang, Chuan-Hsiang; Mandelker, Diana; Schmidt-Kittler, Oleg; Vogelstein, Bert; Amzel, L Mario

    2010-01-01

    Physiological activation of PI3Kα is brought about by the release of the inhibition by p85 when the nSH2 binds the phosphorylated tyrosine of activated receptors or their substrates. Oncogenic mutations of PI3Kα result in a constitutively activated enzyme that triggers downstream pathways that increase tumor aggressiveness and survival. Structural information suggests that some mutations also activate the enzyme by releasing p85 inhibition. Other mutations work by different mechanisms. For example, the most common mutation, His1047Arg, causes a conformational change that increases membrane association resulting in greater accessibility to the substrate, an integral membrane component. These effects are examples of the subtle structural changes that result in increased activity. The structures of these and other mutants are providing the basis for the design of isozyme-specific, mutation-specific inhibitors for individualized cancer therapies.

  9. Le contrôle de gestion environnementale d'une entreprise

    OpenAIRE

    Marquet-Pondeville, Sophie

    2001-01-01

    Dans cette recherche, nous étudions comment s’opère le contrôle de gestion environnementale. Cette problématique est abordée dans une perspective contingente et nous proposons un modèle théorique qui met en évidence l’impact de certaines variables sur les systèmes de contrôle de la gestion environnementale. Certains liens présents dans ce modèle sont discutés à travers une étude de cas.

  10. Le contrôle de gestion environnementale d'une entreprise

    OpenAIRE

    Marquet-Pondeville, Sophie

    2001-01-01

    Dans cette recherche, nous étudions comment s’opère le contrôle de gestion environnementale. Cette problématique est abordée dans une perspective contingente et nous proposons un modèle théorique qui met en évidence l’impact de certaines variables sur les systèmes de contrôle de la gestion environnementale. Certains liens présents dans ce modèle sont discutés à travers une étude de cas.

  11. myc family oncogene amplification in tumor cell lines established from small cell lung cancer patients and its relationship to clinical status and course.

    Science.gov (United States)

    Johnson, B E; Ihde, D C; Makuch, R W; Gazdar, A F; Carney, D N; Oie, H; Russell, E; Nau, M M; Minna, J D

    1987-01-01

    44 small cell lung cancer cell lines established from 227 patients were studied for myc family DNA amplification (c-myc, N-myc, and L-myc). Two of 19 lines (11%) established from untreated patients' tumors had DNA amplification (one N-myc and one L-myc), compared with 11 of 25 (5 c-myc, 3 N-myc, and 3 L-myc) cell lines (44%) established from relapsed patients' tumors (P = 0.04). The 19 patients who had tumor cell lines established before chemotherapy treatment survived a median of 14 wk compared with 48 wk for the 123 extensive stage patients who did not have cell lines established (P less than 0.001). Relapsed patients whose cell lines had c-myc DNA amplification survived a shorter period (median of 33 wk) than patients whose cell lines did not have c-myc amplification (median of 53 wk; P = 0.04). We conclude that myc family DNA amplification is more common in tumor cell lines established from treated than untreated patients' tumors, and c-myc amplification in treated patients' tumor cell lines is associated with shortened survival. Images PMID:3034978

  12. Intrinsic structural disorder confers cellular viability on oncogenic fusion proteins.

    Directory of Open Access Journals (Sweden)

    Hedi Hegyi

    2009-10-01

    Full Text Available Chromosomal translocations, which often generate chimeric proteins by fusing segments of two distinct genes, represent the single major genetic aberration leading to cancer. We suggest that the unifying theme of these events is a high level of intrinsic structural disorder, enabling fusion proteins to evade cellular surveillance mechanisms that eliminate misfolded proteins. Predictions in 406 translocation-related human proteins show that they are significantly enriched in disorder (43.3% vs. 20.7% in all human proteins, they have fewer Pfam domains, and their translocation breakpoints tend to avoid domain splitting. The vicinity of the breakpoint is significantly more disordered than the rest of these already highly disordered fusion proteins. In the unlikely event of domain splitting in fusion it usually spares much of the domain or splits at locations where the newly exposed hydrophobic surface area approximates that of an intact domain. The mechanisms of action of fusion proteins suggest that in most cases their structural disorder is also essential to the acquired oncogenic function, enabling the long-range structural communication of remote binding and/or catalytic elements. In this respect, there are three major mechanisms that contribute to generating an oncogenic signal: (i a phosphorylation site and a tyrosine-kinase domain are fused, and structural disorder of the intervening region enables intramolecular phosphorylation (e.g., BCR-ABL; (ii a dimerisation domain fuses with a tyrosine kinase domain and disorder enables the two subunits within the homodimer to engage in permanent intermolecular phosphorylations (e.g., TFG-ALK; (iii the fusion of a DNA-binding element to a transactivator domain results in an aberrant transcription factor that causes severe misregulation of transcription (e.g. EWS-ATF. Our findings also suggest novel strategies of intervention against the ensuing neoplastic transformations.

  13. Deciphering hepatocellular responses to metabolic and oncogenic stress

    Directory of Open Access Journals (Sweden)

    Kathrina L. Marcelo

    2015-08-01

    Full Text Available Each cell type responds uniquely to stress and fractionally contributes to global and tissue-specific stress responses. Hepatocytes, liver macrophages (MΦ, and sinusoidal endothelial cells (SEC play functionally important and interdependent roles in adaptive processes such as obesity and tumor growth. Although these cell types demonstrate significant phenotypic and functional heterogeneity, their distinctions enabling disease-specific responses remain understudied. We developed a strategy for the simultaneous isolation and quantification of these liver cell types based on antigenic cell surface marker expression. To demonstrate the utility and applicability of this technique, we quantified liver cell-specific responses to high-fat diet (HFD or diethylnitrosamine (DEN, a liver-specific carcinogen, and found that while there was only a marginal increase in hepatocyte number, MΦ and SEC populations were quantitatively increased. Global gene expression profiling of hepatocytes, MΦ and SEC identified characteristic gene signatures that define each cell type in their distinct physiological or pathological states. Integration of hepatic gene signatures with available human obesity and liver cancer microarray data provides further insight into the cell-specific responses to metabolic or oncogenic stress. Our data reveal unique gene expression patterns that serve as molecular “fingerprints” for the cell-centric responses to pathologic stimuli in the distinct microenvironment of the liver. The technical advance highlighted in this study provides an essential resource for assessing hepatic cell-specific contributions to metabolic and oncogenic stress, information that could unveil previously unappreciated molecular mechanisms for the cellular crosstalk that underlies the continuum from metabolic disruption to obesity and ultimately hepatic cancer.

  14. DNA topoisomerases participate in fragility of the oncogene RET.

    Directory of Open Access Journals (Sweden)

    Laura W Dillon

    Full Text Available Fragile site breakage was previously shown to result in rearrangement of the RET oncogene, resembling the rearrangements found in thyroid cancer. Common fragile sites are specific regions of the genome with a high susceptibility to DNA breakage under conditions that partially inhibit DNA replication, and often coincide with genes deleted, amplified, or rearranged in cancer. While a substantial amount of work has been performed investigating DNA repair and cell cycle checkpoint proteins vital for maintaining stability at fragile sites, little is known about the initial events leading to DNA breakage at these sites. The purpose of this study was to investigate these initial events through the detection of aphidicolin (APH-induced DNA breakage within the RET oncogene, in which 144 APH-induced DNA breakpoints were mapped on the nucleotide level in human thyroid cells within intron 11 of RET, the breakpoint cluster region found in patients. These breakpoints were located at or near DNA topoisomerase I and/or II predicted cleavage sites, as well as at DNA secondary structural features recognized and preferentially cleaved by DNA topoisomerases I and II. Co-treatment of thyroid cells with APH and the topoisomerase catalytic inhibitors, betulinic acid and merbarone, significantly decreased APH-induced fragile site breakage within RET intron 11 and within the common fragile site FRA3B. These data demonstrate that DNA topoisomerases I and II are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication.

  15. Oncogenic c-kit transcript is a target for binase.

    Science.gov (United States)

    Mitkevich, Vladimir A; Petrushanko, Irina Y; Kretova, Olga V; Zelenikhin, Pavel V; Prassolov, Vladimir S; Tchurikov, Nickolai A; Ilinskaya, Olga N; Makarov, Alexander A

    2010-07-01

    Mutational activation of c-Kit receptor tyrosine kinase is common in acute myelogenous leukemia (AML). One such activating point mutation is the N822K replacement in the c-Kit protein. Here we investigate the selective cytotoxic effect of binase--RNase from Bacillus intermedius--on FDC-P1-N822K cells. These cells were derived from myeloid progenitor FDC-P1 cells, in which ectopic expression of N822K c-kit gene induces interleukin-3 independent growth. In order to determine whether the sensitivity of these cells to binase is caused by the expression of c-kit oncogene, the cytotoxicity of the RNase was studied in the presence of selective inhibitor of mutated c-Kit imatinib (Gleevec). Inhibition of mutated c-Kit protein leads to the loss of cell sensitivity to the apoptotic effect of binase, while the latter still decreases the amount of cellular RNA. Using green fluorescent protein as an expression marker for the c-Kit oncoprotein, we demonstrate that the elimination of c-Kit is the key factor in selective cytotoxicity of binase. Quantitative RT-PCR with RNA samples isolated from the binase-treated FDC-P1-N822K cells shows that binase treatment results in 41% reduction in the amount of с-kit mRNA. This indicates that the transcript of the activated mutant c-kit is the target for toxic action of binase. Thus, the combination of inhibition of oncogenic protein with the destruction of its mRNA is a promising approach to eliminating malignant cells.

  16. Le verre de la guerre

    OpenAIRE

    Bischoff, Georges

    2012-01-01

    Les historiens du vignoble ne se sont guère intéressés à la Révolution française. À leurs yeux, le chapitre qui s’ouvre en 1789 n’a rien à voir avec les très riches heures du Moyen Âge, de la Renaissance et de l’Ancien régime : il voit sombrer des institutions séculaires – les seigneurs, les corporations, l’organisation communautaire – et se traduit par la fermeture des marchés traditionnels ; ses lendemains sont médiocres. Pourtant, ce jugement mérite d’être nuancé : les guerres de la Révolu...

  17. Chine : le pouvoir en chantant

    OpenAIRE

    TREBINJAC, Sabine

    2015-01-01

    Pour un Occidental, parler de Musique et Pouvoir est une tentative d’évaluer le pouvoir de la musique. Soit il s’agit du pouvoir de l’énoncé, thème central de la musicothérapie. Soit il s’agit du pouvoir du musicien qui, porteur d’un message, souvent politique d’ailleurs, acquiert le statut de modèle et le pouvoir de mobiliser les foules autour de lui : il peut alors lancer un concert pour l’égalité, contre l’apartheid, contre le Sommet des pays les plus industrialisés, par exemple. Ou bien e...

  18. Comme le temps passe !

    OpenAIRE

    Voituriez, Maurice

    2014-01-01

    Voici qu’on nous annonce la disparition programmée en 2012 du Minitel. Dans le n° 138 de notre revue, paru en 1988 M. Seren-Rosso parle du télécopieur, généralement appelé fax. Introduit en France dans les années 1970, il devait prendre la place du télex (connu chez nous après 1960). Le télex a vécu, le fax existe encore mais fortement concurrencé par le courriel (ou e‑mail). Il existe heureusement des créations qui persistent et Jean Maillot cite le correcteur orthographique, déjà existant ...

  19. Le Premier Amendement : un mythe

    Directory of Open Access Journals (Sweden)

    Claude‑Jean Bertrand

    2006-03-01

    Full Text Available Ce papier, plein de verve, d’humeur et d’humour, pose, comme sait si bien le faire l’auteur, des questions profondes sous une apparence paradoxale. Il a été présenté lors d’un colloque sur le Premier amendement organisé à l’Université Lumière-Lyon 2 les 17 et 18 janvier 2003. Certaines communications ont été publiées dans le volume XXIV, n°1 (2003, « Le premier amendement : un modèle américain des libertés » (sous la direction de Vincent Michelot de la Revue Tocqueville.

  20. Jouir du bonheur ou le penser ?

    OpenAIRE

    Guibet-Lafaye, Caroline

    2013-01-01

    « Malheureusement, le concept du bonheur est un concept si indéterminé, que, malgré le désir qu’a tout homme d’arriver à être heureux, personne ne peut jamais dire en termes précis et cohérents ce que véritablement il désire et veut ». L’agir de la plupart des hommes rend manifeste le fait que le bonheur est pour chacun la chose la plus désirable de toutes, la fin de toutes les actions, ce que traduit la philosophie grecque de l’action en soulignant que le bonheur est la seule chose pour laq...

  1. 1. Rôle d’équipage

    OpenAIRE

    Lamikiz, Xabier

    2016-01-01

    le d’équipage du bateau Le Dauphin (TNA, HCA 32/180–1). [image 1] Argazkiak: Xabier LAMIKIZ. Rôle d’équipage du bateau Le Dauphin (TNA, HCA 32/180–1). [image 2] Argazkiak: Xabier LAMIKIZ Rôle d’équipage du bateau Le Dauphin (TNA, HCA 32/180–1). [image 3] Argazkiak: Xabier LAMIKIZ

  2. Functional transition of Pak proto-oncogene during early evolution of metazoans.

    Science.gov (United States)

    Watari, A; Iwabe, N; Masuda, H; Okada, M

    2010-07-01

    Proto-oncogenes encode signaling molecular switches regulating cellular homeostasis in metazoans, and can be converted to oncogenes by gain-of-function mutations. To address the molecular basis for development of the regulatory system of proto-oncogenes during evolution, we screened for ancestral proto-oncogenes from the unicellular choanoflagellate Monosiga ovata by monitoring their transforming activities, and isolated a Pak gene ortholog encoding a serine/threonine kinase as a 'primitive oncogene'. We also cloned Pak orthologs from fungi and the multicellular sponge Ephydatia fluviatilis, and compared their regulatory features with that of M. ovata Pak (MoPak). MoPak is constitutively active and induces cell transformation in mammalian fibroblasts, although the Pak orthologs from multicellular animals are strictly regulated. Analyses of Pak mutants revealed that structural alteration of the auto-inhibitory domain (AID) of MoPak confers higher constitutive kinase activity, as well as greater binding ability to Rho family GTPases than the multicellular Paks, and this structural alteration is responsible for cell transformation and disruption of multicellular tissue organization. These results show that maturation of AID function was required for the development of the strict regulatory system of the Pak proto-oncogene, and suggest a potential link between the establishment of the regulatory system of proto-oncogenes and metazoan evolution.

  3. Le Great Limpopo Transfrontier Park

    Directory of Open Access Journals (Sweden)

    Nadia Belaidi

    2008-10-01

    Full Text Available Cet article a pour objet de présenter quelques problématiques d'une recherche sur la construction d’un mécanisme de valorisation sociale de la protection de l’environnement : l’ordre public écologique. Cette étude s’appuie sur une expérience récente et originale en Afrique australe : la création de Parcs pour la Paix dont relève le Great Limpopo Transfrontier Park. Ces parcs sont officiellement consacrés à la protection et à la conservation de la diversité biologique, des ressources naturelles et culturelles qui y sont associées, ainsi qu’à la promotion de la coopération et de la Paix qu’elle soit civile, sociale, économique ou culturelle. La logique de construction de ces parcs repose sur l’idée que l’articulation des zones de conservation facilite la résolution de conflits territoriaux – de toutes sortes – en transformant les préoccupations environnementales en objet de coopération entre des juridictions politiques diverses. C’est précisément le schéma du concept juridique objet de nos travaux : l’ordre public écologique. Aussi peut-on se demander si le GLTP, en particulier, (peut constitue(r une illustration concrète de ce mécanisme et permettre d’atteindre la Paix recherchée, favorisant ainsi les processus de développement ?This article aims to present some problems of researches on the construction of a mechanism of social valorisation of the environmental protection: ecological public order. This study leans on a recent and original experience in southern Africa: the creation of Peace Park like the Great Limpopo Transfrontier Park (GLTP. These parks are officially dedicated to the protection and to the preservation of biological diversity, natural and cultural resources which are associated with it, as well as in the promotion of the cooperation and the peace. The peace looked for in these parks is not only the opposite of the war but it is also social, economic and cultural peace

  4. LeRoy el invisible

    Directory of Open Access Journals (Sweden)

    Michael M. Meguid

    Full Text Available En agosto de 1976, un joven llamado LeRoy cayó desde una cornisa fracturándose el fémur. Se sospechó una hemorragia interna importante. Durante una laparotomía se comprobó que todos los órganos internos estaban intactos y los cirujanos ortopédicos arreglaron la fractura. Treinta días después, LeRoy murió. Había comido poco; diariamente, tan solo había recibido tres litros de la glucosa, el equivalente a 510 calorías, por vía intravenosa. La glucosa fue insuficiente para satisfacer sus necesidades nutricionales,perdiendo más del 20% de su peso corporal durante su estancia en el hospital. La causa de la muerte se debió a "desnutrición médicamente inducida". Mientras tanto, un artículo científico documentó que la prevalencia de desnutrición en los hospitales de Boston era del 44% y que la desnutrición en sí era un predictor de altas tasas de complicaciones y muerte. Como resultado, los médicos sensibilizados formaron una sociedad que creó programas de formación y alentó la formación de equipos de nutrición en los hospitales. La industria comercializó fórmulas de nutrición y catéteres. Las complicaciones en enfermos hospitalizados cayeron en picado, mientras que las tasas de supervivencia aumentaron. California aprobó una legislación para regular el soporte nutricional. Aunque la industria de la atención sanitaria reconoce la importancia de la nutrición en los cuidados al paciente, el Congreso no proporcionó apoyo fiscal para los equipos de nutrición. Como resultado, los hospitales disolvieron sus equipos de nutrición de reciente creación. La educación y las habilidades en nutrición disminuyeron, y las complicaciones hospitalarias y las tasas de mortalidad aumentaron de nuevo. "No hay nadie más ciego que el que no quiere ver" Matthew Henry Clergyman 1662-1714.

  5. Le soleil devient un mythe

    Directory of Open Access Journals (Sweden)

    Ildikó Lőrinszky

    2009-01-01

    Full Text Available Partant d’une phrase énigmatique datant de 1858 et puisée dans la Correspondance de Flaubert, cet article s’interroge sur la relation entre soleil et mythe, qui constituera l’un des éléments clefs de la dimension mythologique de Salammbô. Il se propose d’examiner la façon dont cette question apparaît dans deux ouvrages représentatifs des études mythographiques : d’une part, L’Origine de tous les cultes de Charles-François Dupuis, d’autre part, Les Religions de l’Antiquité..., publié sous les noms de Frédéric Creuzer et de son adaptateur français, Joseph-Daniel Guigniault. La version française de la grande synthèse de Creuzer, assortie d’une série importante de planches, a été richement exploitée par Flaubert au cours de la genèse du roman carthaginois. Dans Salammbô, le mythe apparaît sous de multiples formes. L’analyse de ce texte peut nous amener à réfléchir sur le « bon usage » du mythe auquel chaque créateur (et chaque lecteur se trouve nécessairement confronté.Starting from an enigmatic phrase in Flaubert’s correspondence, dating from 1858, this article examines the relation between the Sun and myth, which constitutes one of the key elements of the mythological dimension of Salammbô. It especially focuses on the treatment of this question in two representative works of mythographic studies, The Origin of All Religious Worship by Charles-François Dupuis, and Les Religions de l’Antiquité..., the French adaptation of Frédéric Creuzer’s Symbolik und Mythologie der alten Völker by Joseph-Daniel Guigniault. The French version of Creuzer’s great synthesis, supplied with a remarkable set of prints, was abundantly consulted by Flaubert when writing his Carthaginian novel. In Salammbô, myth takes on various forms. Analyzing this text might lead one to reconsider “the right way” to use myths — a problem all writers (and readers find themselves confronted with.

  6. Investiguer le pluralisme de l’agir

    Directory of Open Access Journals (Sweden)

    Jean-Louis Genard

    2011-07-01

    Full Text Available Une des dimensions centrales de la sociologie développée par Laurent Thévenot et notamment dans l’ouvrage L’Action au pluriel qui nous préoccupe ici, se situe dans l’ambition d’assumer sociologiquement le pluralisme, comme l’indique d’ailleurs explicitement le titre de l’ouvrage . Ce pluralisme est un trait distinctif du travail de ce courant sociologique dont on ne sait plus vraiment s’il est pertinent de le nommer « pragmatique » puisque cette appellation est aujourd’hui quelquefois l’objet...

  7. Facial Pain (Le Algie Facciali, Editorial

    Directory of Open Access Journals (Sweden)

    Paolo Marchettini, MD

    2013-09-01

    Full Text Available Il ricorso al trattamento chirurgico delle algie facciali è di norma considerato dai neurologi un’opzione per i casi di nevralgia trigeminale in cui sia identificato con certezza un conflitto neuro vascolare e che non siano responsivi o abbiano intolleranza ai trattamenti farmacologici. Le algie facciali di altra natura non rientrano quasi mai nelle indicazioni al trattamento chirurgico proposte dai clinici, anche nei casi resistenti a molteplici terapie combinate. Eppure negli ultimi trenta-quarant’anni la neurochirurgia a cielo aperto, la chirurgia stereotassica e le metodiche di neuro-modulazione hanno radicalmente cambiato le prospettive terapeutiche dei pazienti con dolore facciale severo

  8. S'orienter dans le virtuel

    OpenAIRE

    Vitali-Rosati, Marcello

    2012-01-01

    Fictif, artificiel, imaginaire, trompeur, immatériel, irréel, impalpable, invisible, mystérieux... Lorsque l'on pense au virtuel, une foule d'idées nous submerge. Concept aux valeurs sémantiques multiformes et aux différents usages, sa signification reste floue et son sens en perpétuel mouvement. Qu'est-ce «réellement» que le virtuel ? Quel rapport entre le sens philosophique et son emploi dans le domaine du num&e...

  9. Methylation status of c-fms oncogene in HCC and its relationship with clinical pathology

    Institute of Scientific and Technical Information of China (English)

    Jun Cui; Dong Hua Yang; Xiang Jun Bi; Zi Rong Fan

    2001-01-01

    @@ INTRODUCTIONThe mechanism that DNA hypomethylation leads toactivation of oncogene and occurrence of malignantneoplasm is being increasingly recognized byresearchers. Normal DNA methylation playsimportant role in stabilizing the phenotype of cell.DNA methylation status reduction and/or patternalteration are related to activation and abnormallyhigh expression of some oncogenes and cellularmalignancy[1-6]. c-fms oncogene encodes for colonystimulating factor 1 receptor (CSF-1R)[7], c-fms/CSF-1R was highly expressed in hepatocellularcarcinoma (HCC) tissue, but the mechanismremained obscure[8,9].

  10. Activating mutation in MET oncogene in familial colorectal cancer

    Directory of Open Access Journals (Sweden)

    Schildkraut Joellen M

    2011-10-01

    Full Text Available Abstract Background In developed countries, the lifetime risk of developing colorectal cancer (CRC is 5%, and it is the second leading cause of death from cancer. The presence of family history is a well established risk factor with 25-35% of CRCs attributable to inherited and/or familial factors. The highly penetrant inherited colon cancer syndromes account for approximately 5%, leaving greater than 20% without clear genetic definition. Familial colorectal cancer has been linked to chromosome 7q31 by multiple affected relative pair studies. The MET proto-oncogene which resides in this chromosomal region is considered a candidate for genetic susceptibility. Methods MET exons were amplified by PCR from germline DNA of 148 affected sibling pairs with colorectal cancer. Amplicons with altered sequence were detected with high-resolution melt-curve analysis using a LightScanner (Idaho Technologies. Samples demonstrating alternative melt curves were sequenced. A TaqMan assay for the specific c.2975C >T change was used to confirm this mutation in a cohort of 299 colorectal cancer cases and to look for allelic amplification in tumors. Results Here we report a germline non-synonymous change in the MET proto-oncogene at amino acid position T992I (also reported as MET p.T1010I in 5.2% of a cohort of sibling pairs affected with CRC. This genetic variant was then confirmed in a second cohort of individuals diagnosed with CRC and having a first degree relative with CRC at prevalence of 4.1%. This mutation has been reported in cancer cells of multiple origins, including 2.5% of colon cancers, and in Conclusions Although the MET p.T992I genetic mutation is commonly found in somatic colorectal cancer tissues, this is the first report also implicating this MET genetic mutation as a germline inherited risk factor for familial colorectal cancer. Future studies on the cancer risks associated with this mutation and the prevalence in different at-risk populations will

  11. Nuevo León

    Directory of Open Access Journals (Sweden)

    Laura Nelly Medellín Mendoza

    2006-01-01

    Full Text Available El ensayo analiza la transición política nuevoleonesa a partir de un contexto de liberalización política. En Nuevo León el régimen político autoritario fue cediendo en el plano electoral, dada la presión que conjuntamente la sociedad política y la sociedad civil ejercieron por lograr reglas democráticas. Este avance gradual permitió garantizar un organismo electoral confiable y que determinó en buena medida la garantía de la alternancia en 1997. El pan fue el partido que capitalizó el bono democrático, pero una vez en la responsabilidad de gobierno, no pudo ampliar el proceso de liberalización política al mediatizar las reformas electorales y no comprometerse para sacar del atolladero legislativo las iniciativas que garantizaban mecanismos de participación ciudadana: referéndum y plebiscito.

  12. Les ERP changent-ils le contrôle de gestion ?

    OpenAIRE

    Meyssonnier, François; Pourtier, Frédéric

    2005-01-01

    L'intégration de l'information de gestion dans le cadre d'ERP se généralise et le contrôle de gestion s'effectue maintenant la plupart du temps en environnement ERP dans les grandes entreprises. Un état de l'art est effectué relativement à l'impact des ERP aussi bien sur les concepts et les outils du contrôle de gestion que sur la fonction et lele des contrôleurs de gestion. La démarche de recherche, fondée sur dix études de cas dans une approche intermédiaire entre les monographies qualit...

  13. Les ERP changent-ils le contrôle de gestion ?

    OpenAIRE

    Meyssonnier, François; Pourtier, Frédéric

    2005-01-01

    L'intégration de l'information de gestion dans le cadre d'ERP se généralise et le contrôle de gestion s'effectue maintenant la plupart du temps en environnement ERP dans les grandes entreprises. Un état de l'art est effectué relativement à l'impact des ERP aussi bien sur les concepts et les outils du contrôle de gestion que sur la fonction et lele des contrôleurs de gestion. La démarche de recherche, fondée sur dix études de cas dans une approche intermédiaire entre les monographies qualit...

  14. Sens et reconnaissance dans le travail

    OpenAIRE

    Loriol, Marc

    2011-01-01

    Traduction d'un texte de Marc Loriol, 2011, publié (en grec) dans le Traité de sociologie du travail, Sous la direction de Christina Karakioulafis, Athènes, AIONIKOS, 2011; La plupart des sociologues ayant interrogé des salariés dans différents secteurs économiques, ont été confrontés à une plainte récurrente : le manque de reconnaissance. Ce désir de reconnaissance peut être vu comme le corollaire, dans de nombreuses activités, d'un sentiment de perte de sens du travail. Si l'on ressent le b...

  15. L'argent et le bonheur

    Institute of Scientific and Technical Information of China (English)

    郑砚心

    2011-01-01

    L'argent et le bonheur,l'un est concret et l'autre ést abstrait.Mais tous les deux sont parmi les sujets les plus traités dans la littérature et dans la vie quotidienne.Maintenant,de plus en plus de personnes aiment mettre les deux ensemble.Il semble que l'argent est devenu le synonyme du bonheur.Mais qu'en est-il en réalité? Chacun a sa propre opinion.Pour dévoiler la relation entre l'argent et le bonheur,il nous faut d'abord connaitre la signification de l'argent et du bonheur.L'argent se produit à mesure de l'évolution de la société.Et le bonheur est un sentiment non-figuratif qui existe depuis l'apparition de l'homme.

  16. Jan Potocki et le "Gothic Novel"

    Science.gov (United States)

    Finne, Jacques

    1970-01-01

    Establishes a parallel between the supernatural and fantastic qualities of Le Comte Jan Potocki's literary works, and the English gothic novels by comparing the elements of terror, mysterious atmosphere, and the supernatural beings involved. (DS)

  17. Savoir gérer le mal

    Directory of Open Access Journals (Sweden)

    Michel Maffesoli

    2015-09-01

    Full Text Available Le sens commun, conservatoire immémorial de la sagesse humaine « sait », de savoir incorporé, que le mal, l’ombre, la mort, la douleur sont des caractéristiques essentielles de l’existence en son entièreté. Dès lors les créatures quelles qu’elles soient, sont des manifestations de la vie et, dès lors, méritent une attitude « compassionnelle », fraternelle, parce qu’ensemble elles constituent le flux vital. C’est ainsi que l’on peut comprendre l’utilité sociale de ces divers « mondes intermédiaires » que sont les croyances, religieuses ou philosophiques, au « double », au « daimon », aux esprits et autres figures tutélaires ou effrayantes. Elles aident à vivre, au jour le jour, la souffrance en la communalisant.

  18. Le furet : peau et glandes annexes

    OpenAIRE

    Barreau, Christelle

    2002-01-01

    Le furet (Mustela putorius furo) fait partie des Nouveaux Animaux de Compagnie que le praticien est de plus en plus souvent amené à rencontrer en clientèle. Les problèmes cutanés sont, comme chez les autres carnivores domestiques, des motifs de consultation très fréquents, après la vaccination et la stérilisation. De plus, l'odeur particulière de cet animal représente parfois un réel désagrément pour son propriétaire. L'auteur commence par faire un rappel sur le furet, son histoire, ses carac...

  19. Kirjad üle mere / Aksel Mark

    Index Scriptorium Estoniae

    Mark, Aksel, 1913-2014

    2001-01-01

    rets. rmt.: Kirjad üle mere : Mart Lepiku kirjavahetus Julius Mägiste, Karl Ristikivi ja Bernard Kangroga / Eesti Kirjandusmuuseum; koostanud ja kommenteerinud Sirje Olesk. Tartu : Eesti Kirjandusmuuseum, 2000. 160 lk. (Litteraria; 19)

  20. FOXM1 is an oncogenic mediator in Ewing Sarcoma.

    Directory of Open Access Journals (Sweden)

    Laura Christensen

    Full Text Available Ewing Family Tumors (Ewing Sarcoma and peripheral Primitive Neuroectodermal Tumor are common bone and soft tissue malignancies of childhood, adolescence and young adulthood. Chromosomal translocation in these tumors produces fusion oncogenes of the EWS/ETS class, with EWS/FLI1 being by far the most common. EWS/ETS chimera are the only well established driver mutations in these tumors and they function as aberrant transcription factors. Understanding the downstream genes whose expression is modified has been a central approach to the study of these tumors. FOXM1 is a proliferation associated transcription factor which has increasingly been found to play a role in the pathogenesis of a wide range of human cancers. Here we demonstrate that FOXM1 is expressed in Ewing primary tumors and cell lines. Reduction in FOXM1 expression in Ewing cell lines results in diminished potential for anchorage independent growth. FOXM1 expression is enhanced by EWS/FLI1, though, unlike other tumor systems, it is not driven by expression of the EWS/FLI1 target GLI1. Thiostrepton is a compound known to inhibit FOXM1 by direct binding. We show that Thiostrepton diminishes FOXM1 expression in Ewing cell lines and this reduction reduces cell viability through an apoptotic mechanism. FOXM1 is involved in Ewing tumor pathogenesis and may prove to be a useful therapeutic target in Ewing tumors.

  1. Oncogenic potential diverge among human papillomavirus type 16 natural variants

    Energy Technology Data Exchange (ETDEWEB)

    Sichero, Laura, E-mail: lsichero@gmail.com [Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Cancer do Estado de Sao Paulo-ICESP, Sao Paulo 01246-000 (Brazil); Department of Virology, Ludwig Institute for Cancer Research, Sao Paulo 01323-903 (Brazil); Simao Sobrinho, Joao [Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Cancer do Estado de Sao Paulo-ICESP, Sao Paulo 01246-000 (Brazil); Department of Virology, Ludwig Institute for Cancer Research, Sao Paulo 01323-903 (Brazil); Lina Villa, Luisa [Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Cancer do Estado de Sao Paulo-ICESP, Sao Paulo 01246-000 (Brazil); Department of Virology, Ludwig Institute for Cancer Research, Sao Paulo 01323-903 (Brazil); Department of Radiology, School of Medicine, University of Sao Paulo (Brazil)

    2012-10-10

    We compared E6/E7 protein properties of three different HPV-16 variants: AA, E-P and E-350G. Primary human foreskin keratinocytes (PHFK) were transduced with HPV-16 E6 and E7 and evaluated for proliferation and ability to grow in soft agar. E-P infected keratinocytes presented the lowest efficiency in colony formation. AA and E-350G keratinocytes attained higher capacity for in vitro transformation. We observed similar degradation of TP53 among HPV-16 variants. Furthermore, we accessed the expression profile in early (p5) and late passage (p30) transduced cells of 84 genes commonly involved in carcinogenesis. Most differences could be attributed to HPV-16 E6/E7 expression. In particular, we detected different expression of ITGA2 and CHEK2 in keratinocytes infected with AA and AA/E-350G late passage cells, respectively, and higher expression of MAP2K1 in E-350G transduced keratinocytes. Our results indicate differences among HPV-16 variants that could explain, at least in part, differences in oncogenic potential attributed to these variants.

  2. Control of autophagy by oncogenes and tumor suppressor genes.

    Science.gov (United States)

    Maiuri, M C; Tasdemir, E; Criollo, A; Morselli, E; Vicencio, J M; Carnuccio, R; Kroemer, G

    2009-01-01

    Multiple oncogenes (in particular phosphatidylinositol 3-kinase, PI3K; activated Akt1; antiapoptotic proteins from the Bcl-2 family) inhibit autophagy. Similarly, several tumor suppressor proteins (such as BH3-only proteins; death-associated protein kinase-1, DAPK1; the phosphatase that antagonizes PI3K, PTEN; tuberous sclerosic complex 1 and 2, TSC1 and TSC2; as well as LKB1/STK11) induce autophagy, meaning that their loss reduces autophagy. Beclin-1, which is required for autophagy induction acts as a haploinsufficient tumor suppressor protein, and other essential autophagy mediators (such as Atg4c, UVRAG and Bif-1) are bona fide oncosuppressors. One of the central tumor suppressor proteins, p53 exerts an ambiguous function in the regulation of autophagy. Within the nucleus, p53 can act as an autophagy-inducing transcription factor. Within the cytoplasm, p53 exerts a tonic autophagy-inhibitory function, and its degradation is actually required for the induction of autophagy. The role of autophagy in oncogenesis and anticancer therapy is contradictory. Chronic suppression of autophagy may stimulate oncogenesis. However, once a tumor is formed, autophagy inhibition may be a therapeutic goal for radiosensitization and chemosensitization. Altogether, the current state-of-the art suggests a complex relationship between cancer and deregulated autophagy that must be disentangled by further in-depth investigation.

  3. Human Papillomavirus 16E6 Oncogene Mutation in Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    Feng Sun; Xiao-qin Ha; Tong-de Lv; Chuan-ping Xing; Bin Liu; Xiao-zhe Cao

    2009-01-01

    Objective: Cervical cancer (CC) is the second most common type of cancer in women worldwide, after breast cancer. High-risk human papillomaviruses (HR-HPVs) are considered to be the major causes of cervical cancer. HPV16 is the most common type of HR-HPVs and HPV16 E6 gene is one of the major oncogenes. Specific mutations are considered as dangerous factors causing CC. This study was designed to find mutations of HPV16 E6 and the relationship between the mutations and the happening of CC.Methods: The tissue DNA was extracted from 15 biopsies of CC. Part of HPV16 E6 gene (nucleotide 201-523) was amplified by polymerase chain reaction (PCR) from the CC tissue DNA. The PCR fragments were sequenced and analyzed.Results: The result of PCR showed that the positive rate of HPV16 E6 was 93.33% (14/15). After sequencing and analyzing, in the 13 out of 14 PCR fragments, 4 maintained prototype (30.77%), 8 had a same 350G mutation (61.54%), and 1 had a 249G mutation (7.69%).Conclusion: This study suggest that there is a high infection rate of HPV in cervical cancer and most of the HPV16 E6 gene has mutations. Those mutations may have an association with the development of cervical cancer.

  4. Re-Configuration of Sphingolipid Metabolism by Oncogenic Transformation

    Directory of Open Access Journals (Sweden)

    Anthony S. Don

    2014-03-01

    Full Text Available The sphingolipids are one of the major lipid families in eukaryotes, incorporating a diverse array of structural variants that exert a powerful influence over cell fate and physiology. Increased expression of sphingosine kinase 1 (SPHK1, which catalyses the synthesis of the pro-survival, pro-angiogenic metabolite sphingosine 1-phosphate (S1P, is well established as a hallmark of multiple cancers. Metabolic alterations that reduce levels of the pro-apoptotic lipid ceramide, particularly its glucosylation by glucosylceramide synthase (GCS, have frequently been associated with cancer drug resistance. However, the simple notion that the balance between ceramide and S1P, often referred to as the sphingolipid rheostat, dictates cell survival contrasts with recent studies showing that highly potent and selective SPHK1 inhibitors do not affect cancer cell proliferation or survival, and studies demonstrating higher ceramide levels in some metastatic cancers. Recent reports have implicated other sphingolipid metabolic enzymes such as acid sphingomyelinase (ASM more strongly in cancer pathogenesis, and highlight lysosomal sphingolipid metabolism as a possible weak point for therapeutic targeting in cancer. This review describes the evidence implicating different sphingolipid metabolic enzymes and their products in cancer pathogenesis, and suggests how newer systems-level approaches may improve our overall understanding of how oncogenic transformation reconfigures sphingolipid metabolism.

  5. RECQL4 helicase has oncogenic potential in sporadic breast cancers.

    Science.gov (United States)

    Arora, Arvind; Agarwal, Devika; Abdel-Fatah, Tarek Ma; Lu, Huiming; Croteau, Deborah L; Moseley, Paul; Aleskandarany, Mohammed A; Green, Andrew R; Ball, Graham; Rakha, Emad A; Chan, Stephen Yt; Ellis, Ian O; Wang, Lisa L; Zhao, Yongliang; Balajee, Adayabalam S; Bohr, Vilhelm A; Madhusudan, Srinivasan

    2016-03-01

    RECQL4 helicase is a molecular motor that unwinds DNA, a process essential during DNA replication and DNA repair. Germ-line mutations in RECQL4 cause type II Rothmund-Thomson syndrome (RTS), characterized by a premature ageing phenotype and cancer predisposition. RECQL4 is widely considered to be a tumour suppressor, although its role in human breast cancer is largely unknown. As the RECQL4 gene is localized to chromosome 8q24, a site frequently amplified in sporadic breast cancers, we hypothesized that it may play an oncogenic role in breast tumourigenesis. To address this, we analysed large cohorts for gene copy number changes (n = 1977), mRNA expression (n = 1977) and protein level (n = 1902). Breast cancer incidence was also explored in 58 patients with type II RTS. DNA replication dynamics and chemosensitivity was evaluated in RECQL4-depleted breast cancer cells in vitro. Amplification or gain in gene copy number (30.6%), high-level mRNA expression (51%) and high levels of protein (23%) significantly associated with aggressive tumour behaviour, including lymph node positivity, larger tumour size, HER2 overexpression, ER-negativity, triple-negative phenotypes and poor survival. RECQL4 depletion impaired the DNA replication rate and increased chemosensitivity in cultured breast cancer cells. Thus, although recognized as a 'safe guardian of the genome', our data provide compelling evidence that RECQL4 is tumour promoting in established breast cancers. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  6. The LMO2 oncogene regulates DNA replication in hematopoietic cells.

    Science.gov (United States)

    Sincennes, Marie-Claude; Humbert, Magali; Grondin, Benoît; Lisi, Véronique; Veiga, Diogo F T; Haman, André; Cazaux, Christophe; Mashtalir, Nazar; Affar, El Bachir; Verreault, Alain; Hoang, Trang

    2016-02-02

    Oncogenic transcription factors are commonly activated in acute leukemias and subvert normal gene expression networks to reprogram hematopoietic progenitors into preleukemic stem cells, as exemplified by LIM-only 2 (LMO2) in T-cell acute lymphoblastic leukemia (T-ALL). Whether or not these oncoproteins interfere with other DNA-dependent processes is largely unexplored. Here, we show that LMO2 is recruited to DNA replication origins by interaction with three essential replication enzymes: DNA polymerase delta (POLD1), DNA primase (PRIM1), and minichromosome 6 (MCM6). Furthermore, tethering LMO2 to synthetic DNA sequences is sufficient to transform these sequences into origins of replication. We next addressed the importance of LMO2 in erythroid and thymocyte development, two lineages in which cell cycle and differentiation are tightly coordinated. Lowering LMO2 levels in erythroid progenitors delays G1-S progression and arrests erythropoietin-dependent cell growth while favoring terminal differentiation. Conversely, ectopic expression in thymocytes induces DNA replication and drives these cells into cell cycle, causing differentiation blockade. Our results define a novel role for LMO2 in directly promoting DNA synthesis and G1-S progression.

  7. Gallium-68: chemistry and radiolabeled peptides exploring different oncogenic pathways.

    Science.gov (United States)

    Morgat, Clément; Hindié, Elif; Mishra, Anil K; Allard, Michèle; Fernandez, Philippe

    2013-03-01

    Abstract Early and specific tumor detection and also therapy selection and response evaluation are some challenges of personalized medicine. This calls for high sensitive and specific molecular imaging such as positron emission tomography (PET). The use of peptides for PET molecular imaging has undeniable advantages: possibility of targeting through peptide-receptor interaction, small size and low-molecular weight conferring good penetration in the tissue or at cellular level, low toxicity, no antigenicity, and possibility of wide choice for radiolabeling. Among β(+)-emitter radioelements, Gallium-68 is a very attractive positron-emitter compared with carbon-11 or fluorine-18 taking into account its easy production via a (68)Ge/(68)Ga generator and well established radiochemistry. Gallium-68 chemistry is based on well-defined coordination complexes with macrocycle or chelates having strong binding properties, particularly suitable for linking peptides that allow resistance to in vivo transchelation of the metal ion. Understanding specific and nonspecific molecular mechanisms involved in oncogenesis is one major key to develop new molecular imaging tools. The present review focuses on peptide signaling involved in different oncogenic pathways. This peptide signalization might be common for tumoral and non-tumoral processes or could be specific of an oncological process. This review describes gallium chemistry and different (68)Ga-radiolabeled peptides already in use or under development aiming at developing molecular PET imaging of different oncological processes.

  8. Le piratage des biens d'information

    OpenAIRE

    Paul Belleflamme

    2003-01-01

    Où se situe le juste milieu entre les propos alarmistes des uns (“le piratage tue la production musicale!”) et les appels libertaires des autres (“l'accès à toute information doit être libre!”) ? Une analyse économique simple nous permet de mieux comprendre les enjeux et de dégager des pistes de réflexion pour l'avenir.

  9. Le géomarketing : introduction critique

    OpenAIRE

    1989-01-01

    The article attempts to analyze the new field of investigation that is the geomarketing address the following issues: definitions, tools and methods, application areas, strengths and weaknesses L'article tente d'analyser le nouveau champ d'investigation que constitue le géomarketing en traitant des points suivants : définition, outils et méthodes, domaines d'application, forces et faiblesses.

  10. Évaluations, impacts et perceptions du changement climatique dans le Grand Ouest : le projet CLIMASTER

    OpenAIRE

    MEROT, Philippe; Corgne, Samuel; Delahaye, Daniel; Desnos, Philippe; Dubreuil, Vincent; Gascuel, Chantal; Giteau, Jean-Luc; Joannon, Alexandre; Planchon, Olivier; Quénol, Hervé

    2012-01-01

    Nous nous proposons dans cette communication de décrire la démarche et les principaux résultats qui ont été obtenus dans le cadre du projet CLIMASTER, pour contribuer au débat sur l’état actuel des connaissances sur le changement climatique (CC) dans le Grand Ouest. Vis-à-vis du climat, nous avons développé des analyses originales portant essentiellement sur différentes longues chroniques climatiques du passé dans le Grand Ouest, pour voir l’évolution déjà en cours du CC. Ces analyses ont por...

  11. Oncogenic and tumor-promoting Spermatophytes and Pteridophytes and their active principles.

    Science.gov (United States)

    Farnsworth, N R; Bingel, A S; Fong, H H; Saleh, A A; Christenson, G M; Saufferer, S M

    1976-08-01

    A survey and discussion are presented of plants classified as Spermatophyta and Pteridophyta, extracts of which have been shown to be oncogenic or tumor-promoting in animals. The active oncogenic and tumor-promoting principles, where known, have been identified. They represent tannins; pyrrolizidine, indole, tropolone, quinoline, purine, and benzophenanthridine alkaloids; nitroso compounds; triterpene glycosides; lignans; isoflavans; allyl benzenoids; simple (nu-pyrenes; and carbocyclic hydroxy acids. A total of 28 compounds of known structure have been identified as oncogens and several phorbol esters as tumor-promoters. Plants known to contain any of the 28 oncogens (excluding shikimic acid and caffeine) have been tabulated; they represent at least 454 species, 110 genera, and 34 families of Spermatophyta and Pteridophyta.

  12. Alterations in metastatic properties of hepatocellular carcinoma cell following H-ras oncogene transfection

    Institute of Scientific and Technical Information of China (English)

    Qing Wang; Zhi Ying Lin; Xiao Li Feng

    2001-01-01

    AIM To demonstrate the relationship betweenH-ras oncogene and hepatocellular carcinoma(HCC) metastasis.METHODS Activated H-ras oncogene wastransfected into SMMC 7721, a cell line derivedfrom human HCC, by calcium phosphatetransfection method. Some metastasis-relatedparameters were detected in vitro, includingadhesion assay, migration assay, expression ofcollagenase ⅣV (c ⅣV ase) and epidermal growthfactor receptor (EGFR).RESULTS The abilities of H-ras-transfected cellclones in adhesion to laminin (LN) or fibronectin(FN), migration, c Ⅳ ase secretion increasedmarkedly, and the expression of EGFR elevatedmoderately. More importantly, these alterationswere consistent positively with the expressionof p21, the protein product of H-ras oncogene.CONCLUSION H-ras oncogene could inducethe metastatic phenotype of HCC cell in vitro toraise its metastatic potential.

  13. Analysis of acquired resistance to cis-diamminedichloroplatinum(II) in oncogene transfected SHOK cells

    Energy Technology Data Exchange (ETDEWEB)

    Kinashi, Yuko; Masunaga, Shinichiro; Suzuki, Minoru; Ono, Koji; Akaboshi, Mitsuhiko [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst.; Watanabe, Masami

    1998-02-01

    SHOK (Syrian hamster Osaka-Kanazawa) cells were transfected with activated oncogenes (v-mos, c-myc, N-ras, H-ras, K-ras). These oncogene transfected cells were treated with {sup 195m}Pt-cis-diamminedichloroplatinum(II) (CDDP). Clonogenic cell survival assay showed that oncogene-transfected cells exhibited a 1.3-4.8 fold increases resistance to cisplatin compared to the parental SHOK cells. The CDDP concentration binding to DNA, RNA and protein were measured by counting the {sup 195m}Pt-radioactivity. The CDDP uptake was decreased in these oncogene transfected cells. The CDDP uptake in DNA of H-ras transfected cells decreased faster than control SHOK cells. (author)

  14. A germline RET proto-oncogene mutation in multiple members of an ...

    African Journals Online (AJOL)

    Makia Marafie

    2016-09-17

    Sep 17, 2016 ... multiple members of an Arab family with variable onset of MEN type ... fashion and caused by germline mutation in RET proto- oncogene. The main .... ing sudden severe high blood pressure crises that required immediate ...

  15. Le patrimoine et ses outils de gestion

    CERN Document Server

    Garcin, J

    2001-01-01

    Les principale taches de gestion du Patrimoine immobilier du CERN sont la saisie des données, leur mise à jour, l'archivage et la mise à disposition des informations. Les outils de gestion actuels : Le Système de Gestion de Base de Données Relationnelles alphanumérique ORACLE permet de gérer toutes les informations du Patrimoine, sur le réseau du CERN. Le logiciel de dessin Graphique MICROSTATION (Bentley) a été installé dans la division ST depuis fin 1991. Les plans de situation des sites, des bâtiments et locaux, des espaces confinés ont été réalisés avec ce logiciel. Les outils de demain : La mise en place du SIG (Système d'Information Graphique) STAR a été réalisée en 1993. Le transfert des plans de locaux de MICROSTATION vers STAR est en cours depuis une année environ. Le dessin de la cartographie des réseaux de canalisations Eaux Usées et Eaux Pluviales est en cours de réalisation. Le Web est l'outil de consultation de l'information par les utilisateurs.

  16. Le concept d’ethos.

    Directory of Open Access Journals (Sweden)

    Bernard Fusulier

    2011-09-01

    Full Text Available Dans cet article, l’auteur traite de la signification et de l’usage du concept d’ethos. Dans la sociologie classique, ce dernier a été utilisé pour comprendre et qualifier la rationalité socialement et éthiquement encastrée des conduites sociales. Exprimant l’intériorisation d’un principe organisateur de pratiques, dessinant une matrice globale des comportements, il est porteur d’une vision qui paraît datée à l’heure du “brouillage des classes sociales”, de la “modernité liquide” et de “l’homme pluriel”. Néanmoins, si l’on reconnaît l’existence d’un univers social non entièrement liquéfié, c’est-à-dire où continuent à exister des milieux sociaux sédimentés qui imprègnent avec plus ou moins de profondeur le système de personnalité de celui qui s’y insère durablement, l’ethos reste un concept heuristique pour saisir et interpréter les récurrences de comportements qui peuvent s’y observer. Permettant de comprendre ce que les espaces d’insertion “font aux individus” ainsi que la façon dont les principes organisateurs de pratiques entrent en transaction (en consonance, en dissonance ou en concurrence, il garde toute sa pertinence dans la boîte à outils théoriques du sociologue et de l’anthropologue d’aujourd’hui.

  17. Dana-Farber Cancer Institute: Discovery of Novel Oncogenes | Office of Cancer Genomics

    Science.gov (United States)

    Widespread recurrent copy number alterations are observed across the majority of human cancers, yet the specific targets of such amplified or deleted regions remain undefined. Here, the CTD2 Center at the Dana Farber Cancer Institute took a systematic approach using cDNA overexpression screening to identify and validate oncogenes residing in such amplified regions. In representative examples, these experiments have identified the adaptor proteins CRKL, GAB2, FRS2 and the TLOC and SKIL proteins as novel amplified oncogenes.

  18. Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Lahortiga, Idoya; De Keersmaecker, Kim; Van Vlierberghe, Pieter; Graux, Carlos; Cauwelier, Barbara; Lambert, Frederic; Mentens, Nicole; Beverloo, H Berna; Pieters, Rob; Speleman, Frank; Odero, Maria D; Bauters, Marijke; Froyen, Guy; Marynen, Peter; Vandenberghe, Peter; Wlodarska, Iwona; Meijerink, Jules P P; Cools, Jan

    2007-05-01

    We identified a duplication of the MYB oncogene in 8.4% of individuals with T cell acute lymphoblastic leukemia (T-ALL) and in five T-ALL cell lines. The duplication is associated with a threefold increase in MYB expression, and knockdown of MYB expression initiates T cell differentiation. Our results identify duplication of MYB as an oncogenic event and suggest that MYB could be a therapeutic target in human T-ALL.

  19. Oncogenic ETS proteins mimic activated RAS/MAPK signaling in prostate cells

    Science.gov (United States)

    Hollenhorst, Peter C.; Ferris, Mary W.; Hull, Megan A.; Chae, Heejoon; Kim, Sun; Graves, Barbara J.

    2011-01-01

    The aberrant expression of an oncogenic ETS transcription factor is implicated in the progression of the majority of prostate cancers, 40% of melanomas, and most cases of gastrointestinal stromal tumor and Ewing's sarcoma. Chromosomal rearrangements in prostate cancer result in overexpression of any one of four ETS transcription factors. How these four oncogenic ETS genes differ from the numerous other ETS genes expressed in normal prostate and contribute to tumor progression is not understood. We report that these oncogenic ETS proteins, but not other ETS factors, enhance prostate cell migration. Genome-wide binding analysis matched this specific biological function to occupancy of a unique set of genomic sites highlighted by the presence of ETS- and AP-1-binding sequences. ETS/AP-1-binding sequences are prototypical RAS-responsive elements, but oncogenic ETS proteins activated a RAS/MAPK transcriptional program in the absence of MAPK activation. Thus, overexpression of oncogenic ETS proteins can replace RAS/MAPK pathway activation in prostate cells. The genomic description of this ETS/AP-1-regulated, RAS-responsive, gene expression program provides a resource for understanding the role of these ETS factors in both an oncogenic setting and the developmental processes where these genes normally function. PMID:22012618

  20. Genetic disruption of oncogenic Kras sensitizes lung cancer cells to Fas receptor-mediated apoptosis.

    Science.gov (United States)

    Mou, Haiwei; Moore, Jill; Malonia, Sunil K; Li, Yingxiang; Ozata, Deniz M; Hough, Soren; Song, Chun-Qing; Smith, Jordan L; Fischer, Andrew; Weng, Zhiping; Green, Michael R; Xue, Wen

    2017-04-04

    Genetic lesions that activate KRAS account for ∼30% of the 1.6 million annual cases of lung cancer. Despite clinical need, KRAS is still undruggable using traditional small-molecule drugs/inhibitors. When oncogenic Kras is suppressed by RNA interference, tumors initially regress but eventually recur and proliferate despite suppression of Kras Here, we show that tumor cells can survive knockout of oncogenic Kras, indicating the existence of Kras-independent survival pathways. Thus, even if clinical KRAS inhibitors were available, resistance would remain an obstacle to treatment. Kras-independent cancer cells exhibit decreased colony formation in vitro but retain the ability to form tumors in mice. Comparing the transcriptomes of oncogenic Kras cells and Kras knockout cells, we identified 603 genes that were specifically up-regulated in Kras knockout cells, including the Fas gene, which encodes a cell surface death receptor involved in physiological regulation of apoptosis. Antibodies recognizing Fas receptor efficiently induced apoptosis of Kras knockout cells but not oncogenic Kras-expressing cells. Increased Fas expression in Kras knockout cells was attributed to decreased association of repressive epigenetic marks at the Fas promoter. Concordant with this observation, treating oncogenic Kras cells with histone deacetylase inhibitor and Fas-activating antibody efficiently induced apoptosis, thus bypassing the need to inhibit Kras. Our results suggest that activation of Fas could be exploited as an Achilles' heel in tumors initiated by oncogenic Kras.

  1. [Oncogenes RET/PTC and mechanisms of their involvement in thyroid cancerogenesis].

    Science.gov (United States)

    Voskoboĭnyk, L H

    2009-01-01

    Papillary thyroid carcinomas are the most common type of thyroid oncopathology, and are rather often associated with the expression of RET/PTC oncogens. The first oncogen RET/PTC1 was isolated more than 20 years ago. Now 13 different forms of RET/PTC are known, and 12 different partner-genes are described, that could be involved in formation of RET/PTC oncogenes. The most common of them are RET/PTC1 and RET/PTC3 forms. The great majority of oncogens RET/PTC, except for two--ELKS-RET and HOOK3-RET, have been founded in radioaction-induced thyroid tumors. There is an opinion that the key role in development of papillary thyroid carcinomas belongs to RET/PTC oncogens. The data about different types of RET/PTC oncogens, factors, that lead to their formation have been described in the present review. Also different mechanisms of activation of transduction pathways and gene's expression in thyroid cells after RET/PTC induction have been presented.

  2. La Vie Politique sous la Restauration a Travers ’Le Rouge et le Noir’ de Stendahl (The Political Life during the Restauration as Depicted in Le Rouge et le Noir by Stendahl)

    Science.gov (United States)

    1989-01-01

    CCESSION NO. 11. TITLE (Include Security Clanification) (UNCLASSIFIED) 4 by Stendhal THE POLITICAL LIFE DURING THE RESTAURATION AS DEPICTED IN Le Rouge...34OVERPRINT" Brian CHRISTENSEN The Political Life during the Restauration as depicted in Le Rouge et le Noir by Stendhal CONSTRUCTION : The overall...Brian CHRISTENSEN La vie politique sous la Restauration A travers Le Rouge et le Noir de Stendhal CONSTRUCTION La construction d’ensemble du mdmoire est

  3. SUMOylation Confers Posttranslational Stability on NPM-ALK Oncogenic Protein

    Directory of Open Access Journals (Sweden)

    Deeksha Vishwamitra

    2015-09-01

    Full Text Available Nucleophosmin-anaplastic lymphoma kinase–expressing (NPM-ALK+ T-cell lymphoma is an aggressive form of cancer that commonly affects children and adolescents. The expression of NPM-ALK chimeric oncogene results from the chromosomal translocation t(2;5(p23;q35 that causes the fusion of the ALK and NPM genes. This translocation generates the NPM-ALK protein tyrosine kinase that forms the constitutively activated NPM-ALK/NPM-ALK homodimers. In addition, NPM-ALK is structurally associated with wild-type NPM to form NPM/NPM-ALK heterodimers, which can translocate to the nucleus. The mechanisms that sustain the stability of NPM-ALK are not fully understood. SUMOylation is a posttranslational modification that is characterized by the reversible conjugation of small ubiquitin-like modifiers (SUMOs with target proteins. SUMO competes with ubiquitin for substrate binding and therefore, SUMOylation is believed to protect target proteins from proteasomal degradation. Moreover, SUMOylation contributes to the subcellular distribution of target proteins. Herein, we found that the SUMOylation pathway is deregulated in NPM-ALK+ T-cell lymphoma cell lines and primary lymphoma tumors from patients. We also identified Lys24 and Lys32 within the NPM domain as the sites where NPM-ALK conjugates with SUMO-1 and SUMO-3. Importantly, antagonizing SUMOylation by the SENP1 protease decreased the accumulation of NPM-ALK and suppressed lymphoma cell viability, proliferation, and anchorage-independent colony formation. One possible mechanism for the SENP1-mediated decrease in NPM-ALK levels was the increase in NPM-ALK association with ubiquitin, which facilitates its degradation. Our findings propose a model in which aberrancies in SUMOylation contribute to the pathogenesis of NPM-ALK+ T-cell lymphoma. Unraveling such pathogenic mechanisms may lead to devising novel strategies to eliminate this aggressive neoplasm.

  4. SUMOylation Confers Posttranslational Stability on NPM-ALK Oncogenic Protein.

    Science.gov (United States)

    Vishwamitra, Deeksha; Curry, Choladda V; Shi, Ping; Alkan, Serhan; Amin, Hesham M

    2015-09-01

    Nucleophosmin-anaplastic lymphoma kinase-expressing (NPM-ALK+) T-cell lymphoma is an aggressive form of cancer that commonly affects children and adolescents. The expression of NPM-ALK chimeric oncogene results from the chromosomal translocation t(2;5)(p23;q35) that causes the fusion of the ALK and NPM genes. This translocation generates the NPM-ALK protein tyrosine kinase that forms the constitutively activated NPM-ALK/NPM-ALK homodimers. In addition, NPM-ALK is structurally associated with wild-type NPM to form NPM/NPM-ALK heterodimers, which can translocate to the nucleus. The mechanisms that sustain the stability of NPM-ALK are not fully understood. SUMOylation is a posttranslational modification that is characterized by the reversible conjugation of small ubiquitin-like modifiers (SUMOs) with target proteins. SUMO competes with ubiquitin for substrate binding and therefore, SUMOylation is believed to protect target proteins from proteasomal degradation. Moreover, SUMOylation contributes to the subcellular distribution of target proteins. Herein, we found that the SUMOylation pathway is deregulated in NPM-ALK+ T-cell lymphoma cell lines and primary lymphoma tumors from patients. We also identified Lys24 and Lys32 within the NPM domain as the sites where NPM-ALK conjugates with SUMO-1 and SUMO-3. Importantly, antagonizing SUMOylation by the SENP1 protease decreased the accumulation of NPM-ALK and suppressed lymphoma cell viability, proliferation, and anchorage-independent colony formation. One possible mechanism for the SENP1-mediated decrease in NPM-ALK levels was the increase in NPM-ALK association with ubiquitin, which facilitates its degradation. Our findings propose a model in which aberrancies in SUMOylation contribute to the pathogenesis of NPM-ALK+ T-cell lymphoma. Unraveling such pathogenic mechanisms may lead to devising novel strategies to eliminate this aggressive neoplasm.

  5. CXCR4 in breast cancer: oncogenic role and therapeutic targeting

    Directory of Open Access Journals (Sweden)

    Xu C

    2015-08-01

    Full Text Available Chao Xu,1,* Hong Zhao,1,* Haitao Chen,1 Qinghua Yao2,3 1First Clinical College of Zhejiang Chinese Medical University, 2Department of Integrated Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, 3Key Laboratory of Integrated Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Chemokines are 8–12 kDa peptides that function as chemoattractant cytokines and are involved in cell activation, differentiation, and trafficking. Chemokines bind to specific G-protein-coupled seven-span transmembrane receptors. Chemokines play a fundamental role in the regulation of a variety of cellular, physiological, and developmental processes. Their aberrant expression can lead to a variety of human diseases including cancer. C-X-C chemokine receptor type 4 (CXCR4, also known as fusin or CD184, is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12. CXCR4 belongs to the superfamily of the seven transmembrane domain heterotrimeric G protein-coupled receptors and is functionally expressed on the cell surface of various types of cancer cells. CXCR4 also plays a role in the cell proliferation and migration of these cells. Recently, CXCR4 has been reported to play an important role in cell survival, proliferation, migration, as well as metastasis of several cancers including breast cancer. This review is mainly focused on the current knowledge of the oncogenic role and potential drugs that target CXCR4 in breast cancer. Additionally, CXCR4 proangiogenic molecular mechanisms will be reviewed. Strict biunivocal binding affinity and activation of CXCR4/CXCL12 complex make CXCR4 a unique molecular target for prevention and treatment of breast cancer. Keywords: breast cancer, CXCR4, drug target, chemokine, angiogenesis

  6. A transcriptome map of cellular transformation by the fos oncogene

    Directory of Open Access Journals (Sweden)

    Ruan Hong

    2005-05-01

    Full Text Available Abstract Background The c-fos gene was originally identified as the cellular homolog of the oncogene v-fos carried by the Finkel-Biskis-Jenkins and Finkel-Biskis-Reilly murine osteogenic sarcoma retroviruses. Sustained expression of fos is sufficient to induce cellular transformation in vitro and tumorigenesis in vivo. Fos functions as a component of the AP-1 transcription factor complex to regulate gene transcription and several differentially expressed genes have been identified in cells transformed by fos. We have extended these studies by constructing a cellular system for conditional transformation by v-fos. Using Affymetrix-based DNA microarray technology, we analyzed transcriptional changes over the course of transformation and reversion in an inducible v-fos system. Results Microarray analyses of temporal gene expression during the process of v-fos mediated cellular transformation and morphological reversion revealed a remarkably dynamic transcriptome. Of the more than 8000 genes analyzed in this study, 3766 genes were categorized into 18 gene-expression patterns by using self-organizing map analysis. By combining the analysis of gene expression profiles in stably transformed cells with the analysis of sequential expression patterns during conditional transformation, we identified a relatively small cohort of genes implicated in v-fos mediated cellular transformation. Conclusion This approach defines a general conditional cell transformation system that can be used to study the endogenous transcription regulatory mechanisms involved in transformation and tumorigenesis. In addition, this study is the first reported analysis of dynamic changes in gene expression throughout experimentally controlled morphological transformation mediated by v-fos.

  7. A screen identifies the oncogenic micro-RNA miR-378a-5p as a negative regulator of oncogene-induced senescence.

    Directory of Open Access Journals (Sweden)

    Susanne Marije Kooistra

    Full Text Available Oncogene-induced senescence (OIS can occur in response to hyperactive oncogenic signals and is believed to be a fail-safe mechanism protecting against tumorigenesis. To identify new factors involved in OIS, we performed a screen for microRNAs that can overcome or inhibit OIS in human diploid fibroblasts. This screen led to the identification of miR-378a-5p and in addition several other miRNAs that have previously been shown to play a role in senescence. We show that ectopic expression of miR-378a-5p reduces the expression of several senescence markers, including p16(INK4A and senescence-associated β-galactosidase. Moreover, cells with ectopic expression of miR-378a-5p retain proliferative capacity even in the presence of an activated Braf oncogene. Finally, we identified several miR-378a-5p targets in diploid fibroblasts that might explain the mechanism by which the microRNA can delay OIS. We speculate that miR-378a-5p might positively influence tumor formation by delaying OIS, which is consistent with a known pro-oncogenic function of this microRNA.

  8. Spi-1, Fli-1 and Fli-3 (miR-17-92 oncogenes contribute to a single oncogenic network controlling cell proliferation in friend erythroleukemia.

    Directory of Open Access Journals (Sweden)

    Samer Kayali

    Full Text Available Clonal erythroleukemia developing in susceptible mice infected by Friend virus complex are associated with highly recurrent proviral insertions at one of three loci called Spi-1, Fli-1 or Fli-3, leading to deregulated expression of oncogenic Spi-1 or Fli-1 transcription factors or miR-17-92 miRNA cluster, respectively. Deregulated expression of each of these three oncogenes has been independently shown to contribute to cell proliferation of erythroleukemic clones. Previous studies showed a close relationship between Spi-1 and Fli-1, which belong to the same ETS family, Spi-1 activating fli-1 gene, and both Spi-1 and Fli-1 activating multiple common target genes involved in ribosome biogenesis. In this study, we demonstrated that Spi-1 and Fli-1 are also involved in direct miR-17-92 transcriptional activation through their binding to a conserved ETS binding site in its promoter. Moreover, we demonstrated that physiological re-expression of exogenous miR-17 and miR-20a are able to partially rescue the proliferation loss induced by Fli-1 knock-down and identified HBP1 as a target of these miRNA in erythroleukemic cells. These results establish that three of the most recurrently activated oncogenes in Friend erythroleukemia are actually involved in a same oncogenic network controlling cell proliferation. The putative contribution of a similar ETS-miR-17-92 network module in other normal or pathological proliferative contexts is discussed.

  9. Spi-1, Fli-1 and Fli-3 (miR-17-92) oncogenes contribute to a single oncogenic network controlling cell proliferation in friend erythroleukemia.

    Science.gov (United States)

    Kayali, Samer; Giraud, Guillaume; Morlé, François; Guyot, Boris

    2012-01-01

    Clonal erythroleukemia developing in susceptible mice infected by Friend virus complex are associated with highly recurrent proviral insertions at one of three loci called Spi-1, Fli-1 or Fli-3, leading to deregulated expression of oncogenic Spi-1 or Fli-1 transcription factors or miR-17-92 miRNA cluster, respectively. Deregulated expression of each of these three oncogenes has been independently shown to contribute to cell proliferation of erythroleukemic clones. Previous studies showed a close relationship between Spi-1 and Fli-1, which belong to the same ETS family, Spi-1 activating fli-1 gene, and both Spi-1 and Fli-1 activating multiple common target genes involved in ribosome biogenesis. In this study, we demonstrated that Spi-1 and Fli-1 are also involved in direct miR-17-92 transcriptional activation through their binding to a conserved ETS binding site in its promoter. Moreover, we demonstrated that physiological re-expression of exogenous miR-17 and miR-20a are able to partially rescue the proliferation loss induced by Fli-1 knock-down and identified HBP1 as a target of these miRNA in erythroleukemic cells. These results establish that three of the most recurrently activated oncogenes in Friend erythroleukemia are actually involved in a same oncogenic network controlling cell proliferation. The putative contribution of a similar ETS-miR-17-92 network module in other normal or pathological proliferative contexts is discussed.

  10. LE LIEN ENTRE FINANCE ET ECONOMIE ISLAMIQUES VIA LE MODELE PRINCIPIEL "ZR"

    OpenAIRE

    BELABES, ABDERRAZAK

    2010-01-01

    A l'heure où certains évoquent l'intégration de la finance islamique à la finance globale, et d'autres rattachent la finance islamique à des thèmes en vogue telles que la finance éthique, la finance participative ou la finance socialement responsable, le présent papier explore le lien entre finance et économie islamiques à partir du modèle principiel "ZR", c’est-à-dire "Zakât" et "Ribâ". Ce modèle montre que les principes invariants de Zakât et Ribâ jouent un rôle central dans l’établissement...

  11. Lele de la confiance dans le système de gouvernance des entreprises

    OpenAIRE

    Gérard Charreaux

    1998-01-01

    La confiance est censée jouer un rôle important pour expliquer les écarts de performance entre les différents systèmes économiques nationaux. Cet article vise à analyser ce rôle en s'appuyant sur la théorie de la gouvernance des entreprises. Après avoir proposé une définition de la confiance comme mécanisme de gouvernance, précisé les caractéristiques ce dernier et analysé son impact sur la latitude managériale, nous avons exploré le lien existant entre la confiance et la création de valeur p...

  12. La Quarantaine de Le Clézio et le vertige intertextuel

    Directory of Open Access Journals (Sweden)

    Madeleine Borgomano

    2006-09-01

    Full Text Available Le terme de vertige employé par M. Schneider convient particulièrement pour qualifier les jeux de l’intertextualité dans La Quarantaine de Le Clézio, même en la limitant aux textes effectivement cités. Intertexte essentiel, et trop évident, Robinson n’est nommé qu’une fois. L’épigraphe, la chanson du voleur et les références aux textes sacrés hindous rattachent le roman à l’Inde et à ses valeurs, qui constituent l’un des pôles signifiants, le côté des parias que Léon (le Disparu, narrateur second, épousera en même temps que Suryavati. Un autre aspect de l’intertexte se rattache aux deux figures de Rimbaud, le jeune voyou de Paris et l’homme malade d’Aden. Le renvoi implicite à la formule « Je est un autre » accentue les complexités de l’énonciation et les glissements de l’identité. Les très nombreuses citations de poèmes soulignent la tendance poétique plus que narrative de l’écriture de Le Clézio. Tandis que les citations du « journal d’un botaniste » révèlent la nostalgie d’un discours descriptif savant et neutre. Ainsi, le vertige intertextuel manifeste et multiplie les contradictions dynamiques qui animent l’écriture de Le Clézio et contribuent à la production du sens.

  13. Oncogenic BRAF regulates melanoma proliferation through the lineage specific factor MITF.

    Directory of Open Access Journals (Sweden)

    Claudia Wellbrock

    Full Text Available The Microphthalmia-associated transcription factor (MITF is an important regulator of cell-type specific functions in melanocytic cells. MITF is essential for the survival of pigmented cells, but whereas high levels of MITF drive melanocyte differentiation, lower levels are required to permit proliferation and survival of melanoma cells. MITF is phosphorylated by ERK, and this stimulates its activation, but also targets it for degradation through the ubiquitin-proteosome pathway, coupling MITF degradation to its activation. We have previously shown that because ERK is hyper-activated in melanoma cells in which BRAF is mutated, the MITF protein is constitutively down-regulated. Here we describe another intriguing aspect of MITF regulation by oncogenic BRAF in melanoma cells. We show oncogenic BRAF up-regulates MITF transcription through ERK and the transcription factor BRN2 (N-Oct3. In contrast, we show that in melanocytes this pathway does not exist because BRN2 is not expressed, demonstrating that MITF regulation is a newly acquired function of oncogenic BRAF that is not performed by the wild-type protein. Critically, in melanoma cells MITF is required downstream of oncogenic BRAF because it regulates expression of key cell cycle regulatory proteins such as CDK2 and CDK4. Wild-type BRAF does not regulate this pathway in melanocytes. Thus, we show that oncogenic BRAF exerts exquisite control over MITF on two levels. It downregulates the protein by stimulating its degradation, but then counteracts this by increasing transcription through BRN2. Our data suggest that oncogenic BRAF plays a critical role in regulating MITF expression to ensure that its protein levels are compatible with proliferation and survival of melanoma cells. We propose that its ability to appropriate the regulation of this critical factor explains in part why BRAF is such a potent oncogene in melanoma.

  14. Le biblioteche di Luigi Crocetti

    Directory of Open Access Journals (Sweden)

    Tommaso Giordano

    2015-05-01

    Full Text Available This article is the text read at the presentation of the book Le Biblioteche di Luigi Crocetti, saggi, recensioni, paperoles (The Libraries of Luigi Crocetti, essays, reviews, paperoles, AIB, 2014, edited by Laura Desideri and Alberto Petrucciani.Luigi Crocetti (died in 2007 was one of the most eminent personalities in the Italian library world of the last fifty years. Some of the most significant milestones of his career are: Director of the Laboratory of Restoration at The National Central Library in Florence, after the flood of the Arno river in 1966; Director of the Library and Archives Department of the Tuscany regional government; President of the Italian Library Association (AIB, Director of the Gabinetto G.P. Vieusseux. Crocetti was also leader of, or influential partner in, the major projects and programs developed in Italy during his professional life, including: the DDC 20 Italian Edition, the project SBN (the Italian Library Network, Editor of the journal Biblioteche Oggi , as well as collaborator in various journals and publishing activities. The numerous writings of Luigi Crocetti, published throughout his professional life, register punctually the evolution of libraries and librarian profession in times of major technological, cultural and social changes. Nevertheless Crocetti’s writings are not only an historical record of a perceptive (and committed observer; they also constitute a collection of profound reflections and inspiring input for further discussion on the role of libraries and of culture in the society. Gifted with uncommon erudition, Crocetti shows an extraordinary ability to interpret the current reality and for see the future with a remarkable farsightedness. His writings touch on all aspects of the profession, from book preservation and restoration to public libraries, from cataloguing and indexing to library cooperation and networking, from national libraries, archives and museums, to user services. It is quite

  15. Judith Butler, Défaire le genre

    OpenAIRE

    Van Woerkens, Martine

    2008-01-01

    Dans le Dictionnaire critique du féminisme paru en France en 2000, à l’entrée « Sexe et genre », Judith Butler figure dans la rubrique « dérives du genre ». Gender trouble « dépasse le genre, en brouillant, “troublant” les catégories de sexe et de sexualité », et l’auteure y privilégie « les aspects symboliques, discursifs et parodiques du genre au détriment de la réalité matérielle et historique des oppressions subies par les femmes » (pp. 197-198). Dans ce dictionnaire, le racisme est renvo...

  16. Le dialogisme intertextuel des contes des Grimm

    OpenAIRE

    2012-01-01

    « Le caractère le plus important de l’énoncé, ou en tous cas le plus ignoré, est son dialogisme, c’est-à-dire sa dimension intertextuelle », constate Todorov en référence à la conception dialogique du langage proposée par Bakthine. Cet article introductif postule que ce constat s’applique aussi aux contes des Grimm. En partant des recherches déjà menées sur Apulée, Straporola, Basile, Perrault, La Fontaine et Lhéritier, il présente des concepts (réponse intertextuelle, reconfiguration génériq...

  17. The oncogenic action of ionizing radiation on rat skin

    Energy Technology Data Exchange (ETDEWEB)

    Burns, F.J.; Garte, S.J.

    1992-01-01

    The multistage theory of carcinogenesis specifies that cells progress to cancer through a series of discrete, irreversible genetic alterations, but data on radiation-induced cancer incidence in rat skin suggests that an intermediate repairable alteration may occur. Data are presented on cancer induction in rat skin exposed to an electron beam (LET=0.34 keV/[mu]), a neon ion beam (LET=45) or an argon ion beam (LET=125). The rats were observed for tumors at least 78 weeks with squamous and basal cell carcinomas observed. The total cancer yield was fitted by the quadratic equation, and the equation parameters were estimated by linear regression for each type of radiation. Analysis of the DNA from the electron-induced carcinomas indicated that K-ras and/or c-myc oncogenes were activated. In situ hybridization indicated that the cancers contain subpopulations of cells with differing amounts of c-myc and H-ras amplification. The results are consistent with the idea that ionizing radiation produces stable, carcinogenically relevant lesions via 2 repairable events at low LET and via a non-repairable linked event pathway at high LET; either pathway may advance the cell by 1 stage. The proliferative response of rat epidermis following exposure to ionizing radiation was quantified by injection of [sup 14]C-thymidine. The return of these cells to S-phase a second time was detected by a second label ([sup 3]H). When the labeled cells were in G1-phase, the dorsal skin was irradiated with X-rays. All labeling indices were determined. The [sup 14]C labeling index was constant and unaffected by the radiation. The proportion of all cells entering S-phase averaged 3.5% at 18 hr and increased after 44, 52 and 75 hr to average levels of 11.8%, 5. 3%, and 6.6% at 0, 10 and 25 Gy respectively. The proportion of S-phase cells labeled with [sup 14]C increased after 42 hr and remained relatively constant thereafter.

  18. Le nom propre dans les manuscrits saussuriens

    Directory of Open Access Journals (Sweden)

    Henriques Stefania

    2012-07-01

    Full Text Available On sait que le signe, selon l’optique saussurienne, est constitué par l’union arbitraire entre signifiant et signifié. Ces deux entités sont psychiques et l'une n’existe qu’en fonction de l’autre. À partir de la délimitation de ces éléments et de l’affirmation que le rapport entre eux est arbitraire, Ferdinand de Saussure rend la référence « non appartenant » au fonctionnement linguistique. Cependant, il y a des indices que Ferdinand de Saussure admet, au moins une fois, la conception triadique du signe (conception aristotélicienne quand il traite des noms propres et des noms géographiques/toponymes. En plus, dans la période entre 1900 et 1904, le linguiste genevois a eu comme thème principal de ses études la catégorie linguistique des noms propres et des noms géographiques. En visant l’importance de ce thème dans les Sciences du Langage (La Linguistique et La philosophie du langage et l’actuelle réorientation de l’étude des manuscrits saussuriens, on propose de rechercher le traitement donné par Ferdinand de Saussure à la catégorie du nom propre et du nom géographique, dans le manuscrit « Notes item. Sôme et sème » présent dans l’archive Ms. Fr. 3951 archivé à la Bibliothèque de Genève, dans le but de comprendre de quelle façon cette catégorie linguistique est traitée et si, effectivement, elle constitue une exception à la théorie générale des signes.

  19. Repression of transcription mediated at a thyroid hormone response element by the v-erb-A oncogene product

    DEFF Research Database (Denmark)

    Sap, J; Muñoz, A; Schmitt, J

    1989-01-01

    Several recent observations, such as the identification of the cellular homologue of the v-erb-A oncogene as a thyroid-hormone receptor, have strongly implicated nuclear oncogenes in transcriptional control mechanisms. The v-erb-A oncogene blocks the differentiation of erythroid cells, and changes......-erb-A protein negatively interferes with normal transcriptional-control mechanisms, and that amino-acid substitutions have altered its DNA-binding properties....

  20. Characteristics of transgenic tomatoes antisensed for the ethylene receptor genes LeERT1 and LeERT2

    Institute of Scientific and Technical Information of China (English)

    WANG Zhong-feng; YING Tie-jin; ZHANG Ying; BAO Bi-li; HUANG Xiao-dan

    2006-01-01

    Two stable transformed lines containing antisense LeERT1 or LeERT2 sequences and their hybridized line were investigated to determine the effect of LeERT1 and LeERT2 specificity in the ethylene receptor family in tomato (Lycopersicon esculentum Mill.) on ethylene signaling. The transgenic line alel containing antisense LeERT1 displayed shorter length of seedling grown in the dark and adult plant in the light, severe epinastic petiole, and accelerated abscission of petiole explant and senescence of flower explant, compared with its wild type B1. The transgenic line ale2 containing antisense LeERT2 also exhibited shorter hypocotyls and slightly accelerated abscission. The phenotypes of cross line dale of LeERT1 and LeERT2 were close to alel in many aspects. These results suggested that LeERT1 probably plays a relatively important role in ethylene signaling of tomato growth and development.

  1. Le continu contre l'espace

    Science.gov (United States)

    Salanskis, Jean-Michel

    Disons pour conclure que, en tout état de cause, la façon de concevoir philosophiquement le conflit du continu et de l'espace que nous avons trouvée chez Hegel n'est pas homogène avec le style et les modalités de la pensée mathématique: 1) d'une part, le lien classique, le lien de référence entre continu et espace en mathématiques n'est pas que l'espace serait premier et privé de pensée, et le continu second, venant dissoudre l'espace en apportant la qualité, l'infini et la pensée, mais tout au contraire, il consiste en ce que l'espace est fondé sur l'abîme infinitaire du continu ; 2) d'autre part, l'éventuel divorce entre l'espace et le continu dans l'aire mathématique n'est pas celui d'une réflexivité purement conceptuelle du continu avec un positivisme géométrique, n'équivaut pas à une rupture disciplinaire ; il est plutôt le symptôme de la dérive d'une herméneutique à l'égard d'une autre, au sein d'un continent juridique commun définissant la discipline (la mathématique ensembliste), cette dérive pouvant, à la limite, induire une refonte de ce sol juridique, sans que jamais il soit question pour autant de nier l'unité des mathématiques, à comprendre ici comme l'unité ultime de responsabilité de la communauté mathématique à l'égard des trois questions Qu'est-ce que l'espace?”, “Qu'est-ce que le continu?” et “Qu'est-ce que l'infini?”.

  2. Le football africain entre immobilisme et extraversion

    OpenAIRE

    Poli, Raffaele; Dietschy Paul

    2007-01-01

    Symbole de l’espoir national des États d’Afrique aux indépendances, le football africain s’est radicalement transformé : lors de la Coupe du monde de 1970, aucun des joueurs zaïrois n’évoluait à l’étranger ; en 2006, aucun des footballeurs ivoiriens ne joue dans son pays. Pour comprendre la dynamique de cette extraversion grandissante, il faut prendre en compte un enchevêtrement de facteurs – l’implication d’acteurs locaux dans le transfert de joueurs à l’étranger, la bienveillante attention ...

  3. Le café en Colombie

    OpenAIRE

    Gilhodes, Pierre

    2003-01-01

    Depuis un siècle, la Colombie produit du café ; elle en est devenue le second exportateur mondial. Au cours de la décennie qui vient de s'achever, le marché mondial du café s'est retourné au bénéfice des producteurs. Cette situation nouvelle a facilité une révolution des pratiques de culture qui est en train de bouleverser les conditions de production de ce grain dans les plantations colombiennes. Sans doute au prix de l'éviction de nombreux petits producteurs, sont en train d'émerger ...

  4. dynamiques migratoires et rapport avec le

    African Journals Online (AJOL)

    _perçu comme un problème majeur dans le pays d'accueil; au contraire, il a été ... une stratégie de sortie de .l'éeoznornie rurale par une scolarisation massive .... bétail (caprins et de bovins) mais qui, après son départ, est utilisé en priorité par ... l'apprentissage de Pintégration, car en réalité, le 'retour' au pays constitue.

  5. LE JAZZ ET L'INSTITUTION

    OpenAIRE

    Calamel, Charles

    2016-01-01

    International audience; Utiliser l'art comme composante de l'humanité, qui est la finalité de ce colloque symbolisant les trente ans de l'ADAGE, m'invite à poser le jazz et l'institution comme un axe dialectique permettant de raisonner sur les dimensions sociales de ces deux mondes interactifs. Ainsi créée, la dialectique jazz et institution propose aux responsables de cette journée d'interroger le travail social et médico-social en institution, du point de vue des dimensions sociales qui son...

  6. Bartole, le Diable et le Tibre. Un cas de libertinage juridique

    Directory of Open Access Journals (Sweden)

    Jérémie Barthas

    2011-01-01

    Full Text Available Dans une fantaisie juridique, le grand juriste médiéval Bartole de Sassoferrato met en scène le procès du Diable revendiquant, devant le Christ, la possession du genre humain. Le Diable fonde cette revendication sur la Genèse. Cet essai propose d’inscrire cette fantaisie juridique à tonalité irréligieuse à l’intérieur des traités formant le livre De Tyberiadis et de le resituer dans le contexte géo-politique de la défense contre la reconstruction de l’hégémonie pontificale en Italie centrale.A legal fantasy of the famous medieval jurist Bartolus of Sassoferrato presents the trial of the Devil who claims, before Christ, ownership on humankind. As his main title, the Devil shows the Book of Genesis. This essay offers a first attempt to link this legal irreligious fantasy with Bartolus’book De Tyberiadis, as recently described by Prof. Osvaldo Cavallar, and proposes consequently its geo-political reading.

  7. Le jeu de la création : Le mangeur (2005 de Ying Chen

    Directory of Open Access Journals (Sweden)

    Nicole Dunham

    2013-11-01

    Full Text Available Le théoricien James Hans définit le jeu comme une déconstruction structurante, un processus de perpétuelle remise en question. Dans Le Mangeur (2005 de Ying Chen, la narratrice revit un épisode d’une de ses vies passées où elle meurt mangée, avalée, par son père, descendant dans le « tunnel » du ventre de ce dernier. Cependant, suite à cet événement, elle se retrouve dans un autre espace-temps où elle rencontre son mari, A.. Une équivalence s’établit dans le roman entre les éléments suivants : le ventre du père, les tableaux peints par ce dernier et l’espace-temps de A., et la fenêtre. Ces éléments deviennent des aires de jeu, remettant en question les concepts de l’intérieur et de l’extérieur et du créateur et de l’œuvre. En nous servant du texte « Le Tunnel » écrit par Ying Chen, nous démontrerons que cette notion du jeu s’applique également à l’ensemble de son œuvre.

  8. RASOnD - A comprehensive resource and search tool for RAS superfamily oncogenes from various species

    Directory of Open Access Journals (Sweden)

    Singh Tej P

    2011-07-01

    Full Text Available Abstract Background The Ras superfamily plays an important role in the control of cell signalling and division. Mutations in the Ras genes convert them into active oncogenes. The Ras oncogenes form a major thrust of global cancer research as they are involved in the development and progression of tumors. This has resulted in the exponential growth of data on Ras superfamily across different public databases and in literature. However, no dedicated public resource is currently available for data mining and analysis on this family. The present database was developed to facilitate straightforward accession, retrieval and analysis of information available on Ras oncogenes from one particular site. Description We have developed the RAS Oncogene Database (RASOnD as a comprehensive knowledgebase that provides integrated and curated information on a single platform for oncogenes of Ras superfamily. RASOnD encompasses exhaustive genomics and proteomics data existing across diverse publicly accessible databases. This resource presently includes overall 199,046 entries from 101 different species. It provides a search tool to generate information about their nucleotide and amino acid sequences, single nucleotide polymorphisms, chromosome positions, orthologies, motifs, structures, related pathways and associated diseases. We have implemented a number of user-friendly search interfaces and sequence analysis tools. At present the user can (i browse the data (ii search any field through a simple or advance search interface and (iii perform a BLAST search and subsequently CLUSTALW multiple sequence alignment by selecting sequences of Ras oncogenes. The Generic gene browser, GBrowse, JMOL for structural visualization and TREEVIEW for phylograms have been integrated for clear perception of retrieved data. External links to related databases have been included in RASOnD. Conclusions This database is a resource and search tool dedicated to Ras oncogenes. It has

  9. Dysfunctional oxidative phosphorylation makes malignant melanoma cells addicted to glycolysis driven by the V600EBRAF oncogene

    DEFF Research Database (Denmark)

    Hall, Arnaldur; Meyle, Kathrine Damm; Lange, Marina Krarup

    2013-01-01

    Oncogene addiction describes how cancer cells exhibit dependence on single oncogenes to escape apoptosis and senescence. While oncogene addiction constitutes the basis for new cancer treatment strategies targeting individual kinases and pathways activated by oncogenic mutations, the biochemical...... basis for this addiction is largely unknown. Here we provide evidence for a metabolic rationale behind the addiction to V600EBRAF in two malignant melanoma cell lines. Both cell lines display a striking addiction to glycolysis due to underlying dysfunction of oxidative phosphorylation (OXPHOS). Notably...

  10. Le stéréotype dans le roman policier

    Directory of Open Access Journals (Sweden)

    Marion François

    2009-12-01

    Full Text Available Le roman policier offre à l’étude du stéréotype une grande variété de redondances, lexicales et structurelles, qui permettent d’éclairer le concept même de genre, en fait issu du constat de stéréotypie. Il est également manifeste que contrairement aux idées reçues, les clichés font du texte policier un texte littéraire, parce qu’ils naissent d’images associées, distinctes de la réalité, qui révèlent d’ailleurs le cheminement même de l’écriture. Par ailleurs ces images jouent un rôle fondamental dans le plaisir du lecteur, comme dans les contes de fées de notre enfance. Les clichés ouvrent la porte des fantasmes : le stéréotype rejoignant l’archétype, les clichés policiers réactivent de nombreux mythes, le texte évoquant l’Autre Scène. Le constat de stéréotypie provoque l’écriture, en particulier parodique, et stimule le renouvellement et l’essaimage des clichés dans toutes sortes de textes, qui bénéficieront de la présence du déjà-lu, laquelle donne au lecteur une assise pour affronter l’inconnu et une expérience pour apprécier la nouveauté.

  11. Stability of simultaneous modified LeFort III/LeFort I osteotomies.

    Science.gov (United States)

    Schmitz, J P; Tiner, B D; Van Sickels, J E

    1995-10-01

    The objective of this study was to examine maxillary skeletal stability after simultaneous modified LeFort III/LeFort I osteotomy in patients who presented for the simultaneous correction of midface and maxillary hypoplasia. Eleven patients underwent simultaneous modified LeFort III/LeFort I osteotomies using transoral and transconjunctival surgical approaches. The mean net surgical movement at A point (A pt) was 5.2 mm anteriorly and 2 mm inferiorly. Titanium mini-plates were used to stabilize both the midface component and the LeFort I segment; iliac crest or calvarial bone grafts as well as freeze-dried cancellous blocks were used at the zygoma and lateral orbital rim regions. All patients had lateral cephalometric radiographs taken immediately postoperatively, and at their sixth week, sixth month, and one year follow-up visits. Five maxillary landmarks (CI, A pt, ANS, PNS, and 2M) were used to examine the horizontal and vertical changes occurring at each time period. The central incisor relapsed vertically 2.8 mm at six months, A pt relapsed vertically 2.3 mm at six months, ANS relapsed posteriorly 1.6 mm at 6 weeks, PNS relapsed 1.5 mm anteriorly at one year. This study demonstrated that the maxilla moved anteriorly 1.5 mm and superiorly 2.8 mm in simultaneous modified LeFort III/LeFort I osteotomies performed with mini-plate fixation and bone grafts. This movement should be considered when planning and performing simultaneous surgical movement of the maxilla and midface using modified LeFort II/LeFort I osteotomies. Appropriate occlusal overcorrection at the time of surgery is necessary.

  12. High frequency of the HRAS oncogene codon 12 mutation in Macedonian patients with urinary bladder cancer

    Directory of Open Access Journals (Sweden)

    Sasho Panov

    2004-01-01

    Full Text Available Point mutations at codon 12 of the HRAS (v-Ha-ras Harvey rat sarcoma viral oncogene homolog oncogene are one of the best defined and widely studied molecular genetic events in transitional cell carcinoma (TCC of the urinary bladder. The aim of this study was to use the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP analysis of paraffin-embedded tissue-derived DNA to determine the frequency of the HRAS oncogene G ->T codon 12 mutation in TCC patients being treated at the University Urology Clinic in Skopje, Republic of Macedonia. DNA isolated from paraffin-embedded tissue (PET surgically removed TCC specimens of 62 (81.58% out of 76 patients were successfully amplified, the remaining 14 (18.42% showing compromised DNA integrity. The codon 12 mutation of the HRAS oncogene was found in 24 (38.71% out of 62 successfully tested TCC urinary bladder samples. No significant relationship between the mutation frequency and the histopathological grade of tumor differentiation was detected (chi² = 0.044; p = 0.978. The relatively high frequency of mutations found in our study was comparable with some of the previously reported data obtained by this and/or other PCR-based methods. This highly sensitive and specific PCR-RFLP analysis was demonstrated to be a suitable method for the detection of mutations at codon 12 of the HRAS oncogene in PET samples of urinary bladder TCC.

  13. Limited Role of Murine ATM in Oncogene-Induced Senescence and p53-Dependent Tumor Suppression

    Science.gov (United States)

    Martinez-Pastor, Barbara; Ortega-Molina, Ana; Soria, Rebeca; Collado, Manuel; Fernandez-Capetillo, Oscar; Serrano, Manuel

    2009-01-01

    Recent studies in human fibroblasts have provided a new general paradigm of tumor suppression according to which oncogenic signaling produces DNA damage and this, in turn, results in ATM/p53-dependent cellular senescence. Here, we have tested this model in a variety of murine experimental systems. Overexpression of oncogenic Ras in murine fibroblasts efficiently induced senescence but this occurred in the absence of detectable DNA damage signaling, thus suggesting a fundamental difference between human and murine cells. Moreover, lung adenomas initiated by endogenous levels of oncogenic K-Ras presented abundant senescent cells, but undetectable DNA damage signaling. Accordingly, K-Ras-driven adenomas were also senescent in Atm-null mice, and the tumorigenic progression of these lesions was only modestly accelerated by Atm-deficiency. Finally, we have examined chemically-induced fibrosarcomas, which possess a persistently activated DNA damage response and are highly sensitive to the activity of p53. We found that the absence of Atm favored genomic instability in the resulting tumors, but did not affect the persistent DNA damage response and did not impair p53-dependent tumor suppression. All together, we conclude that oncogene-induced senescence in mice may occur in the absence of a detectable DNA damage response. Regarding murine Atm, our data suggest that it plays a minor role in oncogene-induced senescence or in p53-dependent tumor suppression, being its tumor suppressive activity probably limited to the maintenance of genomic stability. PMID:19421407

  14. Oncofuse: a computational framework for the prediction of the oncogenic potential of gene fusions.

    Science.gov (United States)

    Shugay, Mikhail; Ortiz de Mendíbil, Iñigo; Vizmanos, José L; Novo, Francisco J

    2013-10-15

    Gene fusions resulting from chromosomal aberrations are an important cause of cancer. The complexity of genomic changes in certain cancer types has hampered the identification of gene fusions by molecular cytogenetic methods, especially in carcinomas. This is changing with the advent of next-generation sequencing, which is detecting a substantial number of new fusion transcripts in individual cancer genomes. However, this poses the challenge of identifying those fusions with greater oncogenic potential amid a background of 'passenger' fusion sequences. In the present work, we have used some recently identified genomic hallmarks of oncogenic fusion genes to develop a pipeline for the classification of fusion sequences, namely, Oncofuse. The pipeline predicts the oncogenic potential of novel fusion genes, calculating the probability that a fusion sequence behaves as 'driver' of the oncogenic process based on features present in known oncogenic fusions. Cross-validation and extensive validation tests on independent datasets suggest a robust behavior with good precision and recall rates. We believe that Oncofuse could become a useful tool to guide experimental validation studies of novel fusion sequences found during next-generation sequencing analysis of cancer transcriptomes. Oncofuse is a naive Bayes Network Classifier trained and tested using Weka machine learning package. The pipeline is executed by running a Java/Groovy script, available for download at www.unav.es/genetica/oncofuse.html.

  15. Limited role of murine ATM in oncogene-induced senescence and p53-dependent tumor suppression.

    Directory of Open Access Journals (Sweden)

    Alejo Efeyan

    Full Text Available Recent studies in human fibroblasts have provided a new general paradigm of tumor suppression according to which oncogenic signaling produces DNA damage and this, in turn, results in ATM/p53-dependent cellular senescence. Here, we have tested this model in a variety of murine experimental systems. Overexpression of oncogenic Ras in murine fibroblasts efficiently induced senescence but this occurred in the absence of detectable DNA damage signaling, thus suggesting a fundamental difference between human and murine cells. Moreover, lung adenomas initiated by endogenous levels of oncogenic K-Ras presented abundant senescent cells, but undetectable DNA damage signaling. Accordingly, K-Ras-driven adenomas were also senescent in Atm-null mice, and the tumorigenic progression of these lesions was only modestly accelerated by Atm-deficiency. Finally, we have examined chemically-induced fibrosarcomas, which possess a persistently activated DNA damage response and are highly sensitive to the activity of p53. We found that the absence of Atm favored genomic instability in the resulting tumors, but did not affect the persistent DNA damage response and did not impair p53-dependent tumor suppression. All together, we conclude that oncogene-induced senescence in mice may occur in the absence of a detectable DNA damage response. Regarding murine Atm, our data suggest that it plays a minor role in oncogene-induced senescence or in p53-dependent tumor suppression, being its tumor suppressive activity probably limited to the maintenance of genomic stability.

  16. LEO1 is regulated by PRL-3 and mediates its oncogenic properties in acute myelogenous leukemia.

    Science.gov (United States)

    Chong, Phyllis S Y; Zhou, Jianbiao; Cheong, Lip-Lee; Liu, Shaw-Cheng; Qian, Jingru; Guo, Tiannan; Sze, Siu Kwan; Zeng, Qi; Chng, Wee Joo

    2014-06-01

    PRL-3, an oncogenic dual-specificity phosphatase, is overexpressed in 50% of acute myelogenous leukemia (AML) and associated with poor survival. We found that stable expression of PRL-3 confers cytokine independence and growth advantage of AML cells. However, how PRL-3 mediates these functions in AML is not known. To comprehensively screen for PRL3-regulated proteins in AML, we performed SILAC-based quantitative proteomics analysis and discovered 398 significantly perturbed proteins after PRL-3 overexpression. We show that Leo1, a component of RNA polymerase II-associated factor (PAF) complex, is a novel and important mediator of PRL-3 oncogenic activities in AML. We described a novel mechanism where elevated PRL-3 protein increases JMJD2C histone demethylase occupancy on Leo1 promoter, thereby reducing the H3K9me3 repressive signals and promoting Leo1 gene expression. Furthermore, PRL-3 and Leo1 levels were positively associated in AML patient samples (N=24; PPRL-3 oncogenic phenotypes in AML. Loss of Leo1 leads to destabilization of the PAF complex and downregulation of SOX2 and SOX4, potent oncogenes in myeloid transformation. In conclusion, we identify an important and novel mechanism by which PRL-3 mediates its oncogenic function in AML.

  17. Viral Oncogenes, Noncoding RNAs, and RNA Splicing in Human Tumor Viruses

    Directory of Open Access Journals (Sweden)

    Zhi-Ming Zheng

    2010-01-01

    Full Text Available Viral oncogenes are responsible for oncogenesis resulting from persistent virus infection. Although different human tumor viruses express different viral oncogenes and induce different tumors, their oncoproteins often target similar sets of cellular tumor suppressors or signal pathways to immortalize and/or transform infected cells. Expression of the viral E6 and E7 oncogenes in papillomavirus, E1A and E1B oncogenes in adenovirus, large T and small t antigen in polyomavirus, and Tax oncogene in HTLV-1 are regulated by alternative RNA splicing. However, this regulation is only partially understood. DNA tumor viruses also encode noncoding RNAs, including viral microRNAs, that disturb normal cell functions. Among the determined viral microRNA precursors, EBV encodes 25 from two major clusters (BART and BHRF1, KSHV encodes 12 from a latent region, human polyomavirus MCV produce only one microRNA from the late region antisense to early transcripts, but HPVs appears to produce no viral microRNAs.

  18. Modulating the strength and threshold of NOTCH oncogenic signals by mir-181a-1/b-1.

    Directory of Open Access Journals (Sweden)

    Rita Fragoso

    Full Text Available Oncogenes, which are essential for tumor initiation, development, and maintenance, are valuable targets for cancer therapy. However, it remains a challenge to effectively inhibit oncogene activity by targeting their downstream pathways without causing significant toxicity to normal tissues. Here we show that deletion of mir-181a-1/b-1 expression inhibits the development of Notch1 oncogene-induced T cell acute lymphoblastic leukemia (T-ALL. mir-181a-1/b-1 controls the strength and threshold of Notch activity in tumorigenesis in part by dampening multiple negative feedback regulators downstream of NOTCH and pre-T cell receptor (TCR signaling pathways. Importantly, although Notch oncogenes utilize normal thymic progenitor cell genetic programs for tumor transformation, comparative analyses of mir-181a-1/b-1 function in normal thymocyte and tumor development demonstrate that mir-181a-1/b-1 can be specifically targeted to inhibit tumor development with little toxicity to normal development. Finally, we demonstrate that mir-181a-1/b-1, but not mir-181a-2b-2 and mir-181-c/d, controls the development of normal thymic T cells and leukemia cells. Together, these results illustrate that NOTCH oncogene activity in tumor development can be selectively inhibited by targeting the molecular networks controlled by mir-181a-1/b-1.

  19. Regulation of autophagy and chloroquine sensitivity by oncogenic RAS in vitro is context-dependent.

    Science.gov (United States)

    Morgan, Michael J; Gamez, Graciela; Menke, Christina; Hernandez, Ariel; Thorburn, Jacqueline; Gidan, Freddi; Staskiewicz, Leah; Morgan, Shellie; Cummings, Christopher; Maycotte, Paola; Thorburn, Andrew

    2014-10-01

    Chloroquine (CQ) is an antimalarial drug and late-stage inhibitor of autophagy currently FDA-approved for use in the treatment of rheumatoid arthritis and other autoimmune diseases. Based primarily on its ability to inhibit autophagy, CQ and its derivative, hydroxychloroquine, are currently being investigated as primary or adjuvant therapy in multiple clinical trials for cancer treatment. Oncogenic RAS has previously been shown to regulate autophagic flux, and cancers with high incidence of RAS mutations, such as pancreatic cancer, have been described in the literature as being particularly susceptible to CQ treatment, leading to the hypothesis that oncogenic RAS makes cancer cells dependent on autophagy. This autophagy "addiction" suggests that the mutation status of RAS in tumors could identify patients who would be more likely to benefit from CQ therapy. Here we show that RAS mutation status itself is unlikely to be beneficial in such a patient selection because oncogenic RAS does not always promote autophagy addiction. Moreover, oncogenic RAS can have opposite effects on both autophagic flux and CQ sensitivity in different cells. Finally, for any given cell type, the positive or negative effect of oncogenic RAS on autophagy does not necessarily predict whether RAS will promote or inhibit CQ-mediated toxicity. Thus, although our results confirm that different tumor cell lines display marked differences in how they respond to autophagy inhibition, these differences can occur irrespective of RAS mutation status and, in different contexts, can either promote or reduce chloroquine sensitivity of tumor cells.

  20. Single nucleotide polymorphisms in microRNA binding sites of oncogenes: implications in cancer and pharmacogenomics.

    Science.gov (United States)

    Manikandan, Mayakannan; Munirajan, Arasambattu Kannan

    2014-02-01

    Cancer, a complex genetic disease involving uncontrolled cell proliferation, is caused by inactivation of tumor suppressor genes and activation of oncogenes. A vast majority of these cancer causing genes are known targets of microRNAs (miRNAs) that bind to complementary sequences in 3' untranslated regions (UTR) of messenger RNAs and repress them from translation. Single Nucleotide Polymorphisms (SNPs) occurring naturally in such miRNA binding regions can alter the miRNA:mRNA interaction and can significantly affect gene expression. We hypothesized that 3'UTR SNPs in miRNA binding sites of proto-oncogenes could abrogate their post-transcriptional regulation, resulting in overexpression of oncogenic proteins, tumor initiation, progression, and modulation of drug response in cancer patients. Therefore, we developed a systematic computational pipeline that integrates data from well-established databases, followed stringent selection criteria and identified a panel of 30 high-confidence SNPs that may impair miRNA target sites in the 3' UTR of 54 mRNA transcripts of 24 proto-oncogenes. Further, 8 SNPs amidst them had the potential to determine therapeutic outcome in cancer patients. Functional annotation suggested that altogether these SNPs occur in proto-oncogenes enriched for kinase activities. We provide detailed in silico evidence for the functional effect of these candidate SNPs in various types of cancer.

  1. Le Peer to Peer: Vers un Nouveau Modèle de Civilization

    Directory of Open Access Journals (Sweden)

    Michel Bauwens

    2006-06-01

    Full Text Available Le « peer to peer » est la dynamique intersubjective caractéristique des réseaux distribués. Le but de cet essai est de montrer qu'il s'agit d'une véritable nouvelle forme d’organisation sociale, apte à produire et échanger des biens, à créer de la valeur. Celle-ci est la conséquence d'un nouvel imaginaire social, et possède le potentiel de devenir le pilier d'un nouveau mode d'économie politique, voire d'un nouveau type de civilisation. Pour cela, nous allons d'abord définir le P2P, décrire en bref ces manifestations, et le différencier d'autres modalités d'échange intersubjectif tel que le marché, la hiérarchie, l'économie du don.Comme principale modalité P2P nous distinguons: Les processus de production P2P, comme troisième mode de production, qui n'est ni géré par un mode hiérarchique ou par l'état, ni répondant à des impératifs de profit ou qui sont modulés par le biais des prix. Les processus de gouvernance P2P, qui gouverne ces processus de production. Les formes de propriété P2P, qui sont destine a empecher l’appropriation prive de cette production pour le commun.Afin d’examiner les characteristiques de cette nouvelle dynamique sociale, nous utilisons la typologie intersubjective de l’anthropologue Alan Page Fisque, qui distingue: 1. l'échange égalitaire (Equality Matching, c..a.d l’economie du don. 2. La relation d’autorité (Authority Ranking tel qu’elle s’exprime dans le mode hierarchique. 3. le marché (Market Pricing. 4. la participation commune (Communal Shareholding.En conclusion, nous examinons les possibilites d’expansion de ce nouveau mode sociale et son insertion dans l’economie capitaliste, en nous nous posons la question: le P2P peut-il etre concu comme alternative sociale et economique aux modeles existants.

  2. La science, la littérature, le rituel: le vrai dire et le plus que mentir

    Directory of Open Access Journals (Sweden)

    Panagiotis Christias

    2005-03-01

    Full Text Available Le scientifique promet la vérité sans être en mesure d'accomplir sa promesse tandis que l'écrivain promet de mentir mais par son mensonge, il fait plus que mentir. Il ne dit certainement pas la vérité, car la vérité n'est pas sa préoccupation première. Voilà comment nous pouvons résumer les deux attitudes, condamnées à un antagonisme stérile par l'attitude positiviste moderne. Compte tenu donc de l'intention fondatrice de la science, de sa promesse donc originaire et fondatrice, la science doit dire la vérité et rien que la vérité. Ce qui, de l'aveu même de cette même science, est impossible. [...] La littérature se permet de reconstruire des mondes par-delà le vrai et le faux. [...] Un récit littéraire ne demande pas la consécration de la vérité, ne demande pas à être suivi parce que vrai, n'impose rien et n'attend rien. Sa vraie destinée est l'errance et sa vraie conscience est celle de sa dissémination. Celui qui renonce à la prétention de vérité renonce en même temps à la volonté de dominer. Dominer signifie créer un espace de vérité dans lequel celui qui énonce la vérité est le maître légitime de ceux qui sont dans le champ de la conception du monde dont cette vérité est la pierre angulaire.

  3. Le Francais Courant: Part V, French.

    Science.gov (United States)

    Dade County Public Schools, Miami, FL.

    Instructional objectives of the Dade County Public Schools Quinmester Program in French for use with "Le Francais Courant: Part 5" focus on the development of mastery of the basic numbering system and other grammatical structures. Structures include the formation of the present tense of the irregular verbs…

  4. Le Chatelier--Right or Wrong?

    Science.gov (United States)

    Helfferich, Friedrich G.

    1985-01-01

    Presents a class exercise designed to find out how well students understand the nature and consequences of the mass action law and Le Chatelier's principle as applied to chemical equilibria. The exercise relates to a practical situation and provides simple relations for maximizing equilibrium quantities not found in standard textbooks. (JN)

  5. Le Chatelier's Principle, Temperature Effects, and Entropy.

    Science.gov (United States)

    Campbell, J. Arthur

    1985-01-01

    One of the most useful methods of understanding chemical equilibria is provided by Le Chatelier's principle. The relationships between this principle, temperature, and entropy are discussed. Tables with thermodynamic data for some net reactions commonly used to illustrate the principle and for reactions involving gases are included. (JN)

  6. Microscopic Description of Le Chatelier's Principle

    Science.gov (United States)

    Novak, Igor

    2005-01-01

    A simple approach that "demystifies" Le Chatelier's principle (LCP) and simulates students to think about fundamental physical background behind the well-known principles is presented. The approach uses microscopic descriptors of matter like energy levels and populations and does not require any assumption about the fixed amount of substance being…

  7. Le Chatelier's principle in replicator dynamics

    Science.gov (United States)

    Allahverdyan, Armen E.; Galstyan, Aram

    2011-10-01

    The Le Chatelier principle states that physical equilibria are not only stable, but they also resist external perturbations via short-time negative-feedback mechanisms: a perturbation induces processes tending to diminish its results. The principle has deep roots, e.g., in thermodynamics it is closely related to the second law and the positivity of the entropy production. Here we study the applicability of the Le Chatelier principle to evolutionary game theory, i.e., to perturbations of a Nash equilibrium within the replicator dynamics. We show that the principle can be reformulated as a majorization relation. This defines a stability notion that generalizes the concept of evolutionary stability. We determine criteria for a Nash equilibrium to satisfy the Le Chatelier principle and relate them to mutualistic interactions (game-theoretical anticoordination) showing in which sense mutualistic replicators can be more stable than (say) competing ones. There are globally stable Nash equilibria, where the Le Chatelier principle is violated even locally: in contrast to the thermodynamic equilibrium a Nash equilibrium can amplify small perturbations, though both types of equilibria satisfy the detailed balance condition.

  8. Le genre Sivanasua (Lophocyoninae, Hyaenodontidae, Creodonta, Mammalia)

    OpenAIRE

    Ginsburg, L.; Morales, Jorge

    1999-01-01

    Two upper teeth from the lower Miocene of Le Chêne de Navère (Gers, France) are interpreted as M1 and M2 of Sivanasua viverroides. The genus is known in Europe by two species. The origin of the Lophocyoninae is re-evaluated. We consider the group as rooted in some African hyaenodontoid Creodonta.

  9. Le radici classiche della meccanica quantica

    CERN Document Server

    Ferretti, Bruno

    1980-01-01

    Due sono state le scoperte che hanno rivoluzionato la fisica del nostro secolo : la relatività e la meccanica quantica. Quest'ultima è quella che sino ad oggi ha avuto il più grande numero di conseguenze verificabili e anche la maggior carica rivoluzionari nel pensiero scientifico. L'insegnamento di quest a disciplina presenta tuttora notevoli difficoltà.

  10. "Le CERN restera un grand employeur"

    CERN Multimedia

    Monin, V

    2002-01-01

    "Pour le porte-parole du CERN, la suppression de 600 postes d'ici 2007 était prévue depuis bien longtemps. Il s'agit de départs en retraite qui ne sont en aucun cas liés au dépassement du budget du LHC" (1 page).

  11. Antimicrobiële eiwitten in speeksel

    NARCIS (Netherlands)

    W. van 't Hof; E.C.I. Veerman

    2014-01-01

    Speeksel bevat verschillende eiwitten en peptiden met antimicrobiële eigenschappen. In kwantitatief opzicht de belangrijkste zijn: Daarnaast bevat speeksel ook bacteriebindende eiwitten, onder andere immuunglobulinen, die hun kolonisatie in de mond remmen. Lysozym: breekt mureïne in de celwand af en

  12. Le attuali prospettive del diritto ecclesiastico italiano

    OpenAIRE

    Valerio Tozzi

    2011-01-01

    SOMMARIO: 1. Ai miei tempi … - 2. Le innovazioni istituzionali dopo gli anni settanta– 3. I problemi di oggi – 4. Immigrazione, pluralismo culturale e confessionismostrisciante – 5. Verso quali assetti futuri andrà il diritto ecclesiastico? – 6. La Dottrina ela società.

  13. Le attuali prospettive del diritto ecclesiastico italiano

    Directory of Open Access Journals (Sweden)

    Valerio Tozzi

    2011-02-01

    Full Text Available SOMMARIO: 1. Ai miei tempi … - 2. Le innovazioni istituzionali dopo gli anni settanta– 3. I problemi di oggi – 4. Immigrazione, pluralismo culturale e confessionismostrisciante – 5. Verso quali assetti futuri andrà il diritto ecclesiastico? – 6. La Dottrina ela società.

  14. Bioinformatics of non small cell lung cancer and the ras proto-oncogene

    CERN Document Server

    Kashyap, Amita; Babu M, Naresh

    2015-01-01

    Cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes. Mutations in the K-ras proto-oncogene are responsible for 10–30% of adenocarcinomas. Clinical Findings point to a wide variety of other cancers contributing to lung cancer incidence. Such a scenario makes identification of lung cancer difficult and thus identifying its mechanisms can contribute to the society. Identifying unique conserved patterns common to contributing proto-oncogenes may further be a boon to Pharmacogenomics and pharmacoinformatics. This calls for ab initio/de novo drug discovery that in turn will require a comprehensive in silico approach of Sequence, Domain, Phylogenetic and Structural analysis of the receptors, ligand screening and optimization and detailed Docking studies. This brief involves extensive role of the RAS subfamily that includes a set of proteins, which cause an over expression of cancer-causing genes like M-ras and initiate tumour formation in lungs. SNP Studies and Structure based ...

  15. Role of papillomavirus oncogenes in human cervical cancer: Transgenic animal studies

    Energy Technology Data Exchange (ETDEWEB)

    Griep, A.E.; Lambert, P.F. [Univ. of Wisconsin School of Medicine, Madison, WI (United States)

    1994-05-01

    Human papillomaviruses are believed to be etiologic agents for the majority of human cervical carcinoma, a common cancer that is a leading cause of death by cancer among women worldwide. In cervical carcinoma, a subset of papillomaviral genes, namely E6 and E7, are expressed. In vitro tissue culture studies indicate that HPV E6 and E7 are oncogenes, and that their oncogenicity is due in part to their capacity to inactivate cellular tumor suppressor genes. The behavior of E6 and E7 in vitro and the genetic evidence from analysis of human cancers suggest that the E6 and E7 genes play a significant role in the development of cervical cancer. This hypothesis is now being tested using animal models. In this review, we summarize our current knowledge of the oncogenicity of papillomavirus genes that has been generated through their study in transgenic mice. 82 refs., 4 figs., 1 tab.

  16. Polymorphic changes of cell phenotype caused by elevated expression of an exogenous NEU proto-oncogene.

    Science.gov (United States)

    Tarakhovsky, A M; Resnikov, M; Zaichuk, T; Tugusheva, M V; Butenko, Z A; Prassolov, V S

    1990-03-01

    The NEU proto-oncogene encodes a 185,000 dalton transmembrane glycoprotein with extensive homology to epidermal growth factor receptor. In the current study the effect of exogenous NEU expression on phenotype and growth properties of cells established lines was examined. The replication defective retroviruses were used to express constitutively NEU cDNA in the Rat-1, NIH3T3 and Balb/c3T3 cells. In spite of the practically similar NEU mRNA and protein content in infected cells only in Balb/c3T3 cells, high NEU expression ultimately led to oncogenic transformation. The Rat-1 cells were practically insensitive to oncogenic action of NEU. Subpopulation divergency with respect to NEU-dependent transformation was also revealed in infected NIH3T3 cells. These results suggest the existence of unknown host-specific factor(s) determining the response of cells to NEU overexpression.

  17. Le détroit de Gibraltar

    Directory of Open Access Journals (Sweden)

    Guillaume Le Boedec

    2008-02-01

    Full Text Available Les assauts sur les grillages de Ceuta et Melilla à l’automne 2005 et le flux continu de migrants vers les îles Canaries en 2006 (+574% par rapport à 2005 ont, par leur surmédiatisation, défini une nouvelle perception du phénomène migratoire. Depuis le début des années 1990, le détroit de Gibraltar, marge naturelle de l’Europe, s’était affirmé comme le point nodal, la centralité, de l’immigration clandestine transméditerranéenne. Il capte et diffuse, depuis l’apparition de la frontière commune de l’Europe Schengen, toutes les évolutions juridiques et techniques mises en place par l’Union européenne pour lutter contre les migrations illégales. Véritable laboratoire de l’externalisation de la politique migratoire européenne et de la coopération maghrébine, le détroit de Gibraltar s’est imposé comme l’espace modèle de la « frontièrisation » de l’espace Schengen, mais aussi le symbole de son inefficacité. La réactivité des migrants et leur capacité à contourner les dispositifs européens soulignent l’impuissance d’une politique de fermeture menée sans projet de développement des pays émetteurs.As they received much media coverage, the assaults on the fences at Ceuta and Melilla in autumn 2005 and the continuous flow of migrants to the Canary Islands in 2006 defined a new perception of migratory phenomena. Since the beginning of the 90’s, the Strait of Gibraltar, the natural limit of Europe, had become the nodal point, the very centre, of transmediterranean illegal immigration. Since the apparition of the common frontier of Schengen, it has caught and spread all legal and technical evolutions set by the European Union to fight illegal migrations. A real testing laboratory for the outsourcing of European migratory policy and of Maghreb cooperation, the Strait of Gibraltar has emerged as a model «frontier-setting» in the Schengen zone, but also as the symbol of its lack of efficiency

  18. Intelligence artificielle et agents collectifs : le modèle EUROSIM

    Directory of Open Access Journals (Sweden)

    Denise Pumain

    2007-07-01

    Full Text Available EUROSIM est un modèle multi-agents conçu pour simuler l’évolution à moyen terme du système des villes européennes. Les agents sont des entités collectives, les grandes villes caractérisées par leur taille et leur fonction dans le système des villes, et dont les interactions (échanges modulés par des relations de proximité ou de réseau déterminent la dynamique relative, tandis que la croissance d’ensemble dépend de l’innovation. Des outils d’analyse multiscalaire ont été développés afin d’interpréter les sorties du modèle et faciliter le calibrage.

  19. Luther contre le protocole de Kyoto ou le retour des « indulgences ».

    Directory of Open Access Journals (Sweden)

    Bernard Jouve

    2005-05-01

    Full Text Available Le 16 février 2005 a marqué la mise en œuvre du Protocole de Kyoto. En fait, depuis l’annonce par la Russie, le 25 octobre 2004, de sa décision de ratifier ce protocole, l’affaire était entendue. Menacé depuis le refus des États-Unis, l’un des plus grands pollueurs de la planète, de ne pas le ratifier pour des raisons purement économiques alors que ce pays produit à lui seul 40 % des gaz à effet de serre ( ges , l’accord survenu à Kyoto en 1997 est enfin entériné et ...

  20. ONCOGENIC HUMAN PAPILLOMAVIRUS (HPV) INFECTIONS IN 18 TO 24 YEAR OLD FEMALE ONLINE DATERS

    Science.gov (United States)

    Barrere, Alexis; Stern, Joshua E.; Feng, Qinghua; Hughes, James P.; Winer, Rachel L.

    2015-01-01

    Background While risk factors for HPV infections in young women are well-defined, the risk associated with meeting male sex partners via the internet is unclear. Methods We analyzed cross-sectional data from 282 18-24-year old women who reported using Internet dating websites in the past year. Women were mailed vaginal self-sampling kits for PCR-based HPV genotyping (including 19 oncogenic types) and sexual behavior and health history questionnaires. Generalized linear models were used to evaluate risk factors for prevalent oncogenic HPV infections. Results 35% of women reported having met a male sex partner via the Internet in the past 6 months, and 42% reported a history of HPV vaccination. The prevalence of oncogenic HPV infection was 37%, and 9% of women tested positive for HPV-16 or HPV-18. Having met a male sex partner via the Internet in the past 6 months was not significantly associated with oncogenic HPV infection. In multivariate analyses, variables associated with an increased likelihood of oncogenic HPV infection included male partners in the past 6 months who were reported to have ≥1 concurrent partnership (adjusted prevalence ratio [aPR]=1.51,95%CI:1.11-2.06) and not always using condoms with male partners in the past 6 months (aPR=1.86,95%CI:1.05-3.30). Self-reporting a history of receiving ≥1 dose of HPV vaccine was inversely associated with testing positive for HPV-16 or HPV-18 (aPR=0.39,95%CI:0.16–0.97). Conclusions While measures of recent sexual behavior were associated with prevalent oncogenic HPV infection, male partners met online were not associated with an increased likelihood of infection in this cohort of young women. PMID:26267875

  1. A view on EGFR-targeted therapies from the oncogene-addiction perspective

    Directory of Open Access Journals (Sweden)

    Rolando ePerez

    2013-04-01

    Full Text Available Tumor cell growth and survival can often be impaired by inactivating a single oncogen – a phenomenon that has been called as 'oncogene addiction'. It is in such scenarios that molecular targeted therapies may succeed. Among known oncogenes, the epidermal growth factor receptor (EGFR has become the target of different cancer therapies. So far, however, the clinical benefit from EGFR-targeted therapies has been rather limited. A critical review of the large amount of clinical data obtained with anti-EGFR agents, carried out from the perspective of the oncogene addiction concept, may help to understand the causes of the unsatisfactory results. In this article we intend to do such an exercise taking as basis for the analysis a few case studies of anti-EGFR agents that are currently in the clinic. There, the 'EGFR addiction' phenomenon becomes apparent in high-responder patients. We further discuss how the concept of oncogene addiction needs to be interpreted on the light of emerging experimental evidences and ideas; in particular, that EGFR addiction may reflect the interconnection of several cellular pathways. In this regard we set forth several hypotheses; namely, that requirement of higher glucose uptake by hypoxic tumor cells may reinforce EGFR addiction; and that chronic use of EGFR-targeted antibodies in EGFR-addicted tumors would induce stable disease by reversing the malignant phenotype of cancer stem cells and also by sustaining an anti-tumor T cell response. Finally, we discuss possible reasons for the failure of certain combinatorial therapies involving anti-EGFR agents, arguing that some of these agents might produce either a negative or a positive trans-modulation effect on other oncogenes. It becomes evident that we need operational definitions of EGFR addiction in order to determine which patient populations may benefit from treatment with anti-EGFR drugs, and to improve the design of these therapies.

  2. [Oncogenic human papillomaviruses in extra-genital Bowen disease revealed by in situ hybridization].

    Science.gov (United States)

    Derancourt, C; Mougin, C; Chopard Lallier, M; Coumes-Marquet, S; Drobacheff, C; Laurent, R

    2001-01-01

    The association between mucosal oncogenic human papillomaviruses (HPV) and bowenoid papulosis or genital Bowen's disease is well documented. In contrast this association with extra-genital Bowen's disease is poorly studied. The aim of this study was to detect oncogenic (16/18, 31/33/51) and non oncogenic (8/11) mucosal HPV using a in situ hybridization method in 28 skin biopsy specimens of extra-genital Bowen's disease. Twenty-eight cases of extra-genital Bowen's disease seen in the period 1990-96 in the Dermatology department were included: 19 women and 9 men (mean age: 72 years). Bowen's disease locations were: hands and feet (8 cases), limbs (11 cases), face (8 cases), trunk (1 case). Blinded histopathologic examination confirmed the diagnosis of Bowen's disease and signs of HPV infection (koilocytosis). In situ hybridization was performed using three biotinylated probes detecting HPV types 6/11, 16/18, 31/33/51. Oncogenic HPV genoma was detected in 8 skin samples (28.6 p. 100). In all these cases, 16/18 probe was positive and in two cases, both 16/18 and 31/33/51 probes were positive; 4/8 Bowen's diseases of the extremities were positive for HPV. Koilocytes were found in 6/8 of skin samples with positive HPV detection. Mucosal oncogenic HPV are detected by in situ hybridization in 28.6 p. 100 of extra-genital Bowen's disease. In situ hybridization is an easier technique than Southern-Blot hybridization which is the gold standard. Five studies reported similar results and three studies reported different results that we discuss. A precise understanding of oncogenic HPV implication in the development of extra-genital Bowen's disease could lead to the development of new therapeutic strategies (topical cidofovir or imiquimod).

  3. Characterization of TRPS1 and ERAS as oncogenes implicated in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lopez Gonzalez, L.

    2015-07-01

    New high throughput technologies have made possible to identify putative oncogenes in breast cancer. In this project we aim to relate and characterise two novel putative oncogenes, ERAS and TRPS1, in their role in human breast cancer. TRPS1, an atypical GATA factor, modulates cell proliferation and controls cell cycle progression through repression of GATA-regulated genes, therefore acting as a tumour suppressor gene. Conversely, TRPS1 expression has been shown to be significantly elevated in luminal and in a lesser extent in basal breast cancer cells, presenting roles both as an oncogene and as a tumour suppressor gene in breast cancer development. The aim of this project is therefore to determine the characteristics of TRPS1 either as a putative novel human oncogene or as a tumour suppressor gene in breast cancer cells. To this aim, we have cloned a novel isoform of TRPS1 and introduced it into several breast cancer cell lines. Our results show that overexpression of this isoform of TRPS1 results in variations in motility in non-carcinogenic cell lines, as well as in a series of EMT-like changes such as the down-regulation of the EMT marker E-cadherin, both of which can be associated to an increase in malignancy, suggesting an oncogenic behaviour for TRPS1. Furthermore, our results suggest that constitutively active members of the RAS protein family induce the expression of TRPS1, establishing a relationship between both genes. We can conclude that the effects of TRPS1 overexpression are moderate, inducing some changes but not fully transforming the cells. Therefore we cannot confirm that TRPS1 is a putative oncogene in breast cancer. (Author)

  4. A Screen Identifies the Oncogenic Micro-RNA miR-378a-5p as a Negative Regulator of Oncogene-Induced Senescence

    DEFF Research Database (Denmark)

    Kooistra, Susanne Marije; Rudkjær, Lise Christine; Lees, Michael James;

    2014-01-01

    fibroblasts. This screen led to the identification of miR-378a-5p and in addition several other miRNAs that have previously been shown to play a role in senescence. We show that ectopic expression of miR-378a-5p reduces the expression of several senescence markers, including p16INK4A and senescence......-associated β-galactosidase. Moreover, cells with ectopic expression of miR-378a-5p retain proliferative capacity even in the presence of an activated Braf oncogene. Finally, we identified several miR-378a-5p targets in diploid fibroblasts that might explain the mechanism by which the microRNA can delay OIS. We...... speculate that miR-378a-5p might positively influence tumor formation by delaying OIS, which is consistent with a known pro-oncogenic function of this microRNA....

  5. Communication intentionnelle dans le domaine du leadership

    Directory of Open Access Journals (Sweden)

    Sophie Ménard

    2013-12-01

    Full Text Available L’existence de toute organisation repose sur le soutien que lui accordent ses membres. Le fonctionnement optimal d’un système est tributaire de la qualité des relations entre ses composantes, c’est-à-dire, pour une organisation, entre ses différents paliers. La qualité de ces relations présente des avantages concurrentiels sur les plans économique, politique et social, car elles se traduisent par une communication claire, directe et régulière entre les niveaux hiérarchiques. Pour les dirigeants, il s’agit de leur capacité à exercer leur leadership. Cette communication a un impact sur le développement des compétences des employés, la productivité de l’entreprise et sa visibilité stratégique dans la sphère politique et, enfin, sur l’attraction et le maintien d’une main-d’œuvre qualifiée et engagée. Il va sans dire qu’au 21e siècle, l’avènement des médias sociaux rend plus délicate la tâche des gestionnaires et présente ainsi un défi bien plus important que la mise en place de bonnes relations de travail qu’on préconisait au siècle dernier. Les auteurs aborderont le leadership autoral comme alternative en vue d’un leadership de conscience plus adapté aux défis des organisations du siècle actuel.

  6. Le devenir actif du corps affectif

    Directory of Open Access Journals (Sweden)

    Pascal Séverac

    2005-09-01

    Full Text Available Le but de cet article est de saisir ce que signifie, pour le corps, être actif. À partir de la proposition 49 de la partie IV de l’Éthique, on propose de distinguer deux manières d’appréhender le corps – soit comme corps organique, soit comme corps affectif -, et l’on montre que la question éthique du devenir actif s’adresse à la dimension affective du corps. Il faut penser le devenir actif du corps affectif comme augmentation de son aptitude non seulement à affecter, mais aussi à être affecté. En effet, être affecté pour le corps n’est pas identique à pâtir : au contraire, plus est grande l’ouverture sensible d’un corps aux autres corps, plus est grande son activité éthique.The aim of this paper is to understand how the body can be active. With the proposition 49 of the fourth part of Ethics, two ways of conceiving of the body are distinguished : like an organic body or like an affective body. The ethics question of becoming active is about the affective body. This becoming active must be understood as increasing of the ability to affect, as well as to be affected. To be affected is different from to be passive. On the contrary, the more the body is able to be affected, the more he becomes active.

  7. Regulation of Proto-Oncogenic Dbl by Chaperone-Controlled, Ubiquitin-Mediated Degradation▿

    OpenAIRE

    Kamynina, Elena; Kauppinen, Krista; Duan, Faping; Muakkassa, Nora; Manor, Danny

    2006-01-01

    The dbl proto-oncogene product is a prototype of a growing family of guanine nucleotide exchange factors (GEFs) that stimulate the activation of small GTP-binding proteins from the Rho family. Mutations that result in the loss of proto-Dbl's amino terminus produce a variant with constitutive GEF activity and high oncogenic potential. Here, we show that proto-Dbl is a short-lived protein that is kept at low levels in cells by efficient ubiquitination and degradation. The cellular fate of proto...

  8. Oncogenic osteomalacia secondary to a hemangiopericytoma of the hip: case report

    Energy Technology Data Exchange (ETDEWEB)

    Baronofsky, S.I.; Kalbhen, C.L.; Demos, T.C.; Sizemore, G.W. [Loyola Univ. Medical Center, Dept. of Medicine, Maywood, IL (United States)

    1999-02-01

    Osteomalacia is characterized by abnormally increased unmineralized osteoid within the bone matrix. This metabolic bone disease is usually the result of decreased uptake or abnormal metabolism of vitamin D or of renal tubular phosphate loss. Dietary deficiency, malabsorption, cirrhosis, renal tubular acidosis and certain drugs can cause osteomalacia., Oncogenic osteomalacia - osteomalacia secondary to tumours - is rare, and the exact mechanisms by which neoplasms induce osteomalacia are not known. We describe a patient with chronic osteomalacia of unknown origin who was subsequently found to have oncogenic osteomalacia secondary to a hemangiopericytoma of the hip. (author)

  9. LTβR signalling preferentially accelerates oncogenic AKT-initiated liver tumours

    Science.gov (United States)

    Scarzello, Anthony J; Jiang, Qun; Back, Timothy; Dang, Hien; Hodge, Deborah; Hanson, Charlotte; Subleski, Jeffrey; Weiss, Jonathan M; Stauffer, Jimmy K; Chaisaingmongkol, Jitti; Rabibhadana, Siritida; Ruchirawat, Mathuros; Ortaldo, John; Wang, Xin Wei; Norris, Paula S; Ware, Carl F; Wiltrout, Robert H

    2016-01-01

    Objectives The relative contributions of inflammatory signalling and sequential oncogenic dysregulation driving liver cancer pathogenesis remain incompletely understood. Lymphotoxin-β receptor (LTβR) signalling is critically involved in hepatitis and liver tumorigenesis. Therefore, we explored the interdependence of inflammatory lymphotoxin signalling and specific oncogenic pathways in the progression of hepatic cancer. Design Pathologically distinct liver tumours were initiated by hydrodynamic transfection of oncogenic V-Akt Murine Thymoma Viral Oncogene Homolog 1 (AKT)/β-catenin or AKT/Notch expressing plasmids. To investigate the relationship of LTβR signalling and specific oncogenic pathways, LTβR antagonist (LTβR-Fc) or agonist (anti-LTβR) were administered post oncogene transfection. Initiated livers/tumours were investigated for changes in oncogene expression, tumour proliferation, progression, latency and pathology. Moreover, specific LTβR-mediated molecular events were investigated in human liver cancer cell lines and through transcriptional analyses of samples from patients with intrahepatic cholangiocarcinoma (ICC). Results AKT/β-catenin-transfected livers displayed increased expression of LTβ and LTβR, with antagonism of LTβR signalling reducing tumour progression and enhancing survival. Conversely, enforced LTβR-activation of AKT/β-catenin-initiated tumours induced robust increases in proliferation and progression of hepatic tumour phenotypes in an AKT-dependent manner. LTβR-activation also rapidly accelerated ICC progression initiated by AKT/Notch, but not Notch alone. Moreover, LTβR-accelerated development coincides with increases of Notch, Hes1, c-MYC, pAKT and β-catenin. We further demonstrate LTβR signalling in human liver cancer cell lines to be a regulator of Notch, pAKTser473 and β-catenin. Transcriptome analysis of samples from patients with ICC links increased LTβR network expression with poor patient survival, increased

  10. Kuidas kirjutatakse ajalugu? / Jacques Le Goff ; interv. Marek Tamm

    Index Scriptorium Estoniae

    Le Goff, Jacques

    2007-01-01

    Prantsuse ajaloolase ja ajakirja Annales ühe peatoimetaja J. Le Goff'i teostest. Varem. ilm.: Ajalugu, antropoloogia ja imaginaarsus : intervjuu Jaques Le Goffiga // Le Goff, Jacques. Raha või elu : majandus ja religioon keskajal. - Tallinn, 2001. - Lk. 108-126

  11. A Screen Identifies the Oncogenic Micro-RNA miR-378a-5p as a Negative Regulator of Oncogene-Induced Senescence

    DEFF Research Database (Denmark)

    Kooistra, Susanne Marije; Rudkjær, Lise Christine; Lees, Michael James

    2014-01-01

    fibroblasts. This screen led to the identification of miR-378a-5p and in addition several other miRNAs that have previously been shown to play a role in senescence. We show that ectopic expression of miR-378a-5p reduces the expression of several senescence markers, including p16INK4A and senescence......Oncogene-induced senescence (OIS) can occur in response to hyperactive oncogenic signals and is believed to be a fail-safe mechanism protecting against tumorigenesis. To identify new factors involved in OIS, we performed a screen for microRNAs that can overcome or inhibit OIS in human diploid......-associated β-galactosidase. Moreover, cells with ectopic expression of miR-378a-5p retain proliferative capacity even in the presence of an activated Braf oncogene. Finally, we identified several miR-378a-5p targets in diploid fibroblasts that might explain the mechanism by which the microRNA can delay OIS. We...

  12. Aggressive transformation of juvenile myelomonocytic leukemia associated with duplication of oncogenic KRAS due to acquired uniparental disomy.

    Science.gov (United States)

    Kato, Motohiro; Yasui, Naoko; Seki, Masafumi; Kishimoto, Hiroshi; Sato-Otsubo, Aiko; Hasegawa, Daisuke; Kiyokawa, Nobutaka; Hanada, Ryoji; Ogawa, Seishi; Manabe, Atsushi; Takita, Junko; Koh, Katsuyoshi

    2013-06-01

    A small fraction of cases of juvenile myelomonocytic leukemia (JMML) develop massive disease activation. Through genomic analysis of JMML, which developed in an individual with mosaicism for oncogenic KRAS mutation with rapid progression, we identified acquired uniparental disomy at 12p. We demonstrated that duplication of oncogenic KRAS is associated with rapid JMML progression.

  13. Deletion mutants of region E1 a of AD12 E1 plasmids: Effect on oncogenic transformation

    NARCIS (Netherlands)

    Bos, J.L.; Jochemsen, A.G.; Bernards, R.A.; Schrier, P.I.; Ormondt, H. van; Eb, A.J. van der

    1983-01-01

    Plasmids containing the El region of Ad12 DNA can transform certain rodent cells into oncogenic cells. To study the role of the Ela subregion in the process of oncogenic transformation, Ad12 region El mutants carrying deletions in the Ela region were constructed. Deletion mutants pR7 and pR8 affect

  14. Effects of c-myc oncogene modulation on differentiation of human small cell lung carcinoma cell lines

    NARCIS (Netherlands)

    Van Waardenburg, RCAM; Meijer, C; Pinto-Sietsma, SJ; De Vries, EGE; Timens, W; Mulder, NM

    1998-01-01

    Amplification and over-expression of oncogenes of the myc family are related to the prognosis of certain solid tumors such as small cell lung cancer (SCLC). For SCLC, c-myc is the oncogene most consistently found to correlate with the end stage behaviour of the tumour, in particular with survival af

  15. CORRÉLATION ENTRE LE FROTTEMENT INTÉRIEUR ET LE COEFFICIENT DE DILATATION LORS DES TRANSFORMATIONS MARTENSITIQUES ISOTHERMES

    OpenAIRE

    Prioul, C.; De A. Rodrigues, C.A.V.; Plusquellec, J.

    1983-01-01

    Nous montrons que le frottement intérieur est proportionnel au coefficient de dilatation lors de la transformation martensitique isotherme d'alliages Fe-Ni-C. Ce résultat montre que le formalisme proposé par Delorme dans le cas des transformations martensitiques athermiques peut être étendu aux transformations martensitiques de type isotherme.

  16. Le Kongo de Sony Labou Tansi

    Directory of Open Access Journals (Sweden)

    Céline Gahungu

    2015-02-01

    Full Text Available Les textes inédits de Sony Labou Tansi proposent une réflexion sur l’histoire, et plus singulièrement sur celle du Kongo. Le souvenir du prestigieux royaume apparaît dès les premiers manuscrits, composés au début des années 1970. Loin d’être circonscrit aux écrits de jeunesse, le Kongo surgit sous de multiples formes dans le dédale des textes rédigés au cours des années suivantes. Cette fascination pousse l’écrivain dans une dynamique de recherche esthétique : comment évoquer cet illo tempore mythique sans sacrifier à une historicité convenue ? Comment inventer une écriture en mesure de rendre compte du fabuleux royaume ?L’analyse littéraire ne peut cependant faire fi du contexte politique dans lequel Sony Labou Tansi s’inscrit. Outre sa dimension historique et toponymique, Kongo est un ethnonyme dont l’auteur s’est réclamé. Celui-ci a revendiqué à de nombreuses reprises son appartenance à une identité kongo au point de s’être engagé, à la fin des années 1980, dans les rangs du MCDDI1. Ce discours identitaire et l’adhésion à un parti ethnique ont troublé l’image d’un auteur volontiers perçu comme un démocrate véritable. Est-il possible d’articuler le Kongo littéraire et le Kongo politique ? Le Kongo, dont l’ombre portée apparaît dans les manuscrits littéraires mais également dans les articles et les déclarations politiques, pourrait-il nous aider à saisir les enjeux de l’écriture protéiforme de Sony Labou Tansi ?

  17. Immunology in the clinic review series; focus on cancer: multiple roles for the immune system in oncogene addiction.

    Science.gov (United States)

    Bachireddy, P; Rakhra, K; Felsher, D W

    2012-02-01

    Despite complex genomic and epigenetic abnormalities, many cancers are irrevocably dependent on an initiating oncogenic lesion whose restoration to a normal physiological activation can elicit a dramatic and sudden reversal of their neoplastic properties. This phenomenon of the reversal of tumorigenesis has been described as oncogene addiction. Oncogene addiction had been thought to occur largely through tumour cell-autonomous mechanisms such as proliferative arrest, apoptosis, differentiation and cellular senescence. However, the immune system plays an integral role in almost every aspect of tumorigenesis, including tumour initiation, prevention and progression as well as the response to therapeutics. Here we highlight more recent evidence suggesting that oncogene addiction may be integrally dependent upon host immune-mediated mechanisms, including specific immune effectors and cytokines that regulate tumour cell senescence and tumour-associated angiogenesis. Hence, the host immune system is essential to oncogene addiction.

  18. Using {sup 18F} FDG PET/CT to Detect an occult Mesenchymal Tumor Causing Oncogenic Osteomalacia

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Hyo Jung; Choi, Yun Jung; Kim, Hyun Jeong; Jeong, Yong Hyu; Cho, Arthur; Lee, Jae Hoon; Yun, Mijin; Lee, Jong Doo; Kang, Won Jun [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    2011-09-15

    Oncogenic osteomalacia is a rare paraneoplastic syndrome characterized by renal phosphate excretion, hypophosphatemia, and osteomalacia. This syndrome is often caused by tumors of mesenchymal origin. Patients with oncogenic osteomalacia have abnormal bone mineralization, resulting in a high frequency of fractures. Tumor resection is the treatment of choice, as it will often correct the metabolic imbalance. Although oncogenic osteomalacia is a potentially curable disease, diagnosis is difficult and often delayed because of the small size and sporadic location of the tumor. Bone scintigraphy and radiography best characterize osteoma lacia; magnetic resonance imaging findings are nonspecific. Here, we report a case of oncogenic osteomalacia secondary to a phosphaturic mesenchymal tumor that was successfully detected by {sup 18F} fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18F} FDG PET/CT). This case illustrates the advantages of {sup 18F} FDG PET/CT in detecting the occult mesenchymal tumor that causes oncogenic osteomalacia.

  19. La construction de la matière le modèle Standard

    CERN Document Server

    Léon, Jacques

    2016-01-01

    Qu'est-ce que la matière ? Voilà une question à laquelle il pourrait sembler facile de répondre car il n'est rien de plus concret que la matière. Et pourtant, la réponse qu'en donne la physique contemporaine est pour le moins déconcertante ! Le concept-même de particules, briques élémentaires de la matière, s'est volatilisé, dissout dans des objets mathématiques abstraits et abscons pour les non-initiés. Plus nos théories sont précises et plus l'image qu'elles nous renvoient est insaisissable. En un siècle, la représentation des particules s'est métamorphosée en nuages de probabilité portés par des champs quantiques régis par des symétries confinées dans des espaces abstraits. Mais dans un même temps, nous avons réussi le tour de force d'expliquer toute cette complexité avec seulement 16 particules… et une seule théorie, véritable construction de notre conception de la matière : le modèle standard. Ce livre tente de guider le lecteur dans le dédale de la physique des particu...

  20. Human gene control by vital oncogenes: revisiting a theoretical model and its implications for targeted cancer therapy.

    Science.gov (United States)

    Willis, Rudolph E

    2012-01-01

    An important assumption of our current understanding of the mechanisms of carcinogenesis has been the belief that clarification of the cancer process would inevitably reveal some of the crucial mechanisms of normal human gene regulation. Since the momentous work of Bishop and Varmus, both the molecular and the biochemical processes underlying the events in the development of cancer have become increasingly clear. The identification of cellular signaling pathways and the role of protein kinases in the events leading to gene activation have been critical to our understanding not only of normal cellular gene control mechanisms, but also have clarified some of the important molecular and biochemical events occurring within a cancer cell. We now know that oncogenes are dysfunctional proto-oncogenes and that dysfunctional tumor suppressor genes contribute to the cancer process. Furthermore, Weinstein and others have hypothesized the phenomenon of oncogene addiction as a distinct characteristic of the malignant cell. It can be assumed that cancer cells, indeed, become dependent on such vital oncogenes. The products of these vital oncogenes, such as c-myc, may well be the Achilles heel by which targeted molecular therapy may lead to truly personalized cancer therapy. The remaining problem is the need to introduce relevant molecular diagnostic tests such as genome microarray analysis and proteomic methods, especially protein kinase identification arrays, for each individual patient. Genome wide association studies on cancers with gene analysis of single nucleotide and other mutations in functional proto-oncogenes will, hopefully, identify dysfunctional proto-oncogenes and allow the development of more specific targeted drugs directed against the protein products of these vital oncogenes. In 1984 Willis proposed a molecular and biochemical model for eukaryotic gene regulation suggesting how proto-oncogenes might function within the normal cell. That model predicted the

  1. Oncogenic GNAQ mutations are not correlated with disease-free survival in uveal melanoma

    NARCIS (Netherlands)

    Bauer, J.; Kilic, E.; Vaarwater, J.; Bastian, B. C.; Garbe, C.; de Klein, A.

    2009-01-01

    BACKGROUND: Recently, oncogenic G protein alpha subunit q (GNAQ) mutations have been described in about 50% of uveal melanomas and in the blue nevi of the skin. METHODS: GNAQ exon 5 was amplified from 75 ciliary body and choroidal melanoma DNAs and sequenced directly. GNAQ mutation status was correl

  2. The Homeodomain Transcription Factor Cdx1 Does Not Behave as an Oncogene in Normal Mouse Intestine

    Directory of Open Access Journals (Sweden)

    Mary Ann S. Crissey

    2008-01-01

    Full Text Available The Caudal-related homeobox genes Cdx1 and Cdx2 are intestine-specific transcription factors that regulate differentiation of intestinal cell types. Previously, we have shown Cdx1 to be antiproliferative and to promote cell differentiation. However, other studies have suggested that Cdx1 may be an oncogene. To test for oncogenic behavior, we used the murine villin promoter to ectopically express Cdx1 in the small intestinal villi and colonic surface epithelium. No changes in intestinal architecture, cell differentiation, or lineage selection were observed with expression of the transgene. Classic oncogenes enhance proliferation and induce tumors when ectopically expressed. However, the Cdx1 transgene neither altered intestinal proliferation nor induced spontaneous intestinal tumors. In a murine model for colitis-associated cancer, the Cdx1 transgene decreased, rather than increased, the number of adenomas that developed. In the polyps, the expression of the endogenous and the transgenic Cdx1 proteins was largely absent, whereas endogenous Villin expression was retained. This suggests that transgene silencing was specific and not due to a general Villin inactivation. In conclusion, neither the ectopic expression of Cdx1 was associated with changes in intestinal cell proliferation or differentiation nor was there increased intestinal cancer susceptibility. Our results therefore suggest that Cdx1 is not an oncogene in normal intestinal epithelium.

  3. N-Linked oligosaccharide changes with oncogenic transformation require sialylation of multiantennae

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Santer, U.V.; DeSantis, R.; Hård, K.; Kuik, J.A. van; Won, B.; Glick, M.C.

    1989-01-01

    Glycopeptides derived from NIH 3T3 fibroblasts and these cells transformed by transfection with human DNA containing oncogene H-ras were analyzed by 500-MHz 1H-NMR spectroscopy and binding to immobilized lectins. The cells were metabolically labeled with D-[3H]glucosamine or L-[3H]fucose and the gly

  4. Escape from premature senescence is not sufficient for oncogenic transformation by Ras

    NARCIS (Netherlands)

    Peeper, D.S.; Dannenberg, J.-H.; Douma, S.; Riele, H. te; Bernards, R.A.

    2001-01-01

    Resistance of primary cells to transformation by oncogenic Ras has been attributed to the induction of replicative growth arrest1, 2, 3. This irreversible 'fail-safe mechanism' resembles senescence and requires induction by Ras of p19ARF and p53 (refs 3−5). Mutation of either p19ARF or p53 alleviate

  5. Somatic Copy Number Alterations at Oncogenic Loci Show Diverse Correlations with Gene Expression

    Science.gov (United States)

    Roszik, Jason; Wu, Chang-Jiun; Siroy, Alan E.; Lazar, Alexander J.; Davies, Michael A.; Woodman, Scott E.; Kwong, Lawrence N.

    2016-01-01

    Somatic copy number alterations (SCNAs) affecting oncogenic drivers have a firmly established role in promoting cancer. However, no agreed-upon standard exists for calling locus-specific amplifications and deletions in each patient sample. Here, we report the correlative analysis of copy number amplitude and length with gene expression across 6,109 samples from The Cancer Genome Atlas (TCGA) dataset across 16 cancer types. Using specificity, sensitivity, and precision-based scores, we assigned optimized amplitude and length cutoffs for nine recurrent SCNAs affecting known oncogenic drivers, using mRNA expression as a functional readout. These cutoffs captured the majority of SCNA-driven, highly-expression-altered samples. The majority of oncogenes required only amplitude cutoffs, as high amplitude samples were almost invariably focal; however, CDKN2A and PTEN uniquely required both amplitude and length cutoffs as primary predictors. For PTEN, these extended to downstream AKT activation. In contrast, SCNA genes located peri-telomerically or in fragile sites showed poor expression-copy number correlations. Overall, our analyses identify optimized amplitude and length cutoffs as efficient predictors of gene expression changes for specific oncogenic SCNAs, yet warn against one-size-fits-all interpretations across all loci. Our results have implications for cancer data analyses and the clinic, where copy number and mutation data are increasingly used to personalize cancer therapy.

  6. Clinical relevance of the K-ras oncogene in colorectal cancer: Experience in a Mexican population

    Directory of Open Access Journals (Sweden)

    F. Cabrera-Mendoza

    2014-07-01

    Conclusions: No relation was found between the K-ras oncogene mutation and reduced survival, in contrast to what has been established in the international medical literature. Further studies that include both a larger number of patients and those receiving monoclonal treatment, need to be conducted. There were only 5 patients in the present study that received cetuximab, resulting in a misleading analysis.

  7. Oncogenic events associated with endometrial and ovarian cancers are rare in endometriosis

    DEFF Research Database (Denmark)

    Vestergaard, Anna Lindeløv; Thorup, Katrine; Knudsen, Ulla Breth

    2011-01-01

    using methylation-specific melting curve analysis (MS-MCA), and 9 genes (BRAF, HRAS, NRAS, CTNNB1, CDK4, FGFR3, PIK3CA, TP53 and PTEN) were analyzed for mutations using denaturing gradient gel electrophoresis (DGGE) and direct sequencing. An oncogenic mutation in KRAS (c. 34G>T; p.G12C) was detected...

  8. Oncogenic human papillomaviruses activate the tumor-associated lens epithelial-derived growth factor (LEDGF gene.

    Directory of Open Access Journals (Sweden)

    Jenny Leitz

    2014-03-01

    Full Text Available The expression of the human papillomavirus (HPV E6/E7 oncogenes is crucial for HPV-induced malignant cell transformation. The identification of cellular targets attacked by the HPV oncogenes is critical for our understanding of the molecular mechanisms of HPV-associated carcinogenesis and may open novel therapeutic opportunities. Here, we identify the Lens Epithelial-Derived Growth Factor (LEDGF gene as a novel cellular target gene for the HPV oncogenes. Elevated LEDGF expression has been recently linked to human carcinogenesis and can protect tumor cells towards different forms of cellular stress. We show that intracellular LEDGF mRNA and protein levels in HPV-positive cancer cells are critically dependent on the maintenance of viral oncogene expression. Ectopic E6/E7 expression stimulates LEDGF transcription in primary keratinocytes, at least in part via activation of the LEDGF promoter. Repression of endogenous LEDGF expression by RNA interference results in an increased sensitivity of HPV-positive cancer cells towards genotoxic agents. Immunohistochemical analyses of cervical tissue specimens reveal a highly significant increase of LEDGF protein levels in HPV-positive lesions compared to histologically normal cervical epithelium. Taken together, these results indicate that the E6/E7-dependent maintenance of intracellular LEDGF expression is critical for protecting HPV-positive cancer cells against various forms of cellular stress, including DNA damage. This could support tumor cell survival and contribute to the therapeutic resistance of cervical cancers towards genotoxic treatment strategies in the clinic.

  9. Assessment of human papillomavirus E6/E7 oncogene expression as cervical disease biomarker

    National Research Council Canada - National Science Library

    Fontecha, Nerea; Basaras, Miren; Hernáez, Silvia; Andía, Daniel; Cisterna, Ramón

    2016-01-01

    .... After RNA extraction, E6/E7 oncogene mRNA detection was performed by NucliSens[R] EasyQ[R] HPV v1 Test (bioM#241;rieux). The results of the present study showed that E6/E7 mRNA positivity rate...

  10. Oncogenic Human Papillomaviruses Activate the Tumor-Associated Lens Epithelial-Derived Growth Factor (LEDGF) Gene

    Science.gov (United States)

    Leitz, Jenny; Reuschenbach, Miriam; Lohrey, Claudia; Honegger, Anja; Accardi, Rosita; Tommasino, Massimo; Llano, Manuel; von Knebel Doeberitz, Magnus; Hoppe-Seyler, Karin; Hoppe-Seyler, Felix

    2014-01-01

    The expression of the human papillomavirus (HPV) E6/E7 oncogenes is crucial for HPV-induced malignant cell transformation. The identification of cellular targets attacked by the HPV oncogenes is critical for our understanding of the molecular mechanisms of HPV-associated carcinogenesis and may open novel therapeutic opportunities. Here, we identify the Lens Epithelial-Derived Growth Factor (LEDGF) gene as a novel cellular target gene for the HPV oncogenes. Elevated LEDGF expression has been recently linked to human carcinogenesis and can protect tumor cells towards different forms of cellular stress. We show that intracellular LEDGF mRNA and protein levels in HPV-positive cancer cells are critically dependent on the maintenance of viral oncogene expression. Ectopic E6/E7 expression stimulates LEDGF transcription in primary keratinocytes, at least in part via activation of the LEDGF promoter. Repression of endogenous LEDGF expression by RNA interference results in an increased sensitivity of HPV-positive cancer cells towards genotoxic agents. Immunohistochemical analyses of cervical tissue specimens reveal a highly significant increase of LEDGF protein levels in HPV-positive lesions compared to histologically normal cervical epithelium. Taken together, these results indicate that the E6/E7-dependent maintenance of intracellular LEDGF expression is critical for protecting HPV-positive cancer cells against various forms of cellular stress, including DNA damage. This could support tumor cell survival and contribute to the therapeutic resistance of cervical cancers towards genotoxic treatment strategies in the clinic. PMID:24604027

  11. Microarray-Based oncogenic pathway profiling in advanced serous papillary ovarian carcinoma

    NARCIS (Netherlands)

    X.B. Trinh; W.A.A. Tjalma (Wiebren); L. Dirix (Luc); P.B. Vermeulen; D. Peeters (Dieter); D. Bachvarov (Dimcho); M. Plante (Marie); P.M.J.J. Berns (Els); J. Helleman (Jozien); S.J. van Laere; P.A. van Dam

    2011-01-01

    textabstractIntroduction: The identification of specific targets for treatment of ovarian cancer patients remains a challenge. The objective of this study is the analysis of oncogenic pathways in ovarian cancer and their relation with clinical outcome. Methodology: A meta-analysis of 6 gene expressi

  12. Gene expression of oncogenes, antimicrobial peptides, and cytokines in the development of oral leukoplakia.

    NARCIS (Netherlands)

    Wenghoefer, M.; Pantelis, A.; Najafi, T.; Deschner, J.; Allam, J.P.; Novak, N.; Reich, R.; Martini, M.; Berge, S.J.; Fischer, H.P.; Jepsen, S.; Winter, J.

    2010-01-01

    OBJECTIVE: The aim of this study was to investigate the expression pattern of oncogenes, antimicrobial peptides, and genes involved in inflammation in leukoplakia of the oral cavity compared with healthy gingiva. STUDY DESIGN: Biopsies of healthy gingiva (n=20) and leukoplakia (n=20), were obtained

  13. K-ras oncogene mutations in sporadic colorectal cancer in The Netherlands Cohort Study

    NARCIS (Netherlands)

    Brink, M.; Goeij, A.F.P.M. de; Weijenberg, M.P.; Roemen, G.M.J.M.; Lentjes, M.H.F.M.; Pachen, M.M.M.; Smits, K.M.; Bruïne, A.P. de; Goldbohm, R.A.; Brandt, P.A. van den

    2003-01-01

    Activation of K-ras oncogene has been implicated in colorectal carcinogenesis, being mutated in 30-60% of the adenocarcinomas. In this study, 737 incident colorectal cancer (CRC) patients, originating from 120 852 men and women (55-69 years at baseline) participating in the Netherlands Cohort Study

  14. For better or for worse : the role of Pim oncogenes in tumorigenesis

    NARCIS (Netherlands)

    Nawijn, Martijn C.; Alendar, Andrej; Berns, Anton

    2011-01-01

    Pim oncogenes are overexpressed in a wide range of tumours from a haematological and epithelial origin. Pim genes encode serine/threonine kinases that have been shown to counteract the increased sensitivity to apoptosis induction that is associated with MYC-driven tumorigenesis. Recently, considerab

  15. Skin carcinomas in organ-transplant recipients : from early oncogenic events to therapy

    NARCIS (Netherlands)

    Graaf, Ymke Grete Leontien de

    2008-01-01

    Skin carcinomas develop at a high rate in organ-transplant recipients who are kept on immune suppressive drugs to prevent graft rejection. The present study dealt with a broad range of aspects of this elevated carcinoma risk, starting from the earliest oncogenic events to the ultimate therapy.

  16. Skin carcinomas in organ-transplant recipients : from early oncogenic events to therapy

    NARCIS (Netherlands)

    Graaf, Ymke Grete Leontien de

    2008-01-01

    Skin carcinomas develop at a high rate in organ-transplant recipients who are kept on immune suppressive drugs to prevent graft rejection. The present study dealt with a broad range of aspects of this elevated carcinoma risk, starting from the earliest oncogenic events to the ultimate therapy. Advan

  17. Oncogenic human papillomaviruses activate the tumor-associated lens epithelial-derived growth factor (LEDGF) gene.

    Science.gov (United States)

    Leitz, Jenny; Reuschenbach, Miriam; Lohrey, Claudia; Honegger, Anja; Accardi, Rosita; Tommasino, Massimo; Llano, Manuel; von Knebel Doeberitz, Magnus; Hoppe-Seyler, Karin; Hoppe-Seyler, Felix

    2014-03-01

    The expression of the human papillomavirus (HPV) E6/E7 oncogenes is crucial for HPV-induced malignant cell transformation. The identification of cellular targets attacked by the HPV oncogenes is critical for our understanding of the molecular mechanisms of HPV-associated carcinogenesis and may open novel therapeutic opportunities. Here, we identify the Lens Epithelial-Derived Growth Factor (LEDGF) gene as a novel cellular target gene for the HPV oncogenes. Elevated LEDGF expression has been recently linked to human carcinogenesis and can protect tumor cells towards different forms of cellular stress. We show that intracellular LEDGF mRNA and protein levels in HPV-positive cancer cells are critically dependent on the maintenance of viral oncogene expression. Ectopic E6/E7 expression stimulates LEDGF transcription in primary keratinocytes, at least in part via activation of the LEDGF promoter. Repression of endogenous LEDGF expression by RNA interference results in an increased sensitivity of HPV-positive cancer cells towards genotoxic agents. Immunohistochemical analyses of cervical tissue specimens reveal a highly significant increase of LEDGF protein levels in HPV-positive lesions compared to histologically normal cervical epithelium. Taken together, these results indicate that the E6/E7-dependent maintenance of intracellular LEDGF expression is critical for protecting HPV-positive cancer cells against various forms of cellular stress, including DNA damage. This could support tumor cell survival and contribute to the therapeutic resistance of cervical cancers towards genotoxic treatment strategies in the clinic.

  18. Gene expression of oncogenes, antimicrobial peptides, and cytokines in the development of oral leukoplakia.

    NARCIS (Netherlands)

    Wenghoefer, M.; Pantelis, A.; Najafi, T.; Deschner, J.; Allam, J.P.; Novak, N.; Reich, R.; Martini, M.; Berge, S.J.; Fischer, H.P.; Jepsen, S.; Winter, J.

    2010-01-01

    OBJECTIVE: The aim of this study was to investigate the expression pattern of oncogenes, antimicrobial peptides, and genes involved in inflammation in leukoplakia of the oral cavity compared with healthy gingiva. STUDY DESIGN: Biopsies of healthy gingiva (n=20) and leukoplakia (n=20), were obtained

  19. Targeted expression of oncogenic K-ras in intestinal epithelium causes spontaneous tumorigenesis in mice

    NARCIS (Netherlands)

    Janssen, KP; El Marjou, F; Pinto, D; Sastre, X; Rouillard, D; Fouquet, C; Soussi, T; Louvard, D; Robine, S

    2002-01-01

    Background & Aims: Ras oncoproteins are mutated in about 50% of human colorectal cancers, but their precise role in tumor initiation or progression is still unclear. Methods: This study presents transgenic mice that express K-ras(V12G), the most frequent oncogenic mutation in human tumors, under con

  20. Correlation between oncogenic mutations and parameter sensitivity of the apoptosis pathway model.

    Directory of Open Access Journals (Sweden)

    Jia Chen

    2014-01-01

    Full Text Available One of the major breakthroughs in oncogenesis research in recent years is the discovery that, in most patients, oncogenic mutations are concentrated in a few core biological functional pathways. This discovery indicates that oncogenic mechanisms are highly related to the dynamics of biologic regulatory networks, which govern the behaviour of functional pathways. Here, we propose that oncogenic mutations found in different biological functional pathways are closely related to parameter sensitivity of the corresponding networks. To test this hypothesis, we focus on the DNA damage-induced apoptotic pathway--the most important safeguard against oncogenesis. We first built the regulatory network that governs the apoptosis pathway, and then translated the network into dynamics equations. Using sensitivity analysis of the network parameters and comparing the results with cancer gene mutation spectra, we found that parameters that significantly affect the bifurcation point correspond to high-frequency oncogenic mutations. This result shows that the position of the bifurcation point is a better measure of the functionality of a biological network than gene expression levels of certain key proteins. It further demonstrates the suitability of applying systems-level analysis to biological networks as opposed to studying genes or proteins in isolation.

  1. Complex Oncogenic Translocations with Gene Amplification are Initiated by Specific DNA Breaks in Lymphocytes

    OpenAIRE

    2009-01-01

    Chromosomal instability is a hallmark of many tumor types. Complex chromosomal rearrangements with associated gene amplification, known as complicons, characterize many hematologic and solid cancers. While chromosomal aberrations, including complicons, are useful diagnostic and prognostic cancer markers, their molecular origins are not known. Although accumulating evidence has implicated DNA double strand break repair in suppression of oncogenic genome instability, the genomic elements requir...

  2. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia

    NARCIS (Netherlands)

    Gröschel, Stefan; Sanders, Mathijs A; Hoogenboezem, Remco; de Wit, Elzo; Bouwman, Britta A M; Erpelinck, Claudia; van der Velden, Vincent H J; Havermans, Marije; Avellino, Roberto; van Lom, Kirsten; Rombouts, Elwin J; van Duin, Mark; Döhner, Konstanze; Beverloo, H Berna; Bradner, James E; Döhner, Hartmut; Löwenberg, Bob; Valk, Peter J M; Bindels, Eric M J; de Laat, Wouter; Delwel, Ruud

    2014-01-01

    Chromosomal rearrangements without gene fusions have been implicated in leukemogenesis by causing deregulation of proto-oncogenes via relocation of cryptic regulatory DNA elements. AML with inv(3)/t(3;3) is associated with aberrant expression of the stem-cell regulator EVI1. Applying functional geno

  3. Role of STAT3 in in vitro transformation triggered by TRK oncogenes.

    Directory of Open Access Journals (Sweden)

    Claudia Miranda

    Full Text Available TRK oncoproteins are chimeric versions of the NTRK1/NGF receptor and display constitutive tyrosine kinase activity leading to transformation of NIH3T3 cells and neuronal differentiation of PC12 cells. Signal Transducer and Activator of Transcription (STAT 3 is activated in response to cytokines and growth factors and it has been recently identified as a novel signal transducer for TrkA, mediating the functions of NGF in nervous system. In this paper we have investigated STAT3 involvement in signalling induced by TRK oncogenes. We showed that TRK oncogenes trigger STAT3 phosphorylation both on Y705 and S727 residues and STAT3 transcriptional activity. MAPK pathway was involved in the induction of STAT3 phosphorylation. Interestingly, we have shown reduced STAT3 protein level in NIH3T3 transformed foci expressing TRK oncogenes. Overall, we have unveiled a dual role for STAT3 in TRK oncogenes-induced NIH3T3 transformation: i decreased STAT3 protein levels, driven by TRK oncoproteins activity, are associated to morphological transformation; ii residual STAT3 transcriptional activity is required for cell growth.

  4. The contribution of tumor and host tissue factor expression to oncogene-driven gliomagenesis.

    Science.gov (United States)

    Magnus, Nathalie; Meehan, Brian; Garnier, Delphine; Hashemi, Maryam; Montermini, Laura; Lee, Tae Hoon; Milsom, Chloe; Pawlinski, Rafal; Ohlfest, John; Anderson, Mark; Mackman, Nigel; Rak, Janusz

    2014-11-14

    Glioblastoma multiforme (GBM) is an aggressive form of glial brain tumors, associated with angiogenesis, thrombosis, and upregulation of tissue factor (TF), the key cellular trigger of coagulation and signaling. Since TF is upregulated by oncogenic mutations occurring in different subsets of human brain tumors we investigated whether TF contributes to tumourigenesis driven by oncogenic activation of EGFR (EGFRvIII) and RAS pathways in the brain. Here we show that TF expression correlates with poor prognosis in glioma, but not in GBM. In situ, the TF protein expression is heterogeneously expressed in adult and pediatric gliomas. GBM cells harboring EGFRvIII (U373vIII) grow aggressively as xenografts in SCID mice and their progression is delayed by administration of monoclonal antibodies blocking coagulant (CNTO 859) and signaling (10H10) effects of TF in vivo. Mice in which TF gene is disrupted in the neuroectodermal lineage exhibit delayed progression of spontaneous brain tumors driven by oncogenic N-ras and SV40 large T antigen (SV40LT) expressed under the control of sleeping beauty transposase. Reduced host TF levels in low-TF/SCID hypomorphic mice mitigated growth of glioma subcutaneously but not in the brain. Thus, we suggest that tumor-associated TF may serve as therapeutic target in the context of oncogene-driven disease progression in a subset of glioma.

  5. Netrin-1 exerts oncogenic activities through enhancing Yes-associated protein stability.

    Science.gov (United States)

    Qi, Qi; Li, Dean Y; Luo, Hongbo R; Guan, Kun-Liang; Ye, Keqiang

    2015-06-09

    Yes-associated protein (YAP), a transcription coactivator, is the major downstream effector of the Hippo pathway, which plays a critical role in organ size control and cancer development. However, how YAP is regulated by extracellular stimuli in tumorigenesis remains incompletely understood. Netrin-1, a laminin-related secreted protein, displays proto-oncogenic activity in cancers. Nonetheless, the downstream signaling mediating its oncogenic effects is not well defined. Here we show that netrin-1 via its transmembrane receptors, deleted in colorectal cancer and uncoordinated-5 homolog, up-regulates YAP expression, escalating YAP levels in the nucleus and promoting cancer cell proliferation and migration. Inactivating netrin-1, deleted in colorectal cancer, or uncoordinated-5 homolog B (UNC5B) decreases YAP protein levels, abrogating cancer cell progression by netrin-1, whereas knockdown of mammalian STE20-like protein kinase 1/2 (MST1/2) or large tumor suppressor kinase 1/2 (Lats1/2), two sets of upstream core kinases of the Hippo pathway, has no effect in blocking netrin-1-induced up-regulation of YAP. Netrin-1 stimulates phosphatase 1A to dephosphorylate YAP, which leads to decreased ubiquitination and degradation, enhancing YAP accumulation and signaling. Hence, our findings support that netrin-1 exerts oncogenic activity through YAP signaling, providing a mechanism coupling extracellular signals to the nuclear YAP oncogene.

  6. Src-like-adaptor protein (SLAP) differentially regulates normal and oncogenic c-Kit signaling.

    Science.gov (United States)

    Kazi, Julhash U; Agarwal, Shruti; Sun, Jianmin; Bracco, Enrico; Rönnstrand, Lars

    2014-02-01

    The Src-like-adaptor protein (SLAP) is an adaptor protein sharing considerable structural homology with Src. SLAP is expressed in a variety of cells and regulates receptor tyrosine kinase signaling by direct association. In this report, we show that SLAP associates with both wild-type and oncogenic c-Kit (c-Kit-D816V). The association involves the SLAP SH2 domain and receptor phosphotyrosine residues different from those mediating Src interaction. Association of SLAP triggers c-Kit ubiquitylation which, in turn, is followed by receptor degradation. Although SLAP depletion potentiates c-Kit downstream signaling by stabilizing the receptor, it remains non-functional in c-Kit-D816V signaling. Ligand-stimulated c-Kit or c-Kit-D816V did not alter membrane localization of SLAP. Interestingly oncogenic c-Kit-D816V, but not wild-type c-Kit, phosphorylates SLAP on residues Y120, Y258 and Y273. Physical interaction between c-Kit-D816V and SLAP is mandatory for the phosphorylation to take place. Although tyrosine-phosphorylated SLAP does not affect c-Kit-D816V signaling, mutation of these tyrosine sites to phenylalanine can restore SLAP activity. Taken together the data demonstrate that SLAP negatively regulates wild-type c-Kit signaling, but not its oncogenic counterpart, indicating a possible mechanism by which the oncogenic c-Kit bypasses the normal cellular negative feedback control.

  7. Calpain Activity Is Generally Elevated during Transformation but Has Oncogene-Specific Biological Functions

    Directory of Open Access Journals (Sweden)

    N.O. Carragher

    2004-01-01

    Full Text Available Several oncogene and tumor-suppressor gene products are known substrates for the calpain family of cysteine proteases, and calpain is required for transformation by v-src and tumor invasion. Thus, we have now addressed whether calpain is generally associated with transformation and how calpain contributes to oncogene function. Our results demonstrate that calpain activity is enhanced upon transformation induced by the v-Src, v-Jun, v-Myc, k-Ras, and v-Fos oncoproteins. Furthermore, elevated calpain activity commonly promotes focal adhesion remodelling, disruption of actin cytoskeleton, morphological transformation, and cell migration, although proteolysis of target substrates (such as focal adhesion kinase, talin, and spectrin is differently specified by individual oncoproteins. Interestingly, v-Fos differs from other common oncoproteins in not requiring calpain activity for actin/adhesion remodelling or migration of v-Fos transformed cells. However, anchorage-independent growth of all transformed cells is sensitive to calpain inhibition. In addition, elevated calpain activity contributes to oncogene-induced apoptosis associated with transformation by v-Myc. Taken together, these studies demonstrate that calpain activity is necessary for full cellular transformation induced by common oncoproteins, but has distinct roles in oncogenic events induced by individual transforming proteins. Thus, targeting calpain activity may represent a useful general strategy for interfering with activated protooncogenes in cancer cells.

  8. Analyses of domains and domain fusions in human proto-oncogenes

    Directory of Open Access Journals (Sweden)

    Wan Ping

    2009-03-01

    Full Text Available Abstract Background Understanding the constituent domains of oncogenes, their origins and their fusions may shed new light about the initiation and the development of cancers. Results We have developed a computational pipeline for identification of functional domains of human genes, prediction of the origins of these domains and their major fusion events during evolution through integration of existing and new tools of our own. An application of the pipeline to 124 well-characterized human oncogenes has led to the identification of a collection of domains and domain pairs that occur substantially more frequently in oncogenes than in human genes on average. Most of these enriched domains and domain pairs are related to tyrosine kinase activities. In addition, our analyses indicate that a substantial portion of the domain-fusion events of oncogenes took place in metazoans during evolution. Conclusion We expect that the computational pipeline for domain identification, domain origin and domain fusion prediction will prove to be useful for studying other groups of genes.

  9. Repeat-element driven activation of proto-oncogenes in human malignancies.

    Science.gov (United States)

    Lamprecht, Björn; Bonifer, Constanze; Mathas, Stephan

    2010-11-01

    Recent data demonstrated that the aberrant activity of endogenous repetitive elements of the DNA in humans can drive the expression of proto-oncogenes. This article summarizes these results and gives an outlook on the impact of these findings on the pathogenesis and therapy of human cancer.

  10. Oncogenic Splicing Factor SRSF1 Is a Critical Transcriptional Target of MYC

    Directory of Open Access Journals (Sweden)

    Shipra Das

    2012-02-01

    Full Text Available The SR protein splicing factor SRSF1 is a potent proto-oncogene that is frequently upregulated in cancer. Here, we show that SRSF1 is a direct target of the transcription factor oncoprotein MYC. These two oncogenes are significantly coexpressed in lung carcinomas, and MYC knockdown downregulates SRSF1 expression in lung-cancer cell lines. MYC directly activates transcription of SRSF1 through two noncanonical E-boxes in its promoter. The resulting increase in SRSF1 protein is sufficient to modulate alternative splicing of a subset of transcripts. In particular, MYC induction leads to SRSF1-mediated alternative splicing of the signaling kinase MKNK2 and the transcription factor TEAD1. SRSF1 knockdown reduces MYC's oncogenic activity, decreasing proliferation and anchorage-independent growth. These results suggest a mechanism for SRSF1 upregulation in tumors with elevated MYC and identify SRSF1 as a critical MYC target that contributes to its oncogenic potential by enabling MYC to regulate the expression of specific protein isoforms through alternative splicing.

  11. Le mythe du bon sauvage Hottentot

    Directory of Open Access Journals (Sweden)

    M-J Boisacq

    1993-05-01

    Full Text Available Two themes in the Voyage á l'intérieur de I'Afrique par le Cap de Bonne-Espérance by Francois le Vaillant, 1790, attracted our attention: firstly, the criticism of the colonial system, modelled on Denis Diderot's criticism, and secondly, the description of the Hottentot people according to the mythical vision of the tribes as suggested by Jean-Jacques Rousseau. A brief explanation of Diderot's anti-colonial ideas and of the myth of the ‘noble Savage' as suggested by Rousseau, will be followed by a critical analysis of the Voyage ... so as to prove that this work is in perfect agreement with the ideologies existing in France during the second half of the 18th century and in line with the reformist notions of the thinkers who reconcile humanity and self-interest.

  12. Le CFEY et après…

    Directory of Open Access Journals (Sweden)

    François Burgat

    2000-09-01

    Full Text Available La livraison des Chroniques Yéménites 2000 s'inscrit dans le droit fil de l'initiative heureuse prise en 1993 par Frank Mermier, tout en prolongeant un effort entrepris dans la livraison précédente : allégées des comptes rendus de recherche cantonnés désormais au rapport scientifique du Centre et à son site Internet, les Chroniques entendent plus que jamais présenter un vaste panorama de la recherche sur le Yémen ou de la production intellectuelle de ce pays. La revue est désormais dotée d'un...

  13. Le possédé spectaculaire

    OpenAIRE

    Aubin-Boltanski, Emma; Aubrée, Marion; Bernand, Carmen; Choron-Baix, Catherine; Claveyrolas, Mathieu; Coiffier, Christian; Dianteill, Erwan; Duco, Suzanne; D’Urso, Andrea; Giobellina Brumana, Fernando; Guigon, Gwénaële; Hell, Bertrand; Hooper, Steven; Kapchan, Deborah; Mauzé, Marie

    2011-01-01

    Le possédé est-il un comédien ou un fou? Telle est l’alternative qu’ont tenté de dépasser en leur temps Roger Bastide, Michel Leiris et Alfred Métraux. Ces trois anthropologues rejettent en effet l’approche psychiatrique de la possession où la transe est conçue comme un état psychopathologique ou une libération incontrôlée de pulsions ; ils acceptent en revanche à différents degrés l’aspect joué de la possession. Dès 1938, Leiris anticipe les développements sur le « vestiaire de personnalités...

  14. Le matérialisme scientifique

    Science.gov (United States)

    Meunier, Jean-François

    2004-03-01

    De nos jours, il arrive quotidiennement aux grands hommes d'avoir à fréquenter d'ignorants mortels épris d'une conviction maladive que la science est la grande responsable de tous les maux du monde. Évidemment sans physique atomique, il n'y aurait pas eu d'Hiroshima et sans révolution industrielle, pas de pollution et etc. Cependant, ces accusations envers le progrès technique sont tout à fait injustes, irréfléchies et, j'irai même jusqu'à dire, irresponsables, puisque le calcul, i.e. la planification, même la plus élémentaire, est ce qui caractérise le mieux, pragmatiquement, la société humaine. À mon avis, les problèmes sociaux tireraient plutôt leur origine de sciences sociales irréalistes, qui, concrètment, inspireraient ou serviraient d'alibis à ceux qui détiennent véritablement le pouvoir. Dans cet article, je tenterai donc de démontrer la meilleure véracité et efficacité du matérialisme scientifique. Cette doctrine, dont Mario Bunge est le plus illustre représentant, s'appuy sur les résultats théoriques et expérimentaux des sciences factuelles ainsi que sur l'exactitude logique des mathématiques, utilisées ici comme langage universel de l'expression des idées. Cette conception philosophique qui s'inspire principalement du modèle des théories physiques, stipule que les réalités sociales sont, comme tout autre réalité, matérielles, mathématisables et représentables comme des systèmes en interaction. En fait, le modèle des physiciens ayant historiquement fait ses preuves en matière de testabilité et de cohérence interne est proposé d'être appliquer aux sciences sociales, aujourd'hui scindées des sciences dites pures sous l'inspiration des pseudo penseurs néo-kantiens, phénoménologiques et post-moderne. Cette nouvelle approche permettrait ainsi d'évoluer plus exactement vers une compréhension des bases sociales et biologiques du comportement humain afin de développer une éthique sans cesse plus r

  15. Le changement de croyances extrêmes

    OpenAIRE

    Sauvayre, Romy

    2012-01-01

    Dans le domaine de l’adhésion et de la désadhésion à un mouvement marginal – appelé «secte» par les uns et «Nouveaux Mouvements Religieux» par les autres –, il semble mystérieux de voir un individu accepter des croyances et des pratiques perçues comme irrationnelles, alors que la désadhésion est vue comme un retour «normal» à la raison. Nous nous proposons d’examiner différentes facettes du changement de croyances en abordant successivement le processus d’adhésion, l’apparente «résistance au ...

  16. Le Corbusier : una arquitectura para el hombre

    Directory of Open Access Journals (Sweden)

    Begoña Fernández Cabaleiro

    2000-01-01

    Full Text Available Le Corbusier conoció diferentes ciudades y pianteamientos arquitectónicos. A través de sus estudios y experiencias se planteó la arquitectura como una importante misión cultural. Pensó una nueva arquitectura que en la era de la máquina, prestase un nuevo servicio al hombre. Sería la búsqueda de la manifestación del pasado en una equivalencia para los tiempos modernos.Le Corbusier knew different cities and ways of architecture all around the world. Through his studies and works, he saw the important cultural mission of the architecture. Architects ought to make new works for the man in the machine time. They must look for the last magnificence according to the present needs.

  17. Le mythe de la femme sauvage

    OpenAIRE

    Pelen, Jean-Noël

    2008-01-01

    Le livre de Clarissa Pinkola Estés, Femmes qui courent avec les loups. Histoires et mythes de l’archétype de la femme sauvage (Paris, 1996, e. o. 1992), connaît, depuis sa parution, un véritable succès mondial. Son objet est de « faire recouvrer à la femme la beauté de ses formes psychiques naturelles ». Le chemin pour y parvenir est longuement décrit à partir d’une analyse jungienne de quatorze récits de tradition orale (contes, mythes, légendes) qui renfermeraient les secrets des « anciens ...

  18. Mel Gibson contre le boulevard Raspail

    Directory of Open Access Journals (Sweden)

    Boris Jeanne

    2007-03-01

    Full Text Available Que peuvent faire les historiens et les anthropologues spécialistes de l’Amérique face à la puissance médiatique et commerciale d’Apocalypto, le dernier film de Mel Gibson, produit par Buena Vista (c'est-à-dire Disney et ayant déjà engrangé plus de 50 millions de dollars de recette avant même sa sortie en France ? Le cinéma est un art du présent, et quelle que soit l’exactitude de la reconstitution historique qu’il prétend parfois présenter, il demeure un puissant vecteur d’analyse de la soc...

  19. Le changement de croyances extrêmes

    OpenAIRE

    Sauvayre, Romy

    2012-01-01

    Dans le domaine de l’adhésion et de la désadhésion à un mouvement marginal – appelé «secte» par les uns et «Nouveaux Mouvements Religieux» par les autres –, il semble mystérieux de voir un individu accepter des croyances et des pratiques perçues comme irrationnelles, alors que la désadhésion est vue comme un retour «normal» à la raison. Nous nous proposons d’examiner différentes facettes du changement de croyances en abordant successivement le processus d’adhésion, l’apparente «résistance au ...

  20. Aiutare le vittime della mafia a ribellarsi

    Directory of Open Access Journals (Sweden)

    Roberto Riccardi

    2007-09-01

    Full Text Available Nino Miceli is a Sicilian man, owner of a small business: at the beginning of 1990s he is concessionnaire of cars in Gela, an quite big town in Sicily. He works hard and soon he starts to earn a lot. Business is very good, and customers are satisfied and everything seems to go on successfully. But the mafia keeps an eye on him and, at a certain point, he was asked to pay them what in Italy is called “pizzo”. Nino Miceli does not want to pay it, he does not want to surrender to the mafia coercion. However, at the beginning he pays the “pizzo” but then he starts to record the conversation he has with those men (the “mafiosi”, in order to prove and demonstrate the crime. He also looks for protection at the local station of Carabinieri; finally, he decides to report the extortion but, from that time on, he starts to experience more and more serious threats.Helped by an officer of Carabinieri, he becomes a witness of justice and, for that reason, he must change his identity. He leaves Sicily along with his family and move into a different region of Italy, far from his town, where nobody knows him. In 2007 he decides to write a book of memories, titled “Io, il fu Nino Miceli” (in English it could sound like “I was Nino Miceli”. This article tells his story, speaking also about the role played by the Arma of Carabinieri in supporting victims of racket and usury.Nino Miceli est un entrepreneur sicilien originaire de Realmonte, une ville en province d'Agrigento. Au début des années 90, il est proprietaire du garage Lancia à Gela. Il s'engage beaucoup dans son travail et les résultats ne tardent pas à arriver. La clientèle augmente, les affaires vont bon train, mais c'est justement quand l'entreprise est en train de prospérer que la mafia lui demande des comptes. Il doit payer le pot-de-vin comme tous les commerçants du quartier. Nino Miceli n'est pas d'accord avec cela. Au début il subit, mais il commence bientôt

  1. Le Japon quatre fois frappé

    Directory of Open Access Journals (Sweden)

    Philippe Pelletier

    2011-03-01

    Full Text Available Illustration 1 – Hauteur du tsunami sur le littoral (en mètresSources : Brunet R. (dir, 1994. Géographie universelle. Belin/Reclus ;Pelletier Ph., Fournier C., 2008. Atlas du Japon. Autrement ; http://silatitudes.teledetection.fr/index.php :actualité/54-mapping-japan-earthquake-and-tsunami Dans un essai polémiste au destin retentissant, du moins auprès de ceux qui s’intéressent sérieusement à l’Asie orientale, le sinologue Jean François Billeter dénonçait l’approche néo-orientaliste du sino...

  2. Le Devenir d’un concept

    Directory of Open Access Journals (Sweden)

    Ioulia Podoroga

    2011-03-01

    Full Text Available Cet article examine l'usage métaphorique, chez Blanchot, du terme de résurrection, et sa transformation chez Jean-Luc Nancy en concept de théorie littéraire. Il s'agit alors de suivre les torsions opérées sur ce terme religieux, d'abord chez Blanchot qui en pervertit poétiquement le sens dans l'image d'une résurrection de la mort où la mort devient le sujet de la résurrection, puis chez Nancy qui, reprenant l'image et les paradoxes qu'elle porte, veut en faire non seulement un motif récurrent dans l'œuvre de Blanchot mais jusqu'au concept permettant de comprendre au plus profond ce qu'est pour ce dernier l'expérience littéraire

  3. LE SECTEUR INFORMEL EN ALGERIE : APPROCHES, ACTEURS ...

    African Journals Online (AJOL)

    ... du secteur. * Maître de conférences en sciences économiques, Université de Bejaia ..... nales et internationales et dans un souci d'harmoniser les statistiques sur le secteur informel dans les ...... Thèse de doctorat,. Université Paris Est Créteil et université de Bejaia, Paris-Alger. ... Institut de la Méditerranée. (France) et ...

  4. Le médecin, mon ami?

    OpenAIRE

    Rieder, Philip Alexander

    2014-01-01

    Cet article retrace l'histoire de la relation thérapeutique au cours de l'Ancien Régime en mettant en évidence l'importance de l'amitié entre le médecin et son malade. Une explication est proposée à la transition, au 19e siècle, vers une relation thérapeutique professionnelle.

  5. Le nouveall visage de la campagne chinoise

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Dans IES vastes territoires de Chine se trouve Un hombre considérable de bourgs de tallies variables, ou vivent 80% de la population chinoise. Après plus de 20 ans de """"""""""""""""réforme et d'ouverture"""""""""""""""", émerge une situation économique route nouvelle; """"""""""""""""Le développement rural avec les technologies modernes"""""""""""""""". Les petits bourgs ont établit un système de soins médicaux,

  6. COMO ENTENDER AS PRINCIPAIS TEORIAS DA LE

    OpenAIRE

    Nascimento, Francisco de Assis do; Carvalho, Jander Ramos; Costa, Priscila Márcia de Andrade; Bastos, Rafael Lira Gomes

    2013-01-01

    O presente artigo mostrará algumas das principais teorias de aquisiçãode LE. Desta forma mostraremos como fatores como afetividadee o meio, encontrados nessas teorias podem influenciar no processode aquisição de uma língua estrangeira. Observaremos também quecada teoria observa pontos diferentes do processo de aquisição de L2,uns tendem ao cognitivismo outras ao social, e outras aos aspectos lingüísticos.

  7. LE SESSE DEL LAGO DI VICO

    Directory of Open Access Journals (Sweden)

    g. pannocchia

    1951-06-01

    Full Text Available Nel presente lavoro si determinano con i metodi di Defant e diHidaka i periodi delle sesse nni-bi e tri-nodale del lago di Vico, lerelative distanze dei nodi e le curve rappresentanti l'andamento delleampiezze di oscillazione con i metodi detti. Con il metodo indicatoda Neumann si determina di nuovo il periodo della sessa uni-nodale.

  8. Spotlight on CERN : Le code de conduite

    CERN Multimedia

    CERN Video Productions

    2010-01-01

    Cette année 2010, le démarrage du LHC a été le témoignage de la réussite de la collaboration scientifique au CERN, rapprochant les personnes, hommes et femmes, tous ensemble pour la plus grande des réalisations. Cette collaboration nécessite une ouverture sur la diversité basée sur des valeurs solides. Pour s’assurer que l'Organisation continue sur la voie du succès, un consensus a été atteint sur des valeurs caractérisant le CERN et celles-ci ont été regroupées dans un Code de conduite, décrivant la norme de base du comportement que nous pouvons tous espérer de nous-mêmes et de nos collègues sur notre lieu de travail. Entrevues avec Rolf Heuer, Directeur Général du CERN, Anne-Sylvie Catherin, Chef du Département des Ressources Humaines, et Vincent Vuillemin, Ombuds au CERN.

  9. L'astronomie dans le monde

    Science.gov (United States)

    Manfroid, J.

    2003-01-01

    Premier plongeon d'Integral dans l'univers du rayonnement gamma; Collisions et cannibalisme galactique; Proplydes dans la Carène; Quasar record; Eta Carinae étoile double; Géantes rouges; La vitesse de la gravité; Sursaut gamma; Une planète lointaine; Un Troyen neptunien; L'univers lointain; Bébé galaxie; Le centre de notre Galaxie version X; Un HERO astronomique; Disque X géant; Electrons mystérieux dans RCW 38; Environnement martien; Interférométrie infrarouge; Méthane titanien; Micro-organismes atmosphériques; Réchauffement planétaire; La meilleure observation infrarouge de l'univers; Planètes en grand nombre?; Pôle sud et Big Bang; SS 433; Volcans et astéroïdes; Amalthée; De l'eau sur Mars; DEM L 106; Gliese 876; La taille des étoiles; Le danger des supernovas; Vieux cailloux

  10. Oncogenic signaling by Kit tyrosine kinase occurs selectively on the Golgi apparatus in gastrointestinal stromal tumors.

    Science.gov (United States)

    Obata, Y; Horikawa, K; Takahashi, T; Akieda, Y; Tsujimoto, M; Fletcher, J A; Esumi, H; Nishida, T; Abe, R

    2017-02-13

    Gastrointestinal stromal tumors (GISTs) are caused by gain-of-function mutations in the Kit receptor tyrosine kinase. Most primary GIST patients respond to the Kit inhibitor imatinib, but this drug often becomes ineffective because of secondary mutations in the Kit kinase domain. The characteristic intracellular accumulation of imatinib-sensitive and -resistant Kit protein is well documented, but its relationship to oncogenic signaling remains unknown. Here, we show that in cancer tissue from primary GIST patients as well as in cell lines, mutant Kit accumulates on the Golgi apparatus, whereas normal Kit localizes to the plasma membrane (PM). In imatinib-resistant GIST with a secondary Kit mutation, Kit localizes predominantly on the Golgi apparatus. Both imatinib-sensitive and imatinib-resistant Kit (Kit(mut)) become fully auto-phosphorylated only on the Golgi and only if in a complex-glycosylated form. Kit(mut) accumulates on the Golgi during the early secretory pathway, but not after endocytosis. The aberrant kinase activity of Kit(mut) prevents its export from the Golgi to the PM. Furthermore, Kit(mut) on the Golgi signals and activates the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathway, signal transducer and activator of transcription 5 (STAT5), and the Mek-Erk pathway. Blocking the biosynthetic transport of Kit(mut) to the Golgi from the endoplasmic reticulum inhibits oncogenic signaling. PM localization of Kit(mut) is not required for its signaling. Activation of Src-family tyrosine kinases on the Golgi is essential for oncogenic Kit signaling. These results suggest that the Golgi apparatus serves as a platform for oncogenic Kit signaling. Our study demonstrates that Kit(mut)'s pathogenicity is related to its mis-localization, and may offer a new strategy for treating imatinib-resistant GISTs.Oncogene advance online publication, 13 February 2017; doi:10.1038/onc.2016.519.

  11. Analysis of multiple sarcoma expression datasets: implications for classification, oncogenic pathway activation and chemotherapy resistance.

    Directory of Open Access Journals (Sweden)

    Panagiotis A Konstantinopoulos

    Full Text Available BACKGROUND: Diagnosis of soft tissue sarcomas (STS is challenging. Many remain unclassified (not-otherwise-specified, NOS or grouped in controversial categories such as malignant fibrous histiocytoma (MFH, with unclear therapeutic value. We analyzed several independent microarray datasets, to identify a predictor, use it to classify unclassifiable sarcomas, and assess oncogenic pathway activation and chemotherapy response. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed 5 independent datasets (325 tumor arrays. We developed and validated a predictor, which was used to reclassify MFH and NOS sarcomas. The molecular "match" between MFH and their predicted subtypes was assessed using genome-wide hierarchical clustering and Subclass-Mapping. Findings were validated in 15 paraffin samples profiled on the DASL platform. Bayesian models of oncogenic pathway activation and chemotherapy response were applied to individual STS samples. A 170-gene predictor was developed and independently validated (80-85% accuracy in all datasets. Most MFH and NOS tumors were reclassified as leiomyosarcomas, liposarcomas and fibrosarcomas. "Molecular match" between MFH and their predicted STS subtypes was confirmed both within and across datasets. This classification revealed previously unrecognized tissue differentiation lines (adipocyte, fibroblastic, smooth-muscle and was reproduced in paraffin specimens. Different sarcoma subtypes demonstrated distinct oncogenic pathway activation patterns, and reclassified MFH tumors shared oncogenic pathway activation patterns with their predicted subtypes. These patterns were associated with predicted resistance to chemotherapeutic agents commonly used in sarcomas. CONCLUSIONS/SIGNIFICANCE: STS profiling can aid in diagnosis through a predictor tracking distinct tissue differentiation in unclassified tumors, and in therapeutic management via oncogenic pathway activation and chemotherapy response assessment.

  12. Le Service Accueil et Contrôle d'Accès

    CERN Document Server

    Ducastel, C

    1999-01-01

    L'utilisateur qui vient au CERN pour la première fois, est accueilli généralement par les membres du service 'Accueil et Contrôle d'Accès'. Cet utilisateur sera tout d'abord orienté vers un des postes d'hôtesses d'accueil en charge de l'enregistrement et de la délivrance de cartes CERN. Les informations seront saisies et immédiatement disponibles et transmises, via le système AMS, aux équipements de contrôle d'accès et à la Centrale de Surveillance des accès, chargée de la supervision de tout le dispositif de contrôle d'accès au domaine. Ces contrôles aux entrées et accueil des visiteurs individuels sont complétés par des missions de surveillance à l'intérieur du Domaine pour les agents, et par des travaux de gestions de dossiers administratifs (service enregistrement) pour les hôtesses. Un contrat commun assure une uniformité de formation des agents et hôtesses. Ce contrat est assorti d'une clause de Bonus Malus afin de tendre vers une optimisation des performances.

  13. Le royaume de Méroé

    Directory of Open Access Journals (Sweden)

    Claude Rilly

    2010-04-01

    Full Text Available La civilisation napato-méroïtique qui domine le cours du Nil moyen, d’Assouan à Khartoum, depuis le viiie siècle av. J.-C. jusqu’au ive siècle apr. J.-C., fait suite à la colonisation égyptienne du Soudan ancien. Par sa religion, son idéologie, ses institutions, sa culture matérielle, elle se rattache étroitement au modèle égyptien à tel point que l’on peut parler d’une « civilisation pharaonique » dont l’Égypte et le Soudan ancien seraient les deux versants. L’histoire du royaume de Méroé est assez mal connue dans le détail, d’une part parce que les textes méroïtiques sont peu nombreux et très partiellement compris, d’autre part en raison d’une couverture archéologique relativement récente et clairsemée. Les sources extérieures, égyptiennes, grecques et romaines, sont assez laconiques et moyennement fiables. Les progrès récents de l’archéologie et de la philologie du Soudan ancien laissent toutefois espérer de prochaines avancées.The Napatan-Meroitic civilisation flourished in the Middle Nile valley from the 8th century BC to the 4th century AD. It inherited from the former Egyptian colonisation cultural patterns that are obvious in religious and ideological fields as much as in institutions or artefacts. One could even speak of a “Pharaonic civilization” with two sides, Egypt and Ancient Sudan. Little is known from the history of the kingdom of Meroe, first because Meroitic texts are in small number and poorly understood and secondly because archaeological excavations are fairly recent and scattered. External sources such as Egyptian, Greek and Roman evidences are scanty and moderately reliable. However recent progress in the archaeology and philology of Ancient Sudan is currently improving the knowledge of this civilisation.

  14. Le temps passe,la lecture reste%Le temps passe, la lecture reste

    Institute of Scientific and Technical Information of China (English)

    张晓霖

    2011-01-01

    Il y a plus de deux mille ans,Confucius insistait déjà sur l'importance de la lecture.En effet,depuis deux mille ans,la lecture est une tradition,qui influence beaucoup les Chinois.De m(e)me,en Occident,l'Eglise chrétienne a demandé très t(o)t à ses fidèles de lire la Bible,car sa lecture était le moyen d'entrer en communication avec Dieu.Selon la tradition juda(i)que,la mère mettait un peu de miel sur la Bible,et laissait ses enfants l'embrasser,ceci dans le but de leur faire comprendre que le Livre est d'une douceur merveilleuse.

  15. P. Maraval, Théodose le Grand, Le pouvoir et la foi

    OpenAIRE

    Vinel, Françoise

    2015-01-01

    Le titre de la nouvelle publication de P. Maraval annonce une monographie, et la succession des chapitres correspond à la chronologie de la vie de Théodose, de la bataille d’Andrinople en 378 et son accession au trône impérial jusqu’à sa mort en 395. Une telle étude comble un manque dans l’édition française, rappelle l’A. en mentionnant le livre d’E. Fléchier, Histoire de Théodose le Grand, paru en 1679 ; mais la bibliographie mentionne deux études allemandes récentes, celle de J. Leppin paru...

  16. le des tendeurs sur le comportement dynamique d’une transmission par courroie

    OpenAIRE

    Michon, Guilhem; Manin, Lionel; Rémond, Didier; Dufour, Regis

    2006-01-01

    Les transmissions par courroie poly-v (striées), utilisées notamment pour l’entraînement des accessoires d’un moteur automobile, sont généralement équipées d’un galet tendeur afin de réduire les vibrations et de garantir une tension minimum suffisante. Deux types de tendeurs peuvent être utilisés, ils diffèrent par la façon dont est généré l’amortissement : le premier, dit ‘mécanique’ utilise le frottement sec ; le second, dit ‘hydraulique’ est équipé d’un amortisseur. Les deux sont équipés d...

  17. Le bois et ses usages dans le De architectura de Vitruve

    Directory of Open Access Journals (Sweden)

    Sylvie Rougier-Blanc

    2011-05-01

    Full Text Available Ni traité d’architecture à proprement parler, ni véritable ouvrage philosophique, le De architectura de Vitruve permet d’aborder la question du matériau bois et de ses usages en architecture de manière à la fois précise et décevante pour l’historien des techniques : précise parce que le paragraphe 9 du livre II est plus particulièrement consacré à cette materia, mais décevante parce que le contenu ne répond pas aux attentes et ne permet pas de dresser un bilan des choix des essences en foncti...

  18. Le monde Gothique de Le Fanu : cryptonymes et mots étrangers

    OpenAIRE

    Berthin, Christine

    2014-01-01

    Cet article examine l’usage des mots et des noms étrangers chez Le Fanu. Dans Uncle Silas le français est la langue de la terreur personnelle, collective et historique. Il est la langue de tous les scélérats dans le texte et ressurgit d’un passé mal refoulé, mal enterré. Dans Carmilla, l’allemand vient offrir une alternative à la langue du récit. Cette autre langue est la langue de l’autre, du revenant, du vampire qui parle à contretemps et à contre-courant de la doxa et dont les mots demeure...

  19. De quoi le genre est-il le nom ?

    OpenAIRE

    Andrieu, Bernard

    2013-01-01

    Cette note de lecture présente une courte évolution des travaux sur le genre sous l’angle du rapport au corps en démontrant comment la dénaturalisation du corps et du sexe biologique a conduit à une description culturaliste des fonctions individuelles et des rôles sociaux. Si le genre dénaturalise le corps c’est en refusant toute référence au sexe ou à la sexualité en tant qu’ils seraient des données naturelles. Depuis son apparition en 1947, sous la plume de John Money, psychologue chargé du...

  20. Lele de l'imagination chez Kant

    OpenAIRE

    Azoulay, Arnaud

    2015-01-01

    Ce travail se propose d'analyser lele fondamental que joue l'imagination relativement à la possibilité de la connaissance, en examinant la fonction propre des deux actes cognitifs essentiels de l'imagination transcendantale, à savoir, la synthèse et le schématisme. La réflexion sur cette faculté originaire et médiatrice de l'esprit irrigue l'ensemble de l’oeuvre critique kantienne, et nous fait découvrir une faculté aussi mystérieuse qu'indispensable, dont les mécanismes insaisissables s'a...

  1. Le théâtre de la politique

    Directory of Open Access Journals (Sweden)

    Michel Contat

    2007-06-01

    Full Text Available Chacun aujourd’hui choisit son Sartre, comme on choisissait son Marx dans les lointaines années 1960, celui des Grundrisse, celui des manuscrits de 1848 ou celui du Capital. Une citation : 'De toute façon, l’ordre social repose aujourd’hui sur la mystification des consciences, comme aussi le désordre. Le nazisme était une mystification et le gaullisme en est une autre, le catholicisme en est une troisième ; il est hors de doute, à présent, que le communisme français en est une quatrième.' C’est Sartre qui parle, le Sartre 1947, celui de Qu’est‐ce que la littérature ? – le Sartre que l’on a peut‐être aujourd’hui le plus de satisfaction à suivre. (Situations II, p. 306. Cité par Julia Kristeva. Le centenaire de 2005 a révélé que Sartre reste toujours l’objet vivant d’une polémique, que ce nom recouvre un homme et une pensée à attaquer, parce que, finalement, comme il le disait, « l’intelligence offense ».

  2. An Interaction with Ewing's Sarcoma Breakpoint Protein EWS Defines a Specific Oncogenic Mechanism of ETS Factors Rearranged in Prostate Cancer.

    Science.gov (United States)

    Kedage, Vivekananda; Selvaraj, Nagarathinam; Nicholas, Taylor R; Budka, Justin A; Plotnik, Joshua P; Jerde, Travis J; Hollenhorst, Peter C

    2016-10-25

    More than 50% of prostate tumors have a chromosomal rearrangement resulting in aberrant expression of an oncogenic ETS family transcription factor. However, mechanisms that differentiate the function of oncogenic ETS factors expressed in prostate tumors from non-oncogenic ETS factors expressed in normal prostate are unknown. Here, we find that four oncogenic ETS (ERG, ETV1, ETV4, and ETV5), and no other ETS, interact with the Ewing's sarcoma breakpoint protein, EWS. This EWS interaction was necessary and sufficient for oncogenic ETS functions including gene activation, cell migration, clonogenic survival, and transformation. Significantly, the EWS interacting region of ERG has no homology with that of ETV1, ETV4, and ETV5. Therefore, this finding may explain how divergent ETS factors have a common oncogenic function. Strikingly, EWS is fused to various ETS factors by the chromosome translocations that cause Ewing's sarcoma. Therefore, these findings link oncogenic ETS function in both prostate cancer and Ewing's sarcoma. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. In Vivo Imaging-Based Mathematical Modeling Techniques That Enhance the Understanding of Oncogene Addiction in relation to Tumor Growth

    Directory of Open Access Journals (Sweden)

    Chinyere Nwabugwu

    2013-01-01

    Full Text Available The dependence on the overexpression of a single oncogene constitutes an exploitable weakness for molecular targeted therapy. These drugs can produce dramatic tumor regression by targeting the driving oncogene, but relapse often follows. Understanding the complex interactions of the tumor’s multifaceted response to oncogene inactivation is key to tumor regression. It has become clear that a collection of cellular responses lead to regression and that immune-mediated steps are vital to preventing relapse. Our integrative mathematical model includes a variety of cellular response mechanisms of tumors to oncogene inactivation. It allows for correct predictions of the time course of events following oncogene inactivation and their impact on tumor burden. A number of aspects of our mathematical model have proven to be necessary for recapitulating our experimental results. These include a number of heterogeneous tumor cell states since cells following different cellular programs have vastly different fates. Stochastic transitions between these states are necessary to capture the effect of escape from oncogene addiction (i.e., resistance. Finally, delay differential equations were used to accurately model the tumor growth kinetics that we have observed. We use this to model oncogene addiction in MYC-induced lymphoma, osteosarcoma, and hepatocellular carcinoma.

  4. Le discours des Comices : un discours modèle

    Directory of Open Access Journals (Sweden)

    Anne Herschberg Pierrot

    2009-10-01

    Full Text Available Dans un discours officiel, publié par le Journal de Rouen du 22 juillet 1853, Flaubert trouve une phrase du discours des Comices qu’il avait écrite la veille. Cet article présente et reproduit les discours cités par le Journal de Rouen.In an official speech, published in the Journal de Rouen on July 22nd 1853, Flaubert found a sentence from the Agricultural association (« Comices agricoles » speeches that he had actually written himself the previous evening. This article presents and reprints the speeches quoted by the Journal de Rouen.

  5. A novel MCF-10A line allowing conditional oncogene expression in 3D culture

    Directory of Open Access Journals (Sweden)

    Danke Christina

    2011-07-01

    Full Text Available Introduction Non-transformed mammary epithelial cell lines such as MCF-10A recapitulate epithelial morphogenesis in three-dimensional (3D tissue culture by forming acinar structures. They represent an important tool to characterize the biological properties of oncogenes and to model early carcinogenic events. So far, however, these approaches were restricted to cells with constitutive oncogene expression prior to the set-up of 3D cultures. Although very informative, this experimental setting has precluded the analysis of effects caused by sudden oncoprotein expression or withdrawal in established epithelial cultures. Here, we report the establishment and use of a stable MCF-10A cell line (MCF-10Atet fitted with a novel and improved doxycycline (dox-regulated expression system allowing the conditional expression of any transgene. Methods MCF-10Atet cells were generated by stable transfection with pWHE644, a vector expressing a second generation tetracycline-regulated transactivator and a novel transcriptional silencer. In order to test the properties of this new repressor/activator switch, MCF-10Atet cells were transfected with a second plasmid, pTET-HABRAF-IRES-GFP, which responds to dox treatment with the production of a bi-cistronic transcript encoding hemagglutinin-tagged B-Raf and green fluorescent protein (GFP. This improved conditional expression system was then characterized in detail in terms of its response to various dox concentrations and exposure times. The plasticity of the phenotype provoked by oncogenic B-RafV600E in MCF-10Atet cells was analyzed in 3D cultures by dox exposure and subsequent wash-out. Results MCF-10Atet cells represent a tightly controlled, conditional gene expression system. Using B-RafV600E as a model oncoprotein, we show that its sudden expression in established 3D cultures results in the loss of acinar organization, the induction of an invasive phenotype and hallmarks of epithelial-to-mesenchymal transition

  6. Oncogenic HPV among HIV infected female population in West Bengal, India

    Directory of Open Access Journals (Sweden)

    Sengupta Sharmila

    2011-03-01

    Full Text Available Abstract Background Prevalence of both cervical cancer and Human Immunodeficiency Virus (HIV infection are very high in India. Natural history of Human Papilloma Virus (HPV infection is known to be altered in HIV positive women and there is an increased possibility of persistence of HPV infections in this population. Therefore, this study was conducted to understand the epidemiology and circulating genotypes of oncogenic HPV among HIV positive and negative female population in West Bengal, India. Methods In this hospital-based cross-sectional study, 93 known HIV positive females attending a pre-ART registration clinic and 1106 HIV negative females attending a Reproductive and Child Health Care Clinic were subjected to study. Cervical cell samples collected from the study population were tested for the presence of HPV 16, 18 using specific primers. Roche PCR assay was used to detect other specific HPV genotypes in the cervical cells specimens of HIV positive cases only. Results Prevalence of HPV 16, 18 among HIV positive females (32.2%; n = 30 was higher than HIV negative females (9.1%; n = 101. About 53% (23/43 of cases with oncogenic HPV were infected with genotypes other than 16, 18 either as single/multiple infections. HPV 18 and HPV 16 were the predominant genotypes among HIV positive and HIV negative subjects respectively. Oncogenic HPV was not found to be associated with age and duration of sexual exposure. But the presence of HIV was found to a statistically significant predictor oncogenic HPV. Conclusion The currently available HPV vaccines offer protection only against HPV 16 and 18 and some cross- protection to few associated genotypes. These vaccines are therefore less likely to offer protection against cervical cancer in HIV positive women a high percentage of who were infected with non-16 and non-18 oncogenic HPV genotypes. Additionally, there is a lack of sufficient evidence of immunogenicity in HIV infected individuals. Therefore

  7. Targeting CK2-driven non-oncogene addiction in B-cell tumors.

    Science.gov (United States)

    Mandato, E; Manni, S; Zaffino, F; Semenzato, G; Piazza, F

    2016-11-24

    Genetic mutations of oncogenes often underlie deranged cell growth and altered differentiation pathways leading to malignant transformation of B-lymphocytes. However, addiction to oncogenes is not the only drive to lymphoid tumor pathogenesis. Dependence on non-oncogenes, which act by propelling basic mechanisms of cell proliferation and survival, has also been recognized in the pathobiology of lymphoid leukemias, lymphomas and multiple myeloma. Among the growing number of molecules that may uphold non-oncogene addiction, a key place is increasingly being recognized to the serine-threonine kinase CK2. This enzyme is overexpressed and overactive in B-acute lymphoblastic leukemia, multiple myeloma, chronic lymphocytic leukemia and non-Hodgkin lymphomas, such as mantle cell, follicular, Burkitt's and diffuse large B-cell lymphomas. In these tumors, CK2 may serve the activity of oncogenes, similar to BCR-ABL and c-MYC, control the activation of critical signaling cascades, such as NF-κB (nuclear factor-κB), STAT3 (signal transducer and activator of transcription 3) and PTEN/PI3K/AKT (phosphatase and tensin homolog protein/phosphoinositide 3-kinase/AKR thymoma), and sustain multiple cellular stress-elicited pathways, such as the proteotoxic stress, unfolded protein and DNA-damage responses. CK2 has also been shown to have an essential role in tuning signals derived from the stromal tumor microenvironment. Not surprisingly, targeting CK2 in lymphoid tumor cell lines or mouse xenograft models can boost the cytotoxic effects of both conventional chemotherapeutics and novel agents, similar to heat-shock protein 90, proteasome and tyrosine kinases inhibitors. In this review, we summarize the evidence indicating how CK2 embodies most of the features of a cancer growth-promoting non-oncogene, focusing on lymphoid tumors. We further discuss the preclinical data of the use of small ATP-competitive CK2 inhibitors, which hold the promise to be additional options in novel drug

  8. BCL3 exerts an oncogenic function by regulating STAT3 in human cervical cancer

    Directory of Open Access Journals (Sweden)

    Zhao H

    2016-10-01

    Full Text Available Hu Zhao,1 Wuliang Wang,1 Qinghe Zhao,1 Guiming Hu,2 Kehong Deng,1 Yuling Liu1 1Department of Gynecology and Obstetrics, 2Department of Pathology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China Abstract: Aberrant expression of oncogenes and/or tumor suppressors play a fundamental effect on the pathogenesis and tumorigenicity of cervical cancer (CC. B-cell CLL/lymphoma 3 (BCL3 was previously found to be a putative proto-oncogene in human cancers and regulated signal transducer and activator of transcription 3 (STAT3, a critical oncogene, in CC cell line. However, its expression status, clinical significance and biological functions in CC remain largely unclear. The expressions of BCL3 and STAT3 in CC specimens were determined by immunohistochemistry. MTT, colony formation assays and flow cytometry analysis were carried out to test proliferation and cell cycle of CC cells. Here, the levels of BCL3 were overexpressed in CC compared to adjacent cervical tissues. Furthermore, high levels of BCL3 protein were confirmed by immunoblotting in CC cells as compared with normal cervical epithelial cells. The positive expression of BCL3 was correlated with adverse prognostic features and reduced survival rate. In addition, BCL3 regulated STAT3 abundance in CC cells. STAT3 was found to be upregulated and positively correlated with BCL3 expression in CC specimens. BCL3 overexpression resulted in prominent increased proliferation and cell cycle progression in Hela cells. By contrast, inhibition of BCL3 in CaSki cells remarkably suppressed proliferative ability and cell cycle progression. In vivo studies showed that knockdown of BCL3 inhibited tumor growth of CC in mice xenograft model. Notably, we confirmed that STAT3 mediated the oncogenic roles of BCL3 in CC. In conclusion, we suggest that BCL3 serves as an oncogene in CC by modulating proliferation and cell cycle progression, and its oncogenic effect is

  9. Le discours fantastique est-il rationnel ?

    Directory of Open Access Journals (Sweden)

    Anouck Linck

    2011-01-01

    Full Text Available L’importance de la contradiction dans la composition du discours fantastique a été signalée par la critique et le carré sémiotique de Greimas assigne au fantastique une place de choix – non reconnue encore à ce jour. Lele structurant de la contradiction est confirmé par notre méthode d’investigation, qui envisage l’acte de lecture sur le mode de l’élaboration d’un acte démonstratif. Cette méthode, appliquée à trois textes emblématiques du discours fantastique, aboutit en effet à l’élaboration de théories inconsistantes (contenant une contradiction du type p  p mais non triviales, au sein desquelles le principe aristotélicien de non-contradiction n’est pas valable. Nous touchons là aux limites de la raison classique, d’où notre questionnement : le discours fantastique est-il rationnel ? Plutôt que de répondre par la négative, nous montrons que la non-absurdité du discours fantastique invite au dépassement des limites de la raison classique et à une extension de cette dernière, car il se place sous l’égide d’une logique formelle moins contraignante et plus générale que la logique classique : la logique paraconsistante de Newton da Costa.La crítica ha señalado la importancia de la contradicción en lo que se refiere a la composición de la narrativa fantástica y ésta tiene su lugar asignado dentro del cuadrado semiótico de Greimas – un lugar hasta ahora no identificado como tal. Al considerar el acto de lectura como elaboración un acto demostrativo, nuestro método de investigación resalta ese papel fundamental de la contradicción. Dicho método, aplicado a tres textos emblemáticos de la narrativa fantástica, desemboca en efecto en la elaboración de teorías inconsistentes (que contienen una contradicción de tipo p  p pero no triviales, dentro de las cuales el principio aristotélico de no-contradicción no es válido. Con esto llegamos al límite de la racionalidad

  10. Le texte prophétique

    Directory of Open Access Journals (Sweden)

    Jacques Halbronn

    2000-05-01

    Full Text Available Littérature et prophétie entretiennent un lien complexe : il s’agit de deux sphères différentes, antagonistes même, ne répondant pas aux mêmes enjeux et ne regardant pas dans la même direction. En revanche l’interface entre prophétisme et actualité politique est beaucoup plus nette : le prophète interpelle son contemporain, cherche à peser sur les événements. Pour être bien comprise la littérature prophétique doit donc être replacée dans le contexte politico-religieux qui l’a vu naître, sans quoi elle risque de n’être prise que pour un délire sans fondement. Les ambiguïtés sémantiques et les incohérences apparentes du texte prophétique s’éclairent ainsi d’un jour nouveau lorsqu’on les envisage à l’aune de certaines réalités contextuelles, mais aussi lorsque l’on parvient à les resituer par rapport à tout un corpus de textes plus ou moins aisément identifiable qui leur a servi de source première et féconde. Le texte prophétique doit être envisagé en réseau, comme une variation au sein d’un vaste continuum textuel et langagier.

  11. Quel contrôle de gestion pour les startups ?

    OpenAIRE

    Meyssonnier, François

    2015-01-01

    Une étude de huit PME fondées sur la science permet d’identifier les spécificités du contrôle de gestion des startups. Dans les startups émergentes le dirigeant n’utilise que des linéaments de contrôle de gestion essentiellement pour développer son approche cognitive du business model. Dans les startups en croissance le contrôle de gestion a un rôle de garde-fou et les outils de pilotage de la performance sont utilisés essentiellement de façon interactive et pour la prévision. Les principaux ...

  12. Reformulation à l’oral et dans le forum Web

    Directory of Open Access Journals (Sweden)

    Eshkol-Taravella Iris

    2016-01-01

    Full Text Available Le cadre du travail réalisé entre dans le domaine de la linguistique de corpus et du Traitement Automatique des Langues (TAL. Les recherches sont fondées sur trois corpus : deux corpus oraux (ESLO1 et ESLO2 et un corpus composé de discussions collectées sur un forum de Doctissimo. Le travail vise à détecter, analyser et comparer la reformulation introduite par trois marqueurs (c’est-à-dire, je veux dire et disons dans le discours oral et le corpus écrit dialogique du Web. L’objectif est d’étudier la raison pour laquelle le locuteur décide de modifier un segment par un autre et de repérer un lien formel entre les deux segments reformulés aux différents niveaux linguistiques (morphologique, lexical, syntaxique, etc..

  13. Compton profile of tantalum

    Indian Academy of Sciences (India)

    Thomas Varghese; K M Balakrishna; K Siddappa

    2003-03-01

    The Compton profile of tantalum (Ta) has been measured using IGP type coaxial photon detector. The target atoms were excited by means of 59.54 keV -rays from Am-241. The measurements were carried out on a high purity thin elemental foil. The data were recoreded in a 4 K multichannel analyzer. These data duly corrected for various effects are presented and compared with theoretical and measured values. Best agreement with experiment is found for the 5d36s2 electron configuration.

  14. Le vespe qualunquiste e la satira politica

    Directory of Open Access Journals (Sweden)

    Maurizio Cocco

    2012-10-01

    Full Text Available The weekly review «L’Uomo Qualunque» was the most popular newspaper in Italy in the second postwar. Created by a Neapolitan playwright, Guglielmo Giannini, it was the voice of the discontent of the middle classes and strongly opposed the CLN governments and the antifascist political parties.The paper aims to provide analysis of the use of satire in the newspaper. It focuses on the section named «Le vespe», in which Giannini used jokes and humorous anecdotes to criticize the transition from fascism to democracy; in particular the epuration, the political system and its personnel.

  15. Le zapping, les ethnologues, et leurs Indiens

    Directory of Open Access Journals (Sweden)

    Frédérique Langue

    2005-06-01

    Full Text Available Comme toujours s'agissant des expositions mises en scène au Grand Palais, la présentation est parfaite, impeccable. La mise en valeur des objets venus aussi bien de musées brésiliens qu'européens, et les commentaires qui les accompagnent, orientent le visiteur dans un labyrinthe "exotique" de poteries et d'objets de plume, coupé de temps à autre de documentaires portant sur les rituels amérindiens, chants psalmodiques à l'appui. L'auditoire y semble comme vissé sur place, davantage d'ailleur...

  16. Le ripetute migrazioni giapponesi in America Latina

    OpenAIRE

    Merler, Alberto; Niihara, Michinobu

    2011-01-01

    Gli autori, un italiano e un giapponese, presentano una sintesi delle considerazioni di partenza e delle ipotesi da cui prendono le mosse alcune ricerche sulle ripetute migra-zioni dei nipponici e dei loro discendenti tra Giappone e America Latina. Si evidenzia l’esistenza di una triangolazione di risorse ed esperienze che comprende pure l’Europa e, in particolare, l’Italia. Los autores, un italiano y un japonés, presentan un resumen de las primeras consideraciones y de las hipótesis que l...

  17. Le Chatelier's principle with multiple relaxation channels

    Science.gov (United States)

    Gilmore, R.; Levine, R. D.

    1986-05-01

    Le Chatelier's principle is discussed within the constrained variational approach to thermodynamics. The formulation is general enough to encompass systems not in thermal (or chemical) equilibrium. Particular attention is given to systems with multiple constraints which can be relaxed. The moderation of the initial perturbation increases as additional constraints are removed. This result is studied in particular when the (coupled) relaxation channels have widely different time scales. A series of inequalities is derived which describes the successive moderation as each successive relaxation channel opens up. These inequalities are interpreted within the metric-geometry representation of thermodynamics.

  18. Books reconsidered: Emile Durkheim, Le Suicide.

    Science.gov (United States)

    Robertson, Michael

    2006-12-01

    To reappraise Emile Durkheim's taxonomy of suicide in Le Suicide in the light of recent experience. While Durkheim's scientific method and argument are fundamentally flawed, some of his concepts have instrumental value in attempting to understand the complex origins of suicidal behaviour. Durkheim's baseless dismissal of mental illness as a key determinant of suicidal behaviour weakens his thesis significantly. However, his conceptualization of anomic, egoistic and altruistic suicide provides a means of comprehending recent trends in suicidal behaviour in the former Soviet states and a possible window into the psyche of the suicides of religious and political extremists.

  19. Images du Mage, images pour le Mage

    Directory of Open Access Journals (Sweden)

    Daniel GREGORIO

    2007-01-01

    Full Text Available Les œuvres d’Alphonse X proposent diverses représentations du mage, qui en font, tour à tour, l’ennemi ou l’allié de la religion chrétienne. Il est vrai que parfois, comme le montre l’histoire de Simon le magicien, la pratique de la magie implique un commerce direct et néfaste avec les forces infernales. Néanmoins, les personnages de Merlin et des Rois Mages, tels qu’ils sont présentés par Alphonse X, démontrent que magie et religion peuvent cohabiter, à condition toutefois que le mage croit en la virginité de Marie et en l’Incarnation et que sa pratique magique soit bénéfique pour la communauté. Ce bénéfice requiert parfois la reconstruction de l’univers quotidien ; pour ce faire, le magicien doit savoir quand et comment utiliser des objets et des pentacles, qui lui permettront de soumettre les forces surnaturelles. Il doit donc posséder une connaissance approfondie du monde naturel et des esprits qui, conjuguée à sa foi religieuse, l’empêchera de tomber dans la démonolâtrie.Las obras alfonsíes proponen diversas aproximaciones al personaje del mago, generalmente considerado como un ser antagónico del hombre religioso. Es cierto que en algunas ocasiones, como ocurre con Simón el mago, la práctica de las artes mágicas significa un trato directo y nefasto con las fuerzas infernales. Sin embargo, personajes como Merlín o los Reyes Magos, tal y como los describe Alfonso X, subrayan una posible cohabitación entre magia y religión sin que la práctica de la una signifique la exclusión de la otra. Sólo hay que cumplir con dos condiciones : creer en la virginidad de María y que Dios se hizo hombre, y proporcionar a la comunidad un beneficio claro. Este beneficio requiere en ocasiones remodelar lo cotidiano, utilizando objetos y pentáculos, en circunstancias extremadamente determinadas, lo que implica un conocimiento exhaustivo tanto del mundo natural como del simbólico y de los espíritus. Es este

  20. Le Verrier magnificent and detestable astronomer

    CERN Document Server

    Lequeux, James

    2013-01-01

    Le Verrier was a superb scientist. His discovery of Neptune in 1846 made him the most famous astronomer of his time. He produced a complete theory of the motions of the planets which served as a basis for planetary ephemeris for a full century. Doing this, he discovered an anomaly in the motion of Mercury which later became the first proof of General Relativity. He also founded European meteorology. However his arrogance and bad temper created many enemies, and he was even fired from his position of Director of the Paris Observatory.

  1. Le soluzioni Building Information Modeling di Bentley

    Directory of Open Access Journals (Sweden)

    Fulvio Bernardini

    2007-04-01

    Full Text Available La questione dell’interoperabilità dei dati negli ultimi anni è stata continuamente dibattuta dai professionisti dei vari settori. L’edilizia col suo ciclo di vita non hanno fatto eccezione e da quando il concetto di Building Information Modeling (BIM ha fatto il suo ingresso nel mondo dell’architettura, dell’ingegneria e delle costruzioni (AEC, le fasi inerenti il processo del buildingnon sono più state considerate separatamente. Bentley Systems, da sempre attiva nel settore delle infrastrutture, propone un’ampia gamma di soluzioni studiate proprio per coprire questo bisogno.

  2. L'astronomie dans le monde

    Science.gov (United States)

    Manfroid, J.

    2014-04-01

    Cartographie d’une naine brune; 2006DP14; Anatomie d’un astéroïde; L’astéroïde P/2013 R3; Formation des planètes; Planètes Kepler; Bêta Pictoris; Cratère Mojave; Les astéroïdes de la ceinture principale; Planète X; Mercure et la gravitation; Gloire sur Vénus; Galaxies elliptiques massives; Cas A; SN 2014J et les supernovae Ia; Le Grand Nuage de Magellan; Nébuleuse d’Andromède; ESO 137-001

  3. Il corpo, lo sport, le immagini

    Directory of Open Access Journals (Sweden)

    Nicola Porro

    2009-07-01

    Full Text Available E’ stato per primo Norbert Elias, nella sua critica al riduzionismo sociologico, a lamentare la difficoltà delle scienze sociali a misurarsi con le problematiche dello sport, così come delle emozioni, della sessualità, del gioco e della guerra. Attività umane che convergono in quell’autentico luogo sociale che è il corpo. Nel caso che ci interessa, si tratta di connettere il corpo, nella sua dimensione biologica, psichica e sociale, con quell’aspetto cruciale della civilizzazione che Elias definisce sportivizzazione.

  4. L'astronomie dans le monde

    OpenAIRE

    Manfroid, Jean

    2007-01-01

    Anions interstellaires; S Orionis; Altaïr; Courants stellaires; Etoiles jeunes; 2MASSW J1207334-393254; Alpha Andromède; Etoiles à neutrons (1); LH54-425; AGNs invisibles; Deux supernovae; Les GRBs selon Swift; Peser les trous noirs; Formation de trous noirs; Trou noir; ondes gravitationnelles : Virgo entre dans sa phase d'exploitation scientifique; Amas de galaxies actifs; Amas de galaxies; Galaxies actives d'amas; L'univers statique: le retour; Macho; Exoplanètes; Exop...

  5. Les Biotechnologies Marines dans le Grand Ouest

    OpenAIRE

    Boyen, Catherine; Jaouen, Pascal

    2015-01-01

    Travaux d'un groupe de réflexion au sein de l'Europole Mer sur le thème des biotechnologies marines.; Marine (= blue) biotechnology, i.e. the utilization of marine bio-resources as a target or source of biotechnologicalapplications, is a field with massive potential for innovation and economic growth. In a context of rapid climate change and increasing pressure on natural resources, renewed interest in marine biotechnology has been promoted by application of recent methodological and technolo...

  6. Kierkegaard - le Philosophe, le Juge et le Droit (Kierkegaard – the Philosopher, the Judge and the Law

    Directory of Open Access Journals (Sweden)

    Ditlev Tamm

    2014-12-01

    Full Text Available Le fameux théologien et philosophe Søren Kierkegaard (1813-1855 dans son oeuvre souvnt utilize expressions et metaphors pris du monde judiciare. Il pare, quíl est bien au courant quant´au monde des jurists de son age et place. La plupart des expressions sont pris du droit penal et de la procédure pénale. Le criminel comme individu ou l’objet de línterrogation et comme coupable es tun des ses images favorites. Dans ses oeuvres Ou-bien … Ou bien et Etapes su la chemin de la vie nous encontrons un juge danois avec la possibilité de suivre ses reflections sur son travail et l’éthique d’un repésentant de la justice locale. Le juge est une des masques sous lesquelles Kierkegaard s’adresse a nous. Les oeuvres de Kierkegaard et l’utilisation des expressions prises du monde du droit sont ici présentées dans un contexte contemporaire du doit et vie á Copenhague dans les années entre 1840 et 1855 en contrastant les différances entre le narrative de Kierkegaard selon lequel le doit peut server comme example et sur l’autre côté son concept transcendental de l’être coupable. The famous Danish theologian and existentialist philosopher Søren Kierkegaard (1813-1855 in his work often used expressions or metaphors taken from judicial life, which reveals him as familiar with the legal world of his time and place. Most expressions are taken from penal law and penal procedure. The criminal as individual or the object of interrogation and guilt is one of his favorite images. In his Enten-Eller (Either/or and Stadier paa Livets Vej (Stages on Life’s Way we even meet a Danish judge and follow his reflections on his work and the ethics of a representative of local Justice. The judge is one of the masks under which Kierkegaard presents his thinking. Kierkegaard’s works and his use of expressions taken from the legal world are presented in the contemporary context of law and life in Copenhagen in the 1840ies however contrasting the

  7. Kierkegaard - le Philosophe, le Juge et le Droit (Kierkegaard – the Philosopher, the Judge and the Law

    Directory of Open Access Journals (Sweden)

    Ditlev Tamm

    2014-12-01

    Full Text Available Le fameux théologien et philosophe Søren Kierkegaard (1813-1855 dans son oeuvre souvnt utilize expressions et metaphors pris du monde judiciare. Il pare, quíl est bien au courant quant´au monde des jurists de son age et place. La plupart des expressions sont pris du droit penal et de la procédure pénale. Le criminel comme individu ou l’objet de línterrogation et comme coupable es tun des ses images favorites. Dans ses oeuvres Ou-bien … Ou bien et Etapes su la chemin de la vie nous encontrons un juge danois avec la possibilité de suivre ses reflections sur son travail et l’éthique d’un repésentant de la justice locale. Le juge est une des masques sous lesquelles Kierkegaard s’adresse a nous. Les oeuvres de Kierkegaard et l’utilisation des expressions prises du monde du droit sont ici présentées dans un contexte contemporaire du doit et vie á Copenhague dans les années entre 1840 et 1855 en contrastant les différances entre le narrative de Kierkegaard selon lequel le doit peut server comme example et sur l’autre côté son concept transcendental de l’être coupable. The famous Danish theologian and existentialist philosopher Søren Kierkegaard (1813-1855 in his work often used expressions or metaphors taken from judicial life, which reveals him as familiar with the legal world of his time and place. Most expressions are taken from penal law and penal procedure. The criminal as individual or the object of interrogation and guilt is one of his favorite images. In his Enten-Eller (Either/or and Stadier paa Livets Vej (Stages on Life’s Way we even meet a Danish judge and follow his reflections on his work and the ethics of a representative of local Justice. The judge is one of the masks under which Kierkegaard presents his thinking. Kierkegaard’s works and his use of expressions taken from the legal world are presented in the contemporary context of law and life in Copenhagen in the 1840ies however contrasting the

  8. New Scientist: le 50 idee che cambieranno la scienza...

    Directory of Open Access Journals (Sweden)

    Redazione

    2012-07-01

    Full Text Available Quali sono le "idee" destinate a cambiare radicalmente la conoscenza che abbiamo del mondo e le relazioni che intratteniamo con esso? Con l'aiuto di esperti di diverse discipline il New Scientist ha raccolto le 50 che sembrano meglio candidarsi a questa sfida. Dalle scienze della vita all'intelligenza artificiale, dalla genetica alle nanotecnologie, dalla cosmologia alla ricerca sul cervello, dall'ingegneria alla vita artificiale...

  9. Barbara Carnevali, Le apparenze sociali. Una filosofia del prestigio

    Directory of Open Access Journals (Sweden)

    Corrado Confalonieri

    2015-11-01

    Full Text Available Non sempre la prima frase di un libro è rappresentativa del suo intero contenuto; non sempre la prima nota a piè di pagina lascia emergere con chiarezza le origini della ricerca, le sue ragioni. Entrambe le cose, invece, accadono nel presente volume di Barbara Carnevali, e un buon modo di ricostruirne l’insieme può essere quello di combinare gli elementi che vengono messi a disposizione del lettore da questi due passaggi testuali d’apertura.

  10. La prolusione di rocco e le dottrine del processo penale

    OpenAIRE

    Orlandi, Renzo

    2015-01-01

    L’articolo analizza le conseguenze del pensiero giuridico di Arturo Rocco, dal 1910 nella dottrina di procedura penale, ossia, il metodo tecnico-giuridico (esegesi, sistematica e critica). La dogmatica di procedura pena- le inizia con la monografia di Giovanni Conso, nel 1955. L’insoddisfazione con il tecnicismo giuridico e con la mancanza di maturità scientifica si è manifestata con Carnelutti nel 1946 (Cerenterola), sottolineando le peculiarità strutturali del procedimento penale. In questa...

  11. Note sur le bassin Houiller de Sabero, Espagne

    NARCIS (Netherlands)

    Henkes, H.

    1961-01-01

    En Espagne septentrionale, dans la province de León, à une dizaine de kilomètres au NO de la ville de Cistierna, s’étend un bassin houiller entre le Rio Porma et le Rio Esla, perpendiculaire à ces fleuves et avec la ville de Sabero au centre. La situation précise peut être retrouvée sur les feuilles

  12. Transforming Exploratory Creativity with DeLeNoX

    DEFF Research Database (Denmark)

    Liapis, Antonios; Martínez, Héctor Pérez; Togelius, Julian

    2013-01-01

    We introduce DeLeNoX (Deep Learning Novelty Explorer), a system that autonomously creates artifacts in constrained spaces according to its own evolving interestingness criterion. DeLeNoX proceeds in alternating phases of exploration and transformation. In the exploration phases, a version...... in games. We also situate DeLeNoX in relation to the distinction between exploratory and transformational creativity, and in relation to Schmidhuber’s theory of creativity through the drive for compression progress...

  13. Le statue di Dedalo: le riviste di filosofia politica italiane di serie A

    Directory of Open Access Journals (Sweden)

    Maria Chiara Pievatolo

    2013-03-01

    Full Text Available Roars ha puntualmente segnalato l’ancipite vicenda delle nuove liste di riviste last minute per l’abilitazione scientifica nazionale. E’ cambiato qualcosa fra le riviste di filosofia politica italiane di serie A, di cui avevamo già avuto modo di discutere?

  14. La culture matérielle enfantine entre le cute et le cool

    Directory of Open Access Journals (Sweden)

    Gilles Brougère

    2012-11-01

    Full Text Available Cet article explore la façon dont on adresse un objet à l’enfant, c’est-à-dire la rhétorique à l’œuvre pour séduire les enfants (et les parents dans certains cas. Si l’éducation peut être présente pour certains produits, domine très largement aujourd’hui une rhétorique du fun, une association de l’objet à l’enfance via le divertissement et l’insertion dans une culture des pairs. Pour partie cet adressage se fait à travers l’utilisation de personnages ou d’univers sous licence qui proposent une rhétorique du fun prête à l’emploi. Mais l’analyse des univers disponibles montre que l’on peut décomposer le fun à travers deux pôles opposés, le cute, dont Hello Kitty constitue un exemple archétypal, et le cool, que Titeuf permet de saisir dans sa logique. A travers la distinction du cute et du cool, il s’agit de contribuer à l’analyse du déploiement contemporain d’une culture du divertissement qui est incorporée aux objets de l’enfance, tout en étant un moyen de capter l’intérêt de ceux-ci.

  15. 'Prendre le BIC': Le combat spirituel Congolais et les transformations sociales

    NARCIS (Netherlands)

    J. Ndaya Tshiteku (Julie)

    2008-01-01

    textabstractLa mondialisation c’est l’intensification des contacts entre les cultures et les formations sociales des différents continents. Elle a été favorisée par le développement rapide des moyens de transport et des technologies de communication sophistiquées, facilitant la diffusion des

  16. [FR] Le developpment du Travail Social et le pluralisme au Québec

    Directory of Open Access Journals (Sweden)

    André Jacob

    2011-06-01

    Full Text Available Normal 0 21 false false false ES X-NONE X-NONE MicrosoftInternetExplorer4 Au Canada et au Québec, traiter des questions liées à la diversité culturelle et au racisme a été un défi pour les gouvernements depuis les années soixante. Auparavant et jusqu'à présent, une grande partie des responsabilités en termes de développement ethnoculturel sensible des services publics (services sociaux, des programmes de formation en travail social, etc. ont été laissés aux mains d’organismes de charité non-lucratifs. Cependant, peu à peu, depuis les années soixante, le gouvernement fédéral et le gouvernement provincial, ont dû développer des politiques et des programmes d'action. Au Québec, le travail social a fait partie du débat face à deux grands courants politiques, l’un canadien basé sur le multiculturalisme, et l’autre québécois basé sur l'interculturalisme. L'article vise à donner une perspective historique

  17. Jakuta Alikavazovic, La blonde et le bunker derrière le miroir…

    Directory of Open Access Journals (Sweden)

    Marjorie Broussin

    2013-11-01

    Full Text Available Le roman que nous propose la romancière française, née en 1979, après le prix Goncourt du premier roman avec Les corps Volatils, a remporté la mention spéciale du jury Wepler. Et l’œuvre perturbe en effet tous nos repères, réalisant les aspirations de son auteure : « L’originalité dans la répétition. Le déjà-vu comme condition du sens, et paradoxalement comme irruption de la nouveauté. » Impossible de se raccrocher longtemps au désir d’élucidation, moteur du roman noir, tant la narration joue du speculum, à la fois jeux de regards et de miroirs, et spéculations de toutes sortes. Et pourtant, Jakuta Alikavazovic a éveillé notre curiosité et notre instinct de détective. C’est pourquoi nous vous proposons de nous suivre dans cette enquête, sur les traces du récit, avec pour seul indice celui qu’a laissé l’auteure derrière elle : « L’un des thèmes de La blonde et le bunker (comme de tous mes livres est la disparition »

  18. Le genre comme rapport d’inégalité sociale dans le discours publicitaire

    Directory of Open Access Journals (Sweden)

    Jean-Claude Soulages

    2016-12-01

    Full Text Available Loin de se réduire à une simple transaction commerciale, une annonce publicitaire est un espace de croyances sur des identités, des rôles et des pratiques sociales. Au même titre que d’autres productions fictionnelles de la culture de masse, elle représente l’une des faces de ce miroir social alimenté par la circulation incessante d’attitudes et de croyances, affichant même s’il s’agit bien souvent pour cette dernière d’un positionnement ludique, un second monde peuplé par nos avatars. La publicité tout comme le fait la fiction télévisée définit l’horizon des possibles d’une communauté donnée. Ce qu’elles réalisent toutes deux c’est l’entrée de l’imaginaire dans le réel. Même si, à partir des années 70, s’opère un lent défigement des stéréotypes sexistes, le publicitaire ne se fera aucunement le porte-parole explicite d’une quelconque lutte féministe, il optera toujours pour une tactique ambivalente de double speak: des effets de décadrage mettant en exergue des situations délibérément décalées ou burlesques (Un homme qui change les couches de bébé! Un clown qui fait la lessive!, mais cristallisant des inégalités de rôles. En jouant tout à la fois sur le défigement et la réactivation des stéréotypes, c’est bien un rôle de passeur et de go between, qu’est assigné le publicitaire en se faisant l’arbitre ventriloque de ces conflits de légitimité et de construction identitaire qui agitent notre modernité.

  19. Analyser le style du dialogue. Quelques remarques sur le dialogue au XIXe siècle

    Directory of Open Access Journals (Sweden)

    Naïm Jérémy

    2014-07-01

    Full Text Available Cet article dresse un état des lieux de l'analyse du dialogue de roman depuis trente ans. Il fait remarquer les difficultés rencontrées par les linguistes à dégager une spécificité du dialogue, empruntant là, et sans le dire, les outils de la narratologie, ici, mais avec précaution, ceux de l'analyse conversationnelle ou des discours rapportés. L'évolution des études sur le dialogue montre tout de même une attention grandissante pour son intégration dans la narration et l'interrogation renouvelée de sa référence extra-textuelle. L'auteur s'est donc proposé de prendre cinq extraits de dialogue du XIXe siècle et de les comparer, à partir de ces deux seuls critères. Il fait remarquer qu'au début du siècle, le dialogue est conçu comme un bloc de texte, autonome, isolé de la masse narrative. Les liens entre la rhétorique et le dialogue contribuent à renforcer cet isolement, en faisant du dialogue un morceau d'éloquence. Le réalisme s'attaque à cette représentation, en accentuant les liens du dialogue et de la narration et en proposant des dialogues qui ne se contentent pas de référer à des réalités verbales. Le naturalisme, à la fin du siècle, a complètement défait l'isolement du dialogue en l'amalgamant avec la narration. Les résultats historiques de cette étude sont à approfondir. Mais elle montre, sur plan théorique, la possibilité de s'affranchir des difficiles questions d'énonciation quand on aborde le dialogue de roman.

  20. Michaux, «Le Jardin Exalté»

    Directory of Open Access Journals (Sweden)

    Vera Lúcia de Carvalho Casa Nova

    2011-10-01

    Full Text Available Resumo: Esse ensaio resulta de uma leitura do texto de H. Michaux, focalizando a relação entre as artes na escritura desse autor.Palavras-chave: Literatura francesa; Henri Michaux; Le Jardin Exalté; artes.Résumé: Cet essai est le résultat d’une lecture qui montre les relations entre les arts dans l’écriture Henri Michaux.Mots-clés: Littérature française; Henri Michaux; Le Jardin Exalté; arts.Keywords: French literature; Henri Michaux; Le Jardin Exalté; arts.

  1. Leïomyosarcome de la prostate: Neoplasie rare

    Directory of Open Access Journals (Sweden)

    D. Basraoui

    2012-03-01

    La TDM et surtout l'IRM jouent un rôle primordial dans le bilan d'extension locale et à distance du léïomyosarcome prostatique et le seul moyen pour affirmer le diagnostic est l'histologie complétée par une étude immuno-histochimique. Leur prise en charge thérapeutique n'est pas codifiée à l'heure actuelle et leur pronostic reste très sombre.

  2. Le paysage anglais: du jardin à la campagne

    Directory of Open Access Journals (Sweden)

    Gilly LEHMANN

    1987-12-01

    Full Text Available Lele des jardins dans le paysage anglais tient tout autant à ce qui se passe dans les esprits qu'aux réalités concrètes. L'apogée dans la création des jardins et des parcs influant sur le paysage campagnard a lieu au 18e siècle. Les créateurs d'alors visent à construire un paysage idéal; les périodes suivantes proposeront aussi les leurs.

  3. Oncogenic transformation through the cell cycle and the LET dependent inverse dose rate effect

    Science.gov (United States)

    Geard, C. R.; Miller, R. C.; Brenner, D. J.; Hall, E. J.; Wachholz, B. W. (Principal Investigator)

    1994-01-01

    Synchronised populations of mouse C3H/10T-1/2 cells were obtained by a stringent mitotic dislodgment procedure. Mitotic cells rapidly attach and progress sequentially through the cell cycle. Irradiation (3 Gy of X rays) was carried out at intervals from 0 to 18 h after initiating cell cycle progression of the mitotic cells. Oncogenic transformation was enhanced 10-fold over cells irradiated soon after replating (G1 and S phases) for cells in a near 2 h period corresponding to cells in G2 phase but not in mitosis. The cell surviving fraction had a 2-1/2-fold variation with resistant peaks corresponding to the late G1 and late S phases. These findings provide experimental support for the hypothesis initiated by Rossi and Kellerer and developed by Brenner and Hall to explain the LET dependent inverse dose rate effect for oncogenic transformation.

  4. Tumor suppression by miR-26 overrides potential oncogenic activity in intestinal tumorigenesis

    Science.gov (United States)

    Zeitels, Lauren R.; Acharya, Asha; Shi, Guanglu; Chivukula, Divya; Chivukula, Raghu R.; Anandam, Joselin L.; Abdelnaby, Abier A.; Balch, Glen C.; Mansour, John C.; Yopp, Adam C.; Richardson, James A.

    2014-01-01

    Down-regulation of miR-26 family members has been implicated in the pathogenesis of multiple malignancies. In some settings, including glioma, however, miR-26-mediated repression of PTEN promotes tumorigenesis. To investigate the contexts in which the tumor suppressor versus oncogenic activity of miR-26 predominates in vivo, we generated miR-26a transgenic mice. Despite measureable repression of Pten, elevated miR-26a levels were not associated with malignancy in transgenic animals. We documented reduced miR-26 expression in human colorectal cancer and, accordingly, showed that miR-26a expression potently suppressed intestinal adenoma formation in Apcmin/+ mice, a model known to be sensitive to Pten dosage. These studies reveal a tumor suppressor role for miR-26 in intestinal cancer that overrides putative oncogenic activity, highlighting the therapeutic potential of miR-26 delivery to this tumor type. PMID:25395662

  5. Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia.

    Science.gov (United States)

    Grembecka, Jolanta; He, Shihan; Shi, Aibin; Purohit, Trupta; Muntean, Andrew G; Sorenson, Roderick J; Showalter, Hollis D; Murai, Marcelo J; Belcher, Amalia M; Hartley, Thomas; Hess, Jay L; Cierpicki, Tomasz

    2012-03-01

    Translocations involving the mixed lineage leukemia (MLL) gene result in human acute leukemias with very poor prognosis. The leukemogenic activity of MLL fusion proteins is critically dependent on their direct interaction with menin, a product of the multiple endocrine neoplasia (MEN1) gene. Here we present what are to our knowledge the first small-molecule inhibitors of the menin-MLL fusion protein interaction that specifically bind menin with nanomolar affinities. These compounds effectively reverse MLL fusion protein-mediated leukemic transformation by downregulating the expression of target genes required for MLL fusion protein oncogenic activity. They also selectively block proliferation and induce both apoptosis and differentiation of leukemia cells harboring MLL translocations. Identification of these compounds provides a new tool for better understanding MLL-mediated leukemogenesis and represents a new approach for studying the role of menin as an oncogenic cofactor of MLL fusion proteins. Our findings also highlight a new therapeutic strategy for aggressive leukemias with MLL rearrangements.

  6. Plac8 Links Oncogenic Mutations to Regulation of Autophagy and Is Critical to Pancreatic Cancer Progression

    Directory of Open Access Journals (Sweden)

    Conan Kinsey

    2014-05-01

    Full Text Available Mutations in p53 and RAS potently cooperate in oncogenic transformation, and correspondingly, these genetic alterations frequently coexist in pancreatic ductal adenocarcinoma (PDA and other human cancers. Previously, we identified a set of genes synergistically activated by combined RAS and p53 mutations as frequent downstream mediators of tumorigenesis. Here, we show that the synergistically activated gene Plac8 is critical for pancreatic cancer growth. Silencing of Plac8 in cell lines suppresses tumor formation by blocking autophagy, a process essential for maintaining metabolic homeostasis in PDA, and genetic inactivation in an engineered mouse model inhibits PDA progression. We show that Plac8 is a critical regulator of the autophagic machinery, localizing to the lysosomal compartment and facilitating lysosome-autophagosome fusion. Plac8 thus provides a mechanistic link between primary oncogenic mutations and the induction of autophagy, a central mechanism of metabolic reprogramming, during PDA progression.

  7. Chemically robust fluoroalkyl phthalocyanine-oligonucleotide bioconjugates and their GRP78 oncogene photocleavage activity.

    Science.gov (United States)

    Patel, Pradeepkumar; Patel, Hemantbhai H; Borland, Emily; Gorun, Sergiu M; Sabatino, David

    2014-06-18

    The first representative of functionalized fluoroalkyl phthalocyanines, F48H7(COOH)PcZn, is reported. The complex generates (1)O2 affording long-lasting photooxidation of an external substrate without self-decomposition. The carboxylic group couples with an antisense oligonucleotide targeting GRP78 oncogenes, resulting in the F48H7PcZn-cancer targeting oligonucleotide (CTO). The bioconjugated fluorophthalocyanine effectively hybridizes complementary GRP78 DNA and mRNA sequences. Piperidine cleavage assays reveal desired photochemical oligonucleotide oxidative degradation for both F48H7PcZn-CTO:DNA and F48H7PcZn-CTO:mRNA hybrids. This new materials strategy could be extended to other functional fluorinated phthalocyanines-antisense oligonucleotide combinations for long-lasting oncogene-targeting photodynamic therapy.

  8. Repurposing a Prokaryotic Toxin-Antitoxin System for the Selective Killing of Oncogenically Stressed Human Cells.

    Science.gov (United States)

    Preston, Mark A; Pimentel, Belén; Bermejo-Rodríguez, Camino; Dionne, Isabelle; Turnbull, Alice; de la Cueva-Méndez, Guillermo

    2016-07-15

    Prokaryotes express intracellular toxins that pass unnoticed to carrying cells until coexpressed antitoxin partners are degraded in response to stress. Although not evolved to function in eukaryotes, one of these toxins, Kid, induces apoptosis in mammalian cells, an effect that is neutralized by its cognate antitoxin, Kis. Here we engineered this toxin-antitoxin pair to create a synthetic system that becomes active in human cells suffering a specific oncogenic stress. Inspired by the way Kid becomes active in bacterial cells, we produced a Kis variant that is selectively degraded in human cells expressing oncoprotein E6. The resulting toxin-antitoxin system functions autonomously in human cells, distinguishing those that suffer the oncogenic insult, which are killed by Kid, from those that do not, which remain protected by Kis. Our results provide a framework for developing personalized anticancer strategies avoiding off-target effects, a challenge that has been hardly tractable by other means thus far.

  9. MiR-191 Regulates Primary Human Fibroblast Proliferation and Directly Targets Multiple Oncogenes.

    Directory of Open Access Journals (Sweden)

    Damon Polioudakis

    Full Text Available miRNAs play a central role in numerous pathologies including multiple cancer types. miR-191 has predominantly been studied as an oncogene, but the role of miR-191 in the proliferation of primary cells is not well characterized, and the miR-191 targetome has not been experimentally profiled. Here we utilized RNA induced silencing complex immunoprecipitations as well as gene expression profiling to construct a genome wide miR-191 target profile. We show that miR-191 represses proliferation in primary human fibroblasts, identify multiple proto-oncogenes as novel miR-191 targets, including CDK9, NOTCH2, and RPS6KA3, and present evidence that miR-191 extensively mediates target expression through coding sequence (CDS pairing. Our results provide a comprehensive genome wide miR-191 target profile, and demonstrate miR-191's regulation of primary human fibroblast proliferation.

  10. RNA-DNA differences are rarer in proto-oncogenes than in tumor suppressor genes.

    Science.gov (United States)

    Gao, Feng; Lin, Yan; Zhang, Randy Ren

    2012-01-01

    It has long been assumed that DNA sequences and corresponding RNA transcripts are almost identical; a recent discovery, however, revealed widespread RNA-DNA differences (RDDs), which represent a largely unexplored aspect of human genome variation. It has been speculated that RDDs can affect disease susceptibility and manifestations; however, almost nothing is known about how RDDs are related to disease. Here, we show that RDDs are rarer in proto-oncogenes than in tumor suppressor genes; the number of RDDs in coding exons, but not in 3'UTR and 5'UTR, is significantly lower in the former than the latter, and this trend is especially pronounced in non-synonymous RDDs, i.e., those cause amino acid changes. A potential mechanism is that, unlike proto-oncogenes, the requirement of tumor suppressor genes to have both alleles affected to cause tumor 'buffers' these genes to tolerate more RDDs.

  11. MiR-191 Regulates Primary Human Fibroblast Proliferation and Directly Targets Multiple Oncogenes.

    Science.gov (United States)

    Polioudakis, Damon; Abell, Nathan S; Iyer, Vishwanath R

    2015-01-01

    miRNAs play a central role in numerous pathologies including multiple cancer types. miR-191 has predominantly been studied as an oncogene, but the role of miR-191 in the proliferation of primary cells is not well characterized, and the miR-191 targetome has not been experimentally profiled. Here we utilized RNA induced silencing complex immunoprecipitations as well as gene expression profiling to construct a genome wide miR-191 target profile. We show that miR-191 represses proliferation in primary human fibroblasts, identify multiple proto-oncogenes as novel miR-191 targets, including CDK9, NOTCH2, and RPS6KA3, and present evidence that miR-191 extensively mediates target expression through coding sequence (CDS) pairing. Our results provide a comprehensive genome wide miR-191 target profile, and demonstrate miR-191's regulation of primary human fibroblast proliferation.

  12. DNA Oncogenic Virus-Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations

    Directory of Open Access Journals (Sweden)

    Mankgopo Magdeline Kgatle

    2017-01-01

    Full Text Available Approximately 20% of human cancers is attributable to DNA oncogenic viruses such as human papillomavirus (HPV, hepatitis B virus (HBV, and Epstein-Barr virus (EBV. Unrepaired DNA damage is the most common and overlapping feature of these DNA oncogenic viruses and a source of genomic instability and tumour development. Sustained DNA damage results from unceasing production of reactive oxygen species and activation of inflammasome cascades that trigger genomic changes and increased propensity of epigenetic alterations. Accumulation of epigenetic alterations may interfere with genome-wide cellular signalling machineries and promote malignant transformation leading to cancer development. Untangling and understanding the underlying mechanisms that promote these detrimental effects remain the major objectives for ongoing research and hope for effective virus-induced cancer therapy. Here, we review current literature with an emphasis on how DNA damage influences HPV, HVB, and EBV replication and epigenetic alterations that are associated with carcinogenesis.

  13. Immortalized cells and one oncogene in malignant transformation: old insights on new explanation

    Science.gov (United States)

    2011-01-01

    Background Nearly thirty years ago, it was first shown that malignant transformation with single oncogene necessarily requires the immortal state of the cell. From that time this thesis for the cells of human origin was not disproved. The basic point which we want to focus on by this short communication is the correct interpretation of the results obtained on the widely used human embryonic kidney 293 (HEK293) cells. Results Intensive literature analysis revealed an increasing number of recent studies discovering new oncogenes with non-overlapping functions. Since the 1970s, dozens of oncogenes have been identified in human cancer. Cultured cell lines are often used as model systems in these experiments. In some investigations the results obtained on such cells are interpreted by the authors as a malignant transformation of normal animal or even normal human cells (as for example with HEK293 cells). However, when a cell line gains the ability to undergo continuous cell division, the cells are not normal any more, they are immortalized cells. Nevertheless, the authors consider these cells as normal human ones, what is basically incorrect. Moreover, it was early demonstrated that the widely used human embryonic kidney 293 (HEK293) cells have a relationship to neurons. Conclusions Thus, the experiments with established cell lines reinforce the notion that immortality is an essential requirement for malignant transformation that cooperates with other oncogenic changes to program the neoplastic state and substances under such investigation should be interpreted as factors which do not malignantly transform normal cells alone, but possess the ability to enhance the tumorigenic potential of already immortalized cells. PMID:21605454

  14. Activation of cellular oncogenes by chemical carcinogens in Syrian hamster embryo fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Ebert, R.; Reiss, E.; Roellich, G.; Schiffmann, D. (Univ. of Wuerzburg (West Germany)); Barrett, J.C.; Wiseman, R.W. (National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)); Pechan, R.

    1990-08-01

    Carcinogen-induced point mutations resulting in activation of ras oncogenes have been demonstrated in various experimental systems such as skin carcinogenesis, mammary, and liver carcinogenesis. In many cases, the data support the conclusion that these point mutations are critical changes in the initiation of these tumors. The Syrian hamster embryo (SHE) cell transformation model system has been widely used to study the multistep process of chemically induced neoplastic transformation. Recent data suggest that activation of the Ha-ras gene via point mutation is one of the crucial events in the transformation of these cells. The authors have now cloned the c-Ha-ras proto-oncogene from SHE cDNA-libraries, and we have performed polymerase chain reaction and direct sequencing to analyze tumor cell lines induced by different chemical carcinogens for the presence of point mutations. No changes were detectable at codons 12, 13, 59, 61, and 117 or adjacent regions in tumor cell lines induced by diethylstilbestrol, asbestos, benzo(a)pyrene, trenbolone, or aflatoxin B{sub 1}. Thus, it is not known whether point mutations in the Ha-ras proto-oncogene are essential for the acquisition of the neoplastic phenotype of SHE cells. Activation of other oncogenes or inactivation of tumor suppressor genes may be responsible for the neoplastic progression of these cells. However, in SHE cells neoplastically transformed by diethylstilbestrol or trenbolone, a significant elevation of the c-Ha-ras expression was observed. Enhanced expression of c-myc was detected in SHE cells transformed by benzo(a)pyrene or trenbolone.

  15. Oncogenic LINE-1 Retroelements Sustain Prostate Tumor Cells and Promote Metastatic Progression

    Science.gov (United States)

    2015-10-01

    elements in prostate cancer contribute to its progression by activating oncogenic DNA sequences, or silencing tumor suppressor like sequences. We have...the use of animals and the use of recombinant DNA /lentiviral vectors. All of these approvals have now been obtained. For Task 1, we cloned the LINE...Books or other non-periodical, one-time publications. Report any book, monograph , dissertation, abstract, or the like published as or in a

  16. Cooperativity Between Oncogenic PKC Epsilon and Pten Loss in Prostate Cancer Progression

    Science.gov (United States)

    2015-10-01

    initiated studies to dissect the signaling mechanisms that mediate CXCL13 induction. We took advantage of a cellular model that we generated in our...metastatic loop that is mediated by CXCL13. We also hypothesize that PKCε is a CXCL13:CXCR5 effector that contributes to positively amplify this oncogenic...shown). Therefore, it is possible that an autocrine CXCL13:CXCR5 loop mediates effects driven by PKCε overexpression and Pten loss. * * R el at iv

  17. PTPN14 interacts with and negatively regulates the oncogenic function of YAP

    OpenAIRE

    Liu, X; Yang, N; Figel, SA; Wilson, KE; Morrison, CD; Gelman, IH; Zhang, J

    2012-01-01

    The Hippo signaling pathway regulates cellular proliferation and survival, thus exerting profound effects on normal cell fate and tumorigenesis. The pivotal effector of this pathway is YAP, a transcriptional co-activator amplified in mouse and human cancers where it promotes epithelial-to-mesenchymal transition and malignant transformation. Here, we report a novel regulatory mechanism for the YAP oncogenic function via direct interaction with non-receptor tyrosine phosphatase 14 (PTPN14) thro...

  18. MSH3-deficiency initiates EMAST without oncogenic transformation of human colon epithelial cells.

    Directory of Open Access Journals (Sweden)

    Christoph Campregher

    Full Text Available BACKGROUND/AIM: Elevated microsatellite instability at selected tetranucleotide repeats (EMAST is a genetic signature in certain cases of sporadic colorectal cancer and has been linked to MSH3-deficiency. It is currently controversial whether EMAST is associated with oncogenic properties in humans, specifically as cancer development in Msh3-deficient mice is not enhanced. However, a mutator phenotype is different between species as the genetic positions of repetitive sequences are not conserved. Here we studied the molecular effects of human MSH3-deficiency. METHODS: HCT116 and HCT116+chr3 (both MSH3-deficient and primary human colon epithelial cells (HCEC, MSH3-wildtype were stably transfected with an EGFP-based reporter plasmid for the detection of frameshift mutations within an [AAAG]17 repeat. MSH3 was silenced by shRNA and changes in protein expression were analyzed by shotgun proteomics. Colony forming assay was used to determine oncogenic transformation and double strand breaks (DSBs were assessed by Comet assay. RESULTS: Despite differential MLH1 expression, both HCT116 and HCT116+chr3 cells displayed comparable high mutation rates (about 4×10(-4 at [AAAG]17 repeats. Silencing of MSH3 in HCECs leads to a remarkable increased frameshift mutations in [AAAG]17 repeats whereas [CA]13 repeats were less affected. Upon MSH3-silencing, significant changes in the expression of 202 proteins were detected. Pathway analysis revealed overexpression of proteins involved in double strand break repair (MRE11 and RAD50, apoptosis, L1 recycling, and repression of proteins involved in metabolism, tRNA aminoacylation, and gene expression. MSH3-silencing did not induce oncogenic transformation and DSBs increased 2-fold. CONCLUSIONS: MSH3-deficiency in human colon epithelial cells results in EMAST, formation of DSBs and significant changes of the proteome but lacks oncogenic transformation. Thus, MSH3-deficiency alone is unlikely to drive human colon

  19. Nuclear Localization and DNA Binding Properties of a Protein Expressed by Human c-myc Oncogene

    Science.gov (United States)

    Persson, Hakan; Leder, Philip

    1984-08-01

    Antisera to the human cellular myc oncogene product were used to identify a human c-myc specific protein with a molecular weight of 65,000. Subcellular fractionation showed that the human c-myc protein is predominantly found in the cell nucleus. The p65 Kc-myc protein binds to double- and single-stranded DNA as measured by a DNA affinity chromatography assay.

  20. Oncogenic HPV among HIV infected female population in West Bengal, India

    OpenAIRE

    Sengupta Sharmila; Bhattacharya Subhasish; Saha Bibhuti; Bal Baishali; Pal Reshmi; Sarkar Kamalesh; Mazumdar Partha; Chakraborti Shekhar

    2011-01-01

    Abstract Background Prevalence of both cervical cancer and Human Immunodeficiency Virus (HIV) infection are very high in India. Natural history of Human Papilloma Virus (HPV) infection is known to be altered in HIV positive women and there is an increased possibility of persistence of HPV infections in this population. Therefore, this study was conducted to understand the epidemiology and circulating genotypes of oncogenic HPV among HIV positive and negative female population in West Bengal, ...

  1. Expression Profiling of Circulating Microvesicles Reveals Intercellular Transmission of Oncogenic Pathways.

    Science.gov (United States)

    Milani, Gloria; Lana, Tobia; Bresolin, Silvia; Aveic, Sanja; Pastò, Anna; Frasson, Chiara; Te Kronnie, Geertruy

    2017-06-01

    Circulating microvesicles have been described as important players in cell-to-cell communication carrying biological information under normal or pathologic condition. Microvesicles released by cancer cells may incorporate diverse biomolecules (e.g., active lipids, proteins, and RNA), which can be delivered and internalized by recipient cells, potentially altering the gene expression of recipient cells and eventually impacting disease progression. Leukemia in vitro model systems were used to investigate microvesicles as vehicles of protein-coding messages. Several leukemic cells (K562, LAMA-87, TOM-1, REH, and SHI-1), each carrying a specific chromosomal translocation, were analyzed. In the leukemic cells, these chromosomal translocations are transcribed into oncogenic fusion transcripts and the transfer of these transcripts was monitored from leukemic cells to microvesicles for each of the cell lines. Microarray gene expression profiling was performed to compare transcriptomes of K562-derived microvesicles and parental K562 cells. The data show that oncogenic BCR-ABL1 transcripts and mRNAs related to basic functions of leukemic cells were included in microvesicles. Further analysis of microvesicles cargo revealed a remarkable enrichment of transcripts related to cell membrane activity, cell surface receptors, and extracellular communication when compared with parental K562 cells. Finally, coculturing of healthy mesenchymal stem cells (MSC) with K562-derived microvesicles displayed the transfer of the oncogenic message, and confirmed the increase of target cell proliferation as a function of microvesicle dosage.Implications: This study provides novel insight into tumor-derived microvesicles as carriers of oncogenic protein-coding messages that can potentially jeopardize cell-directed therapy, and spread to other compartments of the body. Mol Cancer Res; 15(6); 683-95. ©2017 AACR. ©2017 American Association for Cancer Research.

  2. Detection of FLT3 Oncogene Mutations in Acute Myeloid Leukemia Using Conformation Sensitive Gel Electrophoresis

    OpenAIRE

    2008-01-01

    FLT3 (fms-related tyrosine kinase 3) is a receptor tyrosine kinase class III that is expressed on by early hematopoietic progenitor cells and plays an important role in hematopoietic stem cell proliferation, differentiation and survival. FLT3 is also expressed on leukemia blasts in most cases of acute myeloid leukemia (AML). In order to determine the frequency of FLT3 oncogene mutations, we analyzed genomic DNA of adult de novo acute myeloid leukemia (AML). Polymerase chain reaction (PCR) and...

  3. Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation

    OpenAIRE

    Le Rolle, Anne-France; Chiu, Thang K; ZENG, ZHAOSHI; Shia, Jinru; Weiser, Martin R; Paty, Philip B.; Chiu, Vi K

    2016-01-01

    Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut ) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer i...

  4. Oncogenic Alternative Splicing Switches: Role in Cancer Progression and Prospects for Therapy

    OpenAIRE

    Serena Bonomi; Stefania Gallo; Morena Catillo; Daniela Pignataro; Giuseppe Biamonti; Claudia Ghigna

    2013-01-01

    Alterations in the abundance or activities of alternative splicing regulators generate alternatively spliced variants that contribute to multiple aspects of tumor establishment, progression and resistance to therapeutic treatments. Notably, many cancer-associated genes are regulated through alternative splicing suggesting a significant role of this post-transcriptional regulatory mechanism in the production of oncogenes and tumor suppressors. Thus, the study of alternative splicing in cancer ...

  5. Oncogenic action of beta, proton, alpha and electron radiation on the rat skin

    Energy Technology Data Exchange (ETDEWEB)

    Burns, F.J.

    1980-01-01

    Rat skin is being utilized as an empirical model for testing dose and time related aspects of the oncogenic action of ionizing radiation, ultraviolet light, and polycyclic aromatic hydrocarbons. Molecular lesions in the skin DNA, including, strand breaks and thymine dimers, are being measured and compared to tumor induction. The induction and repair kinetics of molcular lesions are being compared to split dose repair. Modifiers and radiosensitizers are being utilized to test specific aspects of a chromosome breakage theory of radiation oncogenesis.

  6. Mutation of RET proto-oncogene in Hirschsprung's disease and intestinal neuronal dysplasia

    Institute of Scientific and Technical Information of China (English)

    Jin-Fa Tou; Min-Ju Li; Tao Guan; Ji-Cheng Li; Xiong-Kai Zhu; Zhi-Gang Feng

    2006-01-01

    AIM: To investigate the genetic relationship between Hirschsprung's disease (HD) and intestinal neuronal dysplasia (IND) in Chinese population.METHODS: Peripheral blood samples were obtained from 30 HD patients, 20 IND patients, 18 HD/IND combined patients and 20 normal individuals as control.Genomic DNA was extracted according to standard procedure. Exons 11,13,15,17 of RET proto-oncogene were amplified by polymerase chain reaction (PCR).The mutations of RET proto-oncogene were analyzed by single strand conformational polymorphism (SSCP)and sequencing of the positive amplified products was performed.RESULTS: Eight germline sequence variants were detected. In HD patients, 2 missense mutations in exon 11at nucleotide 15165 G→A (G667S), 2 frameshift mutations in exon 13 at nucleotide 18974 (18974insG), 1missense mutation in exon 13 at nucleotide 18919 A→G (K756E) and 1silent mutation in exon 15 at nucleotide 20692 G→A(Q916Q) were detected. In HD/IND combined patients, 1 missense mutation in exon 11 at nucleotide 15165 G→A and 1 silent mutation in exon 13at nucleotide 18888 T→G (L745L) were detected. No mutation was found in IND patients and controls.CONCLUSION: Mutation of RET proto-oncogene is involved in the etiopathogenesis of HD. The frequency of RET proto-oncogene mutation is quite different between IND and HD in Chinese population. IND is a distinct clinical entity genetically different from HD.

  7. Exosomes enriched in stemness/metastatic-related mRNAS promote oncogenic potential in breast cancer

    OpenAIRE

    2015-01-01

    Cancer cells efficiently transfer exosome contents (essentially mRNAs and microRNAs) to other cell types, modifying immune responses, cell growth, angiogenesis and metastasis. Here we analyzed the exosomes release by breast tumor cells with different capacities of stemness/metastasis based on CXCR4 expression, and evaluated their capacity to generate oncogenic features in recipient cells. Breast cancer cells overexpressing CXCR4 showed an increase in stemness-related markers, and in prolifera...

  8. Quand le terrain s’impose, le récit aussi

    Directory of Open Access Journals (Sweden)

    Nicolas Journet

    2009-03-01

    Full Text Available Quand le terrain s’impose, le récit aussi. L’exposé synoptique qui, selon Johannes Fabian, caractérise le genre anthropologique savant et marque ses limites laisse, en fait, parfois la place à des épisodes narratifs. Sur la base de quelques exemples, on suggère que ces récits semblent intervenir lorsque l’auteur veut restituer le mouvement par lequel il a été amené à changer d’idées ou de projets par l’évidence que lui impose le terrain. Et souvent aussi, cette articulation est déterminante pour l’orientation de l’écrit proposé. Ce n’est donc pas seulement un procédé rhétorique, mais une forme qui s’impose d’elle-même.When the field imposes itself, so does the narrative. The synoptic account which, according to Johannes Fabian, characterises the learned anthropological genre and its limitations actually leaves room, on occasion, for narrative episodes. Drawing on a number of examples, this article suggests that these narratives appear to occur when the author wishes to reconstruct the movement through which he was led to change his views or projects because of evidence imposed on him by the field. And often, this link is decisive in determining the orientation of the writing. It is therefore more than just a rhetorical procedure, but a form that imposes itself.

  9. Lele de l’omalizumab dans le traitement de l’asthme allergique grave

    Science.gov (United States)

    Chapman, Kenneth R; Cartier, André; Hébert, Jacques; McIvor, R Andrew; Schellenberg, R Robert

    2006-01-01

    CONTEXTE : Un nouveau traitement anti-immunoglobuline E (anti-IgE) contre l’asthme, l’omalizumab, a été approuvé au Canada. OBJECTIF : Passer en revue les données fondamentales et cliniques sur l’omalizumab et examiner lele possible de ce médicament dans la prise en charge de l’asthme au Canada. MÉTHODOLOGIE : Une recherche documentaire a été effectuée dans MEDLINE afin de repérer les études menées de 1960 à 2006 sur l’omalizumab. La recherche a également porté sur les résumés de réunions scientifiques récentes dans le domaine des maladies respiratoires et des allergies; par ailleurs, toute donnée non publiée a été demandée au fabricant. Après avoir revu et résumé les données, un comité mixte constitué de spécialistes des maladies respiratoires et des allergies a rédigé un ensemble de recommandations relatives à l’utilisation de l’omalizumab. RÉSULTATS : L’omalizumab est un anticorps monoclonal humanisé qui se lie au domaine C epsilon 3 de la molécule d’IgE pour former des complexes immuns solubles qui sont éliminés par le système réticulo-endothélial. L’administration d’injections sous-cutanées espacées de deux ou de quatre semaines à la dose recommandée entraîne une diminution rapide des taux d’IgE circulantes libres. Lors de deux essais cliniques de phase III menés auprès de 1 405 adultes et adolescents atteints d’asthme modéré à grave qui recevaient des doses moyennes stables de corticostéroïdes en inhalation (CSI), l’omalizumab a diminué les taux d’exacerbation par rapport au placebo et a été associé à une amélioration des symptômes ainsi qu’à une épargne plus importante des corticostéroïdes. Dans un essai mené auprès de 419 patients atteints d’asthme grave non maîtrisé malgré l’utilisation de doses élevées de CSI et de la prise concomitante d’agonistes bêta-2 à action prolongée, les exacerbations graves étaient de 50 % moins fréquentes chez

  10. Théâtre Le Poche

    CERN Multimedia

    Théâtre Le Poche

    2012-01-01

    Du 9 au 19 février Lundi, vendredi 20h30 Mercredi, jeudi, samedi 19h Dimanche 17h    LES TERRIENS (assurez-vous que vous faites totalement autre chose) Mise en scène Claire Rengade   Obnubilée par la parole, Claire Rengade propose avec Les Terriens une recherche singulière et passionnée, une forme très novatrice entre théâtre, poésie et reportage. Après une enquête au CERN, la jeune auteure et metteure en scène choisit comme thème de sa nouvelle création une grande machine, centre de recherche scientifique de la plus grande avancée technologique. Avec Les Terriens Claire Rengade poursuit sa quête d’un langage au flux impressionniste, foisonnant, jubilatoire, voire délirant, où le plaisir de dire le texte, tel une partition musicale, est toujours au cœur de la repr...

  11. Théâtre Le Poche

    CERN Multimedia

    Théâtre Le Poche

    2012-01-01

    LES TERRIENS (assurez-vous que vous faites totalement autre chose)   Mise en scène Claire Rengade   Obnubilée par la parole, Claire Rengade propose avec Les Terriens une recherche singulière et passionnée, une forme très novatrice entre théâtre, poésie et reportage. Après une enquête au CERN, la jeune auteure et metteure en scène choisit comme thème de sa nouvelle création une grande machine, centre de recherche scientifique de la plus grande avancée technologique. Avec Les Terriens Claire Rengade poursuit sa quête d’un langage au flux impressionniste, foisonnant, jubilatoire, voire délirant, où le plaisir de dire le texte, tel une partition musicale, est toujours au cœur de la représentation. PRIX SPÉCIAL POUR LES EMPLOYÉS DU CERN : CHF 22.- AU LIEU ...

  12. Le caratteristiche linguistiche del foglietto illustrativo

    Directory of Open Access Journals (Sweden)

    Silvia Giumelli

    2013-07-01

    Full Text Available Nell’articolo si affronta il problema della comprensibilità del foglietti illustrativi (i bugiardini” allegati ai medicinali, di cui indicano posologia, modalità d’uso ed effetti indesiderati (FI nel testo. Linguisticamente il testo dei FI si pone nel più ampio contesto dei linguaggi specialistici, ma si distingue per alcune particolarità (il destinatario e la funzione che ricopre. Attraverso l’analisi del FI presente in un comune antipiretico, Tachipirina 1000 ®, si mettono in evidenza le strategie comunicative messe in atto dall’estensore e il grado di comprensione da parte del presunto destinatario. L’analisi mette inoltre in luce le caratteristiche comuni di questo tipo di testi altamente specialistici con il linguaggio settoriale della medicina.  Language features of medicine packaging leaflets This article addresses the problem of the comprehensibility of the leaflets in medicine packaging which indicate dosage, method of use and side effects (FI in the text. Linguistically, the text of the FI is placed in the broader context of specialist languages, but it is characterized by some peculiarities (the recipient and the role it plays. By analyzing the FI of a common antipyretic, paracetamol 1000 ®, we highlight the communicative strategies put in place by the author and the degree of understanding on the part of the intended recipient. The analysis also highlights the common features of this type of highly specialized text with the technical language of medicine.

  13. Le cours de physique de Feynman

    CERN Document Server

    Feynman, Richard; Sands, Matthew

    L’ampleur du succès qu’a rencontré le « Cours de physique de Feynman » dès sa parution s’explique par son caractère fondamentalement novateur. Richard Feynman, qui fut professeur d’université dès l’âge de vingt-quatre ans, a exprimé dans ce cours, avant d’obtenir le prix Nobel de Physique, une vision expérimentale et extrêmement personnelle de l’enseignement de la physique. Cette vision a, depuis, remporté l’adhésion des physiciens du monde entier, faisant de cet ouvrage un grand classique. Ce cours en cinq volumes (Électromagnétisme 1 et 2, Mécanique 1 et 2, Mécanique quantique) s’adresse aux étudiants de tous niveaux qui y trouveront aussi bien les notions de base débarrassées de tout appareil mathématique inutile, que les avancées les plus modernes de cette science passionnante qu’est la physique. Cette nouvelle édition corrigée bénéficie d’une mise en page plus aérée pour un meilleur confort de lecture.

  14. Le Pédantisme dans Lolita

    OpenAIRE

    Delage-Toriel, Lara

    2010-01-01

    A mi-chemin du pédagogue au pédophile, la langue française a – pour pasticher Ponge avec force plosives – « pédant », assorti de ses divers dérivés, « pédantisme » bien sûr, mais également « pédanterie », « pédanter », « pédantiser », « pédantesque », « pédantesquement », « pédantaille », « pédantocratie » et autres coquetteries dont elle a le secret. Comme ses voisins, sieurs pédagogue et pédophile, le terme ‘pédant’ est né de sa relation à l’enfant, ou pais, paidos en grec. Ainsi, à l’égal ...

  15. Le choix de l'excellence

    CERN Document Server

    Collins, Jim

    2012-01-01

    Dix ans après le succès mondial de De la performance à l'excellence (Good to Great), Jim Collins et son associé Morten T. Hansen s'interrogent ici sur la nature de l excellence en période d incertitude. Pourquoi, dans un contexte chaotique, certaines entreprises sont florissantes et d autres non ? Comment, en ces temps troublés, réussir à diriger et vaincre l adversité pour dominer son marché ? La chance peut-elle sérieusement être envisagée comme un facteur de réussite ? À l issue d un programme de recherche ambitieux et rigoureux qui a duré neuf ans, les auteurs exposent dans cet ouvrage les nouveaux principes pour bâtir une entreprise réellement excellente. Leurs conclusions sont, comme toujours, étonnantes. Ils soulignent notamment que la course à l innovation n est pas toujours la meilleure voie à suivre, que discipline et créativité peuvent aller de concert et que malgré le changement permanent, les meilleures décisions sont rarement prises dans l urgence. Quant aux leaders, on...

  16. Panaxquin quefolium diolsaponins dose-dependently inhibits the proliferation of vascular smooth muscle cells by downregulating proto-oncogene expression

    Directory of Open Access Journals (Sweden)

    Zhihao Wang

    2013-01-01

    Conclusions: Our study demonstrates that PQDS may reduce AngII-stimulated VSMC proliferation by suppressing the expression of proto-oncogenes. These results may provide insights for the development of novel traditional Chinese medicines to prevent atherosclerosis.

  17. A human cellular sequence implicated in trk oncogene activation is DNA damage inducible

    Energy Technology Data Exchange (ETDEWEB)

    Ben-Ishai, R.; Scharf, R.; Sharon, R.; Kapten, I. (Technion-Israel Institute of Technology, Haifa (Israel))

    1990-08-01

    Xeroderma pigmentosum cells, which are deficient in the repair of UV light-induced DNA damage, have been used to clone DNA-damage-inducible transcripts in human cells. The cDNA clone designated pC-5 hybridizes on RNA gel blots to a 1-kilobase transcript, which is moderately abundant in nontreated cells and whose synthesis is enhanced in human cells following UV irradiation or treatment with several other DNA-damaging agents. UV-enhanced transcription of C-5 RNA is transient and occurs at lower fluences and to a greater extent in DNA-repair-deficient than in DNA-repair-proficient cells. Southern blot analysis indicates that the C-5 gene belongs to a multigene family. A cDNA clone containing the complete coding sequence of C-5 was isolated. Sequence analysis revealed that it is homologous to a human cellular sequence encoding the amino-terminal activating sequence of the trk-2h chimeric oncogene. The presence of DNA-damage-responsive sequences at the 5' end of a chimeric oncogene could result in enhanced expression of the oncogene in response to carcinogens.

  18. Features and Usage Areas of MicroRNAs as Oncogenes and Tumor Suppressors

    Directory of Open Access Journals (Sweden)

    G. Seyda Seydel

    2009-02-01

    Full Text Available MicroRNAs (miRNA are small non-coding RNA of 19–24 nucleotides in length that were discovered 12 years ago by Victor Ambros and colleagues. They are important regulatory molecules in animals and plants. MicroRNAs are downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. In addition, some miRNAs may function as oncogenes or tumor suppressors. More than 50% of miRNA genes are located in cancer-associated genomic regions or in fragile sites. Overexpressed miRNAs in cancers, such as mir17–92, may function as oncogenes and promote cancer development by negatively regulating tumor suppressor genes and genes that control cell differentiation or apoptosis. Underexpressed miRNAs in cancers, such as let–7, function as tumor suppressor genes and may inhibit cancers by regulating oncogenes and genes that control cell differentiation or apoptosis. miRNA expression profiles may become useful biomarkers for cancer diagnostics. [Archives Medical Review Journal 2009; 18(1.000: 1-12

  19. HER2 missense mutations have distinct effects on oncogenic signaling and migration

    Science.gov (United States)

    Zabransky, Daniel J.; Yankaskas, Christopher L.; Cochran, Rory L.; Wong, Hong Yuen; Croessmann, Sarah; Chu, David; Kavuri, Shyam M.; Red Brewer, Monica; Rosen, D. Marc; Dalton, W. Brian; Cimino-Mathews, Ashley; Cravero, Karen; Button, Berry; Kyker-Snowman, Kelly; Cidado, Justin; Erlanger, Bracha; Parsons, Heather A.; Manto, Kristen M.; Bose, Ron; Lauring, Josh; Arteaga, Carlos L.; Konstantopoulos, Konstantinos; Park, Ben Ho

    2015-01-01

    Recurrent human epidermal growth factor receptor 2 (HER2) missense mutations have been reported in human cancers. These mutations occur primarily in the absence of HER2 gene amplification such that most HER2-mutant tumors are classified as “negative” by FISH or immunohistochemistry assays. It remains unclear whether nonamplified HER2 missense mutations are oncogenic and whether they are targets for HER2-directed therapies that are currently approved for the treatment of HER2 gene-amplified breast cancers. Here we functionally characterize HER2 kinase and extracellular domain mutations through gene editing of the endogenous loci in HER2 nonamplified human breast epithelial cells. In in vitro and in vivo assays, the majority of HER2 missense mutations do not impart detectable oncogenic changes. However, the HER2 V777L mutation increased biochemical pathway activation and, in the context of a PIK3CA mutation, enhanced migratory features in vitro. However, the V777L mutation did not alter in vivo tumorigenicity or sensitivity to HER2-directed therapies in proliferation assays. Our results suggest the oncogenicity and potential targeting of HER2 missense mutations should be considered in the context of cooperating genetic alterations and provide previously unidentified insights into functional analysis of HER2 mutations and strategies to target them. PMID:26508629

  20. Transglutaminase 2 contributes to a TP53-induced autophagy program to prevent oncogenic transformation.

    Science.gov (United States)

    Yeo, Shi Yun; Itahana, Yoko; Guo, Alvin Kunyao; Han, Rachel; Iwamoto, Kozue; Nguyen, Hung Thanh; Bao, Yi; Kleiber, Kai; Wu, Ya Jun; Bay, Boon Huat; Voorhoeve, Mathijs; Itahana, Koji

    2016-03-09

    Genetic alterations which impair the function of the TP53 signaling pathway in TP53 wild-type human tumors remain elusive. To identify new components of this pathway, we performed a screen for genes whose loss-of-function debilitated TP53 signaling and enabled oncogenic transformation of human mammary epithelial cells. We identified transglutaminase 2 (TGM2) as a putative tumor suppressor in the TP53 pathway. TGM2 suppressed colony formation in soft agar and tumor formation in a xenograft mouse model. The depletion of growth supplements induced both TGM2 expression and autophagy in a TP53-dependent manner, and TGM2 promoted autophagic flux by enhancing autophagic protein degradation and autolysosome clearance. Reduced expression of both CDKN1A, which regulates the cell cycle downstream of TP53, and TGM2 synergized to promote oncogenic transformation. Our findings suggest that TGM2-mediated autophagy and CDKN1A-mediated cell cycle arrest are two important barriers in the TP53 pathway that prevent oncogenic transformation.