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Sample records for c-myc transactomes mapped

  1. Time-dependent c-Myc transactomes mapped by Array-based nuclear run-on reveal transcriptional modules in human B cells.

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    Jinshui Fan

    Full Text Available BACKGROUND: The definition of transcriptional networks through measurements of changes in gene expression profiles and mapping of transcription factor binding sites is limited by the moderate overlap between binding and gene expression changes and the inability to directly measure global nuclear transcription (coined "transactome". METHODOLOGY/PRINCIPAL FINDINGS: We developed a method to measure nascent nuclear gene transcription with an Array-based Nuclear Run-On (ANRO assay using commercial microarray platforms. This strategy provides the missing component, the transactome, to fully map transcriptional networks. ANRO measurements in an inducible c-Myc expressing human P493-6 B cell model reveals time-dependent waves of transcription, with a transactome early after c-Myc induction that does not persist at a late, steady-state phase, when genes that are regulated by c-Myc and E2F predominate. Gene set matrix analysis further uncovers functionally related groups of genes putatively regulated by waves of transcription factor motifs following Myc induction, starting with AP1 and CREB that are followed by EGR1, NFkB and STAT, and ending with E2F, Myc and ARNT/HIF motifs. CONCLUSIONS/SIGNIFICANCE: By coupling ANRO with previous global mapping of c-Myc binding sites by chromatin immunoprecipitation (ChIP in P493-6 cells, we define a set of transcriptionally regulated direct c-Myc target genes and pave the way for the use of ANRO to comprehensively map any transcriptional network.

  2. Molecular analysis of the c-myc locus in normal tissue and in avian leukosis virus-induced lymphomas.

    OpenAIRE

    Neel, B G; Gasic, G P; Rogler, C E; Skalka, A M; Ju, G; Hishinuma, F; Papas, T; Astrin, S M; Hayward, W S

    1982-01-01

    We isolated molecular clones of the provirus-host cell junctions (tumor junction fragments) from two avian leukosis virus-induced lymphomas and compared the structures of these clones with a clone of the normal c-myc gene. Restriction mapping and DNA sequencing demonstrated that normal proviral integration events occurred adjacent to c-myc in both tumors, without gross structural alteration of c-myc. The right long terminal repeat of an avian leukosis virus provirus is integrated upstream fro...

  3. Genetic and genomic analysis modeling of germline c-MYC overexpression and cancer susceptibility

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    Nunes Virginia

    2008-01-01

    Full Text Available Abstract Background Germline genetic variation is associated with the differential expression of many human genes. The phenotypic effects of this type of variation may be important when considering susceptibility to common genetic diseases. Three regions at 8q24 have recently been identified to independently confer risk of prostate cancer. Variation at 8q24 has also recently been associated with risk of breast and colorectal cancer. However, none of the risk variants map at or relatively close to known genes, with c-MYC mapping a few hundred kilobases distally. Results This study identifies cis-regulators of germline c-MYC expression in immortalized lymphocytes of HapMap individuals. Quantitative analysis of c-MYC expression in normal prostate tissues suggests an association between overexpression and variants in Region 1 of prostate cancer risk. Somatic c-MYC overexpression correlates with prostate cancer progression and more aggressive tumor forms, which was also a pathological variable associated with Region 1. Expression profiling analysis and modeling of transcriptional regulatory networks predicts a functional association between MYC and the prostate tumor suppressor KLF6. Analysis of MYC/Myc-driven cell transformation and tumorigenesis substantiates a model in which MYC overexpression promotes transformation by down-regulating KLF6. In this model, a feedback loop through E-cadherin down-regulation causes further transactivation of c-MYC. Conclusion This study proposes that variation at putative 8q24 cis-regulator(s of transcription can significantly alter germline c-MYC expression levels and, thus, contribute to prostate cancer susceptibility by down-regulating the prostate tumor suppressor KLF6 gene.

  4. The c-MYC Protooncogene Expression in Cholesteatoma

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    Enikő Palkó

    2014-01-01

    Full Text Available Cholesteatoma is an epidermoid cyst, which is most frequently found in the middle ear. The matrix of cholesteatoma is histologically similar to the matrix of the epidermoid cyst of the skin (atheroma; their epithelium is characterized by hyperproliferation. The c-MYC protooncogene located on chromosome 8q24 encodes a transcription factor involved in the regulation of cell proliferation and differentiation. Previous studies have found aneuploidy of chromosome 8, copy number variation of c-MYC gene, and the presence of elevated level c-MYC protein in cholesteatoma. In this study we have compared the expression of c-MYC gene in samples taken from the matrix of 26 acquired cholesteatomas (15 children and 11 adults, 15 epidermoid cysts of the skin (atheromas; head and neck region and 5 normal skin samples (retroauricular region using RT-qPCR, providing the first precise measurement of the expression of c-MYC gene in cholesteatoma. We have found significantly elevated c-MYC gene expression in cholesteatoma compared to atheroma and to normal skin samples. There was no significant difference, however, in c-MYC gene expression between cholesteatoma samples of children and adults. The significant difference in c-MYC gene expression level in cholesteatoma compared to that of atheroma implies a more prominent hyperproliferative phenotype which may explain the clinical behavior typical of cholesteatoma.

  5. Global regulation of nucleotide biosynthetic genes by c-Myc.

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    Yen-Chun Liu

    Full Text Available BACKGROUND: The c-Myc transcription factor is a master regulator and integrates cell proliferation, cell growth and metabolism through activating thousands of target genes. Our identification of direct c-Myc target genes by chromatin immunoprecipitation (ChIP coupled with pair-end ditag sequencing analysis (ChIP-PET revealed that nucleotide metabolic genes are enriched among c-Myc targets, but the role of Myc in regulating nucleotide metabolic genes has not been comprehensively delineated. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that the majority of genes in human purine and pyrimidine biosynthesis pathway were induced and directly bound by c-Myc in the P493-6 human Burkitt's lymphoma model cell line. The majority of these genes were also responsive to the ligand-activated Myc-estrogen receptor fusion protein, Myc-ER, in a Myc null rat fibroblast cell line, HO.15 MYC-ER. Furthermore, these targets are also responsive to Myc activation in transgenic mouse livers in vivo. To determine the functional significance of c-Myc regulation of nucleotide metabolism, we sought to determine the effect of loss of function of direct Myc targets inosine monophosphate dehydrogenases (IMPDH1 and IMPDH2 on c-Myc-induced cell growth and proliferation. In this regard, we used a specific IMPDH inhibitor mycophenolic acid (MPA and found that MPA dramatically inhibits c-Myc-induced P493-6 cell proliferation through S-phase arrest and apoptosis. CONCLUSIONS/SIGNIFICANCE: Taken together, these results demonstrate the direct induction of nucleotide metabolic genes by c-Myc in multiple systems. Our finding of an S-phase arrest in cells with diminished IMPDH activity suggests that nucleotide pool balance is essential for c-Myc's orchestration of DNA replication, such that uncoupling of these two processes create DNA replication stress and apoptosis.

  6. The c-MYC Protooncogene Expression in Cholesteatoma

    OpenAIRE

    2014-01-01

    Cholesteatoma is an epidermoid cyst, which is most frequently found in the middle ear. The matrix of cholesteatoma is histologically similar to the matrix of the epidermoid cyst of the skin (atheroma); their epithelium is characterized by hyperproliferation. The c-MYC protooncogene located on chromosome 8q24 encodes a transcription factor involved in the regulation of cell proliferation and differentiation. Previous studies have found aneuploidy of chromosome 8, copy number variation of c-MYC...

  7. Transcriptional regulation of Wnt inhibitory factor-1 by Miz-1/c-Myc

    OpenAIRE

    Licchesi, JDF; Van Neste, L; Tiwari, VK; Cope, L; Lin, X.; Baylin, SB; Herman, JG

    2010-01-01

    The Wnt signaling pathway is capable of self-regulation through positive and negative feedback mechanisms. For example, the oncoprotein c-Myc, which is upregulated by Wnt signaling activity, participates in a positive feedback loop of canonical Wnt signaling through repression of Wnt antagonists DKK1 and SFRP1. In this study, we investigated the mechanism of Wnt inhibitory factor-1 (WIF-1) silencing. Mapping of CpG island methylation of the WIF-1 promoter reveals regional methylation (–295 to...

  8. Alteraciones del gen c-Myc en la oncogénesis = c-Myc gene alterations in oncogenesis

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    Ospina Pérez, Mariano

    2011-12-01

    Full Text Available La familia de protooncogenes MYC (c-Myc, N-Myc y L-Myc se relaciona con el origen de diversas neoplasias en seres humanos. Estos genes actúan como factores de transcripción y participan en la regulación del ciclo celular, la proliferación y diferenciación celulares, la apoptosis y la inmortalización. Los genes MYC se expresan en diferentes tejidos y responden a diversas señales internas y externas; codifican para la síntesis de factores de transcripción que se unen al ADN para regular la expresión de múltiples genes. El gen más ampliamente estudiado de esta familia es c-Myc, que se expresa en las células con mayor tasa de proli­feración. C-Myc se encuentra alterado en un gran número de tumores sólidos, leucemias y linfomas. Las alteraciones de c-Myc encontradas con mayor frecuencia en células cancero­sas son las amplificaciones, translocaciones, mutaciones y reordenamientos cromosómicos que involucran el locus de este gen y conducen a que se desregule su expresión en diversas neoplasias humanas. La amplificación de c-Myc es una alteración común en los cánceres de mama, pulmón, ovario y próstata, así como en leucemias y linfomas, mientras que la pérdida de su regulación es común en el cáncer de colon, en tumores ginecológicos y melanoma. En neoplasias con defectos de c-Myc los estudios actuales están dirigidos al desarrollo de nuevas estrategias terapéuticas.

  9. Functional analysis of Burkitt's lymphoma mutant c-Myc proteins

    NARCIS (Netherlands)

    Smith-Sørensen, B.; Hijmans, E.M.; Bernards, R.A.

    1996-01-01

    The c-myc gene encodes a sequence-specific DNA binding protein that activates transcription of cellular genes. Transcription activation by Myc proteins is regulated by phosphorylation of serine and threonine residues within the transactivation domain and by complex formation with the retinoblastoma-

  10. Ezrin mediates c-Myc actions in prostate cancer cell invasion

    DEFF Research Database (Denmark)

    Chuan, Yin Choy; Iglesias-Gato, D; Fernandez-Perez, L;

    2010-01-01

    The forced overexpression of c-Myc in mouse prostate and in normal human prostate epithelial cells results in tumor transformation with an invasive phenotype. How c-Myc regulates cell invasion is poorly understood. In this study, we have investigated the interplay of c-Myc and androgens in the re...

  11. MYCN/c-MYC-induced microRNAs repress coding gene networks associated with poor outcome in MYCN/c-MYC-activated tumors.

    Science.gov (United States)

    Mestdagh, P; Fredlund, E; Pattyn, F; Schulte, J H; Muth, D; Vermeulen, J; Kumps, C; Schlierf, S; De Preter, K; Van Roy, N; Noguera, R; Laureys, G; Schramm, A; Eggert, A; Westermann, F; Speleman, F; Vandesompele, J

    2010-03-01

    Increased activity of MYC protein-family members is a common feature in many cancers. Using neuroblastoma as a tumor model, we established a microRNA (miRNA) signature for activated MYCN/c-MYC signaling in two independent primary neuroblastoma tumor cohorts and provide evidence that c-MYC and MYCN have overlapping functions. On the basis of an integrated approach including miRNA and messenger RNA (mRNA) gene expression data we show that miRNA activation contributes to widespread mRNA repression, both in c-MYC- and MYCN-activated tumors. c-MYC/MYCN-induced miRNA activation was shown to be dependent on c-MYC/MYCN promoter binding as evidenced by chromatin immunoprecipitation. Finally, we show that pathways, repressed through c-MYC/MYCN miRNA activation, are highly correlated to tumor aggressiveness and are conserved across different tumor entities suggesting that c-MYC/MYCN activate a core set of miRNAs for cooperative repression of common transcriptional programs related to disease aggressiveness. Our results uncover a widespread correlation between miRNA activation and c-MYC/MYCN-mediated coding gene expression modulation and further substantiate the overlapping functions of c-MYC and MYCN in the process of tumorigenesis. PMID:19946337

  12. Upregulation of the oncogene c-myc in Barrett’s adenocarcinoma: induction of c-myc by acidified bile acid in vitro

    OpenAIRE

    Tselepis, C; C. D. Morris; Wakelin, D; Hardy, R; Perry, I.; Luong, Q T; Harper, E.; Harrison, R.; Attwood, S E A; Jankowski, J.A.Z.

    2003-01-01

    Background and aims: C-myc over expression is implicated in malignancy although to date this has not been studied in Barrett’s metaplasia. We sought to determine c-myc expression in the malignant progression of Barrett’s metaplasia and whether it may be induced by bile acids seen in gastro-oesophageal refluxate.

  13. Chromosomal localization of the human gene encoding c-myc promoter-binding protein (MPB1) to chromosome 1p35-pter

    Energy Technology Data Exchange (ETDEWEB)

    White, R.A.; Dowler, L.L. [Univ. of Missouri, Kansas City, MO (United States); Adkison, L.R. [Mercer Univ. School of Medicine, Macon, GA (United States); Ray, R.B. [St. Louis Univ. Health Sciences Center, St. Louis, MO (United States)

    1997-02-01

    We report the mapping of the human gene MPB1 (c-myc promoter binding protein), a recently identified gene regulatory protein. MPB1 binds to the c-myc P2 promoter and exerts a negative regulatory role on c-myc transcription. Since exogenous expression from transfection of the MPB1 gene suppresses the tumorigenic property of breast cancer cells, there was interest in determining the chromosomal location of this gene. The human MPB1 gene was assigned to human chromosome 1p35-pter using Southern blot analyses of genomic DNAs from rodent-human somatic hybrid cell lines. A specific human genomic fragment was observed only in the somatic cell lines containing human chromosome 1 or the p35-pter region of the chromosome. 10 refs., 2 figs.

  14. Production of human c-myc protein in insect cells infected with a baculovirus expression vector.

    OpenAIRE

    Miyamoto, C.; Smith, G. E.; Farrell-Towt, J; Chizzonite, R.; Summers, M D; Ju, G.

    1985-01-01

    A cDNA fragment coding for human c-myc was inserted into the genome of the baculovirus Autographa californica nuclear polyhedrosis virus adjacent to the strong polyhedrin promoter. Insect cells infected with the recombinant virus produced significant amounts of c-myc protein, which constituted the major phosphoprotein component in these cells. By immunoprecipitation and immunoblot analysis, two proteins of 61 and 64 kilodaltons were detected with c-myc-specific antisera. The insect-derived pr...

  15. Rictor regulates FBXW7-dependent c-Myc and cyclin E degradation in colorectal cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► Rictor associates with FBXW7 to form an E3 complex. ► Knockdown of rictor decreases ubiquitination of c-Myc and cylin E. ► Knockdown of rictor increases protein levels of c-Myc and cylin E. ► Overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. ► Rictor regulation of c-Myc and cyclin E requires FBXW7. -- Abstract: Rictor (Rapamycin-insensitive companion of mTOR) forms a complex with mTOR and phosphorylates and activates Akt. Activation of Akt induces expression of c-Myc and cyclin E, which are overexpressed in colorectal cancer and play an important role in colorectal cancer cell proliferation. Here, we show that rictor associates with FBXW7 to form an E3 complex participating in the regulation of c-Myc and cyclin E degradation. The Rictor–FBXW7 complex is biochemically distinct from the previously reported mTORC2 and can be immunoprecipitated independently of mTORC2. Moreover, knocking down of rictor in serum-deprived colorectal cancer cells results in the decreased ubiquitination and increased protein levels of c-Myc and cyclin E while overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Genetic knockout of FBXW7 blunts the effects of rictor, suggesting that rictor regulation of c-Myc and cyclin E requires FBXW7. Our findings identify rictor as an important component of FBXW7 E3 ligase complex participating in the regulation of c-Myc and cyclin E protein ubiquitination and degradation. Importantly, our results suggest that elevated growth factor signaling may contribute to decrease rictor/FBXW7-mediated ubiquitination of c-Myc and cyclin E, thus leading to accumulation of cyclin E and c-Myc in colorectal cancer cells.

  16. Detection of circulating antibodies against c-myc protein in cancer patient sera.

    OpenAIRE

    Ben-Mahrez, K.; Thierry, D.; Sorokine, I.; Danna-Muller, A.; Kohiyama, M

    1988-01-01

    We have partially purified an archaebacterial protein of 84 kD which shares common epitopes with the human c-myc protein as shown by its cross-reactivity with a commercialized anti-human c-myc antiserum. An antiserum raised against the 84 kD protein recognizes a 60 kD protein from HL-60 nuclei. This protein is also recognized by the anti-human c-myc antiserum. Using this archaebacterial protein as antigen for Western blot analysis, we found that the human c-myc oncogene product could be immun...

  17. c-Myc activates BRCA1 gene expression through distal promoter elements in breast cancer cells

    International Nuclear Information System (INIS)

    The BRCA1 gene plays an important role in the maintenance of genomic stability. BRCA1 inactivation contributes to breast cancer tumorigenesis. An increasing number of transcription factors have been shown to regulate BRCA1 expression. c-Myc can act as a transcriptional activator, regulating up to 15% of all genes in the human genome and results from a high throughput screen suggest that BRCA1 is one of its targets. In this report, we used cultured breast cancer cells to examine the mechanisms of transcriptional activation of BRCA1 by c-Myc. c-Myc was depleted using c-Myc-specific siRNAs in cultured breast cancer cells. BRCA1 mRNA expression and BRCA1 protein expression were determined by quantitative RT-PCR and western blot, respectively and BRCA1 promoter activities were examined under these conditions. DNA sequence analysis was conducted to search for high similarity to E boxes in the BRCA1 promoter region. The association of c-Myc with the BRCA1 promoter in vivo was tested by a chromatin immunoprecipitation assay. We investigated the function of the c-Myc binding site in the BRCA1 promoter region by a promoter assay with nucleotide substitutions in the putative E boxes. BRCA1-dependent DNA repair activities were measured by a GFP-reporter assay. Depletion of c-Myc was found to be correlated with reduced expression levels of BRCA1 mRNA and BRCA1 protein. Depletion of c-Myc decreased BRCA1 promoter activity, while ectopically expressed c-Myc increased BRCA1 promoter activity. In the distal BRCA1 promoter, DNA sequence analysis revealed two tandem clusters with high similarity, and each cluster contained a possible c-Myc binding site. c-Myc bound to these regions in vivo. Nucleotide substitutions in the c-Myc binding sites in these regions abrogated c-Myc-dependent promoter activation. Furthermore, breast cancer cells with reduced BRCA1 expression due to depletion of c-Myc exhibited impaired DNA repair activity. The distal BRCA1 promoter region is associated with c-Myc

  18. Elevated c-myc protooncogene expression in autosomal recessive polycystic kidney disease

    International Nuclear Information System (INIS)

    The polycystic kidney diseases (PKDs) are a group of disorders characterized by the growth of epithelial cysts from the nephrons and collecting ducts of kidney tubules. The diseases can be inherited or can be provoked by environmental factors. To investigate the molecular basis of the abnormal cell growth associated with PKD, c-myc protooncogene expression was studied in a mouse model for autosomal recessive PKD. Homozygous recessive C57BL/6J (cpk/cpk) mice develop massively enlarged cystic kidneys and die from renal failure shortly after 3 weeks of age. Quantitative dot blot and RNA blot hybridization experiments in which whole kidney poly(A)+ RNA was hybridized with a c-myc RNA probe showed a 2- to 6-fold increase in c-myc mRNA at 2 weeks, and a 25- to 30-fold increase in c-myc mRNA at 3 weeks of age in polycystic mice, as compared to normal littermates. c-myc expression was also examined under two conditions in which kidney cell growth was experimentally induced in normal adult mice: compensatory renal hypertrophy and tubule regeneration following folic acid-induced renal cell injury. While compensatory hypertrophy resulted in only a small increase in c-myc, folic acid treatment gave rise after 24 hr to a 12-fold increase in c-myc RNA. The induction of c-myc by folic acid is consistent with increased cellular proliferation regenerating tubules. In contrast, polycystic kidneys show only a minimal increase in cellular proliferation over that seen in normal kidneys, while c-myc levels were found to be markedly elevated. Thus, the level of c-myc expression in cystic kidneys appears to be out of proportion to the rate of cell division, suggesting that elevated and potentially abnormal c-myc expression may be involved in the pathogenesis of PKD

  19. Acetylation of the c-MYC oncoprotein is required for cooperation with the HTLV-1 p30{sup II} accessory protein and the induction of oncogenic cellular transformation by p30{sup II}/c-MYC

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    Romeo, Megan M.; Ko, Bookyung; Kim, Janice; Brady, Rebecca; Heatley, Hayley C.; He, Jeffrey; Harrod, Carolyn K.; Barnett, Braden [Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design, and Delivery, Southern Methodist University, Dallas, TX 75275-0376 (United States); Ratner, Lee [Departments of Medicine and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Lairmore, Michael D. [University of California-Davis, School of Veterinary Medicine, One Shields Avenue, Davis, CA 95618 (United States); Martinez, Ernest [Department of Biochemistry, University of California, Riverside, CA 92521 (United States); Lüscher, Bernhard [Institute of Biochemistry, Klinikum, RWTH Aachen University, Pauwelsstrasse 30, 52057 Aachen (Germany); Robson, Craig N. [Northern Institute for Cancer Research, Newcastle University, The Medical School, Newcastle upon Tyne, NE2 4HH (United Kingdom); Henriksson, Marie [Department of Microbiology, Cell and Tumor Biology, Karolinska Institutet, Stockholm (Sweden); Harrod, Robert, E-mail: rharrod@smu.edu [Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design, and Delivery, Southern Methodist University, Dallas, TX 75275-0376 (United States)

    2015-02-15

    The human T-cell leukemia retrovirus type-1 (HTLV-1) p30{sup II} protein is a multifunctional latency-maintenance factor that negatively regulates viral gene expression and deregulates host signaling pathways involved in aberrant T-cell growth and proliferation. We have previously demonstrated that p30{sup II} interacts with the c-MYC oncoprotein and enhances c-MYC-dependent transcriptional and oncogenic functions. However, the molecular and biochemical events that mediate the cooperation between p30{sup II} and c-MYC remain to be completely understood. Herein we demonstrate that p30{sup II} induces lysine-acetylation of the c-MYC oncoprotein. Acetylation-defective c-MYC Lys→Arg substitution mutants are impaired for oncogenic transformation with p30{sup II} in c-myc{sup −/−} HO15.19 fibroblasts. Using dual-chromatin-immunoprecipitations (dual-ChIPs), we further demonstrate that p30{sup II} is present in c-MYC-containing nucleoprotein complexes in HTLV-1-transformed HuT-102 T-lymphocytes. Moreover, p30{sup II} inhibits apoptosis in proliferating cells expressing c-MYC under conditions of genotoxic stress. These findings suggest that c-MYC-acetylation is required for the cooperation between p30{sup II}/c-MYC which could promote proviral replication and contribute to HTLV-1-induced carcinogenesis. - Highlights: • Acetylation of c-MYC is required for oncogenic transformation by HTLV-1 p30{sup II}/c-MYC. • Acetylation-defective c-MYC mutants are impaired for foci-formation by p30{sup II}/c-MYC. • The HTLV-1 p30{sup II} protein induces lysine-acetylation of c-MYC. • p30{sup II} is present in c-MYC nucleoprotein complexes in HTLV-1-transformed T-cells. • HTLV-1 p30{sup II} inhibits apoptosis in c-MYC-expressing proliferating cells.

  20. Effect of C-myc Antisense Oligodeoxynucleotides on Hypoxia-induced Proliferation of Pulmonary Vascular Pericytes

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To study the effect of c-myc antisense oligodeoxynucleotides (ODNs) on proliferation of pulmonary vascular pericytes (PC) induced by hypoxia, cell culture, dot hybridization using probe of digoxigenin-11-dUTP-labeled cDNA,3H-thymidine incorporation, immunocytochemical technique and image analysis methods were used to observe the effect of c-myc antisense ODNs on expression of c-myc gene and proliferating cell nuclear antigen (PCNA), and 3H-thymidine incorporation of PC induced by hypoxia. The results showed that hypoxia could significantly enhance the expression of c-myc and PCNA (P<0.01), and elevate 3H-thymidine incorporation of PC (P<0.01), but antisense ODNs could significantly inhibit the expression of c-myc and PCNA (P<0.05), and 3H-thymidine incorporation of PC (P<0.01). It was suggested that hypoxia could promote the proliferation of PC by up-regulating the expression of c-myc gene, but c-myc antisense ODNs could inhibit hypoxia-induced proliferation of PC by downregulating the expression of c-myc gene.

  1. Deregulation of c-myc and SV40Tag causing brain tumor in mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Deregulated expressions of both c-myc and simian virus 40 large T antigen (SV40Tag) are consistent features of lots of tumors. To investigate whether the expression of c-myc and SV40Tag in mouse might help develop a model of human tumor, we generated c-myc transgenics by inserting human c-myc gene into pTRE2 of Tet-On system. We obtained conditional expression of SV40Tag transgenics by the Tet-On system from Yangzhou University. Crossing the c-myc transgenic mouse with the SV40Tag transgenic mice to generate bitransgenics we got double-transgenic mice expressing c-myc and SV40Tag by the Tet-On system. After being treated with doxycycline continuously, single-transgenic SV40Tag mice developed brain tumor infrequently (3 of 84, 3.6%) with a long onset (185 d on average). In contrast, double-transgenic c-myc/SV40Tag mice developed brain tumor with a short onset (96 days on average) and a 41% brain tumor incidence rate (7 of 17, 41%). This tumor was assumed to be medulloblastoma. Our experiments suggest that deregulated expression of c-myc and SV40Tag in brain might generate a mouse model of human brain tumor that recapitulates some features of human medulloblastoma.

  2. Thymidylate synthase binds to c-myc RNA in human colon cancer cells and in vitro.

    Science.gov (United States)

    Chu, E; Takechi, T; Jones, K L; Voeller, D M; Copur, S M; Maley, G F; Maley, F; Segal, S; Allegra, C J

    1995-01-01

    Using an immunoprecipitation-reverse transcription-PCR technique, we characterized a thymidylate synthase (TS) ribonucleoprotein complex in cultured human colon cancer cells that consists of TS protein and the mRNA of the nuclear oncogene c-myc. TS protein is complexed in intact cells with the C-terminal coding region of c-myc mRNA that includes nucleotide positions 1625 to 1790. RNA electrophoretic gel mobility shift assays confirm a specific interaction between TS protein and c-myc mRNA and provide additional evidence that the C-terminal coding region represents an important cis-acting regulatory element. Further evidence demonstrates that the in vitro translational efficiency of c-myc mRNA is inhibited as a result of its direct interaction with TS protein. In addition, the presence of exogenous c-myc mRNA specifically relieves the inhibitory effects of TS protein on TS mRNA translation. PMID:7799924

  3. Glutathione Depletion Induced by c-Myc Downregulation Triggers Apoptosis on Treatment with Alkylating Agents

    Directory of Open Access Journals (Sweden)

    Annamaria Biroccio

    2004-05-01

    Full Text Available Here we investigate the mechanism(s involved in the c-Myc-dependent drug response of melanoma cells. By using three M14-derived c-Myc low-expressing clones, we demonstrate that alkylating agents, cisplatin and melphalan, trigger apoptosis in the c-Myc antisense transfectants, but not in the parental line. On the contrary, topoisomerase inhibitors, adriamycin and camptothecin, induce apoptosis to the same extent regardless of c-Myc expression. Because we previously demonstrated that c-Myc downregulation decreases glutathione (GSH content, we evaluated the role of GSH in the apoptosis induced by the different drugs. In control cells treated with one of the alkylating agents or the others, GSH depletion achieved by L-buthionine-sulfoximine preincubation opens the apoptotic pathway. The apoptosis proceeded through early Bax relocalization, cytochrome c release, concomitant caspase-9 activation, whereas reactive oxygen species production and alteration of mitochondria membrane potential were late events. That GSH was determining in the c-Myc-dependent druginduced apoptosis was demonstrated by altering the intracellular GSH content of the c-Myc low-expressing cells up to the level of controls. Indeed, GSH ethyl ester-mediated increase of GSH abrogated apoptosis induced by cisplatin and melphalan by inhibition of Baxicytochrome c redistribution. The relationship among c-Myc, GSH content, the response to alkylating agent has been also evaluated in the M14 Myc overexpressing clones as well as in the melanoma JR8 c-Myc antisense transfectants. All together, these results demonstrate that GSH plays a key role in governing c-Myc-dependent drug-induced apoptosis.

  4. Acetylation of the c-MYC oncoprotein is required for cooperation with the HTLV-1 p30II accessory protein and the induction of oncogenic cellular transformation by p30II/c-MYC

    International Nuclear Information System (INIS)

    The human T-cell leukemia retrovirus type-1 (HTLV-1) p30II protein is a multifunctional latency-maintenance factor that negatively regulates viral gene expression and deregulates host signaling pathways involved in aberrant T-cell growth and proliferation. We have previously demonstrated that p30II interacts with the c-MYC oncoprotein and enhances c-MYC-dependent transcriptional and oncogenic functions. However, the molecular and biochemical events that mediate the cooperation between p30II and c-MYC remain to be completely understood. Herein we demonstrate that p30II induces lysine-acetylation of the c-MYC oncoprotein. Acetylation-defective c-MYC Lys→Arg substitution mutants are impaired for oncogenic transformation with p30II in c-myc−/− HO15.19 fibroblasts. Using dual-chromatin-immunoprecipitations (dual-ChIPs), we further demonstrate that p30II is present in c-MYC-containing nucleoprotein complexes in HTLV-1-transformed HuT-102 T-lymphocytes. Moreover, p30II inhibits apoptosis in proliferating cells expressing c-MYC under conditions of genotoxic stress. These findings suggest that c-MYC-acetylation is required for the cooperation between p30II/c-MYC which could promote proviral replication and contribute to HTLV-1-induced carcinogenesis. - Highlights: • Acetylation of c-MYC is required for oncogenic transformation by HTLV-1 p30II/c-MYC. • Acetylation-defective c-MYC mutants are impaired for foci-formation by p30II/c-MYC. • The HTLV-1 p30II protein induces lysine-acetylation of c-MYC. • p30II is present in c-MYC nucleoprotein complexes in HTLV-1-transformed T-cells. • HTLV-1 p30II inhibits apoptosis in c-MYC-expressing proliferating cells

  5. Regulation of c-Myc protein stability by proteasome activator REGγ.

    Science.gov (United States)

    Li, S; Jiang, C; Pan, J; Wang, X; Jin, J; Zhao, L; Pan, W; Liao, G; Cai, X; Li, X; Xiao, J; Jiang, J; Wang, P

    2015-06-01

    c-Myc is a key transcriptional factor that has a prominent role in cell growth, differentiation and tumor development. Its protein levels are tightly controlled by ubiquitin-proteasome pathway and frequently deregulated in various cancers. Here, we report that the 11S proteasomal activator REGγ is a novel regulator of c-Myc abundance in cells. We showed that overexpression of wild-type REGγ, but not inactive mutants including N151Y and G250S, significantly promoted the degradation of c-Myc. Depletion of REGγ markedly increased the protein stability of c-Myc. REGγ interacts with the C-terminal region of c-Myc and regulates c-Myc protein turnover. Functionally, REGγ negatively regulates c-Myc-mediated cell proliferation. Interestingly, depletion of the Drosophila Reg homolog (dReg) in developing wings induced the upregulation of Drosophila Myc, which contributes to cell death. Collectively, these results suggest that REGγ proteasome has a conserved role in the regulation of Myc abundance in both mammalian cells and Drosophila. PMID:25412630

  6. TELOMERASE ACTIVITY IN COLORECTAL CARCINOMA AND ITS CORRELATION WITH EXPRESSION OF C-MYC

    Institute of Scientific and Technical Information of China (English)

    LIU Jian-Lun; GE Lian-ying; ZHANG Gui-nian

    2005-01-01

    Objective: To study the role of telomerase activity and c-myc in pathogenesis and progression of colorectal carcinoma,and to investigate the possible regulatory mechanism of telomerase activation. Methods: A modified telomeric repeat amplification protocol (TRAP) and immunohistochemical staining was used to detect telomerase activity and the expression of c-myc in tissue samples from colorectal carcinoma, paracarcinomatousl tissues, normal mucosa, and adenomatoid polyp.Results: The positive rates of telomerase activity and c-myc expression were 83.33% and 80.00% in colorectal carcinoma,13.33% and 23.33% in paracarcinomatousl tissues, 13.33% and 20.00% in normal mucosa, and 10.00% and 45.00% in adenomatoid polyp respectively, they were significantly higher in colorectal carcinoma than in paracarcinomatousl tissues,normal mucosa, and adenomatoid polyp (P<0.05). The rates of telomerase activity and c-myc expression were much higher in colorectal carcinoma with lymph nodes metastases than that without lymph nodes metastases. The expression of c-myc was found being significantly higher in the telomerase positive colorectal carcinoma than in the telomerase negative group(P<0.05). Conclusion: The activation of telomerase and abnormal expression of c-myc might play an important role in the process of carcinogenesis and progression of colorectal carcinoma. The over-expression of c-myc may be related to telomerase activation and up-regulation in colorectal carcinoma.

  7. c-Myc is essential to prevent endothelial pro-inflammatory senescent phenotype.

    Directory of Open Access Journals (Sweden)

    Victoria Florea

    Full Text Available The proto-oncogene c-Myc is vital for vascular development and promotes tumor angiogenesis, but the mechanisms by which it controls blood vessel growth remain unclear. In the present work we investigated the effects of c-Myc knockdown in endothelial cell functions essential for angiogenesis to define its role in the vasculature. We provide the first evidence that reduction in c-Myc expression in endothelial cells leads to a pro-inflammatory senescent phenotype, features typically observed during vascular aging and pathologies associated with endothelial dysfunction. c-Myc knockdown in human umbilical vein endothelial cells using lentivirus expressing specific anti-c-Myc shRNA reduced proliferation and tube formation. These functional defects were associated with morphological changes, increase in senescence-associated-β-galactosidase activity, upregulation of cell cycle inhibitors and accumulation of c-Myc-deficient cells in G1-phase, indicating that c-Myc knockdown in endothelial cells induces senescence. Gene expression analysis of c-Myc-deficient endothelial cells showed that senescent phenotype was accompanied by significant upregulation of growth factors, adhesion molecules, extracellular-matrix components and remodeling proteins, and a cluster of pro-inflammatory mediators, which include Angptl4, Cxcl12, Mdk, Tgfb2 and Tnfsf15. At the peak of expression of these cytokines, transcription factors known to be involved in growth control (E2f1, Id1 and Myb were downregulated, while those involved in inflammatory responses (RelB, Stat1, Stat2 and Stat4 were upregulated. Our results demonstrate a novel role for c-Myc in the prevention of vascular pro-inflammatory phenotype, supporting an important physiological function as a central regulator of inflammation and endothelial dysfunction.

  8. Expression profile of microRNAs in c-Myc induced mouse mammary tumors

    OpenAIRE

    Sun, Yuan; Wu, Jack; Wu, Si-hung; Thakur, Archana; Bollig, Aliccia; Huang, Yong; Liao, D. Joshua

    2008-01-01

    c-Myc is a transcription factor overexpression of which induces mammary cancer in transgenic mice. To explore whether certain microRNAs (mirRNA) mediate c-Myc induced mammary carcinogenesis, we studied mir-RNA expression profile in mammary tumors developed from MMTV-c-myc transgenic mice, and found 50 and 59 mirRNAs showing increased and decreased expression, respectively, compared with lactating mammary glands of wild type mice. Twenty-four of these mirRNAs could be grouped into eight cluste...

  9. Nuclear localization of phosphorylated c-Myc protein in human tumor cells.

    Directory of Open Access Journals (Sweden)

    C. Soldani

    2010-05-01

    Full Text Available Using immunocytochemical techniques at light and electron microscopy, we analysed the distribution of phosphorylated c-Myc in actively proliferating human HeLa cells. The distribution pattern of c-Myc was also compared with those of other ribonucleoprotein (RNP-containing components (PANA, hnRNP-core proteins, fibrillarin or RNP-associated nuclear proteins (SC-35 splicing factor. Our results provide the first evidence that phosphorylated c-Myc accumulates in the nucleus of tumor cells, where it colocalizes with fibrillarin, both in the nucleolus and in extranucleolar structures.

  10. Multiple mechanisms regulate c-myc gene expression during normal T cell activation.

    OpenAIRE

    Lindsten, T; June, C H; Thompson, C. B.

    1988-01-01

    Quiescent normal human T cells express low levels of steady-state c-myc mRNA as a result of low constitutive promoter utilization, a block to transcriptional elongation within the gene, and rapid degradation of c-myc mRNA in the cytoplasm. Following the activation of the T cell receptor (TCR)/CD3 complex, quiescent T cells are induced to express c-myc mRNA. Two intracellular pathways, one involving protein kinase C activation and the other mediated by increased intracellular calcium concentra...

  11. Endogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo

    OpenAIRE

    Phesse, T J; Myant, K.B.; Cole, A M; Ridgway, R.A.; Pearson, H; Muncan, V.; van den Brink, G R; Vousden, K H; Sears, R.; Vassilev, L T; Clarke, A R; Sansom, O J

    2014-01-01

    Recent studies have suggested that C-MYC may be an excellent therapeutic cancer target and a number of new agents targeting C-MYC are in preclinical development. Given most therapeutic regimes would combine C-MYC inhibition with genotoxic damage, it is important to assess the importance of C-MYC function for DNA damage signalling in vivo. In this study, we have conditionally deleted the c-Myc gene in the adult murine intestine and investigated the apoptotic response of intestinal enterocytes ...

  12. Transcription-responsive regulation of c-myc proto-oncogene – structural and biophysical studies

    OpenAIRE

    Cukier, C. D.

    2010-01-01

    The Far-UpStream Element (FUSE) regulatory system tightly controls the expression of c-myc proto-oncogene – a master regulator of cellular proliferation and differentiation. The FUSE mechanism relies on the inter-molecular interactions between a DNA regulatory sequence – the FUSE, a transcriptional activator – FUSEBinding Protein (FBP) and a transcriptional repressor – FBP-Interacting Repressor (FIR). The FUSE DNA element serves as a sensor of the level of ongoing c-myc tran...

  13. Lack of Cyclin-Dependent Kinase 4 Inhibits c-myc Tumorigenic Activities in Epithelial Tissues

    OpenAIRE

    Miliani de Marval, Paula L.; Macias, Everardo; Rounbehler, Robert; Sicinski, Piotr; Kiyokawa, Hiroaki; David G. Johnson; Conti, Claudio J.; Rodriguez-Puebla, Marcelo L

    2004-01-01

    The proto-oncogene c-myc encodes a transcription factor that is implicated in the regulation of cellular proliferation, differentiation, and apoptosis and that has also been found to be deregulated in several forms of human and experimental tumors. We have shown that forced expression of c-myc in epithelial tissues of transgenic mice (K5-Myc) resulted in keratinocyte hyperproliferation and the development of spontaneous tumors in the skin and oral cavity. Although a number of genes involved i...

  14. The functional basis of c-myc and bcl-2 complementation during multistep lymphomagenesis in vivo.

    Science.gov (United States)

    Marin, M C; Hsu, B; Stephens, L C; Brisbay, S; McDonnell, T J

    1995-04-01

    Oncogenes are known to be deregulated by chromosomal translocations occurring at high frequency in specific malignancies. Among the most well characterized of these are c-myc, associated with the t(8;14) in Burkitt's lymphomas, and bcl-2, associated with the t(14;18) in follicular lymphomas. In addition to their role in regulating rates of proliferation, it is known that oncogenes and tumor suppressor genes can also regulate rates of apoptotic cell death. The contribution of c-myc and bcl-2 to the regulation of cell death during lymphomagenesis in vivo is assessed using bcl-2-Ig and emu-myc trangenic mice and bcl-2/myc hybrid transgenic mice. Translocations between the endogenous c-myc gene and immunoglobulin loci, e.g., t(12;15), are common in lymphomas arising in the bcl-2-Ig mice. Furthermore, bcl-2/c-myc double transgenic mice exhibit accelerated lymphomagenesis, indicating cooperation between these two oncogenes. Genetic complementation of c-myc and bcl-2 during lymphomagenesis resulted from the suppression of c-myc-associated apoptosis. Other genes are likely involved in regulating cell death during multistep lymphomagenesis. PMID:7698223

  15. ELL targets c-Myc for proteasomal degradation and suppresses tumour growth

    Science.gov (United States)

    Chen, Yu; Zhou, Chi; Ji, Wei; Mei, Zhichao; Hu, Bo; Zhang, Wei; Zhang, Dawei; Wang, Jing; Liu, Xing; Ouyang, Gang; Zhou, Jiangang; Xiao, Wuhan

    2016-01-01

    Increasing evidence supports that ELL (eleven–nineteen lysine-rich leukaemia) is a key regulator of transcriptional elongation, but the physiological function of Ell in mammals remains elusive. Here we show that ELL functions as an E3 ubiquitin ligase and targets c-Myc for proteasomal degradation. In addition, we identify that UbcH8 serves as a ubiquitin-conjugating enzyme in this pathway. Cysteine 595 of ELL is an active site of the enzyme; its mutation to alanine (C595A) renders the protein unable to promote the ubiquitination and degradation of c-Myc. ELL-mediated c-Myc degradation inhibits c-Myc-dependent transcriptional activity and cell proliferation, and also suppresses c-Myc-dependent xenograft tumour growth. In contrast, the ELL(C595A) mutant not only loses the ability to inhibit cell proliferation and xenograft tumour growth, but also promotes tumour metastasis. Thus, our work reveals a previously unrecognized function for ELL as an E3 ubiquitin ligase for c-Myc and a potential tumour suppressor. PMID:27009366

  16. Evidence that a triplex-forming oligodeoxyribonucleotide binds to the c-myc promoter in HeLa cells, thereby reducing c-myc mRNA levels

    Energy Technology Data Exchange (ETDEWEB)

    Postel, E.H.; Flint, S.J. (Princeton Univ., NJ (United States)); Kessler, D.J.; Hogan, M.E. (Baylor College of Medicine, The Woodlands, TX (United States))

    1991-09-15

    A synthetic 27-base-long oligodeoxyribonucleotide, termed PU1, has been shown to bind to duplex DNA to form a triplex at a single site within the human c-myc P1 promoter. PU1 has been administered to HeLa cells in culture to examine the feasibility of influencing transcription of the c-myc gene in vivo. It is shown that uptake of PU1 into the nucleus of HeLa cells is efficient and that the compound remains intact for at least 4 hours. In nuclei extracted from PU1-treated cells, inhibition of DNase I cleavage is detected within the c-myc P1 promoter at the target site for triplex formation. The inhibition is shown to be both site and oligodeoxyribonucleotide specific. After cellular uptake of PU1, it is shown that steady-state mRNA arising from the c-myc P2 initiation site, and relative to mRNA derived form the {beta}-actin promoter. Significant mRNA repression is not seen upon treating cells with oligodeoxyuribonucleotides that fail to bind to the P1 promoter target. Taken together, these data suggest that triplex formation can occur between an exogenous oligodeoxy-ribonucleotide and duplex DNA in the nucleus of treated cells.

  17. Pim1 promotes human prostate cancer cell tumorigenicity and c-MYC transcriptional activity

    International Nuclear Information System (INIS)

    The serine/threonine kinase PIM1 has been implicated as an oncogene in various human cancers including lymphomas, gastric, colorectal and prostate carcinomas. In mouse models, Pim1 is known to cooperate with c-Myc to promote tumorigenicity. However, there has been limited analysis of the tumorigenic potential of Pim1 overexpression in benign and malignant human prostate cancer cells in vivo. We overexpressed Pim1 in three human prostate cell lines representing different disease stages including benign (RWPE1), androgen-dependent cancer (LNCaP) and androgen-independent cancer (DU145). We then analyzed in vitro and in vivo tumorigenicity as well as the effect of Pim1 overexpression on c-MYC transcriptional activity by reporter assays and gene expression profiling using an inducible MYC-ER system. To validate that Pim1 induces tumorigenicity and target gene expression by modulating c-MYC transcriptional activity, we inhibited c-MYC using a small molecule inhibitor (10058-F4) or RNA interference. Overexpression of Pim1 alone was not sufficient to convert the benign RWPE1 cell to malignancy although it enhanced their proliferation rates when grown as xenografts in vivo. However, Pim1 expression enhanced the in vitro and in vivo tumorigenic potentials of the human prostate cancer cell lines LNCaP and DU145. Reporter assays revealed increased c-MYC transcriptional activity in Pim1-expressing cells and mRNA expression profiling demonstrated that a large fraction of c-MYC target genes were also regulated by Pim1 expression. The c-MYC inhibitor 10058-F4 suppressed the tumorigenicity of Pim1-expressing prostate cancer cells. Interestingly, 10058-F4 treatment also led to a reduction of Pim1 protein but not mRNA. Knocking-down c-MYC using short hairpin RNA reversed the effects of Pim1 on Pim1/MYC target genes. Our results suggest an in vivo role of Pim1 in promoting prostate tumorigenesis although it displayed distinct oncogenic activities depending on the disease stage of the

  18. Interactions between cells with distinct mutations in c-MYC and Pten in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Jongchan Kim

    2009-07-01

    Full Text Available In human somatic tumorigenesis, mutations are thought to arise sporadically in individual cells surrounded by unaffected cells. This contrasts with most current transgenic models where mutations are induced synchronously in entire cell populations. Here we have modeled sporadic oncogene activation using a transgenic mouse in which c-MYC is focally activated in prostate luminal epithelial cells. Focal c-MYC expression resulted in mild pathology, but prostate-specific deletion of a single allele of the Pten tumor suppressor gene cooperated with c-MYC to induce high grade prostatic intraepithelial neoplasia (HGPIN/cancer lesions. These lesions were in all cases associated with loss of Pten protein expression from the wild type allele. In the prostates of mice with concurrent homozygous deletion of Pten and focal c-MYC activation, double mutant (i.e. c-MYC+;Pten-null cells were of higher grade and proliferated faster than single mutant (Pten-null cells within the same glands. Consequently, double mutant cells outcompeted single mutant cells despite the presence of increased rates of apoptosis in the former. The p53 pathway was activated in Pten-deficient prostate cells and tissues, but c-MYC expression shifted the p53 response from senescence to apoptosis by repressing the p53 target gene p21(Cip1. We conclude that c-MYC overexpression and Pten deficiency cooperate to promote prostate tumorigenesis, but a p53-dependent apoptotic response may present a barrier to further progression. Our results highlight the utility of inducing mutations focally to model the competitive interactions between cell populations with distinct genetic alterations during tumorigenesis.

  19. VARIATION AND SIGNIFICANCE OF C-MYC PROTEIN IN RAT CARDIAC VOLUME-OVERLOAD HYP ERTROPHY

    Institute of Scientific and Technical Information of China (English)

    刘华胜; 马爱群; 王一理; 刘勇; 李恒力; 田红燕

    2002-01-01

    Objective To investigate the change of c-myc protein, which was chosen as the response indicator to volume-overload. Methods The time and spatial course of c-myc protein expressi on on the model of rat cardiac volume-overload hyper trophy was examined by immunohistochemical study. Results The immunohistochemica l study indicated the expression of c-myc protein was increased obviously at 4 -6 hours (62.73%) than that of control (45.41%, P<0.01) after the volume-o verload, then decreased gradually along with development of volume-overload hyp ertrophy and was decreased extremely at 5 months(r=-0.514,P<0.01).Conclusion There are disorders in the signal transduction pathways governing the hypertrophic respon se of cardiomyocytes in hypertrophic myocardium. C-myc gene and the product of it may be only the promoter gene of myocardial hypertrophy. Once switching on, c-myc gene and the product of it do not act anymore;While it may be that c-my c gene and the product of it increased following with myocardial hypertrophy, an d have not direct relation to the occurrence and development of myocardial hyper trophy.

  20. Discovery of a Family of Genomic Sequences Which Interact Specifically with the c-MYC Promoter to Regulate c-MYC Expression

    Science.gov (United States)

    Thomas, Shelia D.; Rouchka, Eric C.; Miller, Donald M.

    2016-01-01

    G-quadruplex forming sequences are particularly enriched in the promoter regions of eukaryotic genes, especially of oncogenes. One of the most well studied G-quadruplex forming sequences is located in the nuclease hypersensitive element (NHE) III1 of the c-MYC promoter region. The oncoprotein c-MYC regulates a large array of genes which play important roles in growth regulation and metabolism. It is dysregulated in >70% of human cancers. The silencer NHEIII1 located upstream of the P1 promoter regulates up-to 80% of c-MYC transcription and includes a G-quadruplex structure (Pu27) that is required for promoter inhibition. We have identified, for the first time, a family of seventeen G-quadruplex-forming motifs with >90% identity with Pu27, located on different chromosomes throughout the human genome, some found near or within genes involved in stem cell maintenance or neural cell development. Notably, all members of the Pu27 family interact specifically with NHEIII1 sequence, in vitro. Crosslinking studies demonstrate that Pu27 oligonucleotide binds specifically to the C-rich strand of the NHEIII1 resulting in the G-quadruplex structure stabilization. Pu27 homologous sequences (Pu27-HS) significantly inhibit leukemic cell lines proliferation in culture. Exposure of U937 cells to the Pu27-HS induces cell growth inhibition associated with cell cycle arrest that is most likely due to downregulation of c-MYC expression at the RNA and/or protein levels. Expression of SOX2, another gene containing a Pu27-HS, was affected by Pu27-HS treatment as well. Our data suggest that the oligonucleotides encoding the Pu27 family target complementary DNA sequences in the genome, including those of the c-MYC and SOX2 promoters. This effect is most likely cell type and cell growth condition dependent. The presence of genomic G-quadruplex-forming sequences homologous to Pu27 of c-MYC silencer and the fact that they interact specifically with the parent sequence suggest a common

  1. Endogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo.

    Science.gov (United States)

    Phesse, T J; Myant, K B; Cole, A M; Ridgway, R A; Pearson, H; Muncan, V; van den Brink, G R; Vousden, K H; Sears, R; Vassilev, L T; Clarke, A R; Sansom, O J

    2014-06-01

    Recent studies have suggested that C-MYC may be an excellent therapeutic cancer target and a number of new agents targeting C-MYC are in preclinical development. Given most therapeutic regimes would combine C-MYC inhibition with genotoxic damage, it is important to assess the importance of C-MYC function for DNA damage signalling in vivo. In this study, we have conditionally deleted the c-Myc gene in the adult murine intestine and investigated the apoptotic response of intestinal enterocytes to DNA damage. Remarkably, c-Myc deletion completely abrogated the immediate wave of apoptosis following both ionizing irradiation and cisplatin treatment, recapitulating the phenotype of p53 deficiency in the intestine. Consistent with this, c-Myc-deficient intestinal enterocytes did not upregulate p53. Mechanistically, this was linked to an upregulation of the E3 Ubiquitin ligase Mdm2, which targets p53 for degradation in c-Myc-deficient intestinal enterocytes. Further, low level overexpression of c-Myc, which does not impact on basal levels of apoptosis, elicited sustained apoptosis in response to DNA damage, suggesting c-Myc activity acts as a crucial cell survival rheostat following DNA damage. We also identify the importance of MYC during DNA damage-induced apoptosis in several other tissues, including the thymus and spleen, using systemic deletion of c-Myc throughout the adult mouse. Together, we have elucidated for the first time in vivo an essential role for endogenous c-Myc in signalling DNA damage-induced apoptosis through the control of the p53 tumour suppressor protein. PMID:24583641

  2. Absence of missense mutations in activated c-myc genes in avian leukosis virus-induced B-cell lymphomas.

    OpenAIRE

    Hahn, M; Hayward, W S

    1988-01-01

    We have determined the nucleotide sequences of two independent DNA clones which contained the activated c-myc genes from avian leukosis virus-induced B-cell lymphomas. Neither of these c-myc genes contained missense mutations. This strongly supports the notion that the c-myc proto-oncogene in avian leukosis virus-induced B-cell lymphomas can be oncogenically activated by altered expression of the gene without a change in the primary structure of the gene product.

  3. Transcriptional arrest within the first exon is a fast control mechanism in c-myc gene expression.

    OpenAIRE

    Eick, D; Bornkamm, G W

    1986-01-01

    DMSO (dimethylsulfoxide), a potent inducer of granulocytic differentiation in HL60 cells, causes a rapid decrease of cytoplasmic steady state c-myc RNA. This decrease is regulated mainly at the level of transcript elongation. Elongation is blocked within the untranslated c-myc leader. Twelve hours after transcriptional shut off of c-myc, DNAase I hypersensitive site II was still detectable, indicating that closing of this site upstream of the gene does not correlate with reduction in the stea...

  4. Interrelationship between chromosome 8 aneuploidy, C-MYC amplification and increased expression in individuals from northern Brazil with gastric adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Danielle Queiroz Calcagno; Márcia Valéria Pitombeira Ferreira; Marília de Arruda Cardoso Smith; Rommel Rodríguez Burbano; Mariana Ferreira Leal; Aline Damaceno Seabra; André Salim Khayat; Elizabeth Suchi Chen; Samia Demachki; Paulo Pimentel Assump(c)(a)o; Mario Henrique Gir(a)o Faria; Silvia Helena Barem Rabenhorst

    2006-01-01

    AIM: To investigate chromosome 8 numerical aberrations, C-MYC oncogene alterations and its expression in gastric cancer and to correlate these findings with histopathological characteristics of gastric tumors.METHODS: Specimens were collected surgically from seven patients with gastric adenocarcinomas. Immunostaining for C-MYC and dual-color fluorescence in situ hybridization (FISH) for C-MYC gene and chromosome 8centromere were performed.RESULTS: All the cases showed chromosome 8 aneuploidy and C-MYC amplification, in both the diffuse and intestinal histopathological types of Lauren. No significant difference (P < 0.05) was observed between the level of chromosome 8 ploidy and the site, stage or histological type of the adenocarcinomas. C-MYC high amplification,like homogeneously stained regions (HSRs) and double minutes (DMs), was observed only in the intestinal-type.Structural rearrangement of C-MYC, like translocation,was observed only in the diffuse type. Regarding C-MYC gene, a significant difference (P < 0.05) was observed between the two histological types. The C-MYC protein was expressed in all the studied cases. In the intestinaltype the C-MYC immunoreactivity was localized only in the nucleus and in the diffuse type in the nucleus and cytoplasm.CONCLUSION: Distinct patterns of alterations between intestinal and diffuse types of gastric tumors support the hypothesis that these types follow different genetic pathways.

  5. HBXIP and LSD1 Scaffolded by lncRNA Hotair Mediate Transcriptional Activation by c-Myc.

    Science.gov (United States)

    Li, Yinghui; Wang, Zhen; Shi, Hui; Li, Hang; Li, Leilei; Fang, Runping; Cai, Xiaoli; Liu, Bowen; Zhang, Xiaodong; Ye, Lihong

    2016-01-15

    c-Myc is regarded as a transcription factor, but the basis for its function remains unclear. Here, we define a long noncoding RNA (lncRNA)/protein complex that mediates the transcriptional activation by c-Myc in breast cancer cells. Among 388 c-Myc target genes in human MCF-7 breast cancer cells, we found that their promoters could be occupied by the oncoprotein HBXIP. We confirmed that the HBXIP expression correlated with expression of the c-Myc target genes cyclin A, eIF4E, and LDHA. RNAi-mediated silencing of HBXIP abolished c-Myc-mediated upregulation of these target genes. Mechanistically, HBXIP interacted directly with c-Myc through the leucine zippers and recruited the lncRNA Hotair along with the histone demethylase LSD1, for which Hotair serves as a scaffold. Silencing of HBXIP, Hotair, or LSD1 was sufficient to block c-Myc-enhanced cancer cell growth in vitro and in vivo. Taken together, our results support a model in which the HBXIP/Hotair/LSD1 complex serves as a critical effector of c-Myc in activating transcription of its target genes, illuminating long-standing questions on how c-Myc drives carcinogenesis. PMID:26719542

  6. Increased transcription of the c-myc oncogene in two methylcholanthrene-induced quail fibroblastic cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Saule, S.; Martin, P.; Gegonne, A.; Begue, A.; Lagrou, C.; Stehelin, D.

    1984-12-01

    The expression of three c-onc genes (c-erb, c-myc, c-myb) was investigated in five cell lines established from fibrosarcomas induced with 20-methylcholanthrene (MCA) of Japanese quails. These cell lines showed low levels of the three c-onc genes, with the exception of two cell lines that accumulated moderate (MCAQ 1-4) and large amounts (MCAQ 3-5) of c-myc RNA. Molecular cloning and restriction endonuclease analyses indicated that expression of c-myc in these two cell lines were not associated with detectable rearrangements in the c-myc locus, that the size of the c-myc transcript (2.7 kb) in MCAQ 3-5 was similar to that of the normal c-myc messenger RNAs (mRNA) and that the transcriptional activatin observed in MCAQ 3-5 was not mediated by the LTR (long terminal repeat) of a proximate ALV (avian leukosis virus) provirus. Finally, when analyzed with the restriction enzymes Msp I and Hpa II, the c-myc locus of MCAQ 3-5 and MCAQ 1-4 was found hypomethylated as compared with that of the other cell lines tested that show low levels of c-myc transcripts. Results suggest that one of the ways methylcholanthrene could mediate transformation is by inducing an abnormal regulation of the c-myc gene.

  7. A proteomic study of cMyc improvement of CHO culture

    Directory of Open Access Journals (Sweden)

    Dunn Michael J

    2010-03-01

    Full Text Available Abstract Background The biopharmaceutical industry requires cell lines to have an optimal proliferation rate and a high integral viable cell number resulting in a maximum volumetric recombinant protein product titre. Nutrient feeding has been shown to boost cell number and productivity in fed-batch culture, but cell line engineering is another route one may take to increase these parameters in the bioreactor. The use of CHO-K1 cells with a c-myc plasmid allowing for over-expressing c-Myc (designated cMycCHO gives a higher integral viable cell number. In this study the differential protein expression in cMycCHO is investigated using two-dimensional gel electrophoresis (2-DE followed by image analysis to determine the extent of the effect c-Myc has on the cell and the proteins involved to give the new phenotype. Results Over 100 proteins that were differentially expressed in cMycCHO cells were detected with high statistical confidence, of which 41 were subsequently identified by tandem mass spectrometry (LC-MS/MS. Further analysis revealed proteins involved in a variety of pathways. Some examples of changes in protein expression include: an increase in nucleolin, involved in proliferation and known to aid in stabilising anti-apoptotic protein mRNA levels, the cytoskeleton and mitochondrial morphology (vimentin, protein biosysnthesis (eIF6 and energy metabolism (ATP synthetase, and a decreased regulation of all proteins, indentified, involved in matrix and cell to cell adhesion. Conclusion These results indicate several proteins involved in proliferation and adhesion that could be useful for future approaches to improve proliferation and decrease adhesion of CHO cell lines which are difficult to adapt to suspension culture.

  8. Cloning and characterization of a human c-myc promoter-binding protein.

    OpenAIRE

    Ray, R; Miller, D M

    1991-01-01

    A human cDNA clone encoding a c-myc promoter-binding protein was detected by screening a HeLa cell lambda phage expression cDNA library. The library was screened by using an XhoI-NaeI human c-myc P2 promoter fragment as a probe. The recombinant phage encoded a fusion protein, myc-binding protein 1 (MBP-1), which had an apparent molecular size of 40 kDa. A corresponding protein with a molecular size of 35 kDa was present in a HeLa cell extract. Sequence analysis of the cloned gene reveals an o...

  9. Ikaros and Aiolos Inhibit Pre-B-Cell Proliferation by Directly Suppressing c-Myc Expression▿

    OpenAIRE

    Ma, Shibin; Pathak, Simanta; Mandal, Malay; Trinh, Long; Clark, Marcus R.; Lu, Runqing

    2010-01-01

    Pre-B-cell expansion is driven by signals from the interleukin-7 receptor and the pre-B-cell receptor and is dependent on cyclin D3 and c-Myc. We have shown previously that interferon regulatory factors 4 and 8 induce the expression of Ikaros and Aiolos to suppress pre-B-cell proliferation. However, the molecular mechanisms through which Ikaros and Aiolos exert their growth inhibitory effect remain to be determined. Here, we provide evidence that Aiolos and Ikaros bind to the c-Myc promoter i...

  10. Intragenic pausing and anti-sense transcription within the murine c-myc locus.

    OpenAIRE

    Nepveu, A; Marcu, K B

    1986-01-01

    We present a detailed analysis of strand-specific transcription in different regions of the murine c-myc locus. In normal and transformed cell lines, RNA polymerase II directed transcription occurs in the sense and anti-sense direction. Three noncontiguous regions show a high level of transcription in the anti-sense orientation: upstream of the first exon, within the first intron and in the 3' part of the gene (intron 2 and exon 3). In a cell line carrying a c-myc amplification (54c12), anti-...

  11. Simian Virus 40 Large T Overcomes p300 Repression of c-Myc

    OpenAIRE

    Singhal, Ghata; KADEPPAGARI, RAVI KUMAR; Sankar, Natesan; Thimmapaya, Bayar

    2008-01-01

    We previously showed that in quiescent cells p300/CBP negatively regulates the cell cycle G1-S transition by keeping c-Myc in a repressed state and that adenovirus E1A induces c-Myc by binding to p300/CBP. Studies have shown that p300/CBP binding to simian virus 40 large T is indirect and mediated by p53. By using a series of large T mutants that fail to bind to various cellular proteins including p53 as well as cells where p300 is overexpressed or p53 is knocked down, we show that the associ...

  12. Inhibition of c-Myc overcomes cytotoxic drug resistance in acute myeloid leukemia cells by promoting differentiation.

    Directory of Open Access Journals (Sweden)

    Xiao-Na Pan

    Full Text Available Nowadays, drug resistance still represents a major obstacle to successful acute myeloid leukemia (AML treatment and the underlying mechanism is not fully elucidated. Here, we found that high expression of c-Myc was one of the cytogenetic characteristics in the drug-resistant leukemic cells. c-Myc over-expression in leukemic cells induced resistance to chemotherapeutic drugs, enhanced colony formation capacity and inhibited cell differentiation induced by all-trans retinoic acid (ATRA. Meanwhile, inhibition of c-Myc by shRNA or specific c-Myc inhibitor 10058-F4 rescued the sensitivity to cytotoxic drugs, restrained the colony formation ability and promoted differentiation. RT-PCR and western blotting analysis showed that down-regulation of C/EBPβ contributed to the poor differentiation state of leukemic cells induced by c-Myc over-expression. Importantly, over-expression of C/EBPβ could reverse c-Myc induced drug resistance. In primary AML cells, the c-Myc expression was negatively correlated with C/EBPβ. 10058-F4, displayed anti-proliferative activity and increased cellular differentiation with up-regulation of C/EBPβ in primary AML cells. Thus, our study indicated that c-Myc could be a novel target to overcome drug resistance, providing a new approach in AML therapy.

  13. The reducing agent Dithiothreitol (DTT) increases expression of c-myc and c- fos protooncogenes in human cells

    DEFF Research Database (Denmark)

    Skouv, J.; Sørensen, Ilona Kryspin; Frandsen, H.; Rasmussen, E. S.; Forchhammer, J.

    genes were two proto-oncogenes, c-fos and c-myc, and the tumour suppressor gene, p53. We observed that the expression of the c-fos and c-myc genes was induced when human bladder epithelial cells were treated with a standard solution of N-OH-PhIP and dithiothreitol (DTT), previously shown to be genotoxic...

  14. Metformin elicits anticancer effects through the sequential modulation of DICER and c-MYC.

    Science.gov (United States)

    Blandino, Giovanni; Valerio, Mariacristina; Cioce, Mario; Mori, Federica; Casadei, Luca; Pulito, Claudio; Sacconi, Andrea; Biagioni, Francesca; Cortese, Giancarlo; Galanti, Sergio; Manetti, Cesare; Citro, Gennaro; Muti, Paola; Strano, Sabrina

    2012-01-01

    Diabetic patients treated with metformin have a reduced incidence of cancer and cancer-related mortality. Here we show that metformin affects engraftment and growth of breast cancer tumours in mice. This correlates with the induction of metabolic changes compatible with clear anticancer effects. We demonstrate that microRNA modulation underlies the anticancer metabolic actions of metformin. In fact, metformin induces DICER expression and its effects are severely impaired in DICER knocked down cells. Conversely, ectopic expression of DICER recapitulates the effects of metformin in vivo and in vitro. The microRNAs upregulated by metformin belong mainly to energy metabolism pathways. Among the messenger RNAs downregulated by metformin, we found c-MYC, IRS-2 and HIF1alpha. Downregulation of c-MYC requires AMP-activated protein kinase-signalling and mir33a upregulation by metformin. Ectopic expression of c-MYC attenuates the anticancer metabolic effects of metformin. We suggest that DICER modulation, mir33a upregulation and c-MYC targeting have an important role in the anticancer metabolic effects of metformin. PMID:22643892

  15. Dose-adjusted Chemotherapy for Untreated c-MYC-positive Lymphoma

    Science.gov (United States)

    In this trial, adult patients with newly diagnosed Burkitt lymphoma or c-MYC-positive DLBCL will be separated into low-risk and high-risk groups; those in the low-risk group will be treated with at least three cycles of dose-adjusted EPOCH-R

  16. c-MYC responds to glucose deprivation in a cell-type-dependent manner.

    Science.gov (United States)

    Wu, S; Yin, X; Fang, X; Zheng, J; Li, L; Liu, X; Chu, L

    2015-01-01

    Metabolic reprogramming supports cancer cells' demands for rapid proliferation and growth. Previous work shows that oncogenes, such as MYC, hypoxia-inducible factor 1 (HIF1), have a central role in driving metabolic reprogramming. A lot of metabolic enzymes, which are deregulated in most cancer cells, are the targets of these oncogenes. However, whether metabolic change affects these oncogenes is still unclear. Here we show that glucose deprivation (GD) affects c-MYC protein levels in a cell-type-dependent manner regardless of P53 mutation status. GD dephosphorylates and then decreases c-MYC protein stability through PI3K signaling pathway in HeLa cells, but not in MDA-MB-231 cells. Role of c-MYC in sensitivity of GD also varies with cell types. c-MYC-mediated glutamine metabolism partially improves the sensitivity of GD in MDA-MB-231 cells. Our results reveal that the heterogeneity of cancer cells in response to metabolic stress should be considered in metabolic therapy for cancer. PMID:27551483

  17. Astroglial c-Myc overexpression predisposes mice to primary malignant gliomas

    DEFF Research Database (Denmark)

    Jensen, Niels Aagaard; Pedersen, Karen-Marie; Lihme, Frederikke;

    2003-01-01

    Malignant astrocytomas are common human primary brain tumors that result from neoplastic transformation of astroglia or their progenitors. Here we show that deregulation of the c-Myc pathway in developing astroglia predisposes mice to malignant astrocytomas within 2-3 weeks of age. The genetically...

  18. Overexpression and amplification of the c-myc gene in mouse tumors induced by chemical and radiations

    International Nuclear Information System (INIS)

    We examined expression of the c-myc gene by the dot blot hybridization of total cellular RNA from mouse primary tumors induced by chemicals and radiations. Expression of the c-myc gene was found to be elevated in 69 cases among 177 independently induced tumors of 12 different types. DNA from tumors overexpressing the myc gene was analyzed by Southern blotting. No case of rearrangement was detected. However, amplification of the c-myc gene was found in 7 cases of primary sarcomas. These included 4 cases out of 24 methylcholanthrene-induced sarcomas and 3 cases out of 7 α-tocopherol-induced sacromas. We also analyzed 8 cases of sarcomas induced by radiations, but could not find changes in the gene structure of the c-myc gene. Thus, our data indicate tumor type specificity and agent specificity of c-myc gene amplification. (author)

  19. c-Myc is targeted to the proteasome for degradation in a SUMOylation-dependent manner, regulated by PIAS1, SENP7 and RNF4.

    Science.gov (United States)

    González-Prieto, Román; Cuijpers, Sabine Ag; Kumar, Ramesh; Hendriks, Ivo A; Vertegaal, Alfred Co

    2015-01-01

    c-Myc is the most frequently overexpressed oncogene in tumors, including breast cancer, colon cancer and lung cancer. Post-translational modifications comprising phosphorylation, acetylation and ubiquitylation regulate the activity of c-Myc. Recently, it was shown that c-Myc-driven tumors are strongly dependent on the SUMO pathway. Currently, the relevant SUMO target proteins in this pathway are unknown. Here we show that c-Myc is a target protein for SUMOylation, and that SUMOylated c-Myc is subsequently ubiquitylated and degraded by the proteasome. SUMO chains appeared to be dispensable for this process, polymerization-deficient SUMO mutants supported proteolysis of SUMOylated c-Myc. These results indicate that multiple SUMO monomers conjugated to c-Myc could be sufficient to direct SUMOylated c-Myc to the ubiquitin-proteasome pathway. Knocking down the SUMO-targeted ubiquitin ligase RNF4 enhanced the levels of SUMOylated c-Myc, indicating that RNF4 could recognize a multi-SUMOylated protein as a substrate in addition to poly-SUMOylated proteins. Knocking down the SUMO E3 ligase PIAS1 resulted in reduced c-Myc SUMOylation and increased c-Myc transcriptional activity, indicating that PIAS1 mediates c-Myc SUMOylation. Increased SUMOylation of c-Myc was noted upon knockdown of the SUMO protease SENP7, indicating that it also could regulate a multi-SUMOylated protein in addition to poly-SUMOylated proteins. C-Myc lacks KxE-type SUMOylation consensus motifs. We used mass spectrometry to identify 10 SUMO acceptor lysines: K52, K148, K157, K317, K323, K326, K389, K392, K398 and K430. Intriguingly, mutating all 10 SUMO acceptor lysines did not reduce c-Myc SUMOylation, suggesting that SUMO acceptor lysines in c-Myc act promiscuously. Our results provide novel insight into the complexity of c-Myc post-translational regulation. PMID:25895136

  20. Alteration of microRNAs regulated by c-Myc in Burkitt lymphoma.

    Directory of Open Access Journals (Sweden)

    Anna Onnis

    Full Text Available BACKGROUND: Burkitt lymphoma (BL is an aggressive B-cell lymphoma, with a characteristic clinical presentation, morphology and immunophenotype. Over the past years, the typical translocation t(8;14 and its variants have been considered the molecular hallmark of this tumor. However, BL cases with no detectable MYC rearrangement have been identified. Intriguingly, these cases express MYC at levels comparable with cases carrying the translocation. In normal cells c-Myc expression is tightly regulated through a complex feedback loop mechanism. In cancer, MYC is often dysregulated, commonly due to genomic abnormalities. It has recently emerged that this phenomenon may rely on an alteration of post-transcriptional regulation mediated by microRNAs (miRNAs, whose functional alterations are associated with neoplastic transformation. It is also emerging that c-Myc modulates miRNA expression, revealing an intriguing crosstalk between c-Myc and miRNAs. PRINCIPAL FINDINGS: Here, we investigated the expression of miRNAs possibly regulated by c-Myc in BL cases positive or negative for the translocation. A common trend of miRNA expression, with the exception of hsa-miR-9*, was observed in all of the cases. Intriguingly, down-regulation of this miRNA seems to specifically identify a particular subset of BL cases, lacking MYC translocation. Here, we provided evidence that hsa-miR-9-1 gene is heavily methylated in those cases. Finally, we showed that hsa-miR-9* is able to modulate E2F1 and c-Myc expression. CONCLUSIONS: Particularly, this study identifies hsa-miR-9* as potentially relevant for malignant transformation in BL cases with no detectable MYC translocation. Deregulation of hsa-miR-9* may therefore be useful as a diagnostic tool, suggesting it as a promising novel candidate for tumor cell marker.

  1. Oncogene amplification detected by in situ hybridization in radiation induced rat skin tumors. [C-myc:a3

    Energy Technology Data Exchange (ETDEWEB)

    Yi Jin.

    1991-02-01

    Oncogene activation may play an important role in radiation induced carcinogenesis. C-myc oncogene amplification was detected by in situ hybridization in radiation-induced rat skin tumors, including squamous and basal cell carcinomas. In situ hybridization was performed with a biotinylated human c-myc third exon probe, visualized with an avidin-biotinylated alkaline phosphate detection system. No c-myc oncogene amplification was detected in normal rat skin at very early times after exposure to ionizing radiation, which is consistent with the view that c-myc amplification is more likely to be related to carcinogenesis than to normal cell proliferation. The incorporation of tritiated thymidine into the DNA of rat skin cells showed that the proliferation of epidermal cells reached a peak on the seventh day after exposure to ionizing radiation and then decreased. No connection between the proliferation of epidermal cell and c-myc oncogene amplification in normal or irradiated rat skin was found. The results indicated that c-myc amplification as measured by in situ hybridization was correlated with the Southern bolt results, but only some of the cancer cells were amplified. The c-myc positive cells were distributed randomly within regions of the tumor and exhibited a more uniform nuclear structure in comparison to the more vacuolated c-myc negative cells. No c-myc signal was detected in unirradiated normal skin or in irradiated skin cells near the tumors. C-myc amplification appears to be cell or cell cycle specific within radiation-induced carcinomas. 28 refs., 3 figs., 3 tabs.

  2. Alterations of c-Myc and c-erbB-2 genes in ovarian tumours

    Directory of Open Access Journals (Sweden)

    Pastor Tibor

    2009-01-01

    Full Text Available Introduction. According to clinical and epidemiological studies, ovarian cancer ranks fifth in cancer deaths among women. The causes of ovarian cancer remain largely unknown but various factors may increase the risk of developing it, such as age, family history of cancer, childbearing status etc. This cancer results from a succession of genetic alterations involving oncogenes and tumour suppressor genes, which have a critical role in normal cell growth regulation. Mutations and/or overexpression of three oncogenes, c-erbB-2, c-Myc and K-ras, and of the tumour suppressor gene p53, have been frequently observed in a sporadic ovarian cancer. Objective. The aim of the present study was to analyze c-Myc and c-erbB-2 oncogene alterations, specifically amplification, as one of main mechanisms of their activation in ovarian cancers and to establish a possible association with the pathogenic process. Methods. DNA was isolated from 15 samples of malignant and 5 benign ovarian tumours, using proteinase K digestion, followed by phenol-chloroform isoamyl extraction and ethanol precipitation. C-Myc and c-erbB-2 amplification were detected by differential PCR. The level of gene copy increase was measured using the Scion image software. Results. The amplification of both c-Myc and c-erbB-2 was detected in 26.7% of ovarian epithelial carcinoma specimens. Only one tumour specimen concomitantly showed increased gene copy number for both studied genes. Interestingly, besides amplification, gene deletion was also detected (26.7% for c-erbB-2. Most of the ovarian carcinomas with alterations in c-Myc and c-erbB-2 belonged to advanced FIGO stages. Conclusion. The amplification of c-Myc and c-erbB-2 oncogenes in ovarian epithelial carcinomas is most probably a late event in the pathogenesis conferring these tumours a more aggressive biological behaviour. Similarly, gene deletions point to genomic instability in epithelial carcinomas in higher clinical stages as the

  3. c-Myc over-expression in Ramos Burkitt's lymphoma cell line predisposes to iron homeostasis disruption in vitro

    International Nuclear Information System (INIS)

    Burkitt's lymphoma is an aggressive B-cell neoplasm resulting from deregulated c-myc expression. We have previously shown that proliferation of Burkitt's lymphoma cell lines such as Ramos is markedly reduced by iron treatment. It has been shown that iron induces expression of c-myc which, owing to its transcriptional regulatory functions, regulates genes involved in iron metabolism. Transient enhancement of c-myc expression by iron could increase the expression of genes involved in iron incorporation, which could lead to an accumulation of intracellular free iron. Here, we have investigated whether cells with a high basal level of c-Myc were more likely to accumulate free iron. Our results suggest that the basal level of c-Myc in Ramos cells is twofold higher than what is seen in HL-60 cells. Moreover, in Ramos cells, where c-Myc is expressed at a high level, H-ferritin expression is down-regulated, transferrin receptor (CD71) expression is increased, and ferritin translation is inhibited. These modifications in iron metabolism, resulting from the strong basal expression of c-Myc, and amplified by iron addition, could lead to a disruption in homeostasis and consequently to growth arrest

  4. Cell growth suppression by thanatos-associated protein 11(THAP11) is mediated by transcriptional downregulation of c-Myc.

    Science.gov (United States)

    Zhu, C-Y; Li, C-Y; Li, Y; Zhan, Y-Q; Li, Y-H; Xu, C-W; Xu, W-X; Sun, H B; Yang, X-M

    2009-03-01

    Thanatos-associated proteins (THAPs) are zinc-dependent, sequence-specific DNA-binding factors involved in cell proliferation, apoptosis, cell cycle, chromatin modification and transcriptional regulation. THAP11 is the most recently described member of this human protein family. In this study, we show that THAP11 is ubiquitously expressed in normal tissues and frequently downregulated in several human tumor tissues. Overexpression of THAP11 markedly inhibits growth of a number of different cells, including cancer cells and non-transformed cells. Silencing of THAP11 by RNA interference in HepG2 cells results in loss of cell growth repression. These results suggest that human THAP11 may be an endogenous physiologic regulator of cell proliferation. We also provide evidence that the function of THAP11 is mediated by its ability to repress transcription of c-Myc. Promoter reporter assays indicate a DNA binding-dependent c-Myc transcriptional repression. Chromatin immunoprecipitations and EMSA assay suggest that THAP11 directly binds to the c-Myc promoter. The findings that expression of c-Myc rescues significantly cells from THAP11-mediated cell growth suppression and that THAP11 expression only slightly inhibits c-Myc null fibroblasts cells growth reveal that THAP11 inhibits cell growth through downregulation of c-Myc expression. Taken together, these suggest that THAP11 functions as a cell growth suppressor by negatively regulating the expression of c-Myc. PMID:19008924

  5. Repression of c-Myc responsive genes in cycling cells causes G1 arrest through reduction of cyclin E/CDK2 kinase activity

    NARCIS (Netherlands)

    Berns, K.; Hijmans, E.M.; Bernards, R.A.

    1997-01-01

    The c-myc gene encodes a sequence-specific DNA binding protein involved in proliferation and oncogenesis. Activation of c-myc expression in quiescent cells is sufficient to mediate cell cycle entry, whereas inhibition of c-myc expression causes cycling cells to withdraw from the cell cycle. To searc

  6. Inversed relationship between CD44 variant and c-Myc due to oxidative stress-induced canonical Wnt activation

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Go J., E-mail: medical21go@yahoo.co.jp; Saya, Hideyuki

    2014-01-10

    Highlights: •CD44 variant8–10 and c-Myc are inversely expressed in gastric cancer cells. •Redox-stress enhances c-Myc expression via canonical Wnt signal. •CD44v, but not CD44 standard, suppresses redox stress-induced Wnt activation. •CD44v expression promotes both transcription and proteasome degradation of c-Myc. •Inversed expression pattern between CD44v and c-Myc is often recognized in vivo. -- Abstract: Cancer stem-like cells express high amount of CD44 variant8-10 which protects cancer cells from redox stress. We have demonstrated by immunohistochemical analysis and Western blotting, and reverse-transcription polymerase chain reaction, that CD44 variant8-10 and c-Myc tend to show the inversed expression manner in gastric cancer cells. That is attributable to the oxidative stress-induced canonical Wnt activation, and furthermore, the up-regulation of the downstream molecules, one of which is oncogenic c-Myc, is not easily to occur in CD44 variant-positive cancer cells. We have also found out that CD44v8-10 expression is associated with the turn-over of the c-Myc with the experiments using gastric cancer cell lines. This cannot be simply explained by the model of oxidative stress-induced Wnt activation. CD44v8-10-positive cancer cells are enriched at the invasive front. Tumor tissue at the invasive area is considered to be composed of heterogeneous cellular population; dormant cancer stem-like cells with CD44v8-10 {sup high}/ Fbw7 {sup high}/ c-Myc {sup low} and proliferative cancer stem-like cells with CD44v8-10 {sup high}/ Fbw7 {sup low}/ c-Myc {sup high}.

  7. Inversed relationship between CD44 variant and c-Myc due to oxidative stress-induced canonical Wnt activation

    International Nuclear Information System (INIS)

    Highlights: •CD44 variant8–10 and c-Myc are inversely expressed in gastric cancer cells. •Redox-stress enhances c-Myc expression via canonical Wnt signal. •CD44v, but not CD44 standard, suppresses redox stress-induced Wnt activation. •CD44v expression promotes both transcription and proteasome degradation of c-Myc. •Inversed expression pattern between CD44v and c-Myc is often recognized in vivo. -- Abstract: Cancer stem-like cells express high amount of CD44 variant8-10 which protects cancer cells from redox stress. We have demonstrated by immunohistochemical analysis and Western blotting, and reverse-transcription polymerase chain reaction, that CD44 variant8-10 and c-Myc tend to show the inversed expression manner in gastric cancer cells. That is attributable to the oxidative stress-induced canonical Wnt activation, and furthermore, the up-regulation of the downstream molecules, one of which is oncogenic c-Myc, is not easily to occur in CD44 variant-positive cancer cells. We have also found out that CD44v8-10 expression is associated with the turn-over of the c-Myc with the experiments using gastric cancer cell lines. This cannot be simply explained by the model of oxidative stress-induced Wnt activation. CD44v8-10-positive cancer cells are enriched at the invasive front. Tumor tissue at the invasive area is considered to be composed of heterogeneous cellular population; dormant cancer stem-like cells with CD44v8-10 high/ Fbw7 high/ c-Myc low and proliferative cancer stem-like cells with CD44v8-10 high/ Fbw7 low/ c-Myc high

  8. Aspirin and salicylic acid decrease c-Myc expression in cancer cells: a potential role in chemoprevention.

    Science.gov (United States)

    Ai, Guoqiang; Dachineni, Rakesh; Muley, Pratik; Tummala, Hemachand; Bhat, G Jayarama

    2016-02-01

    Epidemiological studies have demonstrated a significant correlation between regular aspirin use and reduced colon cancer incidence and mortality; however, the pathways by which it exerts its anti-cancer effects are still not fully explored. We hypothesized that aspirin's anti-cancer effect may occur through downregulation of c-Myc gene expression. Here, we demonstrate that aspirin and its primary metabolite, salicylic acid, decrease the c-Myc protein levels in human HCT-116 colon and in few other cancer cell lines. In total cell lysates, both drugs decreased the levels of c-Myc in a concentration-dependent fashion. Greater inhibition was observed in the nucleus than the cytoplasm, and immunofluorescence studies confirmed these observations. Pretreatment of cells with lactacystin, a proteasome inhibitor, partially prevented the downregulatory effect of both aspirin and salicylic acid, suggesting that 26S proteasomal pathway is involved. Both drugs failed to decrease exogenously expressed DDK-tagged c-Myc protein levels; however, under the same conditions, the endogenous c-Myc protein levels were downregulated. Northern blot analysis showed that both drugs caused a decrease in c-Myc mRNA levels in a concentration-dependent fashion. High-performance liquid chromatography (HPLC) analysis showed that aspirin taken up by cells was rapidly metabolized to salicylic acid, suggesting that aspirin's inhibitory effect on c-Myc may occur through formation of salicylic acid. Our result suggests that salicylic acid regulates c-Myc level at both transcriptional and post-transcription levels. Inhibition of c-Myc may represent an important pathway by which aspirin exerts its anti-cancer effect and decrease the occurrence of cancer in epithelial tissues. PMID:26314861

  9. Design of a novel triple helix-forming oligodeoxyribonucleotide directed to the major promoter of the c-myc gene

    OpenAIRE

    McGuffie, E M; Catapano, C. V.

    2002-01-01

    Altered expression of c-myc is implicated in pathogenesis and progression of many human cancers. Triple helix-forming oligonucleotides (TFOs) directed to a polypurine/polypyrimidine sequence in a critical regulatory region near the c-myc P2 promoter have been shown to inhibit c-myc transcription in vitro and in cells. However, these guanine-rich TFOs had moderate binding affinity and required high concentrations for activity. The 23 bp myc P2 sequence is split equally into AT- and GC-rich tra...

  10. Knockdown of c-Myc expression by RNAi inhibits MCF-7 breast tumor cells growth in vitro and in vivo

    International Nuclear Information System (INIS)

    Breast cancer is the leading cause of cancer death in women worldwide. Elevated expression of c-Myc is a frequent genetic abnormality seen in this malignancy. For a better understanding of its role in maintaining the malignant phenotype, we used RNA interference (RNAi) directed against c-Myc in our study. RNAi provides a new, reliable method to investigate gene function and has the potential for gene therapy. The aim of the study was to examine the anti-tumor effects elicited by a decrease in the protein level of c-Myc by RNAi and its possible mechanism of effects in MCF-7 cells. A plasmid-based polymerase III promoter system was used to deliver and express short interfering RNA (siRNA) targeting c-myc to reduce its expression in MCF-7 cells. Western blot analysis was used to measure the protein level of c-Myc. We assessed the effects of c-Myc silencing on tumor growth by a growth curve, by soft agar assay and by nude mice experiments in vivo. Standard fluorescence-activated cell sorter analysis and TdT-mediated dUTP nick end labelling assay were used to determine apoptosis of the cells. Our data showed that plasmids expressing siRNA against c-myc markedly and durably reduced its expression in MCF-7 cells by up to 80%, decreased the growth rate of MCF-7 cells, inhibited colony formation in soft agar and significantly reduced tumor growth in nude mice. We also found that depletion of c-Myc in this manner promoted apoptosis of MCF-7 cells upon serum withdrawal. c-Myc has a pivotal function in the development of breast cancer. Our data show that decreasing the c-Myc protein level in MCF-7 cells by RNAi could significantly inhibit tumor growth both in vitro and in vivo, and imply the therapeutic potential of RNAi on the treatment of breast cancer by targeting overexpression oncogenes such as c-myc, and c-myc might be a potential therapeutic target for human breast cancer

  11. Coding elements in exons 2 and 3 target c-myc mRNA downregulation during myogenic differentiation.

    OpenAIRE

    Yeilding, N M; W.M. Lee

    1997-01-01

    Downregulation in expression of the c-myc proto-oncogene is an early molecular event in differentiation of murine C2C12 myoblasts into multinucleated myotubes. During differentiation, levels of c-myc mRNA decrease 3- to 10-fold despite a lack of change in its transcription rate. To identify cis-acting elements that target c-myc mRNA for downregulation during myogenesis, we stably transfected C2C12 cells with mutant myc genes or chimeric genes in which various myc sequences were fused to the h...

  12. Site-Specific Oligonucleotide Binding Represses Transcription of the Human c-myc Gene in vitro

    Science.gov (United States)

    Cooney, Michael; Czernuszewicz, Graznya; Postel, Edith H.; Flint, S. Jane; Hogan, Michael E.

    1988-07-01

    A 27-base-long DNA oligonucleotide was designed that binds to duplex DNA at a single site within the 5' end of the human c-myc gene, 115 base pairs upstream from the transcription origin P1. On the basis of the physical properties of its bound complex, it was concluded that the oligonucleotide forms a colinear triplex with the duplex binding site. By means of an in vitro assay system, it was possible to show a correlation between triplex formation at -115 base pairs and repression of c-myc transcription. The possibility is discussed that triplex formation (site-specific RNA binding to a DNA duplex) could serve as the basis for an alternative program of gene control in vivo.

  13. Antitumor activity of the c-Myc inhibitor KSI-3716 in gemcitabine-resistant bladder cancer

    OpenAIRE

    Seo, Ho Kyung; Ahn, Kyung-Ohk; Jung, Nae-Rae; Shin, Ji-Sun; Park, Weon Seo; Lee, Kang Hyun; Lee, Sang-Jin; Jeong, Kyung-Chae

    2014-01-01

    Intravesical instillation of chemotherapeutic agents is a well-established treatment strategy to decrease recurrence following transurethral resection in non-muscle invasive bladder cancer. Gemcitabine is a recently developed treatment option. However, the curative effects of gemcitabine are far from satisfactory due to de novo or acquired drug resistance. In a previous study, we reported that intravesical administration of the c-Myc inhibitor KSI-3716 suppresses tumor growth in an orthotopic...

  14. Temporal Requirements of cMyc Protein for Reprogramming Mouse Fibroblasts

    Directory of Open Access Journals (Sweden)

    Corey Heffernan

    2012-01-01

    Full Text Available Exogenous expression of Oct4, Sox2, Klf4, and cMyc forces mammalian somatic cells to adopt molecular and phenotypic characteristics of embryonic stem cells, commencing with the required suppression of lineage-associated genes (e.g., Thy1 in mouse. Although omitting cMyc from the reprogramming cocktail minimizes risks of uncontrolled proliferation, its exclusion results in fold reductions in reprogramming efficiency. Thus, the feasibility of substituting cMyc transgene with (non-integrative recombinant “pTAT-mcMyc” protein delivery was assessed, without compromising reprogramming efficiency or the pluripotent phenotype. Purification and delivery of semisoluble/particulate pTAT-mcMyc maintained Oct4-GFP+ colony formation (i.e., reprogramming efficiency whilst supporting pluripotency by various criteria. Differential repression of Thy1 by pTAT-mcMyc ± Oct4, Sox2, and Klf4 (OSK suggested differential (and non-additive mechanisms of repression. Extending these findings, attempts to enhance reprogramming efficiency through a staggered approach (prerepression of Thy1 failed to improve reprogramming efficiency. We consider protein delivery a useful tool to decipher temporal/molecular events characterizing somatic cell reprogramming.

  15. Detection of immunoglobulin/c-myc recombinations in mice that are resistant to plasmacytoma induction.

    Science.gov (United States)

    Müller, J R; Jones, G M; Potter, M; Janz, S

    1996-01-15

    Interchromosomal recombinations between c-myc and immunoglobulin sequences can be found in preneoplastic lesions (oil granulomata) during pristane-induced plasmacytoma development in susceptible BALB/cAn mice. In this study we used a more sensitive approach, hybridization-enriched templates with nested PCR, to detect microclones with Ig alpha/c-myc recombinations in oil granulomata of susceptible and resistant mice. Recombinations were detected in as many as 73% (32/44) of plasmacytoma-susceptible BALB/cAn mice 30 days after an injection of pristane. Mice that are resistant to plasmacytoma induction can also harbor recombination-positive cells, but these are less frequent [2/20 DBA/2N, 8/20 (BALB/cAn x DBA/2N)F1, hereafter called CD2F1]. The clones in DBA/2N mice were small (< 400 cells), whereas in BALB/cAn, the oil granuloma harbored up to several thousand of these cells. We conclude that the molecular machinery for generating characteristic interchromosomal recombinations can be found in all strains of mice. Both the frequency of generating Ig alpha/c-myc recombinations and the expansion of recombination-positive cells are greater in susceptible mice than in resistant strains. PMID:8542601

  16. Analysis of the c-myc IRES; a potential role for cell-type specific trans-acting factors and the nuclear compartment

    OpenAIRE

    Stoneley, Mark; Subkhankulova, Tatyana; Le Quesne, John P.C.; Coldwell, Mark J; Jopling, Catherine L; Belsham, Graham J.; Willis, Anne E.

    2000-01-01

    The 5′ UTR of c-myc mRNA contains an internal ribosome entry segment (IRES) and consequently, c-myc mRNAs can be translated by the alternative mechanism of internal ribosome entry. However, there is also some evidence suggesting that c-myc mRNA translation can occur via the conventional cap-dependent scanning mechanism. Using both bicistronic and monocistronic mRNAs containing the c-myc 5′ UTR, we demonstrate that both mechanisms can contribute to c-myc protein synthesis. A wide range of cell...

  17. A role for transcriptional repression of p21CIP1 by c-Myc in overcoming transforming growth factor β-induced cell-cycle arrest

    OpenAIRE

    Claassen, Gisela F.; Hann, Stephen R.

    2000-01-01

    c-Myc plays a vital role in cell-cycle progression. Deregulated expression of c-Myc can overcome cell-cycle arrest in order to promote cellular proliferation. Transforming growth factor β (TGFβ) treatment of immortalized human keratinocyte cells inhibits cell-cycle progression and is characterized by down-regulation of c-Myc followed by up-regulation of p21CIP1. A direct role of c-Myc in this pathway was demonstrated by the observation that ectopic expression of c-Myc overcame the cell-cycle ...

  18. An Epigenetic Pathway Regulates Sensitivity of Breast Cancer Cells to HER2 Inhibition via FOXO/c-Myc Axis

    Science.gov (United States)

    Matkar, Smita; Sharma, Paras; Gao, Shubin; Gurung, Buddha; Katona, Bryson W; Liao, Jennifer; Muhammad, Abdul Bari; Kong, Xiang-Cheng; Wang, Lei; Jin, Guanghui; Dang, Chi; Hua, Xianxin

    2016-01-01

    SUMMARY Human epidermal growth factor receptor 2 (HER2) is upregulated in a subset of human breast cancers. However, the cancer cells often quickly develop an adaptive response to HER2 kinase inhibitors. We found that an epigenetic pathway involving MLL2 is crucial for growth of HER2+ cells and MLL2 reduces sensitivity of the cancer cells to a HER2 inhibitor, Lapatinib. Lapatinib-induced FOXO transcription factors, normally tumor-suppressing, paradoxically upregulate c-Myc epigenetically, in concert with a cascade of MLL2-associating epigenetic regulators, to dampen sensitivity of the cancer cells to Lapatinib. An epigenetic inhibitor suppressing c-Myc synergizes with Lapatinib to suppress cancer growth in vivo, partly by repressing the FOXO/c-Myc axis, unraveling an epigenetically regulated FOXO/c-Myc axis as a potential target to improve therapy. PMID:26461093

  19. c-MYC expression sensitizes medulloblastoma cells to radio- and chemotherapy and has no impact on response in medulloblastoma patients

    International Nuclear Information System (INIS)

    To study whether and how c-MYC expression determines response to radio- and chemotherapy in childhood medulloblastoma (MB). We used DAOY and UW228 human MB cells engineered to stably express different levels of c-MYC, and tested whether c-MYC expression has an effect on radio- and chemosensitivity using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) -2H-tetrazolium inner salt (MTS) assay, clonogenic survival, apoptosis assays, cell cycle analysis, and western blot assessment. In an effort to validate our results, we analyzed c-MYC mRNA expression in formalin-fixed paraffin-embedded tumor samples from well-documented patients with postoperative residual tumor and compared c-MYC mRNA expression with response to radio- and chemotherapy as examined by neuroradiological imaging. In DAOY - and to a lesser extent in UW228 - cells expressing high levels of c-MYC, the cytotoxicity of cisplatin, and etoposide was significantly higher when compared with DAOY/UW228 cells expressing low levels of c-MYC. Irradiation- and chemotherapy-induced apoptotic cell death was enhanced in DAOY cells expressing high levels of c-MYC. The response of 62 of 66 residual tumors was evaluable and response to postoperative radio- (14 responders (CR, PR) vs. 5 non-responders (SD, PD)) or chemotherapy (23 CR/PR vs. 20 SD/PD) was assessed. c-MYC mRNA expression was similar in primary MB samples of responders and non-responders (Mann-Whitney U test, p = 0.50, ratio 0.49, 95% CI 0.008-30.0 and p = 0.67, ratio 1.8, 95% CI 0.14-23.5, respectively). c-MYC sensitizes MB cells to some anti-cancer treatments in vitro. As we failed to show evidence for such an effect on postoperative residual tumors when analyzed by imaging, additional investigations in xenografts and larger MB cohorts may help to define the exact function of c-MYC in modulating response to treatment

  20. The regulatory role of c-MYC on HDAC2 and PcG expression in human multipotent stem cells

    OpenAIRE

    Bhandari, Dilli Ram; Seo, Kwang-Won; Jung, Ji-Won; Kim, Hyung-Sik; YANG, Se-Ran; Kang, Kyung-Sun

    2011-01-01

    Abstract Myelocytomatosis oncogene (c-MYC) is a well-known nuclear oncoprotein having multiple functions in cell proliferation, apoptosis and cellular transformation. Chromosomal modification is also important to the differentiation and growth of stem cells. Histone deacethylase (HDAC) and polycomb group (PcG) family genes are well-known chromosomal modification genes. The aim of this study was to elucidate the role of c-MYC in the expression of chromosomal modification via the HDAC family ge...

  1. hTERT protein expression is independent of clinicopathological parameters and c-Myc protein expression in human breast cancer

    Directory of Open Access Journals (Sweden)

    Meligonis G

    2005-01-01

    Full Text Available Abstract Background Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal length and stability thus leading to cellular immortalisation. The hTERT (human telomerase reverse transcriptase subunit seems to be the rate-limiting determinant of telomerase and knowledge of factors controlling hTERT transcription may be useful in therapeutic strategies. The hTERT promoter contains binding sites for c-Myc and there is some experimental and in vitro evidence that c-Myc may increase hTERT expression. We previously reported no correlation between c-Myc mRNA expression and hTERT mRNA or telomerase activity in human breast cancer. This study aims to examine the correlation between hTERT expression as determined by immunohistochemistry and c-Myc expression, lymph node status, and tumour size and grade in human breast cancer. Materials and methods The immunohistochemical expression of hTERT and c-Myc was investigated in 38 malignant breast tumours. The expression of hTERT was then correlated with the lymph node status, c-Myc expression and other clinicopathological parameters of the tumours. Results hTERT expression was positive in 27 (71% of the 38 tumours. 15 (79% of 19 node positive tumours were hTERT positive compared with 11 (63% of 19 node negative tumours. The expression was higher in node positive tumours but this failed to reach statistical significance (p = 0.388. There was no significant association with tumour size, tumour grade or c-Myc expression. However, hTERT expression correlated positively with patients' age (correlation coefficient = 0.415, p = 0.0097. Conclusion hTERT protein expression is independent of lymph node status, tumour size and grade and c-Myc protein expression in human breast cancer

  2. Absence of missense mutations in activated c-myc genes in avian leukosis virus-induced B-cell lymphomas

    International Nuclear Information System (INIS)

    The authors determined the nucleotide sequences of two independent DNA clones which contained the activated c-myc genes from avian leukosis virus-induced B-cell lymphomas. Neither of these c-myce genes contained missense mutations. This strongly supports the notion that the c-myc photo-oncogene in avian leukosis virus-induced B-cell lymphomas can be oncogenically activated by altered expression of the gene without a change in the primary structure of the gene product

  3. Absence of missense mutations in activated c-myc genes in avian leukosis virus-induced B-cell lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, M.; Hayward, W.S.

    1988-06-01

    The authors determined the nucleotide sequences of two independent DNA clones which contained the activated c-myc genes from avian leukosis virus-induced B-cell lymphomas. Neither of these c-myce genes contained missense mutations. This strongly supports the notion that the c-myc photo-oncogene in avian leukosis virus-induced B-cell lymphomas can be oncogenically activated by altered expression of the gene without a change in the primary structure of the gene product.

  4. Transcriptional and post-transcriptional regulation of c-myc expression during the differentiation of murine erythroleukemia Friend cells.

    OpenAIRE

    Mechti, N; Piechaczyk, M; Blanchard, J. M.; Marty, L.; Bonnieu, A; Jeanteur, P; Lebleu, B

    1986-01-01

    c-myc RNA rapidly decreases to barely detectable levels in Friend erythroleukemia cells induced to differentiate upon the addition of dimethylsulfoxide. We show here that c-myc gene is down-regulated both at the transcriptional level presumably by a block in the elongation of primary transcripts and at the post-transcriptional level by an increase in the degradation of its mRNA.

  5. A critical appraisal of the immunohistochemical detection of the c-myc oncogene product in colorectal cancer.

    OpenAIRE

    Jones, D J; Ghosh, A. K.; Moore, M.; Schofield, P. F.

    1987-01-01

    Expression of c-myc was studied immunohistochemically in 100 colorectal carcinomas, using a monoclonal antibody, Myc 1-6E10, which is purported to recognize the oncoprotein (p62c-myc) in paraffin-embedded material. In normal epithelium, maturing crypt cells and terminally differentiated surface cells were positive, and proliferating basal crypt cells negative. All carcinomas stained positively, but intensity was independent of histological differentiation, Dukes' stage, DNA ploidy and surviva...

  6. C-Myc negatively controls the tumor suppressor PTEN by upregulating miR-26a in glioblastoma multiforme cells

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Pin; Nie, Quanmin; Lan, Jin; Ge, Jianwei [Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127 (China); Qiu, Yongming, E-mail: qiuzhoub@hotmail.com [Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127 (China); Shanghai Institute of Head Trauma, Shanghai 200127 (China); Mao, Qing, E-mail: maoq@netease.com [Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127 (China); Shanghai Institute of Head Trauma, Shanghai 200127 (China)

    2013-11-08

    Highlights: •The c-Myc oncogene directly upregulates miR-26a expression in GBM cells. •ChIP assays demonstrate that c-Myc interacts with the miR-26a promoter. •Luciferase reporter assays show that PTEN is a specific target of miR-26a. •C-Myc–miR-26a suppression of PTEN may regulate the PTEN/AKT pathway. •Overexpression of c-Myc enhances the proliferative capacity of GBM cells. -- Abstract: The c-Myc oncogene is amplified in many tumor types. It is an important regulator of cell proliferation and has been linked to altered miRNA expression, suggesting that c-Myc-regulated miRNAs might contribute to tumor progression. Although miR-26a has been reported to be upregulated in glioblastoma multiforme (GBM), the mechanism has not been established. We have shown that ectopic expression of miR-26a influenced cell proliferation by targeting PTEN, a tumor suppressor gene that is inactivated in many common malignancies, including GBM. Our findings suggest that c-Myc modulates genes associated with oncogenesis in GBM through deregulation of miRNAs via the c-Myc–miR-26a–PTEN signaling pathway. This may be of clinical relevance.

  7. Coordinate increase of telomerase activity and c-Myc expression in Helicobacter pylori-associated gastric diseases

    Institute of Scientific and Technical Information of China (English)

    Guo-Xin Zhang; Yan-Hong Gu; Zhi-Quan Zhao; Shun-Fu Xu; Hong-Ji Zhang; Hong-Di Wang; Bo Hao

    2004-01-01

    AIM: To detect the telomerase activity and c-Myc expression in gastric diseases and to examine the relation between these values and Helicobacter pylori (H pylori) as a risk factor for gastric cancer.METHODS: One hundred and seventy-one gastric samples were studied to detect telomerase activity using a telomerase polymerase chain reaction enzyme linked immunosorbent assay (PCR-ELTSA), and c-Myc expression using immunohistochemistry.RESULTS: The telomerase activity and c-Myc expression were higher in cancers (87.69% and 61.54%) than in noncancerous tissues. They were higher in chronic atrophic gastritis with severe intestinal metaplasia (52.38% and 47.62%) than in chronic atrophic gastritis with mild intestinal metaplasia (13.33% and 16.67%). Tn chronic atrophic gastritis with severe intestinal metaplasia, the telomerase activity and c-Myc expression were higher in cases with -H pylori infection (67.86% and 67.86%) than in those without infection (21.43%and 7.14%). c-Myc expression was higher in gastric cancer with H pylori infection (77.27%) than in that without infection (28.57%). The telomerase activity and c-Nyc expression were coordinately up-regulated in H pylori infected gastric cancer and chronic atrophic gastritis with severe intestinal metaplasia.CONCLUSION: H pylori infection may influence both telomerase activity and c-Myc expression in gastric diseases,especially in chronic atrophic gastritis.

  8. C-Myc negatively controls the tumor suppressor PTEN by upregulating miR-26a in glioblastoma multiforme cells

    International Nuclear Information System (INIS)

    Highlights: •The c-Myc oncogene directly upregulates miR-26a expression in GBM cells. •ChIP assays demonstrate that c-Myc interacts with the miR-26a promoter. •Luciferase reporter assays show that PTEN is a specific target of miR-26a. •C-Myc–miR-26a suppression of PTEN may regulate the PTEN/AKT pathway. •Overexpression of c-Myc enhances the proliferative capacity of GBM cells. -- Abstract: The c-Myc oncogene is amplified in many tumor types. It is an important regulator of cell proliferation and has been linked to altered miRNA expression, suggesting that c-Myc-regulated miRNAs might contribute to tumor progression. Although miR-26a has been reported to be upregulated in glioblastoma multiforme (GBM), the mechanism has not been established. We have shown that ectopic expression of miR-26a influenced cell proliferation by targeting PTEN, a tumor suppressor gene that is inactivated in many common malignancies, including GBM. Our findings suggest that c-Myc modulates genes associated with oncogenesis in GBM through deregulation of miRNAs via the c-Myc–miR-26a–PTEN signaling pathway. This may be of clinical relevance

  9. c-Myc inhibits TP53INP1 expression via promoter methylation in esophageal carcinoma

    International Nuclear Information System (INIS)

    Research highlights: → TP53INP1 expression is down-regulated in esophageal carcinoma and is associated with CGI-131 methylation. → Inhibition of CGI-131 methylation upregulates TP53INP1 expression in ESCC cell lines. → Ectopic expression of TP53INP1 inhibits growth of ESCC cells by inducing apoptosis and inhibiting cell cycle progression. → c-Myc binds to the promoter of TP53INP1 in vivo and vitro and recruits DNMT3A to TP53INP1 promoter for CGI-131 methylation. -- Abstract: Tumor protein p53-induced nuclear protein 1 (TP53INP1) is a well known stress-induced protein that plays a role in both cell cycle arrest and p53-mediated apoptosis. Loss of TP53INP1 expression has been reported in human melanoma, breast carcinoma, and gastric cancer. However, TP53INP1 expression and its regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. Our findings are in agreement with previous reports in that the expression of TP53INP1 was downregulated in 28% (10/36 cases) of ESCC lesions, and this was accompanied by significant promoter methylation. Overexpression of TP53INP1 induced G1 cell cycle arrest and increased apoptosis in ESCC cell lines (EC-1, EC-109, EC-9706). Furthermore, our study showed that the oncoprotein c-Myc bound to the core promoter of TP53INP1 and recruited DNA methyltransferase 3A to methylate the local promoter region, leading to the inhibition of TP53INP1 expression. Our findings revealed that TP53INP1 is a tumor suppressor in ESCC and that c-Myc-mediated DNA methylation-associated silencing of TP53INP1 contributed to the pathogenesis of human ESCC.

  10. WT1 Enhances Proliferation and Impedes Apoptosis in KRAS Mutant NSCLC via Targeting cMyc

    OpenAIRE

    Wu, Chen; Wang, Sihan; Xu, Caihua; Tyler, Andreas; Li, Xingru; Andersson, Charlotta; Oji, Yusuke; Sugiyama, Haruo; Chen, Yijiang; Li, Aihong

    2015-01-01

    Background: A novel link between oncogenic KRAS signalling and WT1 was recently identified. We sought to investigate the role of WT1 and KRAS in proliferation and apoptosis. Methods: KRAS mutations and WT1 (cMyc) expression were detected using Sanger sequencing and real-time PCR in 77 patients with non-small cell lung cancer (NSCLC). Overexpression and knockdown of WT1 were generated with plasmid and siRNA via transient transfection technology in H1299 and H1568 cells. MTT assay for detection...

  11. Erythropoietin activates two distinct signaling pathways required for the initiation and the elongation of c-myc

    Science.gov (United States)

    Chen, C.; Sytkowski, A. J.

    2001-01-01

    Erythropoietin (Epo) stimulation of erythroid cells results in the activation of several kinases and a rapid induction of c-myc expression. Protein kinase C is necessary for Epo up-regulation of c-myc by promoting elongation at the 3'-end of exon 1. PKCepsilon mediates this signal. We now show that Epo triggers two signaling pathways to c-myc. Epo rapidly up-regulated Myc protein in BaF3-EpoR cells. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 blocked Myc up-regulation in a concentration-dependent manner but had no effect on the Epo-induced phosphorylation of ERK1 and ERK2. LY294002 also had no effect on Epo up-regulation of c-fos. MEK1 inhibitor PD98059 blocked both the c-myc and the c-fos responses to Epo. PD98059 and the PKC inhibitor H7 also blocked the phosphorylation of ERK1 and ERK2. PD98059 but not LY294002 inhibited Epo induction of ERK1 and ERK2 phosphorylation in normal erythroid cells. LY294002 blocked transcription of c-myc at exon 1. PD98059 had no effect on transcription from exon 1 but, rather, blocked Epo-induced c-myc elongation at the 3'-end of exon 1. These results identify two Epo signaling pathways to c-myc, one of which is PI3K-dependent operating on transcriptional initiation, whereas the other is mitogen-activated protein kinase-dependent operating on elongation.

  12. TCEAL7 Inhibition of c-Myc Activity in Alternative Lengthening of Telomeres Regulates hTERT Expression

    Directory of Open Access Journals (Sweden)

    Kyle Lafferty-Whyte

    2010-05-01

    Full Text Available Replicative senescence forms a major barrier to tumor progression. Cancer cells bypass this by using one of the two known telomere maintenance mechanisms: telomerase or the recombination-based alternative lengthening of telomeres (ALT mechanism. The molecular details of ALT are currently poorly understood. We have previously shown that telomerase is actively repressed through complex networks of kinase, gene expression, and chromatin regulation. In this study, we aimed to gain further understanding of the role of kinases in the regulation of telomerase expression in ALT cells. Using a whole human kinome small interfering RNA (siRNA screen, we highlighted 106 kinases whose expression is linked to human telomerase reverse transcriptase (hTERT promoter activity. Network modeling of transcriptional regulation implicated c-Myc as a key regulator of the 106 kinase hits. Given our previous observations of lower c-Myc activity in ALT cells, we further explored its potential to regulate telomerase expression in ALT. We found increased c-Myc binding at the hTERT promoter in telomerase-positive compared with ALT cells, although no expression differences in c-Myc, Mad, or Max were observed between ALT and telomerase-positive cells that could explain decreased c-Myc activity in ALT. Instead, we found increased expression of the c-Myc competitive inhibitor TCEAL7 in ALT cells and tumors and that alteration of TCEAL7 expression levels in ALT and telomerase-positive cells affects hTERT expression. Lower c-Myc activity in ALT may therefore be obtained through TCEAL7 regulation. Thus, TCEAL7 may present an interesting novel target for cancer therapy, which warrants further investigation.

  13. Transient in utero knockout (TIUKO of C-MYC affects late lung and intestinal development in the mouse

    Directory of Open Access Journals (Sweden)

    Zhou Pengbo

    2004-04-01

    Full Text Available Abstract Background Developmentally important genes often result in early lethality in knockout animals. Thus, the direct role of genes in late gestation organogenesis cannot be assessed directly. In utero delivery of transgenes was shown previously to result in high efficiency transfer to pulmonary and intestinal epithelial stem cells. Thus, this technology can be used to evaluate late gestation development. Results In utero gene transfer was used to transfer adenovirus with either an antisense c-myc or a C-MYC ubiquitin targeting protein to knockout out c-myc expression in late gestation lung and intestines. Using either antisense or ubiquitin mediated knockout of C-MYC levels in late gestation resulted in similar effects. Decreased complexity was observed in both intestines and lungs. Stunted growth of villi was evident in the intestines. In the lung, hypoplastic lungs with disrupted aveolarization were observed. Conclusions These data demonstrated that C-MYC was required for cell expansion and complexity in late gestation lung and intestinal development. In addition they demonstrate that transient in utero knockout of proteins may be used to determine the role of developmentally important genes in the lungs and intestines.

  14. Effect of c-myc on the ultrastructural structure of cochleae in guinea pigs with noise induced hearing loss

    Energy Technology Data Exchange (ETDEWEB)

    Han, Yu; Zhong, Cuiping [Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 Shaanxi Province (China); Hong, Liu [First Division of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 Shaanxi Province (China); Wang, Ye; Qiao, Li [Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 Shaanxi Province (China); Qiu, Jianhua, E-mail: qiujh@fmmu.edu.cn [Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 Shaanxi Province (China)

    2009-12-18

    Noise over-stimulation may induce hair cells loss and hearing deficit. The c-myc oncogene is a major regulator for cell proliferation, growth, and apoptosis. However, the role of this gene in the mammalian cochlea is still unclear. The study was designed to firstly investigate its function under noise condition, from the aspect of cochlear ultrastructural changes. We had established the adenoviral vector of c-myc gene and delivered the adenovirus suspension into the scala tympani of guinea pigs 4 days before noise exposure. The empty adenoviral vectors were injected as control. Then, all subjects were exposed to 4-kHz octave-band noise at 110 dB SPL for 8 h/day, 3 days consecutively. Auditory thresholds were assessed by auditory brainstem response, prior to and 7 days following noise exposure. On the seventh days after noise exposure, the cochlear sensory epithelia surface was observed microscopically and the cochleae were taken to study the ultrastructural changes. The results indicated that auditory threshold shift after noise exposure was higher in the ears treated with Ad.EGFP than that treated with Ad.c-myc-EGFP. Stereocilia loss and the disarrangement of outer hair cells were observed, with greater changes found in the Ad.EGFP group. Also, the ultrastructure changes were severe in the Ad.EGFP group, but not obvious in the Ad.c-myc-EGFP group. Therefore, c-myc gene might play an unexpected role in hearing functional and morphological protection from acoustic trauma.

  15. Depressive Effect of the Antisense Oligonucleotides of C-myc and PCNA on the Proliferation of VSMC

    Institute of Scientific and Technical Information of China (English)

    Qingxian Li; Yanfu Wang; Yuhua Liao; Huiling Zhang; Yanying Jiang

    2007-01-01

    To study the depressive effect of the antisense oligonuceotides (ASODN) of c-myc and proliferating cell nuclear antigen (PCNA) on the proliferation of VSMC.Methods Taking the VSMC obtained from rat aorta thoracalis cultured 4 ~ 8 generation as research object.The objects were divided into three groups to carry out control study:control group,PCNA ASODN group and c-myc ASODN group.The ASODNs' working concentration all were 1:50.The depressive effect of ASODN on VSMC proliferation was investigated by cell counting,MTT and 3H-TdR incorporation assay;PCNA and c-myc expression were detected by immunohistochemical method after transferring PCNA successfully;the corresponding gene was inhibited obviously;compared with control group ( P < 0.05 ).Conclusions PCNA and c-myc might play a considerable role in the VSMC proliferation process.The corresponding gene could be depressed successfully after transferring PCNA and c-myc ASODN into VSMC,and then the proliferation of VSMC was slowed down.This study presented a beneficial proposal and theoretical fundament for atherosclerotic treatment.

  16. Effect of c-myc on the ultrastructural structure of cochleae in guinea pigs with noise induced hearing loss

    International Nuclear Information System (INIS)

    Noise over-stimulation may induce hair cells loss and hearing deficit. The c-myc oncogene is a major regulator for cell proliferation, growth, and apoptosis. However, the role of this gene in the mammalian cochlea is still unclear. The study was designed to firstly investigate its function under noise condition, from the aspect of cochlear ultrastructural changes. We had established the adenoviral vector of c-myc gene and delivered the adenovirus suspension into the scala tympani of guinea pigs 4 days before noise exposure. The empty adenoviral vectors were injected as control. Then, all subjects were exposed to 4-kHz octave-band noise at 110 dB SPL for 8 h/day, 3 days consecutively. Auditory thresholds were assessed by auditory brainstem response, prior to and 7 days following noise exposure. On the seventh days after noise exposure, the cochlear sensory epithelia surface was observed microscopically and the cochleae were taken to study the ultrastructural changes. The results indicated that auditory threshold shift after noise exposure was higher in the ears treated with Ad.EGFP than that treated with Ad.c-myc-EGFP. Stereocilia loss and the disarrangement of outer hair cells were observed, with greater changes found in the Ad.EGFP group. Also, the ultrastructure changes were severe in the Ad.EGFP group, but not obvious in the Ad.c-myc-EGFP group. Therefore, c-myc gene might play an unexpected role in hearing functional and morphological protection from acoustic trauma.

  17. Abnormal expression of c-Myc in human bronchial epithelial cells malignantly transformed by anti-BPDE

    Institute of Scientific and Technical Information of China (English)

    Juan FU; Yiguo JIANG; Xuemin CHEN

    2008-01-01

    Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) is a metabolite of benzo[a]pyrene (B[a] P) and acts as a potent mutagen in mammalian systems. However, molecular mechanisms related to anti-BPDE-induced carcinogenesis are poorly understood. Here, we investigated the expression of proto-oncogene c-myc in human bronchial epithelial cells (16H BE-T) transformed by exposure to anti-BPDE. The levels ofmRNA and pro-tein of c-M yc were examined in the 16HBE-T and vehicle-treated control cells (16HBE-N) by using different meth-ods respectively, including reverse transcriptase-polymer-ase chain reaction (RT-PCR), quantitative real-time PCR (Q-PCR), western blot and immunocytochemical meth-ods. The level of c-myc mRNA appeared to be signifi-cantly increased in 16HBE-T, as compared with those of the 16H BE-N. Likewise, the expression of c-Myc protein was significantly enhanced as compared with those of the control cells. Moreover, the localization of c-Myc protein shows mainly nuclear staining in 16HBE-T. In conclu-sion, the abnormal expression of c-Myc was present in anti-BPDE malignantly transformed 16HBE cells, which may be involved in the carcinogenesis molecular mech-anism of anti-BPDE.

  18. c-myc gene sequences and the phylogeny of bats and other eutherian mammals.

    Science.gov (United States)

    Miyamoto, M M; Porter, C A; Goodman, M

    2000-09-01

    The complete protein-coding sequences of the c-myc proto-oncogene were determined for five species of four new orders of eutherian (placental) mammals. These newly obtained sequences were aligned to each other and to other available orthologs for the phylogenetic estimation of eutherian interordinal relationships. Several measures of sequence difference and base composition were first calculated to assess the major evolutionary properties of the three codon positions and two protein-coding exons of the gene. On the basis of these calculations, different parsimony, distance, and maximum likelihood approaches were adopted, with the most sophisticated involving the separate, then combined, likelihood analyses of the third codon positions of exon 2 versus all other sites. These phylogenetic approaches provided clear support for the grouping of Chiroptera (bats) with Artiodactyla (ruminants, camels, and pigs) and Carnivora (cats, dogs, and their allies), an interordinal arrangement that receives strong corroboration from other lines of evidence including complete mitochondrial DNA sequences. In contrast, these analyses failed to provide strong to reasonable support for any other interordinal group. This study concludes with specific recommendations about sampling and other strategies for maximizing the phylogenetic contributions of the c-myc gene to the continued resolution of the eutherian ordinal tree. PMID:12116424

  19. The c-MYC-ABCB5 axis plays a pivotal role in 5-fluorouracil resistance in human colon cancer cells

    OpenAIRE

    Kugimiya, Naruji; Nishimoto, Arata; Hosoyama, Tohru; Ueno, Koji; Enoki, Tadahiko; Li, Tao-Sheng; Hamano, Kimikazu

    2015-01-01

    c-MYC overexpression is frequently observed in various cancers including colon cancer and regulates many biological activities such as aberrant cell proliferation, apoptosis, genomic instability, immortalization and drug resistance. However, the mechanism by which c-MYC confers drug resistance remains to be fully elucidated. In this study, we found that the c-MYC expression level in primary colorectal cancer tissues correlated with the recurrence rate following 5-fluorouracil (5-FU)-based adj...

  20. Acidosis Decreases c-Myc Oncogene Expression in Human Lymphoma Cells: A Role for the Proton-Sensing G Protein-Coupled Receptor TDAG8

    OpenAIRE

    Zhigang Li; Lixue Dong; Eric Dean; Yang, Li V.

    2013-01-01

    Acidosis is a biochemical hallmark of the tumor microenvironment. Here, we report that acute acidosis decreases c-Myc oncogene expression in U937 human lymphoma cells. The level of c-Myc transcripts, but not mRNA or protein stability, contributes to c-Myc protein reduction under acidosis. The pH-sensing receptor TDAG8 (GPR65) is involved in acidosis-induced c-Myc downregulation. TDAG8 is expressed in U937 lymphoma cells, and the overexpression or knockdown of TDAG8 further decreases or partia...

  1. Acidosis decreases c-Myc oncogene expression in human lymphoma cells: a role for the proton-sensing G protein-coupled receptor TDAG8.

    Science.gov (United States)

    Li, Zhigang; Dong, Lixue; Dean, Eric; Yang, Li V

    2013-01-01

    Acidosis is a biochemical hallmark of the tumor microenvironment. Here, we report that acute acidosis decreases c-Myc oncogene expression in U937 human lymphoma cells. The level of c-Myc transcripts, but not mRNA or protein stability, contributes to c-Myc protein reduction under acidosis. The pH-sensing receptor TDAG8 (GPR65) is involved in acidosis-induced c-Myc downregulation. TDAG8 is expressed in U937 lymphoma cells, and the overexpression or knockdown of TDAG8 further decreases or partially rescues c-Myc expression, respectively. Acidic pH alone is insufficient to reduce c-Myc expression, as it does not decrease c-Myc in H1299 lung cancer cells expressing very low levels of pH-sensing G protein-coupled receptors (GPCRs). Instead, c-Myc is slightly increased by acidosis in H1299 cells, but this increase is completely inhibited by ectopic overexpression of TDAG8. Interestingly, TDAG8 expression is decreased by more than 50% in human lymphoma samples in comparison to non-tumorous lymph nodes and spleens, suggesting a potential tumor suppressor function of TDAG8 in lymphoma. Collectively, our results identify a novel mechanism of c-Myc regulation by acidosis in the tumor microenvironment and indicate that modulation of TDAG8 and related pH-sensing receptor pathways may be exploited as a new approach to inhibit Myc expression. PMID:24152439

  2. Acidosis Decreases c-Myc Oncogene Expression in Human Lymphoma Cells: A Role for the Proton-Sensing G Protein-Coupled Receptor TDAG8

    Directory of Open Access Journals (Sweden)

    Zhigang Li

    2013-10-01

    Full Text Available Acidosis is a biochemical hallmark of the tumor microenvironment. Here, we report that acute acidosis decreases c-Myc oncogene expression in U937 human lymphoma cells. The level of c-Myc transcripts, but not mRNA or protein stability, contributes to c-Myc protein reduction under acidosis. The pH-sensing receptor TDAG8 (GPR65 is involved in acidosis-induced c-Myc downregulation. TDAG8 is expressed in U937 lymphoma cells, and the overexpression or knockdown of TDAG8 further decreases or partially rescues c-Myc expression, respectively. Acidic pH alone is insufficient to reduce c-Myc expression, as it does not decrease c-Myc in H1299 lung cancer cells expressing very low levels of pH-sensing G protein-coupled receptors (GPCRs. Instead, c-Myc is slightly increased by acidosis in H1299 cells, but this increase is completely inhibited by ectopic overexpression of TDAG8. Interestingly, TDAG8 expression is decreased by more than 50% in human lymphoma samples in comparison to non-tumorous lymph nodes and spleens, suggesting a potential tumor suppressor function of TDAG8 in lymphoma. Collectively, our results identify a novel mechanism of c-Myc regulation by acidosis in the tumor microenvironment and indicate that modulation of TDAG8 and related pH-sensing receptor pathways may be exploited as a new approach to inhibit Myc expression.

  3. Bombesin stimulation of c-fos and c-myc gene expression in cultured of Swiss 3T3 cells

    International Nuclear Information System (INIS)

    Bombesin has been show to be a potent mitogen for Swiss 3T3 cells. At nanomolar concentrations it stimulates DNA synthesis in quiescent cultures of 3T3 cells and also induces the expression of c-fos and c-myc mRNA. c-fos mRNA transcripts dramatically increase 15 min after the addition of bombesin, are still abundant after 30-60 min and then decrease. c-myc mRNA induction is detectable later, 1 h after bombesin treatment. Conversely, no changes in c-Ki-ras expression are observed after stimulation with bombesin. These results demonstrate that the increased expression of c-fos and c-myc mRNAs appears to be a common response to diverse agents that induce DNA synthesis and cell proliferation

  4. AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-MYC dephosphorylation and degradation

    Science.gov (United States)

    Cianfanelli, Valentina; Fuoco, Claudia; Lorente, Mar; Salazar, Maria; Quondamatteo, Fabio; Gherardini, Pier Federico; De Zio, Daniela; Nazio, Francesca; Antonioli, Manuela; D’Orazio, Melania; Skobo, Tatjana; Bordi, Matteo; Rohde, Mikkel; Dalla Valle, Luisa; Helmer-Citterich, Manuela; Gretzmeier, Christine; Dengjel, Joern; Fimia, Gian Maria; Piacentini, Mauro; Di Bartolomeo, Sabrina; Velasco, Guillermo; Cecconi, Francesco

    2016-01-01

    Inhibition of a main regulator of cell metabolism, the protein kinase mTOR, induces autophagy and inhibits cell proliferation. However, the molecular pathways involved in the cross-talk between these two mTOR-dependent cell processes are largely unknown. Here we show that the scaffold protein AMBRA1, a member of the autophagy signalling network and a downstream target of mTOR, regulates cell proliferation by facilitating the dephosphorylation and degradation of the proto-oncogene C-MYC. We found that AMBRA1 favors the interaction between C-MYC and its phosphatase PP2A and that, when mTOR is inhibited, it enhances PP2A activity on this specific target, thereby reducing the cell division rate. As expected, such a de-regulation of C-MYC correlates with increased tumorigenesis in AMBRA1-defective systems, thus supporting a role for AMBRA1 as a haploinsufficient tumour suppressor gene. PMID:25438055

  5. EFFECT OF STENT ABSORBED c-myc ANTISENSE OLIGODEOXYNUCLEOTIDE ON SMOOTH MUSCLE CELLS APOPTOSIS IN RABBIT CAROTID ARTERY

    Institute of Scientific and Technical Information of China (English)

    张新霞; 崔长琮; 李江; 崔翰斌; 徐仓宝; 朱参战

    2002-01-01

    Objective To investigate the effect of gelatin coated Platinium-Iridium stent absorbed c-myc antisense oligodeoxynucleotide (ASODN) on smooth muscle cells apoptosis in a normal rabbit carotid arteries. Methods Gelatin coated Platinium-Iridium stents were implanted in the right carotid arteries of 32 rabbits under vision. Animals were randomly divided into control group and treated group receiving c-myc ASODN (n=16, respectively). On 7, 14, 30 and 90 days following the stenting procedure ,morphometry for caculation of neointimal area and mean neointimal thickness were performed.The expression of c-myc protein was detected by immunohistochemical method. Apoptotic smooth muscle cells was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL). Results At 7 and 14 days after stenting,there were no detectable apoptotic cells in both groups. The apoptotic cells occurred in the neointima 30 and 90 days after stenting, and the number of apoptotic cells at 30 days were less [4.50±1.29 vs 25.75±1.89 (number/0.1mm2)] than that at 90 days [13.50±1.91 vs 41.50±6.46 (number/0.1mm2)]. Meanwhile c-myc ASODN induced more apoptotic cells than the control group(P<0.0001). c-myc protein expression was weak positive or negative in treated group and positive in control group.Conclusion c-myc ASODN can induce smooth muscle cells apoptosis after stenting in normal rabbit carotid arteries,and it can be used to prevent in-stent restenosis.

  6. Cancer-associated fibroblasts promote endometrial cancer growth via activation of interleukin-6/STAT-3/c-Myc pathway.

    Science.gov (United States)

    Subramaniam, Kavita S; Omar, Intan Sofia; Kwong, Soke Chee; Mohamed, Zahurin; Woo, Yin Ling; Mat Adenan, Noor Azmi; Chung, Ivy

    2016-01-01

    Cancer-associated fibroblasts (CAFs) secrete various pro-tumorigenic cytokines, yet the role of these cytokines in the progression of endometrial cancer remains unclear. We found that CAFs isolated from human endometrial cancer (EC) tissues secreted high levels of interleukin-6 (IL-6), which promotes EC cell proliferation in vitro. Neutralizing IL-6 in CAF-conditioned media reduced (47% inhibition) while IL-6 recombinant protein increased cell proliferation (~2.4 fold) of both EC cell lines and primary cultures. IL-6 receptors (IL-6R and gp130) were expressed only in EC epithelial cells but not in CAF, indicating a one-way paracrine signaling. In the presence of CAF-conditioned media, Janus kinase/signal transducers and activators of transcription (JAK/STAT3) pathway was activated in EC cells. Treatment with JAK and STAT3 specific inhibitors, AD412 and STATTIC, respectively, significantly abrogated CAF-mediated cell proliferation, indicating the role of IL-6 activation in EC cell proliferation. We further showed that one of STAT-3 target genes, c-Myc, was highly induced in EC cells after exposure to CAF-conditioned medium at both mRNA (>105-fold vs. control) and protein level (>2-fold vs. control). EC cell proliferation was dependent on c-Myc expression, as RNAi-mediated c-Myc down-regulation led to a significant 46% reduction in cell viability when compared with scrambled control. Interestingly, CAF-conditioned media failed to promote proliferation in EC cells with reduced c-Myc expression, suggesting that CAF-mediated cell proliferation was also dependent on c-Myc expression. Subcutaneous tumor xenograft model showed that EC cells grew at least 1.4 times larger when co-injected with CAF, when compared to those injected with EC cells alone. Mice injected with EC cells with down-regulated c-Myc expression, however, showed at least 2.5 times smaller tumor compared to those in control group. Notably, there was no increase of tumor size when co-injected with CAFs

  7. Interferon modulation of c-myc expression in cloned Daudi cells: relationship to the phenotype of interferon resistance.

    OpenAIRE

    Dron, M; Modjtahedi, N; Brison, O; Tovey, M G

    1986-01-01

    Treatment of interferon-sensitive Daudi cell with electrophoretically pure human interferon alpha markedly reduced the level of c-myc mRNA, increased the level of class I histocompatibility antigen (HLA) mRNA, and did not affect the level of actin mRNA within the same cells. In contrast, the level of c-myc mRNA or HLA mRNA did not change significantly following interferon treatment in different clones of Daudi cells selected for resistance to the antiproliferative action of interferon. These ...

  8. c-Myc affects mRNA translation, cell proliferation and progenitor cell function in the mammary gland

    Directory of Open Access Journals (Sweden)

    Trumpp Andreas

    2009-09-01

    Full Text Available Abstract Background The oncoprotein c-Myc has been intensely studied in breast cancer and mouse mammary tumor models, but relatively little is known about the normal physiological role of c-Myc in the mammary gland. Here we investigated functions of c-Myc during mouse mammary gland development using a conditional knockout approach. Results Generation of c-mycfl/fl mice carrying the mammary gland-specific WAPiCre transgene resulted in c-Myc loss in alveolar epithelial cells starting in mid-pregnancy. Three major phenotypes were observed in glands of mutant mice. First, c-Myc-deficient alveolar cells had a slower proliferative response at the start of pregnancy, causing a delay but not a block of alveolar development. Second, while milk composition was comparable between wild type and mutant animals, milk production was reduced in mutant glands, leading to slower pup weight-gain. Electron microscopy and polysome fractionation revealed a general decrease in translational efficiency. Furthermore, analysis of mRNA distribution along the polysome gradient demonstrated that this effect was specific for mRNAs whose protein products are involved in milk synthesis. Moreover, quantitative reverse transcription-polymerase chain reaction analysis revealed decreased levels of ribosomal RNAs and ribosomal protein-encoding mRNAs in mutant glands. Third, using the mammary transplantation technique to functionally identify alveolar progenitor cells, we observed that the mutant epithelium has a reduced ability to repopulate the gland when transplanted into NOD/SCID recipients. Conclusion We have demonstrated that c-Myc plays multiple roles in the mouse mammary gland during pregnancy and lactation. c-Myc loss delayed, but did not block proliferation and differentiation in pregnancy. During lactation, lower levels of ribosomal RNAs and proteins were present and translation was generally decreased in mutant glands. Finally, the transplantation studies suggest a role

  9. Cancer-associated fibroblasts promote endometrial cancer growth via activation of interleukin-6/STAT-3/c-Myc pathway

    Science.gov (United States)

    Subramaniam, Kavita S; Omar, Intan Sofia; Kwong, Soke Chee; Mohamed, Zahurin; Woo, Yin Ling; Mat Adenan, Noor Azmi; Chung, Ivy

    2016-01-01

    Cancer-associated fibroblasts (CAFs) secrete various pro-tumorigenic cytokines, yet the role of these cytokines in the progression of endometrial cancer remains unclear. We found that CAFs isolated from human endometrial cancer (EC) tissues secreted high levels of interleukin-6 (IL-6), which promotes EC cell proliferation in vitro. Neutralizing IL-6 in CAF-conditioned media reduced (47% inhibition) while IL-6 recombinant protein increased cell proliferation (~2.4 fold) of both EC cell lines and primary cultures. IL-6 receptors (IL-6R and gp130) were expressed only in EC epithelial cells but not in CAF, indicating a one-way paracrine signaling. In the presence of CAF-conditioned media, Janus kinase/signal transducers and activators of transcription (JAK/STAT3) pathway was activated in EC cells. Treatment with JAK and STAT3 specific inhibitors, AD412 and STATTIC, respectively, significantly abrogated CAF-mediated cell proliferation, indicating the role of IL-6 activation in EC cell proliferation. We further showed that one of STAT-3 target genes, c-Myc, was highly induced in EC cells after exposure to CAF-conditioned medium at both mRNA (>105-fold vs. control) and protein level (>2-fold vs. control). EC cell proliferation was dependent on c-Myc expression, as RNAi-mediated c-Myc down-regulation led to a significant 46% reduction in cell viability when compared with scrambled control. Interestingly, CAF-conditioned media failed to promote proliferation in EC cells with reduced c-Myc expression, suggesting that CAF-mediated cell proliferation was also dependent on c-Myc expression. Subcutaneous tumor xenograft model showed that EC cells grew at least 1.4 times larger when co-injected with CAF, when compared to those injected with EC cells alone. Mice injected with EC cells with down-regulated c-Myc expression, however, showed at least 2.5 times smaller tumor compared to those in control group. Notably, there was no increase of tumor size when co-injected with CAFs

  10. USP10 Antagonizes c-Myc Transcriptional Activation through SIRT6 Stabilization to Suppress Tumor Formation

    Directory of Open Access Journals (Sweden)

    Zhenghong Lin

    2013-12-01

    Full Text Available The reduced protein expression of SIRT6 tumor suppressor is involved in tumorigenesis. The molecular mechanisms underlying SIRT6 protein downregulation in human cancers remain unknown. Using a proteomic approach, we have identified the ubiquitin-specific peptidase USP10, another tumor suppressor, as one of the SIRT6-interacting proteins. USP10 suppresses SIRT6 ubiquitination to protect SIRT6 from proteasomal degradation. USP10 antagonizes the transcriptional activity of the c-Myc oncogene through SIRT6, as well as p53, to inhibit cell-cycle progression, cancer cell growth, and tumor formation. To support this conclusion, we detected significant reductions in both USP10 and SIRT6 protein expression in human colon cancers. Our study discovered crosstalk between two tumor-suppressive genes in regulating cell-cycle progression and proliferation and showed that dysregulated USP10 function promotes tumorigenesis through SIRT6 degradation.

  11. Cytotoxicity and altered c-myc gene expression by medical polyacrylamide hydrogel.

    Science.gov (United States)

    Xi, T F; Fan, C X; Feng, X M; Wan, Z Y; Wang, C R; Chou, L L

    2006-08-01

    Medical Polyacrylamide Hydrogel (PAMG)has been used in plastic and aesthetic surgery for years. However, its safety is still in doubt in many countries. In the current research, first an approach, using high performance liquid chromatography (HPLC), to determine the amount of residual acrylamide monomer (AM) in the PAMG was presented. Then the cytotoxicity of PAMG was investigated using cell counting and methyl thiazolyl tetrazolium (MTT) assay. To explore the mechanism of this toxicity, normal human fibroblasts cultured in medium extracts were analyzed. Membrane changes and other related parameters were investigated using flow cytometry (FCM). Real time fluorescent polymerase chain reaction (real time PCR) was also introduced to determine the biological response of the fibroblasts. During this process, three representative genes (p53, beta-actin, and c-myc, which are tumor suppressor genes, housekeeping genes, and proto-oncogenes respectively) were selected for examination. Results indicated that a method based on HPLC is practical and simple for determining AM in PAMG. The detection limits can reach the desired ppb level, and so it can fully meet the requirements of the studies of PAMG. Polyacylamide Hydrogel inhibits the growth of human fibroblasts and may cause the apoptosis of human fibroblasts. Moreover, it can alter physical parameters such as the size and the granularity of these cells. Furthermore, these three genes have a relatively typical amplification plot and highly related, wide-range standard curves, and so this reaction system is definitely suitable for the semiquantification of these genes. PAMG induces the increase of the message ribonucleic acid (mRNA) expression of c-myc, while the p53 and beta-actin remain even. This change is not related to the concentration of AM in the gel and may be incited by other components in the extract of PMAG. PMID:16637045

  12. XPC Promotes Pluripotency of Human Dental Pulp Cells through Regulation of Oct-4/Sox2/c-Myc.

    Science.gov (United States)

    Liu, Lu; Peng, Zhengjun; Xu, Zhezhen; Wei, Xi

    2016-01-01

    Introduction. Xeroderma pigmentosum group C (XPC), essential component of multisubunit stem cell coactivator complex (SCC), functions as the critical factor modulating pluripotency and genome integrity through interaction with Oct-4/Sox2. However, its specific role in regulating pluripotency and multilineage differentiation of human dental pulp cells (DPCs) remains unknown. Methods. To elucidate the functional role XPC played in pluripotency and multilineage differentiation of DPCs, expressions of XPC in DPCs with long-term culture were examined by real-time PCR and western blot. DPCs were transfected with lentiviral-mediated human XPC gene; then transfection rate was investigated by real-time PCR and western blot. Cell cycle, apoptosis, proliferation, senescence, multilineage differentiation, and expression of Oct-4/Sox2/c-Myc in transfected DPCs were examined. Results. XPC, Oct-4, Sox2, and c-Myc were downregulated at P7 compared with P3 in DPCs with long-term culture. XPC genes were upregulated in DPCs at P2 after transfection and maintained high expression level at P3 and P7. Cell proliferation, PI value, and telomerase activity were enhanced, whereas apoptosis was suppressed in transfected DPCs. Oct-4/Sox2/c-Myc were significantly upregulated, and multilineage differentiation in DPCs with XPC overexpression was enhanced after transfection. Conclusions. XPC plays an essential role in the modulation of pluripotency and multilineage differentiation of DPCs through regulation of Oct-4/Sox2/c-Myc. PMID:27127517

  13. XPC Promotes Pluripotency of Human Dental Pulp Cells through Regulation of Oct-4/Sox2/c-Myc

    Directory of Open Access Journals (Sweden)

    Lu Liu

    2016-01-01

    Full Text Available Introduction. Xeroderma pigmentosum group C (XPC, essential component of multisubunit stem cell coactivator complex (SCC, functions as the critical factor modulating pluripotency and genome integrity through interaction with Oct-4/Sox2. However, its specific role in regulating pluripotency and multilineage differentiation of human dental pulp cells (DPCs remains unknown. Methods. To elucidate the functional role XPC played in pluripotency and multilineage differentiation of DPCs, expressions of XPC in DPCs with long-term culture were examined by real-time PCR and western blot. DPCs were transfected with lentiviral-mediated human XPC gene; then transfection rate was investigated by real-time PCR and western blot. Cell cycle, apoptosis, proliferation, senescence, multilineage differentiation, and expression of Oct-4/Sox2/c-Myc in transfected DPCs were examined. Results. XPC, Oct-4, Sox2, and c-Myc were downregulated at P7 compared with P3 in DPCs with long-term culture. XPC genes were upregulated in DPCs at P2 after transfection and maintained high expression level at P3 and P7. Cell proliferation, PI value, and telomerase activity were enhanced, whereas apoptosis was suppressed in transfected DPCs. Oct-4/Sox2/c-Myc were significantly upregulated, and multilineage differentiation in DPCs with XPC overexpression was enhanced after transfection. Conclusions. XPC plays an essential role in the modulation of pluripotency and multilineage differentiation of DPCs through regulation of Oct-4/Sox2/c-Myc.

  14. Telomerase in relation to expression of p53, c-Myc and estrogen receptor in ovarian tumours

    NARCIS (Netherlands)

    Wisman, GBA; Hollema, H; Helder, MN; Knol, AJ; Van Der Meer, GT; Krans, M; De Jong, S; De Vries, EGE; Van Der Zee, AGJ

    2003-01-01

    Telomerase activity and its subunits (hTERC, hTERT mRNA) were evaluated in ovarian tumours in relation to the expression of p53, c-Myc and estrogen receptor (ER). Furthermore, relations between telomerase activity, hTERC and hTERT with known clinicopathologic prognostic factors and survival in patie

  15. β2-adrenergic receptor signaling promotes pancreatic ductal adenocarcinoma (PDAC) progression through facilitating PCBP2-dependent c-myc expression.

    Science.gov (United States)

    Wan, Chunhua; Gong, Chen; Zhang, Haifeng; Hua, Lu; Li, Xiaohong; Chen, Xudong; Chen, Yinji; Ding, Xiaoling; He, Song; Cao, Wei; Wang, Yingying; Fan, Shaoqing; Xiao, Ying; Zhou, Guoxiong; Shen, Aiguo

    2016-04-01

    The β2-adrenergic receptor (β2-AR) plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) progression. In this report, we identified poly(rC)-binding protein 2 (PCBP2) as a novel binding partner for β2-AR using immunoprecipitation-mass spectrometry (IP-MS) approach. The association between β2-AR and PCBP2 was verified using reciprocal immunoprecipitation. Importantly, we found significant interaction and co-localization of the two proteins in the presence of β2-AR agonist in Panc-1 and Bxpc3 PDAC cells. β2-AR-induced recruitment of PCBP2 led to augmented protein level of c-myc in PDAC cells, likely as a result of enhanced internal ribosome entry segment (IRES)-mediated translation of c-myc. The activation of β2-AR accelerated cell proliferation and colony formation, while knockdown of PCBP2 or c-myc restrained the effect. Furthermore, overexpression of PCBP2 was observed in human PDAC cell lines and tissue specimens compared to the normal pancreatic ductal epithelial cells and the non-cancerous tissues respectively. Overexpression of β2-AR and PCBP2 was associated with advanced tumor stage and significantly worsened prognosis in patients with PDAC. Our results elucidate a new molecular mechanism by which β2-AR signaling facilitates PDAC progression through triggering PCBP2-dependent c-myc expression. PMID:26803058

  16. c-Myc regulates proliferation and Fgf10 expression in airway smooth muscle after airway epithelial injury in mouse.

    Science.gov (United States)

    Volckaert, Thomas; Campbell, Alice; De Langhe, Stijn

    2013-01-01

    During lung development, Fibroblast growth factor 10 (Fgf10), which is expressed in the distal mesenchyme and regulated by Wnt signaling, acts on the distal epithelial progenitors to maintain them and prevent them from differentiating into proximal (airway) epithelial cells. Fgf10-expressing cells in the distal mesenchyme are progenitors for parabronchial smooth muscle cells (PSMCs). After naphthalene, ozone or bleomycin-induced airway epithelial injury, surviving epithelial cells secrete Wnt7b which then activates the PSMC niche to induce Fgf10 expression. This Fgf10 secreted by the niche then acts on a subset of Clara stem cells to break quiescence, induce proliferation and initiate epithelial repair. Here we show that conditional deletion of the Wnt target gene c-Myc from the lung mesenchyme during development does not affect proper epithelial or mesenchymal differentiation. However, in the adult lung we show that after naphthalene-mediated airway epithelial injury c-Myc is important for the activation of the PSMC niche and as such induces proliferation and Fgf10 expression in PSMCs. Our data indicate that conditional deletion of c-Myc from PSMCs inhibits airway epithelial repair, whereas c-Myc ablation from Clara cells has no effect on airway epithelial regeneration. These findings may have important implications for understanding the misregulation of lung repair in asthma and COPD. PMID:23967208

  17. SirT1 confers hypoxia-induced radioresistance via the modulation of c-Myc stabilization on hepatoma cells

    International Nuclear Information System (INIS)

    Intratumoral hypoxia is an important contributory factor to tumor cell resistance to radiotherapy. SirT1, a nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylase, has been linked to the decrease of radiation-induced DNA damage and seems to be critical for cancer therapy. The purpose of this study was to investigate the role of SirT1 in hypoxia-induced radiation response on hepatoma cells. It was found that the administration with resveratrol, a putative SirT1 activator, enhanced the resistance of HepG2 cells against radiation-induced DNA damage of MN formation under hypoxia condition; while nicotinamide, a well-known SirT1 inhibitor, sensitized this radiation damage. Nevertheless, pretreatment of cells with 10058-F4, a specific inhibitor of c-Myc, almost eliminated the nicotinamide-induced radiosensitive effect. Further studies revealed that resveratrol inhibited c-Myc protein accumulation via up-regulation of SirT1 expression and deacetylase activity, and this loss of c-Myc protein was abolished by inhibiting its degradation in the presence of MG132, a potent inhibitor of proteasome. In contrast, nicotinamide attenuated c-Myc protein degradation induced by radiation under hypoxia through inhibition of SirT1 deacetylase activity. Our findings suggest that SirT1 could serve as a novel potent target of radiation-induced DNA damage and thus as a potential strategy to advance the efficiency of radiation therapy in hepatoma entities. (author)

  18. XPC Promotes Pluripotency of Human Dental Pulp Cells through Regulation of Oct-4/Sox2/c-Myc

    Science.gov (United States)

    Liu, Lu; Peng, Zhengjun; Xu, Zhezhen; Wei, Xi

    2016-01-01

    Introduction. Xeroderma pigmentosum group C (XPC), essential component of multisubunit stem cell coactivator complex (SCC), functions as the critical factor modulating pluripotency and genome integrity through interaction with Oct-4/Sox2. However, its specific role in regulating pluripotency and multilineage differentiation of human dental pulp cells (DPCs) remains unknown. Methods. To elucidate the functional role XPC played in pluripotency and multilineage differentiation of DPCs, expressions of XPC in DPCs with long-term culture were examined by real-time PCR and western blot. DPCs were transfected with lentiviral-mediated human XPC gene; then transfection rate was investigated by real-time PCR and western blot. Cell cycle, apoptosis, proliferation, senescence, multilineage differentiation, and expression of Oct-4/Sox2/c-Myc in transfected DPCs were examined. Results. XPC, Oct-4, Sox2, and c-Myc were downregulated at P7 compared with P3 in DPCs with long-term culture. XPC genes were upregulated in DPCs at P2 after transfection and maintained high expression level at P3 and P7. Cell proliferation, PI value, and telomerase activity were enhanced, whereas apoptosis was suppressed in transfected DPCs. Oct-4/Sox2/c-Myc were significantly upregulated, and multilineage differentiation in DPCs with XPC overexpression was enhanced after transfection. Conclusions. XPC plays an essential role in the modulation of pluripotency and multilineage differentiation of DPCs through regulation of Oct-4/Sox2/c-Myc. PMID:27127517

  19. c-Myc Enhances Sonic Hedgehog-Induced Medulloblastoma Formation from Nestin-Expressing Neural Progenitors in Mice

    Directory of Open Access Journals (Sweden)

    Ganesh Rao

    2003-05-01

    Full Text Available Medulloblastomas are malignant brain tumors that arise in the cerebella of children. The presumed cellsof-origin are undifferentiated precursors of granule neurons that occupy the external granule layer (EGL of the developing cerebellum. The overexpression of proteins that normally stimulate proliferation of neural progenitor cells may initiate medulloblastoma formation. Two known mitogens for neural progenitors are the c-Myc oncoprotein and Sonic hedgehog (Shh, a crucial determinant of embryonic pattern formation in the central nervous system. We modeled the ability of c-Myc and Shh to induce medulloblastoma in mice using the RCAS/tv-a system, which allows postnatal gene transfer and expression in a cell type-specific manner. We targeted the expression of Shh and c-Myc to nestin-expressing neural progenitor cells by injecting replication-competent ALV splice acceptor (RCAS vectors into the cerebella of newborn mice. Following injection with RCAS-Shh alone, 3/32 (9% mice developed medulloblastomas and 5/32 showed multifocal hyperproliferation of the EGL, possibly a precursor stage of medulloblastoma. Following injection with RCAS-Shh plus RCAS-Myc, 9/39 (23% mice developed medulloblastomas. We conclude that nestin-expressing neural progenitors, present in the cerebellum at birth, can act as the cells-of-origin for medulloblastoma, and that c-Myc cooperates with Shh to enhance tumorigenicity.

  20. Modification of the Tumor Microenvironment in KRAS or c-MYC-Induced Ovarian Cancer-Associated Peritonitis

    Science.gov (United States)

    Kawana, Kei; Adachi, Katsuyuki; Kawata, Akira; Ogishima, Juri; Nakamura, Hiroe; Fujimoto, Asaha; Sato, Masakazu; Inoue, Tomoko; Nishida, Haruka; Furuya, Hitomi; Tomio, Kensuke; Arimoto, Takahide; Koga, Kaori; Wada-Hiraike, Osamu; Oda, Katsutoshi; Nagamatsu, Takeshi; Kiyono, Tohru; Osuga, Yutaka; Fujii, Tomoyuki

    2016-01-01

    The most common properties of oncogenes are cell proliferation and the prevention of apoptosis in malignant cells, which, as a consequence, induce tumor formation and dissemination. However, the effects of oncogenes on the tumor microenvironment (TME) have not yet been examined in detail. The accumulation of ascites accompanied by chronic inflammation and elevated concentrations of VEGF is a hallmark of the progression of ovarian cancer. We herein demonstrated the mechanisms by which oncogenes contribute to modulating the ovarian cancer microenvironment. c-MYC and KRAS were transduced into the mouse ovarian cancer cell line ID8. ID8, ID8-c-MYC, or ID8-KRAS cells were then injected into the peritoneal cavities of C57/BL6 mice and the production of ascites was assessed. ID8-c-MYC and ID8-KRAS both markedly accelerated ovarian cancer progression in vivo, whereas no significant differences were observed in proliferative activity in vitro. ID8-KRAS in particular induced the production of ascites, which accumulated between approximately two to three weeks after the injection, more rapidly than ID8 and ID8-c-MYC (between nine and ten weeks and between six and seven weeks, respectively). VEGF concentrations in ascites significantly increased in c-MYC-induced ovarian cancer, whereas the concentrations of inflammatory cytokines in ascites were significantly high in KRAS-induced ovarian cancer and were accompanied by an increased number of neutrophils in ascites. A cytokine array revealed that KRAS markedly induced the expression of granulocyte macrophage colony-stimulating factor (GM-CSF) in ID8 cells. These results suggest that oncogenes promote cancer progression by modulating the TME in favor of cancer progression. PMID:27483433

  1. Tissue array for Tp53, C-myc, CCND1 gene over-expression in different tumors

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To rapidly detect molecular alterations in different malignancies and investigate the possible role of Tp53, C-myc, and CCND1 genes in development of tumors in human organs and their adjacent normal tissues, as well as the possible relation between well- and poorly-differentiated tumors. METHODS: A tissue array consisting of seven different tumors was generated. The tissue array included 120 points of esophagus, 120 points of stomach, 80 points of rectum, 60 points of thyroid gland, 100 points of mammary gland, 80 points ofliver, and 80 points of colon. Expressions of Tp53, C-myc, and CCND1 were determined by RNA in situ hybridization. 3' terminal digoxin-labeled anti-sense single stranded oligonucleotide and locked nucleic acid modifying probe were used.RESULTS: The expression level of Tp53 gene was higher in six different carcinoma tissue samples than in paracancerous tissue samples with the exception in colon carcinoma tissue samples (P < 0.05). The expression level of CCND1 gene was significantly different in different carcinoma tissue samples with the exception in esophagus and colon carcinoma tissue samples. The expression level of C-myc gene was different in esophagus carcinoma tissue samples (x2 = 18.495, P = 0.000), stomach carcinoma tissue samples (x2 = 23.750, P = 0.000), and thyroid gland tissue samples (x2 = 10.999, P = 0.004). The intensity of signals was also different in different carcinoma tissue samples and paracancerous tissue samples.CONCLUSION: Over-expression of the Tp53, CCND1, and C-myc genes appears to play a role in development of human cancer by regulating the expression of mRNA. Tp53, CCND1 and C-myc genes are significantly correlated with the development of different carcinomas.

  2. Integrin α6Bβ4 inhibits colon cancer cell proliferation and c-Myc activity

    International Nuclear Information System (INIS)

    Integrins are known to be important contributors to cancer progression. We have previously shown that the integrin β4 subunit is up-regulated in primary colon cancer. Its partner, the integrin α6 subunit, exists as two different mRNA splice variants, α6A and α6B, that differ in their cytoplasmic domains but evidence for distinct biological functions of these α6 splice variants is still lacking. In this work, we first analyzed the expression of integrin α6A and α6B at the protein and transcript levels in normal human colonic cells as well as colorectal adenocarcinoma cells from both primary tumors and established cell lines. Then, using forced expression experiments, we investigated the effect of α6A and α6B on the regulation of cell proliferation in a colon cancer cell line. Using variant-specific antibodies, we observed that α6A and α6B are differentially expressed both within the normal adult colonic epithelium and between normal and diseased colonic tissues. Proliferative cells located in the lower half of the glands were found to predominantly express α6A, while the differentiated and quiescent colonocytes in the upper half of the glands and surface epithelium expressed α6B. A relative decrease of α6B expression was also identified in primary colon tumors and adenocarcinoma cell lines suggesting that the α6A/α6B ratios may be linked to the proliferative status of colonic cells. Additional studies in colon cancer cells showed that experimentally restoring the α6A/α6B balance in favor of α6B caused a decrease in cellular S-phase entry and repressed the activity of c-Myc. The findings that the α6Bβ4 integrin is expressed in quiescent normal colonic cells and is significantly down-regulated in colon cancer cells relative to its α6Aβ4 counterpart are consistent with the anti-proliferative influence and inhibitory effect on c-Myc activity identified for this α6Bβ4 integrin. Taken together, these findings point out the importance of integrin

  3. Driving gradual endogenous c-myc overexpression by flow-sorting: intracellular signaling and tumor cell phenotype correlate with oncogene expression

    DEFF Research Database (Denmark)

    Knudsen, Kasper Jermiin; Holm, G.M.N.; Krabbe, J.S.;

    2009-01-01

    Insulin-exposed rat mammary cancer cells were flow sorted based on a c-myc reporter plasmid encoding a destabilized green fluorescent protein. Sorted cells exhibited gradual increases in c-myc levels. Cells overexpressing c-myc by only 10% exhibited phenotypic changes attributable to c-myc overex...... alternative modeling of the receptor-mediated carcinogenic process, compared to the currently used approaches of recombinant constitutive or conditional overexpression of oncogenic transmembrane receptor tyrosine kinases or oncogenic transcription factors.......Insulin-exposed rat mammary cancer cells were flow sorted based on a c-myc reporter plasmid encoding a destabilized green fluorescent protein. Sorted cells exhibited gradual increases in c-myc levels. Cells overexpressing c-myc by only 10% exhibited phenotypic changes attributable to c...... exhibited overexpression of the IGF-1R, and slightly elevated expression of the IR. Increased susceptibility to the mitogenic effect of insulin was seen in a small proportion of the sorted cells, and insulin was more effective in activating the p44/42 MAPK pathway, but not the PI3K pathway, in the sorted...

  4. The FUSE binding proteins FBP1 and FBP3 are potential c-myc regulators in renal, but not in prostate and bladder cancer

    Directory of Open Access Journals (Sweden)

    Meyer Hellmuth-Alexander

    2008-12-01

    Full Text Available Abstract Background The three far-upstream element (FUSE binding proteins (FBP1, FBP2, and FBP3 belong to an ancient family of single-stranded DNA binding proteins which are required for proper regulation of the c-myc proto-oncogene. Whereas it is known that c-myc alterations play a completely different role in various carcinomas of the urogenital tract, the relevance of FBPs is unclear. Methods FBP1, FBP3 and c-myc expression was studied in 105 renal cell, 95 prostate and 112 urinary bladder carcinomas by immunohistochemistry using tissue microarrays. Results High rates of FBP1 and FBP3 expression were observed in all cancer types. There was a concomitant up-regulation of FBP1 and FBP3 in renal cell and prostate carcinomas (p C-myc expression was detectable in 21% of prostate, 30% of renal and 34% of urothelial carcinomas. Interestingly, strong FBP1 and FBP3 expression was associated with c-myc up-regulation in clear cell renal cell carcinomas (p Conclusion The correlation between FBP1/FBP3, c-myc and high proliferation rate in renal cell carcinoma provides strong in vivo support for the suggested role of FBP1 and FBP3 as activators of c-myc. The frequent up-regulation of FBP1 and FBP3 in urothelial and prostate carcinoma suggests that FBPs also have an important function in gene regulation of these tumors.

  5. RNAi delivery by exosome-mimetic nanovesicles - Implications for targeting c-Myc in cancer.

    Science.gov (United States)

    Lunavat, Taral R; Jang, Su Chul; Nilsson, Lisa; Park, Hyun Taek; Repiska, Gabriela; Lässer, Cecilia; Nilsson, Jonas A; Gho, Yong Song; Lötvall, Jan

    2016-09-01

    To develop RNA-based therapeutics, it is crucial to create delivery vectors that transport the RNA molecule into the cell cytoplasm. Naturally released exosomes vesicles (also called "Extracellular Vesicles") have been proposed as possible RNAi carriers, but their yield is relatively small in any cell culture system. We have previously generated exosome-mimetic nanovesicles (NV) by serial extrusions of cells through nano-sized filters, which results in 100-times higher yield of extracellular vesicles. We here test 1) whether NV can be loaded with siRNA exogenously and endogenously, 2) whether the siRNA-loaded NV are taken up by recipient cells, and 3) whether the siRNA can induce functional knock-down responses in recipient cells. A siRNA against GFP was first loaded into NV by electroporation, or a c-Myc shRNA was expressed inside of the cells. The NV were efficiently loaded with siRNA with both techniques, were taken up by recipient cells, which resulted in attenuation of target gene expression. In conclusion, our study suggests that exosome-mimetic nanovesicles can be a platform for RNAi delivery to cell cytoplasm. PMID:27344366

  6. Mitochondrial structure, function and dynamics are temporally controlled by c-Myc.

    Directory of Open Access Journals (Sweden)

    J Anthony Graves

    Full Text Available Although the c-Myc (Myc oncoprotein controls mitochondrial biogenesis and multiple enzymes involved in oxidative phosphorylation (OXPHOS, the coordination of these events and the mechanistic underpinnings of their regulation remain largely unexplored. We show here that re-expression of Myc in myc-/- fibroblasts is accompanied by a gradual accumulation of mitochondrial biomass and by increases in membrane polarization and mitochondrial fusion. A correction of OXPHOS deficiency is also seen, although structural abnormalities in electron transport chain complexes (ETC are not entirely normalized. Conversely, the down-regulation of Myc leads to a gradual decrease in mitochondrial mass and a more rapid loss of fusion and membrane potential. Increases in the levels of proteins specifically involved in mitochondrial fission and fusion support the idea that Myc affects mitochondrial mass by influencing both of these processes, albeit favoring the latter. The ETC defects that persist following Myc restoration may represent metabolic adaptations, as mitochondrial function is re-directed away from producing ATP to providing a source of metabolic precursors demanded by the transformed cell.

  7. A STUDY OF C-MYC ONCOGENE EXPRESSIONAND AMPLIFICATION IN COLORECTAL CANCER

    Institute of Scientific and Technical Information of China (English)

    王建明; 李凌; 李申德; 崔惠云; 沈桂华

    1994-01-01

    Expression of c-myc oncogene transcripts in colorectal neoplasia was studied in paraffin embedded tissus sec-tions from 25 patients undergoin surgery and from the rectal carcinoma cell line HR-8348 by using in situ hy-bridization,and its amplification was investigated in tumor and normal mucosa tissue from 25 coloproctomy sam-ples by slot blot hybridization.Overexpression of this gene was seen in 78%(7/9)of the benign adenomas and 91%(20/22)of the malignancies sampled.There was no significant correlation between overexpression and the histologic type or grade,and no significant relationship between the level of expression and clinical stage was found,although overexpression was apparently more common in tumors with metastasis.Ampli-fication was also found in 2 adenomas with malignant change.The results suggest that multiple factors are in-volved in the progression of colorectal cancer,and in situ hybridization with nonradiolabeled probe is useful in the detection of gene expression.

  8. RNA Interference Using c-Myc-Conjugated Nanoparticles Suppresses Breast and Colorectal Cancer Models.

    Science.gov (United States)

    Tangudu, Naveen K; Verma, Vinod K; Clemons, Tristan D; Beevi, Syed S; Hay, Trevor; Mahidhara, Ganesh; Raja, Meera; Nair, Rekha A; Alexander, Liza E; Patel, Anant B; Jose, Jedy; Smith, Nicole M; Zdyrko, Bogdan; Bourdoncle, Anne; Luzinov, Igor; Iyer, K Swaminathan; Clarke, Alan R; Dinesh Kumar, Lekha

    2015-05-01

    In this article, we report the development and preclinical validation of combinatorial therapy for treatment of cancers using RNA interference (RNAi). RNAi technology is an attractive approach to silence genes responsible for disease onset and progression. Currently, the critical challenge facing the clinical success of RNAi technology is in the difficulty of delivery of RNAi inducers, due to low transfection efficiency, difficulties of integration into host DNA and unstable expression. Using the macromolecule polyglycidal methacrylate (PGMA) as a platform to graft multiple polyethyleneimine (PEI) chains, we demonstrate effective delivery of small oligos (anti-miRs and mimics) and larger DNAs (encoding shRNAs) in a wide variety of cancer cell lines by successful silencing/activation of their respective target genes. Furthermore, the effectiveness of this therapy was validated for in vivo tumor suppression using two transgenic mouse models; first, tumor growth arrest and increased animal survival was seen in mice bearing Brca2/p53-mutant mammary tumors following daily intratumoral treatment with nanoparticles conjugated to c-Myc shRNA. Second, oral delivery of the conjugate to an Apc-deficient crypt progenitor colon cancer model increased animal survival and returned intestinal tissue to a non-wnt-deregulated state. This study demonstrates, through careful design of nonviral nanoparticles and appropriate selection of therapeutic gene targets, that RNAi technology can be made an affordable and amenable therapy for cancer. PMID:25695957

  9. Induction of Pluripotency in Adult Equine Fibroblasts without c-MYC

    Directory of Open Access Journals (Sweden)

    Khodadad Khodadadi

    2012-01-01

    Full Text Available Despite tremendous efforts on isolation of pluripotent equine embryonic stem (ES cells, to date there are few reports about successful isolation of ESCs and no report of in vivo differentiation of this important companion species. We report the induction of pluripotency in adult equine fibroblasts via retroviral transduction with three transcription factors using OCT4, SOX2, and KLF4 in the absence of c-MYC. The cell lines were maintained beyond 27 passages (more than 11 months and characterized. The equine iPS (EiPS cells stained positive for alkaline phosphatase by histochemical staining and expressed OCT4, NANOG, SSEA1, and SSEA4. Gene expression analysis of the cells showed the expression of OCT4, SOX2 NANOG, and STAT3. The cell lines retained a euploid chromosome count of 64 after long-term culture cryopreservation. The EiPS demonstrated differentiation capacity for the three embryonic germ layers both in vitro by embryoid bodies (EBs formation and in vivo by teratoma formation. In conclusion, we report the derivation of iPS cells from equine adult fibroblasts and long-term maintenance using either of the three reprogramming factors.

  10. Inhibition of c-MYC with involvement of ERK/JNK/MAPK and AKT pathways as a novel mechanism for shikonin and its derivatives in killing leukemia cells.

    Science.gov (United States)

    Zhao, Qiaoli; Assimopoulou, Andreana N; Klauck, Sabine M; Damianakos, Harilaos; Chinou, Ioanna; Kretschmer, Nadine; Rios, José-Luis; Papageorgiou, Vassilios P; Bauer, Rudolf; Efferth, Thomas

    2015-11-17

    Leukemia remains life-threatening despite remarkable advances in chemotherapy. The poor prognosis and drug resistance are challenging treatment. Novel drugs are urgently needed. Shikonin, a natural naphthoquinone, has been previously shown by us to be particularly effective towards various leukemia cell lines compared to solid tumors. However, the underlying mechanisms are still poorly understood. Here, we investigated shikonin and 14 derivatives on U937 leukemia cells. Four derivatives (isobutyrylshikonin, 2-methylbutyrylshikonin, isovalerylshikonin and β,β-dimethylacrylshikonin) were more active than shikonin. AnnexinV-PI analysis revealed that shikonins induced apoptosis. Cell cycle G1/S check point regulation and the transcription factor c-MYC, which plays a vital role in cell cycle regulation and proliferation, were identified as the most commonly down-regulated mechanisms upon treatment with shikonins in mRNA microarray hybridizations. Western blotting and DNA-binding assays confirmed the inhibition of c-MYC expression and transcriptional activity by shikonins. Reduction of c-MYC expression was closely associated with deregulated ERK, JNK MAPK and AKT activity, indicating their involvement in shikonin-triggered c-MYC inactivation. Molecular docking studies revealed that shikonin and its derivatives bind to the same DNA-binding domain of c-MYC as the known c-MYC inhibitors 10058-F4 and 10074-G5. This finding indicates that shikonins bind to c-MYC. The effect of shikonin on U937 cells was confirmed in other leukemia cell lines (Jurkat, Molt4, CCRF-CEM, and multidrug-resistant CEM/ADR5000), where shikonin also inhibited c-MYC expression and influenced phosphorylation of AKT, ERK1/2, and SAPK/JNK. In summary, inhibition of c-MYC and related pathways represents a novel mechanism of shikonin and its derivatives to explain their anti-leukemic activity. PMID:26472107

  11. Changes of c-Myc and DNMT1 mRNA and protein levels in the rat livers induced by dibutyl phthalate treatment.

    Science.gov (United States)

    Urbanek-Olejnik, Katarzyna; Liszewska, Monika; Winczura, Alicja; Kostka, Grażyna

    2016-05-01

    We investigated the relationship between dibutyl phthalate (DBP)-induced hypomethylation of the c-Myc promoter region (as evident in our early study) and the expression of c-Myc and DNMT1 genes (at messenger RNA (mRNA) and protein level) in the rat liver. Male Wistar rats received DBP in 1, 3, or 14 daily doses of 1800 mg kg(-1) body weight. Levels of DNMT1, c-Myc mRNA, and proteins were detected using real-time polymerase chain reaction and Western blot analysis, respectively. Our findings indicate that DBP caused an increase in mRNA levels of c-Myc at all time points. The results showed that protein levels of c-Myc in rat liver also increased significantly by DBP treatment, which were more pronounced at last time point (after 14 doses). Furthermore, overexpression of DNMT1gene have been found after one dose of DBP, which was confirmed at the protein level by Western blot analysis. Reduced levels of DNMT1mRNA and proteins (3 and 14 doses) were coordinated with depletion DNA synthesis (reported previously). Based on our previous results and those presented here, the following conclusion could be drawn: (1) DBP exerted biological activity through epigenetic modulation of c-Myc gene expression; (2) it seems possible that DBP-induced active demethylation of c-Myc gene through mechanism(s) linked to generation of reactive oxygen species by activated c-Myc; and (3) control of DNA replication was not directly dependent on c-Myc transcriptional activity and we attribute this finding to DNMT1gene expression which was tightly coordinated with DNA synthesis. PMID:24311629

  12. Signaling Pathway of GP88 (Progranulin) in Breast Cancer Cells: Upregulation and Phosphorylation of c-myc by GP88/Progranulin in Her2-Overexpressing Breast Cancer Cells

    OpenAIRE

    Kim, Wes E; Yue, Binbin; Serrero, Ginette

    2016-01-01

    Her2 is a receptor tyrosine kinase overexpressed in 25% of breast tumors. We have shown that the 88 kDa autocrine growth and survival factor GP88 (progranulin) stimulated Her2 phosphorylation and proliferation and conferred Herceptin resistance in Her2-overexpressing cells. Herein, we report that GP88 stimulates c-myc phosphorylation and upregulates c-myc levels in Her2-overexpressing cells. c-myc phosphorylation and upregulation by GP88 were not observed in non-Her2-overexpressing breast can...

  13. Dual Targeting of Bromodomain and Extraterminal Domain Proteins, and WNT or MAPK Signaling, Inhibits c-MYC Expression and Proliferation of Colorectal Cancer Cells.

    Science.gov (United States)

    Tögel, Lars; Nightingale, Rebecca; Chueh, Anderly C; Jayachandran, Aparna; Tran, Hoanh; Phesse, Toby; Wu, Rui; Sieber, Oliver M; Arango, Diego; Dhillon, Amardeep S; Dawson, Mark A; Diez-Dacal, Beatriz; Gahman, Timothy C; Filippakopoulos, Panagis; Shiau, Andrew K; Mariadason, John M

    2016-06-01

    Inhibitors of the bromodomain and extraterminal domain (BET) protein family attenuate the proliferation of several tumor cell lines. These effects are mediated, at least in part, through repression of c-MYC. In colorectal cancer, overexpression of c-MYC due to hyperactive WNT/β-catenin/TCF signaling is a key driver of tumor progression; however, effective strategies to target this oncogene remain elusive. Here, we investigated the effect of BET inhibitors (BETi) on colorectal cancer cell proliferation and c-MYC expression. Treatment of 20 colorectal cancer cell lines with the BETi JQ1 identified a subset of highly sensitive lines. JQ1 sensitivity was higher in cell lines with microsatellite instability but was not associated with the CpG island methylator phenotype, c-MYC expression or amplification status, BET protein expression, or mutation status of TP53, KRAS/BRAF, or PIK3CA/PTEN Conversely, JQ1 sensitivity correlated significantly with the magnitude of c-MYC mRNA and protein repression. JQ1-mediated c-MYC repression was not due to generalized attenuation of β-catenin/TCF-mediated transcription, as JQ1 had minimal effects on other β-catenin/TCF target genes or β-catenin/TCF reporter activity. BETi preferentially target super-enhancer-regulated genes, and a super-enhancer in c-MYC was recently identified in HCT116 cells to which BRD4 and effector transcription factors of the WNT/β-catenin/TCF and MEK/ERK pathways are recruited. Combined targeting of c-MYC with JQ1 and inhibitors of these pathways additively repressed c-MYC and proliferation of HCT116 cells. These findings demonstrate that BETi downregulate c-MYC expression and inhibit colorectal cancer cell proliferation and identify strategies for enhancing the effects of BETi on c-MYC repression by combinatorial targeting the c-MYC super-enhancer. Mol Cancer Ther; 15(6); 1217-26. ©2016 AACR. PMID:26983878

  14. Polymorphisms cMyc-N11S and p27-V109G and breast cancer risk and prognosis

    International Nuclear Information System (INIS)

    cMyc and p27 are key genes implicated in carcinogenesis. Whether polymorphisms in these genes affect breast cancer risk or prognosis is still unclear. In this study, we focus on a rare non-synonymous polymorphism in cMyc (N11S) and a common polymorphism in p27 (V109G) and determine their role in risk and prognosis using data collected from the Ontario Breast Cancer Family Registry. Risk factor data was collected at baseline on a large group of women (cases = 1,115 and population-based controls = 710) and clinical data (including treatment and follow-up) were collected prospectively by periodic review of medical records for a subset of cases (N = 967) for nearly a decade. A centralized pathology review was conducted. Unconditional logistic regression was used to determine the association of polymorphisms with breast cancer risk and the Cox proportional hazards model was used to determine their association with survival. Our results suggest that while cMyc-N11S can be considered a putatively functional polymorphism located in the N-terminal domain, it is not associated with risk, tumor characteristics or survival. The p27-G109 allele was associated with a modest protective effect in adjusted analyses and higher T stage. We found no evidence to suggest that p27-V109G alone or in combination with cMyc-N11S was associated with survival. Age at onset and first-degree family history of breast or ovarian cancer did not significantly modify the association of these polymorphisms with breast cancer risk. Further work is recommended to understand the potential functional role of these specific non-synonymous amino acid changes and a larger, more comprehensive investigation of genetic variation in these genes (e.g., using a tagSNP approach) in combination with other relevant genes is needed as well as consideration for treatment effects when assessing their potential role in prognosis

  15. c-Myc Enhances Sonic Hedgehog-Induced Medulloblastoma Formation from Nestin-Expressing Neural Progenitors in Mice1

    OpenAIRE

    Rao, Ganesh; Pedone, Carolyn A; Coffin, Cheryl M.; Holland, Eric C.; Fults, Daniel W.

    2003-01-01

    Medulloblastomas are malignant brain tumors that arise in the cerebella of children. The presumed cells-of-origin are undifferentiated precursors of granule neurons that occupy the external granule layer (EGL) of the developing cerebellum. The overexpression of proteins that normally stimulate proliferation of neural progenitor cells may initiate medulloblastoma formation. Two known mitogens for neural progenitors are the c-Myc oncoprotein and Sonic hedgehog (Shh), a crucial determinant of em...

  16. Focal Adhesion Kinase Is Required for Intestinal Regeneration and Tumorigenesis Downstream of Wnt/c-Myc Signaling

    OpenAIRE

    Ashton, Gabrielle H.; Morton, Jennifer P; Myant, Kevin; Phesse, Toby J.; Ridgway, Rachel A.; Marsh, Victoria; Wilkins, Julie A.; Athineos, Dimitris; Muncan, Vanesa; Kemp, Richard; Neufeld, Kristi; Clevers, Hans; Brunton, Valerie; Winton, Douglas J.; Wang, Xiaoyan

    2010-01-01

    The intestinal epithelium has a remarkable capacity to regenerate after injury and DNA damage. Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration following DNA damage. Given Wnt/c-Myc signaling is activated following intestinal regeneration, we investigated the functional importance of FAK following deletion of the Apc tumor suppressor protein withi...

  17. Convergence of cMyc and β-catenin on Tcf7l1 enables endoderm specification.

    Science.gov (United States)

    Morrison, Gillian; Scognamiglio, Roberta; Trumpp, Andreas; Smith, Austin

    2016-02-01

    The molecular machinery that directs formation of definitive endoderm from pluripotent stem cells is not well understood. Wnt/β-catenin and Nodal signalling have been implicated, but the requirements for lineage specification remain incompletely defined. Here, we demonstrate a potent effect of inhibiting glycogen synthase kinase 3 (GSK3) on definitive endoderm production. We find that downstream of GSK3 inhibition, elevated cMyc and β-catenin act in parallel to reduce transcription and DNA binding, respectively, of the transcriptional repressor Tcf7l1. Tcf7l1 represses FoxA2, a pioneer factor for endoderm specification. Deletion of Tcf7l1 is sufficient to allow upregulation of FoxA2 in the presence of Activin. In wild-type cells, cMyc contributes by reducing Tcf7l1 mRNA, while β-catenin acts on Tcf7l1 protein. GSK3 inhibition is further required for consolidation of endodermal fate via upregulation of Sox17, highlighting sequential roles for Wnt signalling. The identification of a cMyc/β-catenin-Tcf7l1-FoxA2 axis reveals a de-repression mechanism underlying endoderm induction that may be recapitulated in other developmental and patho-logical contexts. PMID:26675138

  18. Primary structure and functional scFv antibody expression of an antibody against the human protooncogen c-myc.

    Science.gov (United States)

    Fuchs, P; Breitling, F; Little, M; Dübel, S

    1997-06-01

    The immunoglobulin heavy- and light-chain variable region (Vh and Vl) genes were isolated from Myc1-9E10 hybridoma cells, which secreted monoclonal antibody against human oncogen c-myc. The expression vector pOPE52-c-myc was constructed for the recombinant production in E. coli. A 30 kDa single chain fragment (scFv) expression product was found in the periplasmic space by SDS-PAGE and immunoblotting. A significant fraction was processed correctly as demonstrated with an antiserum recognizing the processed aminoterminus only. The specific binding of the scFv fragment to the peptide epitope of the maternal monoclonal antibody was demonstrated and the primary sequence of the variable regions was determined. Sequence comparison with previously published partial Vh and Vl sequences from this hybridoma cell line revealed a genetic heterogeneity for the light chain variable region. The potential use of this scFv as a new tool for detection and purification of tagged proteins, for adding costimulatory signals to the surface of cancer cells as well as for analyzing c-myc function in the living cell by cytoplasmic expression is discussed. PMID:9219032

  19. c-Myc and AMPK Control Cellular Energy Levels by Cooperatively Regulating Mitochondrial Structure and Function.

    Directory of Open Access Journals (Sweden)

    Lia R Edmunds

    Full Text Available The c-Myc (Myc oncoprotein and AMP-activated protein kinase (AMPK regulate glycolysis and oxidative phosphorylation (Oxphos although often for different purposes. Because Myc over-expression depletes ATP with the resultant activation of AMPK, we explored the potential co-dependency of and cross-talk between these proteins by comparing the consequences of acute Myc induction in ampk+/+ (WT and ampk-/- (KO murine embryo fibroblasts (MEFs. KO MEFs showed a higher basal rate of glycolysis than WT MEFs and an appropriate increase in response to activation of a Myc-estrogen receptor (MycER fusion protein. However, KO MEFs had a diminished ability to increase Oxphos, mitochondrial mass and reactive oxygen species in response to MycER activation. Other differences between WT and KO MEFs, either in the basal state or following MycER induction, included abnormalities in electron transport chain function, levels of TCA cycle-related oxidoreductases and cytoplasmic and mitochondrial redox states. Transcriptional profiling of pathways pertinent to glycolysis, Oxphos and mitochondrial structure and function also uncovered significant differences between WT and KO MEFs and their response to MycER activation. Finally, an unbiased mass-spectrometry (MS-based survey capable of quantifying ~40% of all mitochondrial proteins, showed about 15% of them to be AMPK- and/or Myc-dependent in their steady state. Significant differences in the activities of the rate-limiting enzymes pyruvate kinase and pyruvate dehydrogenase, which dictate pyruvate and acetyl coenzyme A abundance, were also differentially responsive to Myc and AMPK and could account for some of the differences in basal metabolite levels that were also detected by MS. Thus, Myc and AMPK are highly co-dependent and appear to engage in significant cross-talk across numerous pathways which support metabolic and ATP-generating functions.

  20. C-Myc regulates substrate oxidation patterns during early pressure-overload hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Ledee, Dolena R. [Seattle Children' s Research Inst., Seattle, WA (United States); Smith, Lincoln [Seattle Children' s Hospital, Seattle, WA (United States); Kajimoto, Masaki [Seattle Children' s Research Inst., Seattle, WA (United States); Bruce, Margaret [Seattle Children' s Research Inst., Seattle, WA (United States); Isern, Nancy G. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL); Xu, Chun [Seattle Children' s Research Inst., Seattle, WA (United States); Portman, Michael A. [Seattle Children' s Research Inst., Seattle, WA (United States); Olson, Aaron [Seattle Children' s Research Inst., Seattle, WA (United States)

    2013-11-26

    Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of glycolytic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected FVB mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketones and unlabeled glucose and insulin. Western blots were used to evaluate metabolic enzymes. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (presumably glucose) contribution. Myc inactivation (MycKO-TAC) inhibited these metabolic changes. Hypertrophy in general increased protein levels of PKM2; however this change was not linked to Myc status. Protein post-translation modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. In conclusion, Myc regulates substrate utilization during early pressure overload hypertrophy. Our results show that the metabolic switch during hypertrophy is not necessary to maintain cardiac function, but it may be important mechanism to promote cardiomyocyte growth. Myc also regulates protein O-GlcNAcylation during hypertrophy.

  1. Use of a transfected and amplified Drosophila heat shock promoter construction for inducible production of toxic mouse c-myc proteins in CHO cells

    International Nuclear Information System (INIS)

    After transfection and selection with methotrexate, CHO cell lines were established which contained up to 2000 copies of an expression vector for c-myc protein. The vector contained the Drosophila heat shock protein 70 (hsp70) promoter fused with the coding region of the mouse c-myc gene. Incubation of cells for up to 3 hours at 430C resulted in at least a 100-fold induction of recombinant c-myc mRNA. When cells were shifted back to 370C, within 1 to 4 hours, this RNA was translated into protein to yield about 250 μg per 109 cells. Cells died a few hours later, suggesting that high concentrations of intracellular c-myc are cytotoxic. 47 refs., 5 figs

  2. Use of a transfected and amplified Drosophila heat shock promoter construction for inducible production of toxic mouse c-myc proteins in CHO cells

    Energy Technology Data Exchange (ETDEWEB)

    Wurm, F.M.; Gwinn, K.A.; Papoulas, O.; Pallavicini, M.; Kingston, R.E.

    1987-07-24

    After transfection and selection with methotrexate, CHO cell lines were established which contained up to 2000 copies of an expression vector for c-myc protein. The vector contained the Drosophila heat shock protein 70 (hsp70) promoter fused with the coding region of the mouse c-myc gene. Incubation of cells for up to 3 hours at 43/sup 0/C resulted in at least a 100-fold induction of recombinant c-myc mRNA. When cells were shifted back to 37/sup 0/C, within 1 to 4 hours, this RNA was translated into protein to yield about 250 ..mu..g per 10/sup 9/ cells. Cells died a few hours later, suggesting that high concentrations of intracellular c-myc are cytotoxic. 47 refs., 5 figs.

  3. c-Myc regulates expression of NKG2D ligands ULBP1/2/3 in AML and modulates their susceptibility to NK-mediated lysis

    OpenAIRE

    Nanbakhsh, Arash; Pochon, Cécile; Mallavialle, Aude; Amsellem, Sophie; Bourhis, Jean Henri; Chouaib, Salem

    2014-01-01

    AML cells resistant to cytarabine are more susceptible to NK-mediated cell lysis.c-Myc regulates ULBP1/2/3 expression and interferes with NK cell susceptibility in primary cytarabine resistant AML blasts.

  4. Effects of epidermal growth factor and platelet-derived growth factor on c-fos and c-myc mRNA levels in normal human fibroblasts

    International Nuclear Information System (INIS)

    The mRNA levels of two proto-oncogenes, c-fos and c-myc, were determined in human foreskin fibroblasts exposed to epidermal growth factor (EGF) or platelet-derived growth factor (PDGF) in a serum-free, defined medium (MCDB 104). Untreated, quiescent cells were found to have low or undetectable levels of c-fos and c-myc mRNA. Within 10 min after the addition of EGF or PDGF the c-fos mRNA level increased, reached a peak at 30 min, and then declined to the control level after 60 min. The level of c-myc mRNA increased somewhat later and peaked after 8 h in cultures treated with either of the growth factors. The c-myc mRNA level remained elevated throughout the 24 h of investigation. The concentrations of EGF and PDGF required for a maximal effect on c-fos or c-myc expression were found to be similar to those that give maximal effect on cell proliferation. Both c-fos and c-myc mRNA expression were superinduced by the addition of cycloheximide. The present results conform to the view that the c-fos and c-myc proto-oncogenes may be important (or necessary) but not sufficient for the initiation of DNA synthesis. Moreover, the finding that both EGF and PDGF increase c-fos and c-myc expression supports the previous suggestion that these two growth factors may in part act via a common intracellular pathway in the prereplicative phase of human fibroblasts

  5. Activation of a Novel c-Myc-miR27-Prohibitin 1 Circuitry in Cholestatic Liver Injury Inhibits Glutathione Synthesis in Mice

    OpenAIRE

    YANG, Heping; Li, Tony W. H.; Zhou, Yu; Peng, Hui; Liu, Ting; Zandi, Ebrahim; Martínez-Chantar, María Luz; Mato, José M.; Lu, Shelly C.

    2015-01-01

    Aims: We showed that chronic cholestatic liver injury induced the expression of c-Myc but suppressed that of glutamate-cysteine ligase (GCL, composed of catalytic and modifier subunits GCLC and GCLM, respectively). This was associated with reduced nuclear antioxidant response element (ARE) binding by nuclear factor-erythroid 2 related factor 2 (Nrf2). Here, we examined whether c-Myc is involved in this process. Results: Similar to bile duct ligation (BDL), lithocholic acid (LCA) treatment in ...

  6. Down-regulation of Thanatos-associated protein 11 by BCR-ABL promotes CML cell proliferation through c-Myc expression.

    Science.gov (United States)

    Nakamura, Satoki; Yokota, Daisuke; Tan, Lin; Nagata, Yasuyuki; Takemura, Tomonari; Hirano, Isao; Shigeno, Kazuyuki; Shibata, Kiyoshi; Fujisawa, Shinya; Ohnishi, Kazunori

    2012-03-01

    Bcr-Abl activates various signaling pathways in chronic myelogenous leukemia (CML) cells. The proliferation of Bcr-Abl transformed cells is promoted by c-Myc through the activation of Akt, JAK2 and NF-κB. However, the mechanism by which c-Myc regulates CML cell proliferation is unclear. In our study, we investigated the role of Thanatos-associated protein 11 (THAP11), which inhibits c-Myc transcription, in CML cell lines and in hematopoietic progenitor cells derived from CML patients. The induction of THAP11 expression by Abl kinase inhibitors in CML cell lines and in CML-derived hematopoietic progenitor cells resulted in the suppression of c-Myc. In addition, over-expression of THAP11 inhibited CML cell proliferation. In colony forming cells derived from CML-aldehyde dehydrogenase (ALDH)(hi) /CD34(+) cells, treatment with Abl kinase inhibitors and siRNA depletion of Bcr-Abl induced THAP11 expression and reduced c-Myc expression, resulting in inhibited colony formation. Moreover, overexpression of THAP11 significantly decreased the colony numbers, and also inhibited the expression of c-myc target genes such as Cyclin D1, ODC and induced the expression of p21(Cip1) . The depletion of THAP11 inhibited JAK2 or STAT5 inactivation-mediated c-Myc reduction in ALDH(hi) /CD34(+) CML cells. Thus, the induced THAP11 might be one of transcriptional regulators of c-Myc expression in CML cell. Therefore, the induction of THAP11 has a potential possibility as a target for the inhibition of CML cell proliferation. PMID:21400515

  7. Self-assembly of c-myc DNA promoted by a single enantiomer ruthenium complex as a potential nuclear targeting gene carrier

    Science.gov (United States)

    Wu, Qiong; Mei, Wenjie; Zheng, Kangdi; Ding, Yang

    2016-01-01

    Gene therapy has long been limited in the clinic, due in part to the lack of safety and efficacy of the gene carrier. Herein, a single enantiomer ruthenium(II) complex, Λ-[Ru(bpy)2(p-BEPIP)](ClO4)2 (Λ-RM0627, bpy = 4,4′-bipyridine, p-BEPIP = 2-(4-phenylacetylenephenyl)imidazole [4,5f][1, 10] phenanthroline), has been synthesized and investigated as a potential gene carrier that targets the nucleus. In this report, it is shown that Λ-RM0627 promotes self-assembly of c-myc DNA to form a nanowire structure. Further studies showed that the nano-assembly of c-myc DNA that induced Λ-RM0627 could be efficiently taken up and enriched in the nuclei of HepG2 cells. After treatment of the nano-assembly of c-myc DNA with Λ-RM0627, over-expression of c-myc in HepG2 cells was observed. In summary, Λ-RM0627 played a key role in the transfer and release of c-myc into cells, which strongly indicates Λ-RM0627 as a potent carrier of c-myc DNA that targets the nucleus of tumor cells. PMID:27381008

  8. Three-dimensional imaging of the metabolic state of c-MYC-induced mammary tumor with the cryo-imager

    Science.gov (United States)

    Zhang, Zhihong; Liu, Qian; Luo, Qingming; Zhang, Min Z.; Blessington, Dana M.; Zhou, Lanlan; Chodosh, Lewis A.; Zheng, Gang; Chance, Britton

    2003-07-01

    This study imaged the metabolic state of a growing tumor and the relationship between energy metabolism and the ability of glucose uptake in whole tumor tissue with cryo-imaging at 77° K. A MTB/TOM mouse model, bearing c-MYC-induced mammary tumor, was very rapidly freeze-trapped 2 hrs post Pyro-2DG injection. The fluorescence signals of oxidized flavoprotein (Fp), reduced pyridine nucleotide (PN), pyro-2DG, and the reflection signal of deoxy-hemoglobin were imaged every 100 μm from the top surface to the bottom of the tumor sequentially, 9 sections in total. Each of the four signals was constructed into 3D images with Amira software. Both Fp and PN signals could be detected in the growing tumor regions, and a higher reduction state where was shown in the ratio images. The necrotic tumor regions displayed a very strong Fp signal and weak PN signal. In the bloody extravasation regions, Fp and PN signals were observably diminished. Therefore, the regions of high growth and necrosis in the tumor could be determined according to the Fp and PN signals. The content of deoxy-hemoglobin (Hb) in the tumor was positively correlated with the reduced PN signal. Pyro-2DG signal was only evident in the growing condition region in the tumor. Normalized 3D cross-correlation showed that Pyro-2DG signal was similar to the redox ratio. The results indicated that glucose uptake in the tumor was consistent with the redox state of the tumor. And both Pyro-2DG and mitochondrial NADH fluorescence showed bimodal histograms suggesting that the two population of c-MYC induced mammary tumor, one of which could be controlled by c-MYC transgene.

  9. Chromosomal breakpoints and structural alterations of the c-myc locus differ in endemic and sporadic forms of Burkitt lymphoma.

    OpenAIRE

    Pelicci, P.G.; Knowles, D M; Magrath, I; Dalla-Favera, R

    1986-01-01

    We have examined the position of the chromosomal breakpoint relative to the human c-myc gene (MYC) and the presence of other structural alterations of the same locus in 19 fresh samples of Burkitt lymphoma (BL) and 13 BL-derived cell lines. This panel includes the two pathogenetic forms of BL: the endemic (African-type) BL (eBL) and sporadic (American-type) BL (sBL). In all cases tested, including fresh samples and cell lines, structural alterations of the 5' portion of the gene were detected...

  10. Sleeping Beauty transposon system harboring HRAS, c-Myc and shp53 induces sarcomatoid carcinomas in mouse skin

    Science.gov (United States)

    JUNG, SUNYOUNG; RO, SIMON WEONSANG; JUNG, GEUNYOUNG; JU, HYE-LIM; YU, EUN-SIL; SON, WOO-CHAN

    2013-01-01

    The Sleeping Beauty transposon system is used as a tool for insertional mutagenesis and oncogenesis. However, little is known about the exact histological phenotype of the tumors induced. Thus, we used immunohistochemical markers to enable histological identification of the type of tumor induced by subcutaneous injection of the HRAS, c-Myc and shp53 oncogenes in female C57BL/6 mice. The tumor was removed when it reached 100 mm3 in volume. Subsequently, we used 13 immunohistochemical markers to histologically identify the tumor type. The results suggested that the morphology of the tumor was similar to that of sarcomatoid carcinoma. PMID:23380875

  11. The FUSE binding proteins FBP1 and FBP3 are potential c-myc regulators in renal, but not in prostate and bladder cancer

    International Nuclear Information System (INIS)

    The three far-upstream element (FUSE) binding proteins (FBP1, FBP2, and FBP3) belong to an ancient family of single-stranded DNA binding proteins which are required for proper regulation of the c-myc proto-oncogene. Whereas it is known that c-myc alterations play a completely different role in various carcinomas of the urogenital tract, the relevance of FBPs is unclear. FBP1, FBP3 and c-myc expression was studied in 105 renal cell, 95 prostate and 112 urinary bladder carcinomas by immunohistochemistry using tissue microarrays. High rates of FBP1 and FBP3 expression were observed in all cancer types. There was a concomitant up-regulation of FBP1 and FBP3 in renal cell and prostate carcinomas (p < 0.001 both). C-myc expression was detectable in 21% of prostate, 30% of renal and 34% of urothelial carcinomas. Interestingly, strong FBP1 and FBP3 expression was associated with c-myc up-regulation in clear cell renal cell carcinomas (p < 0.001 and 0.09 resp.), but not in bladder or prostate cancer. The correlation between FBP1/FBP3, c-myc and high proliferation rate in renal cell carcinoma provides strong in vivo support for the suggested role of FBP1 and FBP3 as activators of c-myc. The frequent up-regulation of FBP1 and FBP3 in urothelial and prostate carcinoma suggests that FBPs also have an important function in gene regulation of these tumors

  12. In vivo distribution of c-myc antisense oligodeoxynucleotides local delivered by gelatin-coated platinmn-iridium stents in rabbits and its effect on apoptosis

    Institute of Scientific and Technical Information of China (English)

    张新霞; 崔长琮; 许香广; 胡雪松; 方卫华; 邝碧娟

    2004-01-01

    Background Post-stenting restenosis is a significant clinical problem, involving vascular smooth muscle cells(VSMCs) proliferation and apoptosis. It is reported that c-myc antisense oligodeoxynucleotides (ASODNs) local delivered by catheter can inhibit VSMCs proliferation. This study was designed to assess tissue distribution of c-myc ASODN local delivered using gelatin-coated platinum-iridium (Pt-Ir) stents, and its effect on apoptosis of VSMCs. Methods Gelatin-coated Pt-Ir stents that had absorbed caroboxyfluorescein-5-succimidyl ester (FAM) labeled c-myc ASODNs (550 μg per stent) were implanted into the right carotid arteries of 6 rabbits. Tissue samples were obtained at 45 minutes, 2 hours, and 6 hours. Tissue distribution of c- myc ASODNs was assessed by fluorescence microscopy. In addition, 32 rabbits were randomly divided into two groups. Rabbits in the control group (n=16) were implanted with gelatin-coated Pt-Ir stents, and those in the treatment group (n=16) were implanted with gelatin-coated stents that had absorbed c-myc ASODNs. 7, 14, 30, or 90 days (n=4, respectively, for each group) after the stenting procedure, the stented segments were harvested, and histopathological examinations were performed to calculate neointimal area and mean neointimal thickness. The expression of c-myc was assessed using in situ hybridization (ISH) and immunohistochemical methods. Apoptotic VSMCs were detected using terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and transmission electron microscope (TEM). Results According to fluorescence microscopic results, FAM-labeled c-myc ASODNs were concentrated in the target vessel media at the 45 minutes time point, and then dispersed to the adventitia. Morphometric analysis showed that neointimal area and mean neointimal thickness increased continuously up to 90 days after stent implantation, but that total neointimal area and mean neointimal thickness were less in the treatment group than in the

  13. Involvement of SIRT1 in hypoxic down-regulation of c-Myc and β-catenin and hypoxic preconditioning effect of polyphenols

    International Nuclear Information System (INIS)

    SIRT1 has been found to function as a Class III deacetylase that affects the acetylation status of histones and other important cellular nonhistone proteins involved in various cellular pathways including stress responses and apoptosis. In this study, we investigated the role of SIRT1 signaling in the hypoxic down-regulations of c-Myc and β-catenin and hypoxic preconditioning effect of the red wine polyphenols such as piceatannol, myricetin, quercetin and resveratrol. We found that the expression of SIRT1 was significantly increased in hypoxia-exposed or hypoxic preconditioned HepG2 cells, which was closely associated with the up-regulation of HIF-1α and down-regulation of c-Myc and β-catenin expression via deacetylation of these proteins. In addition, blockade of SIRT1 activation using siRNA or amurensin G, a new potent SIRT1 inhibitor, abolished hypoxia-induced HIF-1α expression but increased c-Myc and β-catenin expression. SIRT1 was also found to stabilize HIF-1α protein and destabilize c-Myc, β-catenin and PHD2 under hypoxia. We also found that myricetin, quercetin, piceatannol and resveratrol up-regulated HIF-1α and down-regulated c-Myc, PHD2 and β-catenin expressions via SIRT1 activation, in a manner that mimics hypoxic preconditioning. This study provides new insights of the molecular mechanisms of hypoxic preconditioning and suggests that polyphenolic SIRT1 activators could be used to mimic hypoxic/ischemic preconditioning. -- Graphical abstract: Polyphenols mimicked hypoxic preconditioning by up-regulating HIF-1α and SIRT1 and down-regulating c-Myc, PHD2, and β-catenin. HepG2 cells were pretreated with the indicated doses of myricetin (MYR; A), quercetin (QUR; B), or piceatannol (PIC; C) for 4 h and then exposed to hypoxia for 4 h. Levels of HIF-1α, SIRT1, c-Myc, β-catenin, and PHD2 were determined by western blot analysis. The data are representative of three individual experiments. Highlights: ► SIRT1 expression is increased in hypoxia

  14. Involvement of SIRT1 in hypoxic down-regulation of c-Myc and β-catenin and hypoxic preconditioning effect of polyphenols

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Kyung-Soo [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Park, Jun-Ik [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Kim, Mi-Ju; Kim, Hak-Bong; Lee, Jae-Won [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Dao, Trong Tuan; Oh, Won Keun [BK21 Project Team, College of Pharmacy, Chosun University, Gwangju (Korea, Republic of); Kang, Chi-Dug, E-mail: kcdshbw@pusan.ac.kr [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Kim, Sun-Hee, E-mail: ksh7738@pusan.ac.kr [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of)

    2012-03-01

    SIRT1 has been found to function as a Class III deacetylase that affects the acetylation status of histones and other important cellular nonhistone proteins involved in various cellular pathways including stress responses and apoptosis. In this study, we investigated the role of SIRT1 signaling in the hypoxic down-regulations of c-Myc and β-catenin and hypoxic preconditioning effect of the red wine polyphenols such as piceatannol, myricetin, quercetin and resveratrol. We found that the expression of SIRT1 was significantly increased in hypoxia-exposed or hypoxic preconditioned HepG2 cells, which was closely associated with the up-regulation of HIF-1α and down-regulation of c-Myc and β-catenin expression via deacetylation of these proteins. In addition, blockade of SIRT1 activation using siRNA or amurensin G, a new potent SIRT1 inhibitor, abolished hypoxia-induced HIF-1α expression but increased c-Myc and β-catenin expression. SIRT1 was also found to stabilize HIF-1α protein and destabilize c-Myc, β-catenin and PHD2 under hypoxia. We also found that myricetin, quercetin, piceatannol and resveratrol up-regulated HIF-1α and down-regulated c-Myc, PHD2 and β-catenin expressions via SIRT1 activation, in a manner that mimics hypoxic preconditioning. This study provides new insights of the molecular mechanisms of hypoxic preconditioning and suggests that polyphenolic SIRT1 activators could be used to mimic hypoxic/ischemic preconditioning. -- Graphical abstract: Polyphenols mimicked hypoxic preconditioning by up-regulating HIF-1α and SIRT1 and down-regulating c-Myc, PHD2, and β-catenin. HepG2 cells were pretreated with the indicated doses of myricetin (MYR; A), quercetin (QUR; B), or piceatannol (PIC; C) for 4 h and then exposed to hypoxia for 4 h. Levels of HIF-1α, SIRT1, c-Myc, β-catenin, and PHD2 were determined by western blot analysis. The data are representative of three individual experiments. Highlights: ► SIRT1 expression is increased in hypoxia

  15. Expression of telomerase hTERT in human non-small cell lung cancer and its correlation with c-myc gene

    Institute of Scientific and Technical Information of China (English)

    耿志华; 张敦华; 刘银坤

    2003-01-01

    Objective To investigate the expression of human telomerase catalytic subunit, hTERT, in human non-small cell lung cancer (NSCLC) and its correlations to c-myc gene.Methods hTERT and c-myc mRNA expressions were detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Statistical correlation analysis was made to estimate whether there was interrelation between them.Results Positive rate of hTERT expression in 51 surgically resected lung cancer specimens was 86.3%, significantly higher than that in adjacent non-neoplastic lung tissues and benign lesions, which were 14.3% and 27.3% respectively. No statistical significance was observed between the frequency of hTERT expression and histologic types, degree of differentiation, TNM stages, tumor size or lymph nodes metastases. Correlation analysis revealed that the expression of c-myc gene was significantly related to that of hTERT (correlation coefficient, r=0.633, P<0.001).Conclusions hTERT may be a useful tumor marker in diagnosing lung cancer. Significant correlation between the expression of hTERT and c-myc mRNA indicates that the activation and up-regulation of hTERT might be conferred by over-expression of c-myc gene.

  16. Local Delivery of C-myc Antisense Oligodeoxynucleotide by Gelatin Coated Platinium-Iridium Stent to Prevent Restenosis in a Normal Rabbit Carotid Artery

    Institute of Scientific and Technical Information of China (English)

    Zhang Xinxia; Wei Wenbin; Duan Wen; Xu Xiangguang; Hu Xuesong

    2005-01-01

    Objectives To investigate the feasibility and effect of local deliveryof c-myc antisense oligodeoxynucleotide (ASODN) by gelatin coated Platinium-Iridium stent to prevent restenosis in a normal rabbit carotid artery. Methods Gelatin coated Platinium-Iridium stent were implanted in the right carotid arteries of 32 rabbits under vision. Animals were randomized to the control group and the treated group receiving c-myc ASODN (n=16 respectively).7,14,30,90 days following the stenting procedure,morphometry for caculation of neointimal area and mean neointimal thickness were performed.The expression of c-myc protein was detected by immunohistochemical methods. Results 32 stents were successfully implanted into the right carotid arteries in 32 animals. Morphometric analysis showed that neointimal area and mean neointimal thickness siginificantly increased continuously up to 12 weeks after stent implantation,and at each time point ,neointimal area and mean neointimal thickness were siginificantly smaller in the treated group than control group. (P<0.001 ,respectively).c-myc protein expression was weak positive or negative in treated group and positive in control group. Conclusions Gelatin coated Platinium-Iridium stent mediated local delivery of c-myc ASODN is feasibility , and it can inhibit neointimal hyperplasia to prevent restenosis in a normal rabbit carotid artery.

  17. Farnesiferol c induces apoptosis via regulation of L11 and c-Myc with combinational potential with anticancer drugs in non-small-cell lung cancers.

    Science.gov (United States)

    Jung, Ji Hoon; Kim, Moon Joon; Lee, Hyemin; Lee, Jihyun; Kim, Jaekwang; Lee, Hyun Joo; Shin, Eun Ah; Kim, Yoon Hyeon; Kim, Bonglee; Shim, Bum Sang; Kim, Sung-Hoon

    2016-01-01

    Though Farnesiferol c (FC) has been reported to have anti-angiogenic and antitumor activity, the underlying antitumor mechanism of FC still remains unclear. Thus, in the present study, we investigated the apoptotic mechanism of FC in human H1299 and H596 non-small lung cancer cells (NSCLCs). FC significantly showed cytotoxicity, increased sub-G1 accumulation, and attenuated the expression of Bcl-2, Bcl-xL, Survivin and procaspase 3 in H1299 and H596 cells. Furthermore, FC effectively suppressed the mRNA expression of G1 arrest related genes such as Cyclin D1, E2F1 transcription factor and CDC25A by RT-PCR. Interestingly, FC inhibited the expression of c-Myc, ribosomal protein L11 (L11) and nucleolin (NCL) in H1299 and H596 cells. Of note, silencing of L11 by siRNA transfection enhanced the expression of c-Myc through a negative feedback mechanism, while c-Myc knockdown downregulated L11 in H1299 cells. Additionally, combined treatment of FC and puromycin/doxorubicin promoted the activation of caspase 9/3, and attenuated the expression of c-Myc, Cyclin D1 and CDK4 in H1299 cells compared to single treatment. Taken together, our findings suggest that FC induces apoptosis and G1 arrest via regulation of ribosomal protein L11 and c-Myc and also enhances antitumor effect of puromycin or doxorubicin in NSCLCs. PMID:27231235

  18. Expressions of beta-catenin, APC Protein, C-myc and Cyclin D1 in Ovarian Epithelial Tumor and Their Implication

    Institute of Scientific and Technical Information of China (English)

    LIN Xiao; LI Yu; MI Can

    2007-01-01

    Objective: To investigate the expressions of beta-catenin, protein APC (adenomatous polyposis coli protein), c-myc and cyclin D1 and their implication in ovarian epithelial tumor. Methods: Immunohistochemical staining with SP method was conducted to identify the expressions of beta-catenin, APC protein, c-myc and cyclin D1 in ovarian epithelial tumor in 48 cases. Results: The abnormal expression rate of beta-catenin in malignant and borderline ovarian epithelial tumors was higher than that in benign epithelial tumors (P<0.01). The expression rates of c-myc and cyclin-D1 in ovarian malignant and borderline epithelial tumors were higher than those in benign epithelial tumors too(P<0.05). The prevalence of APC protein positive expression in benign epithelial tumors were significantly greater than that in malignant epithelial tumors (P<0.05). A significant negative correlation was found between beta-catenin and APC protein in ovarian epithelial tumors; while a significant positive correlation was found between beta-catenin, c-myc and cyclin-D1 in ovarian epithelial tumor (P<0.05). Conclusion: The abnormal expressions of Beta-catenin, APC protein, c-myc and cyclin-D1 might be used to indicate the malignance transform of ovarian epithelial tumors.

  19. Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice

    Directory of Open Access Journals (Sweden)

    Liao Dezhong J

    2008-01-01

    Full Text Available Abstract Background Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela-c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR. To further evaluate the relevance of some of the selected differentially expressed genes, we investigated their expression pattern in human pancreatic cancer cell lines with high and low metastatic potentials. Results Data indicate that genes involved in posttranscriptional regulation were a major functional category of upregulated genes in both primary pancreatic tumors (PT and liver metastatic lesions (LM compared to normal pancreas (NP. In particular, differential expression for splicing factors, RNA binding/pre-mRNA processing factors and spliceosome related genes were observed, indicating that RNA processing and editing related events may play critical roles in pancreatic tumor development and progression. High expression of insulin growth factor binding protein-1 (Igfbp1 and Serine proteinase inhibitor A1 (Serpina1, and low levels or absence of Wt1 gene expression were exclusive to liver metastatic lesion samples. Conclusion We identified Igfbp1, Serpina1 and Wt1 genes that are likely to be clinically useful biomarkers for prognostic or therapeutic purposes in metastatic pancreatic cancer, particularly in pancreatic cancer where c-Myc is overexpressed.

  20. SALL4 as an Epithelial-Mesenchymal Transition and Drug Resistance Inducer through the Regulation of c-Myc in Endometrial Cancer.

    Directory of Open Access Journals (Sweden)

    Lei Liu

    Full Text Available SALL4 plays important roles in the development and progression of many cancers. However, the role and molecular mechanism of SALL4 in endometrial cancer remain elusive. In the present research, we have demonstrated that the expression of SALL4 was upregulated in endometrial cancer and correlated positively with tumor stage, metastases and poor survival of patients. The overexpression of SALL4 promoted the invasiveness in endometrial cancer cells, as indicated by the upregulation of mesenchymal cell marker N-cadherin and downregulation of the epithelial marker E-cadherin, and invasion assays in vitro. Additionally, there was also an increase in drug resistance in these cell models due to the upregulation of ATP-binding cassette multidrug transporter ABCB1 expression. Moreover, we also found that ABCB1 was critical for SALL4-induced drug resistance. In contrast, SALL4 knockdown restored drug sensitivity, reversed EMT, diminished cell metastasis and suppressed the downregulation of E-cadherin and the upregulation of N-cadherin and ABCB1. Furthermore, we showed that SALL4 upregulated c-Myc expression and c-Myc was a direct target for SALL4 by ChIP assay, depletion of c-Myc with siRNA abolished the SALL4-induced downregulation of E-cadherin, upregulation of N-cadherin and ABCB1, suggesting that c-Myc was a downstream target for SALL4 and required for SALL4-induced EMT, invasion and drugs resistance in endometrial cancer cells. These results indicated that SALL4 could induce EMT and resistance to antineoplastic drugs through the regulation of c-Myc. SALL4 and c-Myc may be novel therapeutic targets for endometrial cancer.

  1. Detection of HER-2/neu, c-myc amplification and p53 inactivation by FISH in Egyptian patients with breast cancer

    Directory of Open Access Journals (Sweden)

    Mohamed, Hanaa M.

    2009-05-01

    Full Text Available Breast cancer is a leading cause of cancer-related deaths in women worldwide. The clinical course of this disease is highly variable and clinicians continuously search for prognostic parameters that can accurately predict prognosis, and indicate a suitable adjuvant therapy for each patient. Amplification of the two oncogenes HER-2/neu and c-myc and inactivation of the tumor suppressor gene p53 are frequently encountered in breast carcinomas. The purpose of this study was to use the fluorescence in situ hybridization (FISH for the assessment of HER-2/neu and c-myc amplification and p53 inactivation and to relate these molecular markers with the commonly used clinical and pathological factors. The study was conducted on 34 tissue samples obtained from 33 females and 1 male with breast carcinomas and 17 samples obtained from 16 females and 1 male with benign breast lesions. Results revealed that the level of HER-2/neu, c-myc and p53 in the malignant group was significantly increased as compared to the benign group. On relating the level of the molecular markers to clinicopathological factors, p53 was significantly associated with increased patient’s age. The sensitivity of the investigated markers significantly increased with larger tumor size. Concerning tumor grade, HER-2/neu and p53 showed a significant increase in low-grade tumors whereas c-myc showed a highly significant increase in high-grade tumors. With regard to disease staging, HER-2/neu and c-myc were the only markers that showed significant increase at late stages of disease. p53 and HER-2/neu were significantly associated with positive lymph nodal status. A significant correlation was obtained between the levels of the three biomarkers to each other. Conclusively, the combination of HER-2/neu, c-myc and p53 can stratify patients into different risk groups.

  2. Detection of HER-2/neu, c-myc amplification and p53 inactivation by FISH in Egyptian patients with breast cancer.

    Science.gov (United States)

    Ismail, Manal F; Aly, Magdy Sayed; Khaled, Hussein M; Mohamed, Hanaa M

    2009-01-01

    Breast cancer is a leading cause of cancer-related deaths in women worldwide. The clinical course of this disease is highly variable and clinicians continuously search for prognostic parameters that can accurately predict prognosis, and indicate a suitable adjuvant therapy for each patient. Amplification of the two oncogenes HER-2/neu and c-myc and inactivation of the tumor suppressor gene p53 are frequently encountered in breast carcinomas. The purpose of this study was to use the fluorescence in situ hybridization (FISH) for the assessment of HER-2/neu and c-myc amplification and p53 inactivation and to relate these molecular markers with the commonly used clinical and pathological factors. The study was conducted on 34 tissue samples obtained from 33 females and 1 male with breast carcinomas and 17 samples obtained from 16 females and 1 male with benign breast lesions. Results revealed that the level of HER-2/neu, c-myc and p53 in the malignant group was significantly increased as compared to the benign group. On relating the level of the molecular markers to clinicopathological factors, p53 was significantly associated with increased patient's age. The sensitivity of the investigated markers significantly increased with larger tumor size. Concerning tumor grade, HER-2/neu and p53 showed a significant increase in low-grade tumors whereas c-myc showed a highly significant increase in high-grade tumors. With regard to disease staging, HER-2/neu and c-myc were the only markers that showed significant increase at late stages of disease. p53 and HER-2/neu were significantly associated with positive lymph nodal status. A significant correlation was obtained between the levels of the three biomarkers to each other. Conclusively, the combination of HER-2/neu, c-myc and p53 can stratify patients into different risk groups. PMID:19675743

  3. DNA repair in the c-myc proto-oncogene locus: Possible involvement in susceptibility or resistance to plasmacytoma induction in BALB/c mice

    International Nuclear Information System (INIS)

    This report describes an unexpected difference in the efficiency of removal of UV-induced DNA damage in the c-myc locus in splenic B lymphoblasts from two inbred strains of mice. In cells from plasmacytoma-resistant DBA/2N mice, 35% of UV-induced damage in the regulatory and 5' flank of c-myc is removed by 12 h. However, in cells from plasmacytoma-susceptible BALB/cAn mice, damage is not removed from this region. In the protein-encoding region and 3' flank of c-myc as well as in two dihydrofolate reductase gene fragments, UV damage is repaired with similar efficiency in B lymphoblasts from both strains of mice. Furthermore, in the protein-encoding portion and 3' flank of c-myc, damage is selectively removed from only the transcribed strand. No repair is detected in the nontranscribed strand. In contrast, DNA repair in the 5' flank of c-myc is not strand specific; in DNA from DBA/2N cells, UV damage is rapidly removed from both the transcribed and nontranscribed strands. In BALB/cAn cells no repair was detected in either strand in the 5'flank, consistent with the results with double-stranded, nick-translated probes to this region of c-myc. In addition to the repair studies, we have detected post-UV-damage formation: in most of the genes studied, we find that additional T4 endonuclease-sensitive sites are formed in the DNA 2 h after irradiation. Our findings provide new insights into the details of gene-specific and strand-specific DNA repair and suggest that there may be close links between DNA repair and B-cell neoplastic development

  4. Identification of a c-Jun N-terminal kinase-2-dependent signal amplification cascade that regulates c-Myc levels in ras transformation

    DEFF Research Database (Denmark)

    Mathiasen, D.P.; Egebjerg, C.; Andersen, S.H.;

    2012-01-01

    Ras is one of the most frequently activated oncogenes in cancer. Two mitogen-activated protein kinases (MAPKs) are important for ras transformation: extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase 2 (JNK2). Here we present a downstream signal amplification cascade that is...... essential for ras transformation. Previous studies show that ERK-mediated serine 62 phosphorylation protects c-Myc from proteasomal degradation. ERK is, however, not alone sufficient to stabilize c-Myc but requires the cooperation of cancerous inhibitor of protein phosphatase 2A (CIP2A), an oncogene that...

  5. EFFECT OF HYPOXIA ON DNA SYNTHESIS AND C-MYC GENE EXPRESSION OF PULMONARY ARTERY SMOOTH MUSCLE CELLS

    Institute of Scientific and Technical Information of China (English)

    罗兰; 李世强; 蔡英年

    1996-01-01

    The neonate is particularly susceptible to the development of hypoxie pulmonary hypertension. The present study was undertaken to observe the effect of hypoxia on DNA synthesis and c-mye gene expressionbetween newborn calf and adult bovine PASMC in vitro DNA synthesis measured by 3H-TdR incorporation was increased after hypoxie challenge for 24h. Hypoxia enhanced the increment in 3H-TdR incorporationinduced by EGF. Northern blot analysis revealed that PASMC cultured in both normoxia and hypoxia expressed c-mye gene transcript of 2.2Kb ,but there is a higher 2.2Kb mRNA expression in hypoxie PASMC than that in normoxia. We speculate that newborn calf PASMC exhibited potential response to hypoxia than adult,which was augmented by EGF. Enhanced c-myc gene expression may lead to a great understanding of the mechanism of PASMC growth in the development of pulmonary hypertension.

  6. Nucleolus disassembly in mitosis and apoptosis: dynamic redistribution of phosphorylated-c-Myc, fibrillarin and Ki-67

    Directory of Open Access Journals (Sweden)

    C Soldani

    2009-06-01

    Full Text Available The nucleolus may undergo disassembly either reversibly during mitosis, or irreversibly in apoptosis, thus allowing the redistribution of the nucleolar proteins.We investigated here by immunocytochemistry the fate of three representative proteins, namely phosphorylated c-Myc, fibrillarin and Ki-67, and found that they behave independently in both processes: they relocate in distinct compartments during mitosis, whereas during apoptosis they may either be cleaved (Ki-67 or be extruded into the cytoplasm with a different kinetics and following an ordered, non chaotic program. The separation of these nucleolar proteins which occurs in early apoptotic nuclei continues also in the cytoplasm, and culminates in the final formation of apoptotic blebs containing different nucleolar proteins: this evidence confirms that the apoptotic bodies may be variable in size, content and surface reactivity, and include heterogeneous aggregates of nuclear proteins and/or nucleic acids.

  7. THE HEPARIN-BINDING DOMAIN AND V REGION OF FIBRONECTIN REGULATE APOPTOSIS BY SUPPRESSION OF P53 AND C-MYC IN HUMAN PRIMARY CELLS

    Science.gov (United States)

    In apoptosis the tumor suppressor p53 and oncogene c-myc, are usually upregulated. However, we report here an alternate pathway of regulation that is triggered by inflammatory-associated matrix fragments of fibronectin (FN) and leads to apoptosis. It is mediated by transcriptio...

  8. Suppression of RAD21 Induces Senescence of MDA-MB-231 Human Breast Cancer Cells Through RB1 Pathway Activation Via c-Myc Downregulation.

    Science.gov (United States)

    Zhu, Shan; Zhao, Li; Li, Yueyang; Hou, Pingfu; Yao, Ruosi; Tan, Jiang; Liu, Dongxu; Han, Liping; Huang, Baiqu; Lu, Jun; Zhang, Yu

    2016-06-01

    Cellular senescence impedes cancer progression by limiting uncontrolled cell proliferation. To identify new genetic events controlling senescence, we performed a small interfering RNA screening human cancer cells and identified a number of targets potentially involved in senescence of MDA-MB-231 human breast cancer cells. Importantly, we showed that knockdown of RAD21 resulted in the appearance of several senescent markers, including enhanced senescence-associated β-galactosidase activity and heterochromatin focus formation, as well as elevated p21 protein levels and RB1 pathway activation. Further biochemical analyses revealed that RAD21 knockdown led to the downregulation of c-Myc and its targets, including CDK4, a negative regulator of RB1, and blockedRB1 phosphorylation (pRB1), and the RB1-mediated transcriptional repression of E2F. Moreover, c-Myc downregulation was partially mediated by proteasome-dependent degradation within promyelocytic leukemia (PML) nuclear bodies, which were found to be highly abundant during RAD21 knockdown-induced senescence. Exogenous c-Myc reconstitution rescued cells from RAD21 silencing-induced senescence. Altogether, data arising from this study implicate a novel function of RAD21 in cellular senescence in MDA-MB-231 cells that is mainly dependent onRB1 pathway activation via c-Myc downregulation. J. Cell. Biochem. 117: 1359-1369, 2016. © 2015 Wiley Periodicals, Inc. PMID:26529363

  9. The intra-nucleus integration of mitochondrial DNA (mtDNAin cervical mucosa cells and its relation with c-myc expression

    Directory of Open Access Journals (Sweden)

    Xiang Jinying

    2008-09-01

    Full Text Available Abstract Objective To explore the relationship between the integration of mitochondrial DNA(mtDNA in the nuclei of cervical epithelium cells and the expression of c-myc. Methods The expression of c-myc protein was measured by immunohistochemical test in 40 cases of the uterine cervix cancer, 30 cases of cervical intraepithelial neoplasia (CIN and 30 cases of normal cervical epithelium; the sequence of mtDNA in the nuclei was detected by in situ hybridization technique. Results The detection rates of mtDNA in the nuclei of cervical epithelium cells were 27.5%, 13.3% and 0% in cervical carcinoma, CIN, and normal cervical epithelium respectively. The expression rate of c-myc in cervical mucoma cells was 67% in the mtDNA sequence positive group and was significantly higher than that in the negative group (36%. Conclusion The integration of mtDNA into the nuclei of cervical epithelium cells may be involved in the carcinogenesis of cervical epithelium cells and the expression of c-myc might be related to the integration of mtDNA sequence into nuclei of cervical epithelium cells.

  10. Triplex-forming oligonucleotides targeting c-MYC potentiate the anti-tumor activity of gemcitabine in a mouse model of human cancer.

    Science.gov (United States)

    Boulware, Stephen B; Christensen, Laura A; Thames, Howard; Coghlan, Lezlee; Vasquez, Karen M; Finch, Rick A

    2014-09-01

    Antimetabolite chemotherapy remains an essential cancer treatment modality, but often produces only marginal benefit due to the lack of tumor specificity, the development of drug resistance, and the refractoriness of slowly proliferating cells in solid tumors. Here, we report a novel strategy to circumvent the proliferation-dependence of traditional antimetabolite-based therapies. Triplex-forming oligonucleotides (TFOs) were used to target site-specific DNA damage to the human c-MYC oncogene, thereby inducing replication-independent, unscheduled DNA repair synthesis (UDS) preferentially in the TFO-targeted region. The TFO-directed UDS facilitated incorporation of the antimetabolite, gemcitabine (GEM), into the damaged oncogene, thereby potentiating the anti-tumor activity of GEM. Mice bearing COLO 320DM human colon cancer xenografts (containing amplified c-MYC) were treated with a TFO targeted to c-MYC in combination with GEM. Tumor growth inhibition produced by the combination was significantly greater than with either TFO or GEM alone. Specific TFO binding to the genomic c-MYC gene was demonstrated, and TFO-induced DNA damage was confirmed by NBS1 accumulation, supporting a mechanism of enhanced efficacy of GEM via TFO-targeted DNA damage-induced UDS. Thus, coupling antimetabolite chemotherapeutics with a strategy that facilitates selective targeting of cells containing amplification of cancer-relevant genes can improve their activity against solid tumors, while possibly minimizing host toxicity. PMID:23681918

  11. Labdane type diterpenes down-regulate the expression of c-Myc protein, but not of Bcl-2, in human leukemia T-cells undergoing apoptosis.

    Science.gov (United States)

    Dimas, K; Demetzos, C; Vaos, V; Ioannidis, P; Trangas, T

    2001-06-01

    Sclareol (1) and ent-3beta-hydroxy-13-epi-manoyl oxide (2) belong to the labdane type diterpenes. They were isolated from the leaves and from the fruits of Cistus creticus subsp. creticus, and were found to be active against human leukemic cell lines. Compound 2 was converted to its thiomidazolide derivative (3). Compounds 1 and 3 were found to induce apoptotic cell death in human T-cell leukemia lines and to interfere with their cell cycle, arresting cells at G(0/1) phase. Apoptosis can involve the activation and/or suppression of critical genes such as c-myc whose reduction or its inappropriate expression can be associated with induction of cell death and bcl-2 whose activation prevents apoptosis in the latter case. In order to detect any concomitant effect (1 and 3) upon c-myc and bcl-2 oncogene expression, we performed Western blot analysis to determine the levels of expression of these two genes upon treatment with the above compounds. Western blot analysis showed that of c-myc proto-oncogene levels were markedly reduced before massive apoptosis ensued in H33AJ-JA1 and MOLT3 cells, while bcl-2 expression remained unaffected. Thus, induction of apoptosis due to compounds 1 and 3 in these T-cell leukemic cell lines is preceded by c-myc down regulation and furthermore sustained bcl-2 expression does not rescue cells from apoptosis under the conditions used. PMID:11337016

  12. Effect of Neem Leaf Extract (Azadirachta indica on c-MycOncogene Expression in 4T1 Breast Cancer Cells of BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Chong Pei Pei

    2012-01-01

    Full Text Available Objective: Breast cancer is the most common cause of cancer-related deaths in women both worldwide and in Malaysia. Azadirachta indica (A. Juss, commonly known as neem, is one of the most versatile medicinal plants that has gained worldwide prominence due to its medicinal properties. However, the anticancer effect of ethanolic neem leaf extract against breast cancer has not been documented. The purpose of the present study is to investigate the effect of neem leaf extract on c-Myc oncogene expression in 4T1 breast cancer BALB/c mice.Materials and Methods: In this experimental study, A total of 48 female BALB/c mice were divided randomly into four groups of 12 mice per group: i.cancer control (CC treated with 0.5% Tween 20 in PBS, ii. 0.5 μg/mL tamoxifen citrate (CT, iii. 250 mg/kg neem leaf extract (C250, and iv. 500 mg/kg neem leaf extract (C500. In situ reverse transcription polymerase chain reaction (in situ RT-PCR was applied to evaluate suppression of c-Myc oncogene expression in breast cancer tissue.Results: The C500 group showed significant (p<0.05 suppression of c-Myc oncogene expression compared to the CC group.Conclusion: c-Myc was found to be down regulated under the effect of 500 mg/kg ethanolicneem leaf extract.

  13. Cooperation of c-raf-1 and c-myc protooncogenes in the neoplastic transformation of simian virus 40 large tumor antigen-immortalized human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Overexpression of c-raf-1 and the myc family of protooncogenes is primarily associated with small cell carcinoma, which accounts for ∼ 25% of human lung cancer. To determine the functional significance of the c-raf-1 and/or c-myc gene expression in lung carcinogenesis and to delineate the relationship between protooncogene expression and tumor phenotype, the authors introduced both protooncogenes, alone or in combination, into human bronchial epithelial cells. Two retroviral recombinants, pZip-raf and pZip-myc, containing the complete coding sequences of the human c-raf-1 and murine c-myc genes, respectively, were constructed and transfected into simian virus 40 large tumor antigen-immortalized bronchial epithelial cells (BEAS-2B); this was followed by selection for G418 resistance. Cell lines established from tumors (designated RMT) revealed the presence of the cotransfected c-raf-1 and c-myc sequences and expressed morphological, chromosomal, and isoenzyme markers, which identified BEAS-2B cells as the progenitor line of the tumors. The data demonstrate that the concomitant expression of the c-raf and c-myc protooncogenes causes neoplastic transformation of human bronchial epithelial cells resulting in large cell carcinomas with certain neuroendocrine markers. The presented model system should be useful in studies of molecular events involved in multistage lung carcinogenesis

  14. Generation of Genome Integration-free Induced Pluripotent Stem Cells from Fibroblasts of C57BL/6 Mice without c-Myc Transduction*

    Science.gov (United States)

    Jincho, Yuko; Araki, Ryoko; Hoki, Yuko; Tamura, Chihiro; Nakamura, Miki; Ando, Shunsuke; Kasama, Yasuji; Abe, Masumi

    2010-01-01

    Although the induction of genome integration-free induced pluripotent stem cells (iPSCs) has been reported, c-Myc was still required for the efficient generation of these cells. Herein, we report mouse strain-dependent differences in the c-Myc dependence for iPSC generation and the successful generation of genome integration-free iPSCs without c-Myc transduction using C57BL/6 mouse embryonic fibroblasts. We performed 49 independent experiments and obtained a total of 24 iPSC clones, including 18 genome integration-free iPSC clones. These iPSCs were indistinguishable from embryonic stem cells and from iPSCs generated using other methods. Furthermore, the generation of three-factor iPSCs free of virus vectors revealed the contribution of c-Myc to the genomic integration of external genes. C57BL/6 is an inbred mouse strain with substantial advantages for use in genetic and molecular biological studies due to its use in the whole mouse genome sequencing project. Thus, the present series of C57BL/6 iPSCs generated by various procedures will serve as a valuable resource for future genetic studies of iPSC generation. PMID:20554535

  15. EFFECT OF ACTIVE COMPOUNDS ISOLATED FROM PTERIS SEMIPINNATA L ON DNA TOPOISOMERASES AND TYROSINE PROTEIN KINASE AND EXPRESSION OF C-MYC IN LUNG ADENOCARCINOMA CELLS

    Institute of Scientific and Technical Information of China (English)

    李金华; 梁念慈; 莫丽儿; 张晓; 何承伟

    2001-01-01

    Objective: To study the effect of active compound 6F and A from Pteris semipinnata L.(PsL) on the activities of DNA topoisomerase (TOPO) I and II, activities of cytosolic and membrane TPK, and expression of oncogene c-myc in lung adenocarcinoma cells. Methods: The effect of compound 6F and A on activities of cytosolic and membrane TPK was measured by scintillation counting; the effect of compound A on expression of oncogene c-myc was determined by flow cytometry indirect fluorimetry. Results: compound 6F and A could inhibit the activities of TOPO I, and they strongly inhibited the TOPO II in 0.01 mg/L and 10.0 mg/L respectively. Compound A slightly inhibited the activities of membrane TPK, but not the cytosolic one. Compound A could inhibit the expression of oncogene c-myc. Conclusion: Topoisomerases are target of compound 6F and A. Compound A could slightly inhibit the activities of TPK, and showed an inhibitory effect on the expression of oncogene c-myc.

  16. DNA Damage, Apoptosis and C-myc, C-fos, and C-jun Overexpression Induced by Selenium in Rat Hepatocytes

    Institute of Scientific and Technical Information of China (English)

    RI-AN YU; CHENG-FENG YANG; XUE-MIN CHEN

    2006-01-01

    Objective To study the effects of selenium on DNA damage, apoptosis and c-myc, c-fos, and c-jun expression in rat hepatocytes. Methods Sodium selenite at the doses of 5, 10, and 20 μmol/kg was given to rats by i.p. and there were 5 male SD rats in each group. Hepatocellular DNA damage was detected by single cell gel electrophoresis (or comet assay).Hepatocellular apoptosis was determined by TUNEL (TdT-mediated dUTP nick end labelling) and flow cytometry. C-myc,c-fos, and c-jun expression in rat hepatocytes were assayed by Northern dot hybridization. C-myc, c-fos, and c-jun protein were detected by immunohistochemical method. Results At the doses of 5, 10, and 20 μmol/kg, DNA damage was induced by sodium selenite in rat hepatocytes and the rates of comet cells were 34.40%, 74.80%, and 91.40% respectively. Results also showed an obvious dose-response relationship between the rates of comet cells and the doses of sodium selenite (r=0.9501,P<0.01). Sodium selenite at the doses of 5, 10, and 20 μmol/kg caused c-myc, c-fos, and c-jun overexpression obviously. The positive brown-yellow signal for proteins of c-myc, c-fos, and c-jun was mainly located in the cytoplasm of hepatocytes with immunohistochemical method. TUNEL-positive cells were detected in selenium-treated rat livers. Apoptotic rates (%) of selenium-treated liver cells at the doses of 5, 10, and 20 μmol/kg were (3.72±1.76), (5.82±1.42), and (11.76±1.87) respectively, being much higher than those in the control. Besides an obvious dose-response relationship between apoptotic rates and the doses of sodium selenite (r=0.9897, P<0.01), these results displayed a close relationship between DNA damage rates and apoptotic rates, and the relative coefficient was 0.9021, P<0.01. Conclusion Selenium at 5-20 μmol/kg can induce DNA damage, apoptosis, and overexpression of c-myc, c-fos, and c-jun in rat hepatocytes.

  17. Pokemon、c-myc在结直肠癌中的表达及意义%EXPRESSION AND CLINICAL SIGNIFICANCE OF POKEMON AND C-MYC IN COLORECTAL CANCER

    Institute of Scientific and Technical Information of China (English)

    刘叔敏; 范玉磊; 梁婷婷; 孙影

    2014-01-01

    Objective: To investigate the expression and clinical significance of Pokemon and c-myc in human colorectal cancer.Methods: SP immunohistochemical staining was used to detect the expression of Pokemon and c-myc in 60 cases colorectal cancer and matched para-carcinoma tissues.Results:The positive expression rate of Pokemon and c-myc in colorectal cancer were obviously higher than that in normal tissue (P<0.01). In colorectal cancer, the positive expression of Pokemon and c-myc were related with differentiation degree, Dukes stage and lymph node metastasis (P<0.01,P<0.05). The positive expression of Pokemon in colorectal cancer was positively correlated with c-myc expression (r=0.615,P<0.05). Conclusions: Pokemon and c-myc have certain value for diagnosing and prognosis of colorectal cancer.%目的:探讨结直肠癌组织Pokemon和c-myc蛋白表达的变化和意义。方法:SP免疫组化法检测60例结直肠癌组织和癌旁正常组织Pokemon和c-myc蛋白的表达情况。结果:结直肠癌组织Pokemon和c-myc蛋白的阳性表达率均明显高于正常组织(P<0.01);结直肠癌组织Pokemon和c-myc蛋白的阳性表达与分化程度、Dukes分期和淋巴结转移有关(P<0.01,P<0.05);结直肠癌组织中,Pokemon和c-myc蛋白的表达呈显著正相关(r=0.615,P<0.05)。结论:Pokemon和c-myc对结直肠癌的诊断和预后评判具有一定的价值。

  18. The function of apoptosis and protein expression of bcl-2, p53 and C-myc inthe development of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    An Gao Xu; Shao Guang Li; Ji Hong Liu; Ai Hua Gan

    2000-01-01

    AIM To understand the rule and possible function of apoptosis and protein expression of bcl-2, p53 and C-myc in chronic gastritis, gastric ulcer, non-classic proliferation of gastric mucosa and gastric cancer.METHODS Apoptosis was detected by using in situ terminal labelling (TUNEL). The protein expression ofbcl-2, p53 and C-myc was detected by immunohistochemical method.RESULTS The indexes of apoptosis in chronic active gastritis, gastric ulcer, mild and severe non-classicproliferation of gastric mucosa, early and progressive gastric cancer were 16.8%±12.3%, 24.1%±20.0%,19.3%±16.4%, 15.7%±15.2%, 10.1%±9.1% and 6.3%±6.0%, respectively. The index of progressivegastric cancer was lower than that of early gastric cancer and non-classic proliferation of gastric mucosa(P<0.05). The positive rate of bcl-2 protein was 9.4%, 27.6%, 52.9%, 75.0%, 83.3% and 46.7%,respectively. The positive rate of bcl-2 of early gastric cancer was higher than that of progressive gastriccancer. The positive rates of p53 protein of severe non-classic proliferation, early and progressive gastriccancer were 25.0%, 33.3% and 63.3%, respectively. The positive rate of p53 of progressive gastric cancerwas higher than that of early gastric cancer and non-classic proliferation (P<0.05). In Lauren types, theindex of apoptosis, protein expression rates of bcl-2, p53 and C-myc of intestinal type were 8.3%±7.2%,38.9%, 77.7% and 56.6%, while that of diffuse type were 5.1%±4.9%, 58.3%, 50.0% and 8.3%,respectively. All markers had statistical difference between two types (P<0.05).CONCLUSION Apoptosis was inhibited stepwise in the development of non-classic proliferation of gastricmucosa to early gastric cancer and then to progressive gastric cancer. The high expression of bcl-2, p53 andC-myc was related to the development of gastric cancer, bcl-2 might play an important role in early gastriccancer while p53 and C-myc act mostly in middle and late stage gastric cancer. The Lauren typing of

  19. Critical B-lymphoid cell intrinsic role of endogenous MCL-1 in c-MYC-induced lymphomagenesis.

    Science.gov (United States)

    Grabow, S; Kelly, G L; Delbridge, A R D; Kelly, P N; Bouillet, P; Adams, J M; Strasser, A

    2016-01-01

    Evasion of apoptosis is critical for tumorigenesis, and sustained survival of nascent neoplastic cells may depend upon the endogenous levels of pro-survival BCL-2 family members. Indeed, previous studies using gene-targeted mice revealed that BCL-XL, but surprisingly not BCL-2, is critical for the development of c-MYC-induced pre-B/B lymphomas. However, it remains unclear whether another pro-survival BCL-2 relative contributes to their development. MCL-1 is an intriguing candidate, because it is required for cell survival during early B-lymphocyte differentiation. It is expressed abnormally high in several types of human B-cell lymphomas and is implicated in their resistance to chemotherapy. To test the B-cell intrinsic requirement for endogenous MCL-1 in lymphoma development, we conditionally deleted Mcl-1 in B-lymphoid cells of Eμ-Myc transgenic mice. We found that MCL-1 loss in early B-lymphoid progenitors delayed MYC-driven lymphomagenesis. Moreover, the lymphomas that arose when MCL-1 levels were diminished appeared to have been selected for reduced levels of BIM and/or increased levels of BCL-XL. These results underscore the importance of MCL-1 in lymphoma development and show that alterations in the levels of other cell death regulators can compensate for deficiencies in MCL-1 expression. PMID:26962682

  20. Nucleotide sequence 5′ of the chicken c-myc coding region: Localization of a noncoding exon that is absent from myc transcripts in most avian leukosis virus-induced lymphomas

    OpenAIRE

    1984-01-01

    We have determined the nucleotide sequence of the 2.2-kilobase-pair region upstream of the chicken c-myc coding exons. Using RNA blot analysis, we have localized a noncoding exon to a region that is separated from the c-myc coding sequences by an intron of 700-800 base pairs. In most avian leukosis virus-induced lymphomas proviral integration has occurred within, or downstream of, the first exon, thus presumably displacing the regulatory sequences that normally control c-myc expression. More ...

  1. c-myc, not her-2/neu, can predict the prognosis of breast cancer patients: how novel, how accurate, and how significant?

    International Nuclear Information System (INIS)

    The predictive and prognostic implication of oncogene amplification in breast cancer has received great attention in the past two decades. her-2/neu and c-myc are two oncogenes that are frequently amplified and overexpressed in breast carcinomas. Despite the extensive data on these oncogenes, their prognostic and predictive impact on breast cancer patients remains controversial. Schlotter and colleagues have recently suggested that c-myc, and not her-2/neu, could predict the recurrence and mortality of patients with node-negative breast carcinomas. Regardless of the promising results, caution should be exercised in the interpretation of data from studies assessing gene amplification without in situ analysis. We address the novelty, accuracy and clinical significance of the study by Schlotter and colleagues

  2. Mutations induced at the promoter region of the c-myc gene due to dual exposure to ionizing radiation and methyl nitroso urea

    International Nuclear Information System (INIS)

    Malignant tumors were arising from a sequence of events including mutation in proto-oncogenes and tumor suppressor genes.The accretion of these mutations is apparently facilitated by acquired or inherited defects inguardianmechanisms that maintain the integrity of the cellular genome. The proto-oncogene c-myc, which is frequently over expressed in tumors at the center of a transcription factor network, requlates cellular proliferation replicate potential, growth, differentiation and apoptosis. Expression of c-myc is down reglated during differentiation and is rapidly induced by a diverse catalog of mutagens including ionizing radiation and many alkylating agents. In the present study, the dual exposure to methyl nitroso urea(MNU) and ionizing radiation were assessed. These induced effects were assessed histopathologically and biochemically and were correlated at the molecular level by assessing single strand conformation polymorphism (SSCP)

  3. A Comparative Docking Strategy to Identify Polyphenolic Derivatives as Promising Antineoplastic Binders of G-quadruplex DNA c-myc and bcl-2 Sequences.

    Science.gov (United States)

    Costa, Giosuè; Rocca, Roberta; Moraca, Federica; Talarico, Carmine; Romeo, Isabella; Ortuso, Francesco; Alcaro, Stefano; Artese, Anna

    2016-09-01

    Polyphenols are compounds ubiquitously expressed in plants and used for their multiple healthy effects in humans as anti-inflammatory, antimicrobial, antiviral, anticancer and immunomodulatory agents. Due to their ability to modulate the activity of multiple targets involved in carcinogenesis, polyphenols can be employed to inhibit the growth of cancer cells. Several studies reported their high affinity to different G-quadruplex DNA structures, including the oncogene promoters c-myc and bcl-2. In this work we applied a structure-based virtual screening approach in order to screen a database of polyphenolic derivatives and human metabolites against both c-myc and bcl-2 DNA G-quadruplex structures. A Delphinidine derivative was identified as the best "dual" candidate and, after molecular dynamics simulations, resulted able to well stabilize both receptors. PMID:27546043

  4. In vivo MRS assessment of altered fatty acyl unsaturation in liver tumor formation of a TGFα/c-myc transgenic mouse model*

    OpenAIRE

    Griffitts, J.; Tesiram, Y.; Reid, G. E.; Saunders, D; Floyd, R A; Towner, R. A.

    2009-01-01

    Current detection methods (computed tomography, ultrasound, and MRI) for hepatocarcinogenesis in humans rely on visual confirmation of neoplastic formations. A more effective early detection method is needed. Using in vivo magnetic resonance spectroscopy (MRS), we show that alterations in the integral ratios of the bis-allyl to vinyl hydrogen protons in unsaturated lipid fatty acyl groups correlate with the development of neoplastic formations in vivo in a TGFα/c-myc mouse hepatocellular carc...

  5. Assessment of the effect of betaine on p16 and c-myc DNA methylation and mRNA expression in a chemical induced rat liver cancer model

    Directory of Open Access Journals (Sweden)

    Ling Wen-hua

    2009-07-01

    Full Text Available Abstract Background The development and progression of liver cancer may involve abnormal changes in DNA methylation, which lead to the activation of certain proto-oncogenes, such as c-myc, as well as the inactivation of certain tumor suppressors, such as p16. Betaine, as an active methyl-donor, maintains normal DNA methylation patterns. However, there are few investigations on the protective effect of betaine in hepatocarcinogenesis. Methods Four groups of rats were given diethylinitrosamine (DEN and fed with AIN-93G diets supplemented with 0, 10, 20 or 40 g betaine/kg (model, 1%, 2%, and 4% betaine, respectively, while the control group, received no DEN, fed with AIN-93G diet. Eight or 15 weeks later, the expression of p16 and c-myc mRNA was examined by Real-time PCR (Q-PCR. The DNA methylation status within the p16 and c-myc promoter was analyzed using methylation-specific PCR. Results Compared with the model group, numbers and areas of glutathione S-transferase placental form (GST-p-positive foci were decreased in the livers of the rats treated with betaine (P . Although the frequency of p16 promoter methylation in livers of the four DEN-fed groups appeared to increase, there is no difference among these groups after 8 or 15 weeks (P > 0.05. Betaine supplementation attenuated the down-regulation of p16 and inhibited the up-regulation of c-myc induced by DEN in a dose-dependent manner (P P . Finally, enhanced antioxidative capacity (T-AOC was observed in both the 2% and 4% betaine groups. Conclusion Our data suggest that betaine attenuates DEN-induced damage in rat liver and reverses DEN-induced changes in mRNA levels.

  6. Cytotoxic effect of γ-sitosterol from Kejibeling (Strobilanthes crispus and its mechanism of action towards c-myc gene expression and apoptotic pathway

    Directory of Open Access Journals (Sweden)

    Susi Endrini

    2015-01-01

    Full Text Available Background: This study aimed to analyze the cytotoxicity effect of γ-sitosterol isolated from “Kejibeling” (Strobilanthes crispus, a medicinal plant, on several cancer cell lines. The mechanisms of the effects were studied through the expression of cancer-caused gene, c-myc and apoptotic pathways.Methods: This in vitro study was done using human colon cancer cell lines (Caco-2, liver cancer cell lines (HepG2, hormone-dependent breast cancer cell lines (MCF-7 and the normal liver cell lines (Chang Liver. The cytotoxic effect was measured through MTT assay and the potential cytotoxic value was calculated by determining the toxic concentration which may kill up to 50% of the total cell used (IC50. Meanwhile, the cytotoxic mechanism was studied by determining the effect of adding γ-sitosterol to the c-myc gene expression by reverse transciptase-polymerase chain reaction (RT-PCR. The effect of γ-sitosterol through apoptotic pathway was studied by using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay.Results: γ-sitosterol was cytotoxic against Caco-2, HepG2, and MCF-7 with IC50-values of 8.3, 21.8, and 28.8 μg/mL, respectively. There were no IC50-values obtained from this compound against Chang Liver cell line. This compound induced apotosis on Caco-2 and HepG2 cell lines and suppressed the c-myc genes expression in both cells.Conclusion: γ-sitosterol was cytotoxic against colon and liver cancer cell lines and the effect was mediated by down-regulation of c-myc expression and induction of the apoptotic pathways.

  7. Growth inhibition and apoptosis induced by daunomycin-conjugated triplex-forming oligonucleotides targeting the c-myc gene in prostate cancer cells

    OpenAIRE

    Napoli, Sara; Negri, Umberto; Arcamone, Federico; Capobianco, Massimo L.; Giuseppina M. Carbone; Catapano, Carlo V

    2006-01-01

    Covalent attachment of intercalating agents to triplex-forming oligonucleotides (TFOs) is a promising strategy to enhance triplex stability and biological activity. We have explored the possibility to use the anticancer drug daunomycin as triplex stabilizing agent. Daunomycin-conjugated TFOs (dauno-TFOs) bind with high affinity and maintain the sequence-specificity required for targeting individual genes in the human genome. Here, we examined the effects of two dauno-TFOs targeting the c-myc ...

  8. Triplex-forming oligonucleotides targeting c-MYC potentiate the anti-tumor activity of gemcitabine in a mouse model of human cancer

    OpenAIRE

    Boulware, Stephen B.; Christensen, Laura A.; Thames, Howard; Coghlan, Lezlee; Vasquez, Karen M.; Finch, Rick A.

    2013-01-01

    Antimetabolite chemotherapy remains an essential cancer treatment modality, but often produces only marginal benefit due to the lack of tumor specificity, the development of drug resistance, and the refractoriness of slowly-proliferating cells in solid tumors. Here, we report a novel strategy to circumvent the proliferation-dependence of traditional antimetabolite-based therapies. Triplex-forming oligonucleotides (TFOs) were used to target site-specific DNA damage to the human c-MYC oncogene,...

  9. SirT1 knockdown potentiates radiation-induced bystander effect through promoting c-Myc activity and thus facilitating ROS accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Yuexia [Institute of Radiation Medicine, Fudan University, Shanghai (China); Central Laboratory, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China); Tu, Wenzhi; Zhang, Jianghong; He, Mingyuan; Ye, Shuang; Dong, Chen [Institute of Radiation Medicine, Fudan University, Shanghai (China); Shao, Chunlin, E-mail: clshao@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, Shanghai (China)

    2015-02-15

    Highlights: • γ-Irradiation induced bystander effects between hepatoma cells and hepatocyte cells. • SirT1 played a protective role in regulating this bystander effect. • SirT1 contributed to the protective effects via elimination the accumulation of ROS. • The activity of c-Myc is critical for maintaining the protective role of SirT1. - Abstract: Radiation-induced bystander effect (RIBE) has important implications for secondary cancer risk assessment during cancer radiotherapy, but the bystander signaling processes, especially under hypoxic condition, are still largely unclear. The present study found that micronuclei (MN) formation could be induced in the non-irradiated HL-7702 hepatocyte cells after being treated with the conditioned medium from irradiated hepatoma HepG2 and SK-Hep-1 cells under either normoxia or hypoxia. This bystander response was dramatically diminished or enhanced when the SirT1 gene of irradiated hepatoma cells was overexpressed or knocked down, respectively, especially under hypoxia. Meanwhile, SirT1 knockdown promoted transcriptional activity for c-Myc and facilitated ROS accumulation. But both of the increased bystander responses and ROS generation due to SirT1-knockdown were almost completely suppressed by c-Myc interference. Moreover, ROS scavenger effectively abolished the RIBE triggered by irradiated hepatoma cells even with SirT1 depletion. These findings provide new insights that SirT1 has a profound role in regulating RIBE where a c-Myc-dependent release of ROS may be involved.

  10. Assessment of the effect of betaine on p16 and c-myc DNA methylation and mRNA expression in a chemical induced rat liver cancer model

    International Nuclear Information System (INIS)

    The development and progression of liver cancer may involve abnormal changes in DNA methylation, which lead to the activation of certain proto-oncogenes, such as c-myc, as well as the inactivation of certain tumor suppressors, such as p16. Betaine, as an active methyl-donor, maintains normal DNA methylation patterns. However, there are few investigations on the protective effect of betaine in hepatocarcinogenesis. Four groups of rats were given diethylinitrosamine (DEN) and fed with AIN-93G diets supplemented with 0, 10, 20 or 40 g betaine/kg (model, 1%, 2%, and 4% betaine, respectively), while the control group, received no DEN, fed with AIN-93G diet. Eight or 15 weeks later, the expression of p16 and c-myc mRNA was examined by Real-time PCR (Q-PCR). The DNA methylation status within the p16 and c-myc promoter was analyzed using methylation-specific PCR. Compared with the model group, numbers and areas of glutathione S-transferase placental form (GST-p)-positive foci were decreased in the livers of the rats treated with betaine (P < 0.05). Although the frequency of p16 promoter methylation in livers of the four DEN-fed groups appeared to increase, there is no difference among these groups after 8 or 15 weeks (P > 0.05). Betaine supplementation attenuated the down-regulation of p16 and inhibited the up-regulation of c-myc induced by DEN in a dose-dependent manner (P < 0.01). Meanwhile, increases in levels of malondialdehyde (MDA) and glutathione S-transferase (GST) in model, 2% and 4% betaine groups were observed (P < 0.05). Finally, enhanced antioxidative capacity (T-AOC) was observed in both the 2% and 4% betaine groups. Our data suggest that betaine attenuates DEN-induced damage in rat liver and reverses DEN-induced changes in mRNA levels

  11. INCREASED EXPRESSION OF PDGF AND C-MYC GENES IN LUNGS AND PULMONARY ARTERIES OF PULMONARY HYPERTENSIVE RATS INDUCED BY HYPOXIA

    Institute of Scientific and Technical Information of China (English)

    蔡英年; 韩梅; 罗兰; 宋为; 周晓梅

    1996-01-01

    The role of growth factors and proto-oncogene in pulmonary vascular structural remodelling is not well known.The present study examined gene expression of plateler-derived growth factor(PDGF)-A and -B chain and proto-oncogene,c-myc,in lung tissue and pulmonary artery of rats exposed to hypoxia and compred to those levels of gene expression in normal rats.Normal lungs and pulmonary artery expressed PDGF-A chain transcripr of 1.7kb and PDGF-B chain transcript of 3.5 Kb. The c-myc transcript of 2.2 kb was expressed as well.After hypoxic exposure for 7 and 14 days mRNA levels of PDGF-B chain and c-myc were elevated significantly compared with those of control rats.PDGF-A chain mRNA increased after hypoxia for 7 days,and then declined.These results suggest that activation of sutocrine and /or paracrine is important in proliferation mechanism of pulmonary artery smooth muscle cells in bypoxic pulmonary hypertensive rats.

  12. Susceptibility of striatal neurons to excitotoxic injury correlates with basal levels of Bcl-2 and the induction of P53 and c-Myc immunoreactivity.

    Science.gov (United States)

    Liang, Zhong-Qin; Wang, Xiao-Xia; Wang, Yumei; Chuang, De-Maw; DiFiglia, Marian; Chase, Thomas N; Qin, Zheng-Hong

    2005-11-01

    The present studies evaluated the potential contribution of Bcl-2, p53, and c-Myc to the differential vulnerability of striatal neurons to the excitotoxin quinolinic acid (QA). In normal rat striatum, Bcl-2 immunoreactivity (Bcl-2-i) was most intense in large aspiny interneurons including choline acetyltransferase positive (CAT+) and parvalbumin positive (PARV+) neurons, but low in a majority of medium-sized neurons. In human brain, intense Bcl-2-i was seen in large striatal neurons but not in medium-sized spiny projection neurons. QA produced degeneration of numerous medium-sized neurons, but not those enriched in Bcl-2-i. Many Bcl-2-i-enriched interneurons including those with CAT+ and PARV+ survived QA injection, while medium-sized neurons labeled for calbindin D-28K (CAL D-28+) did not. In addition, proapoptotic proteins p53-i and c-Myc-i were robustly induced in medium-sized neurons, but not in most large neurons. The selective vulnerability of striatal medium spiny neurons to degeneration in a rodent model of Huntington's disease appears to correlate with their low levels of Bcl-2-i and high levels of induced p53-i and c-Myc-i. PMID:15922606

  13. Induction of C-FOS, C-MYC and P53 by β-adrenergic receptor (β-AR) stimulation of rat parotid acinar cells (RPAC)

    International Nuclear Information System (INIS)

    Treatment of rats with the β-agonist isoproterenol (ISO) results in dramatically increased parotid gland protein synthesis, processing and cell proliferation. The authors have shown that in RPAC in vitro, β-AR stimulation has similar effect on protein synthesis and processing. Proto-oncogenes have been implicated in growth regulation, differentiation and in mediating some extracellular stimulated events at the level of gene expression. To understand the regulation of cellular events after β-AR stimulation, the expression of c-fos, c-myc and p53 was investigated. RPAC were incubated with or without 10-5M ISO for 15, 30, 60 min. mRNA was isolated from cells and hybridization analysis was performed on nitrocellulose paper-transferred mRNA using 32P-labeled DNA probes. At early time points, the levels of c-fos gene activation in ISO-treated and control cells were comparable. After 60 min of ISO treatment, a sharp 20-30 fold induction of c-fos expression occurred. Similar increases in c-myc and p53 gene expression were observed after 60 min of ISO treatment. The authors data indicate that early effects of β-AR stimulation of RPAC include induction of c-fos, c-myc and p53 gene expression as well as enhanced protein synthesis and processing

  14. A novel rapid-onset high-penetrance plasmacytoma mouse model driven by deregulation of cMYC cooperating with KRAS12V in BALB/c mice

    International Nuclear Information System (INIS)

    Our goal is to develop a rapid and scalable system for functionally evaluating deregulated genes in multiple myeloma (MM). Here, we forcibly expressed human cMYC and KRAS12V in mouse T2 B cells (IgM+B220+CD38+IgD+) using retroviral transduction and transplanted these cells into lethally irradiated recipient mice. Recipients developed plasmacytomas with short onset (70 days) and high penetrance, whereas neither cMYC nor KRAS12V alone induced disease in recipient mice. Tumor cell morphology and cell surface biomarkers (CD138+B220−IgM−GFP+) indicate a plasma cell neoplasm. Gene set enrichment analysis further confirms that the tumor cells have a plasma cell gene expression signature. Plasmacytoma cells infiltrated multiple loci in the bone marrow, spleen and liver; secreted immunoglobulins; and caused glomerular damage. Our findings therefore demonstrate that deregulated expression of cMYC with KRAS12V in T2 B cells rapidly generates a plasma cell disease in mice, suggesting utility of this model both to elucidate molecular pathogenesis and to validate novel targeted therapies

  15. Detecção imunoistoquímica das oncoproteínas p21ras, c-myc E p53 no carcinoma hepatocelular e no tecido hepático não-neoplásico Immunohistochemical detection of p21ras, c-myc and p53 oncoproteins in hepatocellular carcinoma and in non-neoplastic liver tissue

    Directory of Open Access Journals (Sweden)

    Vera Lucia Nunes Pannain

    2004-12-01

    Full Text Available RACIONAL: A hepatocarcinogênese é um processo no qual as alterações genéticas e epigenéticas são bem conhecidas em modelos animais, mas carece de estudos no homem. OBJETIVOS: Analisar a freqüência das oncoproteínas p21ras, c-myc e p53 no carcinoma hepatocelular e no fígado não-neoplásico. Verificar ainda a associação destas oncoproteínas com os padrões e graus histológicos, assim como com as infecções pelos vírus das hepatites B e C. MÉTODOS: Foi analisada por método imunoistoquímico a detecção das oncoproteínas p21ras, c-myc e p53 em 47 casos de carcinoma hepatocelular e no tecido não-neoplásico circunjacente ao tumor (40 casos. RESULTADOS: As oncoproteínas p21ras, c-myc e p53 foram detectadas, respectivamente, em 44,7%, 53,2% e 36,2% dos casos de carcinoma hepatocelular. A imunorreatividade do p21ras e c-myc mostrou uma associação significativa. Contudo, não houve associação significativa entre a detecção do p21ras, c-myc e p53 com os diferentes graus e padrões histológicos, nem tampouco com as infecções pelos vírus das hepatites B e C. A mesma associação significativa entre o p21ras e c-myc foi encontrada no tecido não-neoplásico dos casos de cirrose em relação aos que não apresentaram cirrose, enquanto que o p53 foi negativo em todos os casos. CONCLUSÕES: A imunorreatividade das oncoproteínas p21ras, c-myc e p53 corrobora evidências prévias de sua detecção no carcinoma hepatocelular, o que sugere poder haver participação destas proteínas na hepatocarcinogênese humana. A significativa associação entre as proteínas p21ras, c-myc e p53 no carcinoma hepatocelular e na cirrose pode apontar uma interação entre as mesmas, sobretudo na hepatocarcinogênese pela via da cirrose.BACKGROUND: Genetic and epigenetic alterations have been described in animal hepatocarcinogenesis models but need to be studied in human being. AIMS: To assess the immunoreactivity of p21ras, c-myc and p53

  16. Establishment of c-myc-immortalized Kupffer cell line from a C57BL/6 mouse strain

    Directory of Open Access Journals (Sweden)

    Hiroshi Kitani

    2014-01-01

    Full Text Available We recently demonstrated in several mammalian species, a novel procedure to obtain liver-macrophages (Kupffer cells in sufficient numbers and purity using a mixed primary culture of hepatocytes. In this study, we applied this method to the C57BL/6 mouse liver and established an immortalized Kupffer cell line from this mouse strain. The hepatocytes from the C57BL/6 adult mouse liver were isolated by a two-step collagenase perfusion method and cultured in T25 culture flasks. Similar to our previous studies, the mouse hepatocytes progressively changed their morphology into a fibroblastic appearance after a few days of culture. After 7–10 days of culture, Kupffer-like cells, which were contaminants in the hepatocyte fraction at the start of the culture, actively proliferated on the mixed fibroblastic cell sheet. At this stage, a retroviral vector containing the human c-myc oncogene and neomycin resistance gene was introduced into the mixed culture. Gentle shaking of the culture flask, followed by the transfer and brief incubation of the culture supernatant, resulted in a quick and selective adhesion of Kupffer cells to a plastic dish surface. After selection with G418 and cloning by limiting dilutions, a clonal cell line (KUP5 was established. KUP5 cells displayed typical macrophage morphology and were stably passaged at 4–5 days intervals for more than 5 months, with a population doubling time of 19 h. KUP5 cells are immunocytochemically positive for mouse macrophage markers, such as Mac-1, F4/80. KUP5 cells exhibited substantial phagocytosis of polystyrene microbeads and the release of inflammatory cytokines upon lipopolysaccharide stimulation. Taken together, KUP5 cells provide a useful means to study the function of Kupffer cells in vitro.

  17. Physiological Expression and Accumulation of the Products of Two Upstream Open Reading Frames mrtl and MycHex1 Along With p64 and p67 Myc From the Human c-myc Locus.

    Science.gov (United States)

    Ji, Mi Hong; Kim, Seung-Ki; Kim, Chae-Yong; Phi, Ji Hoon; Jun, Hyun Jin; Blume, Scott W; Choi, Hyoung Soo

    2016-06-01

    In addition to the canonical c-Myc p64 and p67 proteins, the human c-myc locus encodes two distinct proteins, mrtl (myc-related translation/localization regulatory factor) and MycHex1 (Myc Human Exon 1), from the upstream open reading frames within the 5'-untranslated region of the c-myc P0 mRNA. The aim of this study is to examine simultaneously, for the first time, mrtl, MycHex1, c-Myc p64, and p67 in human tumor cell lines and pediatric brain tumor tissues. Western blot analysis demonstrated endogenous mrtl, MycHex1, c-Myc p64, and p67 simultaneously. The relative abundance of mrtl and MycHex1 were consistent among a variety of human tumor cell lines, and the relative intensities of mrtl and MycHex1 correlated positively. Confocal imaging revealed mrtl predominantly localized to the nuclear envelope, along with prominent reticular pattern in the cytoplasm. MycHex1 was observed as a series of bright foci located within the nucleus, a subset of which colocalized with fibrillarin. mrtl and MycHex1 co-immunoprecipitated with RACK1, c-Myc, fibrillarin, coilin, and with each other. These findings suggest that mrtl and MycHex1 have multiple interaction partners in both the nucleus and cytoplasm. Sequence analyses confirmed a known polymorphism of mrtl at base 1965 (G>T) and new mutations at bases 1900 (C>G) and 1798 (C>G). Evidence is presented for expression and stable accumulation of all four proteins encoded by three distinct non-overlapping open reading frames within the human c-myc locus. Additional work is warranted to further elucidate the functional or regulatory roles of these molecules in regulation of c-Myc and in oncogenesis. J. Cell. Biochem. 117: 1407-1418, 2016. © 2015 Wiley Periodicals, Inc. PMID:26552949

  18. C-Myc Induced Compensated Cardiac Hypertrophy Increases Free Fatty Acid Utilization for the Citric Acid Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Olson, Aaron; Ledee, Dolena; Iwamoto, Kate; Kajimoto, Masaki; O' Kelly-Priddy, Colleen M.; Isern, Nancy G.; Portman, Michael A.

    2013-02-01

    The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc-induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam). Isolated working hearts and 13Carbon (13C )-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing 13C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was confirmed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contribution in NTG. Substrate utilization was not significantly altered in 3dMyc versus cont. The free fatty acid FC was significantly greater in 7dMyc vs cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the mechanisms whereby this change maintained

  19. Cell type-specific conditional regulation of the c-myc proto-oncogene by combining Cre/loxP recombination and tamoxifen-mediated activation.

    Science.gov (United States)

    Jäger, Richard; Maurer, Jochen; Jacob, Andrea; Schorle, Hubert

    2004-03-01

    Development of inducible genetic switches for in vivo use with transgenic mice has revolutionized many areas in modern molecular biology. Combining two techniques, Cre/loxP-based genetic recombination and ligand-dependent activation of a chimeric protein, we generated transgenic mice which allow for the spatiotemporal control of expression and of activity of the proto-oncogene c-myc. To these ends, the gene encoding the tamoxifen-inducible c-mycER(T) fusion protein (mycER(T)) was inserted in the ubiquitously active ROSA 26 gene locus by gene targeting. In the resulting ROSAMER allele, generalized transcription of the mycER(T) gene is prevented by a preceding transcriptional stop sequence which is flanked by loxP sites. Crosses of ROSAMER transgenic mice with Mox2 cre transgenic mice revealed tight control of mycER(T) transcription in various tissues unless the transcriptional stop sequence was removed by cre-mediated excision. Furthermore, we were able to demonstrate tamoxifen-dependent activation of the MycER(T) protein in embryonic fibroblasts derived from such mice. As a proof of principle, we demonstrate that primary neural crest cultures established from ROSAMER mice maintain their proliferative capacity in a 4-OHT-dependent manner. Furthermore, we demonstrate that such neural crest cells retain their differentiation potential as shown by expression of NF 160, a marker of neuronal differentiation upon 4-OHT withdrawal. The transgenic mice produced may thus be valuable tools for studying the cell type-specific effects of c-myc activity in development and disease. PMID:15048812

  20. Liver tumor formation by a mutant retinoblastoma protein in the transgenic mice is caused by an upregulation of c-Myc target genes

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Bo; Hikosaka, Keisuke; Sultana, Nishat; Sharkar, Mohammad Tofael Kabir [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Noritake, Hidenao [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Kimura, Wataru; Wu, Yi-Xin [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Kobayashi, Yoshimasa [Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Uezato, Tadayoshi [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Miura, Naoyuki, E-mail: nmiura@hama-med.ac.jp [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Fifty percent of the mutant Rb transgenic mice produced liver tumors. Black-Right-Pointing-Pointer In the tumor, Foxm1, Skp2, Bmi1 and AP-1 mRNAs were up-regulated. Black-Right-Pointing-Pointer No increase in expression of the Myc-target genes was observed in the non-tumorous liver. Black-Right-Pointing-Pointer Tumor formation depends on up-regulation of the Myc-target genes. -- Abstract: The retinoblastoma (Rb) tumor suppressor encodes a nuclear phosphoprotein that regulates cellular proliferation, apoptosis and differentiation. In order to adapt itself to these biological functions, Rb is subjected to modification cycle, phosphorylation and dephosphorylation. To directly determine the effect of phosphorylation-resistant Rb on liver development and function, we generated transgenic mice expressing phosphorylation-resistant human mutant Rb (mt-Rb) under the control of the rat hepatocyte nuclear factor-1 gene promoter/enhancer. Expression of mt-Rb in the liver resulted in macroscopic neoplastic nodules (adenomas) with {approx}50% incidence within 15 months old. Interestingly, quantitative reverse transcriptase-PCR analysis showed that c-Myc was up-regulated in the liver of mt-Rb transgenic mice irrespective of having tumor tissues or no tumor. In tumor tissues, several c-Myc target genes, Foxm1, c-Jun, c-Fos, Bmi1 and Skp2, were also up-regulated dramatically. We determined whether mt-Rb activated the Myc promoter in the HTP9 cells and demonstrated that mt-Rb acted as an inhibitor of wild-type Rb-induced repression on the Myc promoter. Our results suggest that continued upregulation of c-Myc target genes promotes the liver tumor formation after about 1 year of age.

  1. Liver tumor formation by a mutant retinoblastoma protein in the transgenic mice is caused by an upregulation of c-Myc target genes

    International Nuclear Information System (INIS)

    Highlights: ► Fifty percent of the mutant Rb transgenic mice produced liver tumors. ► In the tumor, Foxm1, Skp2, Bmi1 and AP-1 mRNAs were up-regulated. ► No increase in expression of the Myc-target genes was observed in the non-tumorous liver. ► Tumor formation depends on up-regulation of the Myc-target genes. -- Abstract: The retinoblastoma (Rb) tumor suppressor encodes a nuclear phosphoprotein that regulates cellular proliferation, apoptosis and differentiation. In order to adapt itself to these biological functions, Rb is subjected to modification cycle, phosphorylation and dephosphorylation. To directly determine the effect of phosphorylation-resistant Rb on liver development and function, we generated transgenic mice expressing phosphorylation-resistant human mutant Rb (mt-Rb) under the control of the rat hepatocyte nuclear factor-1 gene promoter/enhancer. Expression of mt-Rb in the liver resulted in macroscopic neoplastic nodules (adenomas) with ∼50% incidence within 15 months old. Interestingly, quantitative reverse transcriptase-PCR analysis showed that c-Myc was up-regulated in the liver of mt-Rb transgenic mice irrespective of having tumor tissues or no tumor. In tumor tissues, several c-Myc target genes, Foxm1, c-Jun, c-Fos, Bmi1 and Skp2, were also up-regulated dramatically. We determined whether mt-Rb activated the Myc promoter in the HTP9 cells and demonstrated that mt-Rb acted as an inhibitor of wild-type Rb-induced repression on the Myc promoter. Our results suggest that continued upregulation of c-Myc target genes promotes the liver tumor formation after about 1 year of age.

  2. The c-myc and PyMT oncogenes induce different tumor types in a somatic mouse model for pancreatic cancer

    OpenAIRE

    Lewis, Brian C.; Klimstra, David S.; Varmus, Harold E

    2003-01-01

    We have generated a mouse model for pancreatic cancer through the somatic delivery of oncogene-bearing avian retroviruses to mice that express TVA, the receptor for avian leukosis sarcoma virus subgroup A (ALSV-A), under the control of the elastase promoter. Delivery of ALSV-A-based RCAS vectors encoding either mouse polyoma virus middle T antigen (PyMT) or c-Myc to elastase-tv-a transgenic, Ink4a/Arf null mice induced the formation of pancreatic tumors. RCAS-PyMT induced pancreatic tumors wi...

  3. PET/CT Imaging of c-Myc Transgenic Mice Identifies the Genotoxic N-Nitroso-Diethylamine as Carcinogen in a Short-Term Cancer Bioassay

    OpenAIRE

    Katja Hueper; Mahmoud Elalfy; Florian Laenger; Roman Halter; Thomas Rodt; Michael Galanski; Juergen Borlak

    2012-01-01

    BACKGROUND: More than 100,000 chemicals are in use but have not been tested for their safety. To overcome limitations in the cancer bioassay several alternative testing strategies are explored. The inability to monitor non-invasively onset and progression of disease limits, however, the value of current testing strategies. Here, we report the application of in vivo imaging to a c-Myc transgenic mouse model of liver cancer for the development of a short-term cancer bioassay. METHODOLOGY/PRINCI...

  4. Angiotensin II reduces cardiac AdipoR1 expression through AT1 receptor/ROS/ERK1/2/c-Myc pathway.

    Directory of Open Access Journals (Sweden)

    Li Li

    Full Text Available Adiponectin, an abundant adipose tissue-derived protein, exerts protective effect against cardiovascular disease. Adiponectin receptors (AdipoR1 and AdipoR2 mediate the beneficial effects of adiponectin on the cardiovascular system. However, the alteration of AdipoRs in cardiac remodeling is not fully elucidated. Here, we investigated the effect of angiotensin II (AngII on cardiac AdipoRs expression and explored the possible molecular mechanism. AngII infusion into rats induced cardiac hypertrophy, reduced AdipoR1 but not AdipoR2 expression, and attenuated the phosphorylations of adenosine monophosphate-activated protein kinase and acetyl coenzyme A carboxylase, and those effects were all reversed by losartan, an AngII type 1 (AT1 receptor blocker. AngII reduced expression of AdipoR1 mRNA and protein in cultured neonatal rat cardiomyocytes, which was abolished by losartan, but not by PD123319, an AT2 receptor antagonist. The antioxidants including reactive oxygen species (ROS scavenger NAC, NADPH oxidase inhibitor apocynin, Nox2 inhibitor peptide gp91 ds-tat, and mitochondrial electron transport chain complex I inhibitor rotenone attenuated AngII-induced production of ROS and phosphorylation of extracellular signal-regulated kinase (ERK 1/2. AngII-reduced AdipoR1 expression was reversed by pretreatment with NAC, apocynin, gp91 ds-tat, rotenone, and an ERK1/2 inhibitor PD98059. Chromatin immunoprecipitation assay demonstrated that AngII provoked the recruitment of c-Myc onto the promoter region of AdipoR1, which was attenuated by PD98059. Moreover, AngII-induced DNA binding activity of c-Myc was inhibited by losartan, NAC, apocynin, gp91 ds-tat, rotenone, and PD98059. c-Myc small interfering RNA abolished the inhibitory effect of AngII on AdipoR1 expression. Our results suggest that AngII inhibits cardiac AdipoR1 expression in vivo and in vitro and AT1 receptor/ROS/ERK1/2/c-Myc pathway is required for the downregulation of AdipoR1 induced by AngII.

  5. Wogonin has multiple anti-cancer effects by regulating c-Myc/SKP2/Fbw7α and HDAC1/HDAC2 pathways and inducing apoptosis in human lung adenocarcinoma cell line A549.

    Directory of Open Access Journals (Sweden)

    Xin-mei Chen

    Full Text Available Wogonin is a plant monoflavonoid which has been reported to inhibit cell growth and/or induce apoptosis in various tumors. The present study examined the apoptosis-inducing activity and underlying mechanism of action of wogonin in A549 cells. The results showed that wogonin was a potent inhibitor of the viability of A549 cells. Apoptotic protein changes detected after exposure to wogonin included decreased XIAP and Mcl-1 expression, increased cleaved-PARP expression and increased release of AIF and cytochrome C. Western blot analysis showed that the activity of c-Myc/Skp2 and HDAC1/HDAC2 pathways, which play important roles in tumor progress, was decreased. Quantitative PCR identified increased levels of c-Myc mRNA and decreased levels of its protein. Protein levels of Fbw7α, GSK3β and Thr58-Myc, which are involved in c-Myc ubiquitin-dependent degradation, were also analyzed. After exposure to wogonin, Fbw7α and GSK3β expression decreased and Thr58-Myc expression increased. However, MG132 was unable to prevent c-Myc degradation. The present results suggest that wogonin has multiple anti-cancer effects associated with degradation of c-Myc, SKP2, HDAC1 and HDAC2. Its ability to induce apoptosis independently of Fbw7α suggests a possible use in drug-resistance cancer related to Fbw7 deficiency. Further studies are needed to determine which pathways are related to c-Myc and Fbw7α reversal and whether Thr58 phosphorylation of c-Myc is dependent on GSK3β.

  6. SIRT1 activation by a c-MYC oncogenic network promotes the maintenance and drug resistance of human FLT3-ITD acute myeloid leukemia stem cells.

    Science.gov (United States)

    Li, Ling; Osdal, Tereza; Ho, Yinwei; Chun, Sookhee; McDonald, Tinisha; Agarwal, Puneet; Lin, Allen; Chu, Su; Qi, Jing; Li, Liang; Hsieh, Yao-Te; Dos Santos, Cedric; Yuan, Hongfeng; Ha, Trung-Quang; Popa, Mihaela; Hovland, Randi; Bruserud, Oystein; Gjertsen, Bjørn Tore; Kuo, Ya-Huei; Chen, Wenyong; Lain, Sonia; McCormack, Emmet; Bhatia, Ravi

    2014-10-01

    The FLT3-ITD mutation is frequently observed in acute myeloid leukemia (AML) and is associated with poor prognosis. In such patients, FLT3 tyrosine kinase inhibitors (TKIs) are only partially effective and do not eliminate the leukemia stem cells (LSCs) that are assumed to be the source of treatment failure. Here, we show that the NAD-dependent SIRT1 deacetylase is selectively overexpressed in primary human FLT3-ITD AML LSCs. This SIRT1 overexpression is related to enhanced expression of the USP22 deubiquitinase induced by c-MYC, leading to reduced SIRT1 ubiquitination and enhanced stability. Inhibition of SIRT1 expression or activity reduced the growth of FLT3-ITD AML LSCs and significantly enhanced TKI-mediated killing of the cells. Therefore, these results identify a c-MYC-related network that enhances SIRT1 protein expression in human FLT3-ITD AML LSCs and contributes to their maintenance. Inhibition of this oncogenic network could be an attractive approach for targeting FLT3-ITD AML LSCs to improve treatment outcomes. PMID:25280219

  7. Partial Dedifferentiation of Murine Radial Glia-Type Neural Stem Cells by Brn2 and c-Myc Yields Early Neuroepithelial Progenitors.

    Science.gov (United States)

    Bung, Raffaela; Wörsdörfer, Philipp; Thier, Marc Christian; Lemke, Kathrin; Gebhardt, Martina; Edenhofer, Frank

    2016-04-10

    Direct cell conversion developed into an important paradigm for generating cells with enhanced differentiation capability. We combined a transcription-factor-based cell fate conversion strategy with the use of pharmacological compounds to derive early neuroepithelial progenitor cells from developmentally more restricted radial glia-type neural stem cells. By combining the small molecules CHIR99021, Tranylcypromine, SB431542 and valproic acid with viral transduction of the transcription factor c-Myc and the POU domain transcription factor Brn2, we dedifferentiated radial glia-type neural stem cells into an early neuroepithelial progenitor cell state within 6days. Reverse transcription PCR analyses showed a rapid down-regulation of the radial glia markers Olig2 and Vimentin during conversion, whereas the neuroepithelial markers Dach1 and Sox1 were fastly up-regulated. Furthermore, a switch from N-Cadherin to E-Cadherin indicates a mesenchymal-to-epithelial transition. The differentiation of cells converted by Brn2/c-Myc yielded smooth muscle actin- and Peripherin-positive cells in addition to the neuronal marker TUJ1 and cells that are positive for the glial marker GFAP. This differentiation potential suggests that the applied reprogramming strategy induced an early neuroepithelial cell population, which might resemble cells of the neural border or even more primitive neuroepithelial cells. PMID:26555748

  8. Mycobacterium tuberculosis 6-kDa Early Secreted Antigenic Target (ESAT-6 protein downregulates Lipopolysaccharide induced c-myc expression by modulating the Extracellular Signal Regulated Kinases 1/2

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    Mir Fayaz

    2007-10-01

    Full Text Available Abstract Background Mycobacterium tuberculosis (Mtb causes death of 2–3 million people every year. The persistence of the pathogenic mycobacteria inside the macrophage occurs through modulation of host cell signaling which allows them, unlike the other non-pathogenic species, to survive inside the host. The secretory proteins of M. tuberculosis have gained attention in recent years both as vaccine candidates and diagnostic tools; they target the immune system and trigger a putatively protective response; however, they may also be involved in the clinical symptoms of the disease. Results Our studies showed that RD-1-encoded secretory protein ESAT-6 is involved in modulation of the mitogen-activated protein (MAP kinase-signaling pathway inside the macrophage. ESAT-6 induced phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2 in the cytoplasm but not in the nucleus, which normally is the case for MAP kinases. ESAT-6 also antagonized LPS-induced ERK1/2 phosphorylation in the nucleus. Stimulation of cells by ESAT-6 along with sodium orthovanadate (a tyrosine phosphatase inhibitor restored phosphorylation of ERK1/2 in the nucleus, suggesting active dephosphorylation of ERK1/2 by some putative phosphatase(s in the nucleus. Further, ESAT-6 was found to down regulate the expression of LPS-inducible gene c-myc in an ERK1/2-dependent manner. Conclusion This study showed the effect of secretory proteins of M. tuberculosis in the modulation of macrophage signaling pathways particularly ERK1/2 MAP kinase pathway. This modulation appears to be achieved by limiting the ERK1/2 activation in the nucleus which ultimately affects the macrophage gene expression. This could be a mechanism by which secretory proteins of Mtb might modulate gene expression inside the macrophages.

  9. Expressão dos protooncogenes c-fos, c-myc e c-jun em miométrio normal e mioma humanos Expression of the protooncogenes c-fos, c-myc and c-jun in human normal miometrium and leiomyoma

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    Ana Luiza Ferrari

    2006-10-01

    Full Text Available OBJETIVO: Comparar a expressão gênica (mRNA e protéica dos protooncogenes c-fos, c-myc e c-jun em miométrio normal e mioma humanos. MÉTODOS: Foi realizado um estudo do tipo caso-controle. O material foi coletado de 12 pacientes submetidas a histerectomia no Hospital de Clínicas de Porto Alegre. A expressão do mRNA específico para c-myc, c-fos, c-jun e beta-microglobulina foi avaliada pela técnica de RT-PCR, utilizando primers específicos para cada gene. A expressão protéica destes protooncogenes foi avaliada através de Western blot com anticorpos específicos. RESULTADOS: Não houve diferença significativa para expressão gênica desses protooncogenes entre miométrio normal e mioma (c-myc: 0,87 ± 0,08 vs 0,87 ± 0,08, p = 0,952; c-fos: 1,10 ± 0,17 vs 1,01 ± 0,11, p = 0,21; c-jun: 1,03 ± 0,12 vs 0,96 ± 0,09, p = 0,168, respectivamente. Não houve diferença significativa para expressão protéica desses protooncogenes entre miométrio normal e mioma (c-myc: 1,36 ± 0,48 vs 1,53 ± 0,29, p = 0,569; c-fos: 8,85 ± 5,5 vs 6,56 ± 4,22, p = 0,434; e c-jun: 6,47 ± 3,04 vs 5,42 ± 2,03, p = 0,266, respectivamente. CONCLUSÃO: A expressão gênica (transcrição e a expressão protéica (tradução dos protooncogenes c-myc, c-fos e c-jun em mioma e miométrio normal são semelhantes.Uterine myomas are common benign tumors of the female genital tract. The expression of growth factor signal transduction cascade components including the protooncogenes c-myc, c-fos, and c-jun seem to be involved in the development of myomas. PURPOSE: To compare the gene (mRNA and protein expression of the protooncogenes c-fos, c-myc, and c-jun in human normal myometrium and leiomyoma. METHOD: A case-control study was performed. Samples were collected from 12 patients submitted to hysterectomy at the Hospital de Clínicas at Porto Alegre. The expression of the specific mRNA for c-myc, c-fos, c-jun, and beta-microglobulin was assessed through the RT

  10. Gene expression profiling reveals different pathways related to Abl and other genes that cooperate with c-Myc in a model of plasma cell neoplasia

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    Zhan Fenghuang

    2007-08-01

    Full Text Available Abstract Background To elucidate the genes involved in the neoplastic transformation of B cells, global gene expression profiles were generated using Affymetrix U74Av2 microarrays, containing 12,488 genes, for four different groups of mouse B-cell lymphomas and six subtypes of pristane-induced mouse plasma cell tumors, three of which developed much earlier than the others. Results Unsupervised hierarchical cluster analysis exhibited two main sub-clusters of samples: a B-cell lymphoma cluster and a plasma cell tumor cluster with subclusters reflecting mechanism of induction. This report represents the first step in using global gene expression to investigate molecular signatures related to the role of cooperating oncogenes in a model of Myc-induced carcinogenesis. Within a single subgroup, e.g., ABPCs, plasma cell tumors that contained typical T(12;15 chromosomal translocations did not display gene expression patterns distinct from those with variant T(6;15 translocations, in which the breakpoint was in the Pvt-1 locus, 230 kb 3' of c-Myc, suggesting that c-Myc activation was the initiating factor in both. When integrated with previously published Affymetrix array data from human multiple myelomas, the IL-6-transgenic subset of mouse plasma cell tumors clustered more closely with MM1 subsets of human myelomas, slow-appearing plasma cell tumors clustered together with MM2, while plasma cell tumors accelerated by v-Abl clustered with the more aggressive MM3-MM4 myeloma subsets. Slow-appearing plasma cell tumors expressed Socs1 and Socs2 but v-Abl-accelerated plasma cell tumors expressed 4–5 times as much. Both v-Abl-accelerated and non-v-Abl-associated tumors exhibited phosphorylated STAT 1 and 3, but only v-Abl-accelerated plasma cell tumors lost viability and STAT 1 and 3 phosphorylation when cultured in the presence of the v-Abl kinase inhibitor, STI-571. These data suggest that the Jak/Stat pathway was critical in the transformation

  11. Combined loss of PUMA and p21 accelerates c-MYC-driven lymphoma development considerably less than loss of one allele of p53.

    Science.gov (United States)

    Valente, L J; Grabow, S; Vandenberg, C J; Strasser, A; Janic, A

    2016-07-21

    The tumor suppressor p53 is mutated in ~50% of human cancers. P53 is activated by a range of stimuli and regulates several cellular processes, including apoptotic cell death, cell cycle arrest, senescence and DNA repair. P53 induces apoptosis via transcriptional induction of the BH3-only proteins PUMA (p53-upregulated modulator of apoptosis) and NOXA, and cell cycle arrest via p21. Induction of these processes was proposed to be critical for p53-mediated tumor suppression. It is therefore surprising that mice lacking PUMA, NOXA and p21, as well as mice bearing mutations in p53 that impair the transcriptional activation of these genes, are not tumor prone, unlike mice lacking p53 function, which spontaneously develop tumors with 100% incidence. These p53 target genes and the processes they regulate may, however, impact differently on tumor development depending on the oncogenic drivers. For example, loss of PUMA enhances c-MYC-driven lymphoma development in mice, but, interestingly, the acceleration was less impressive compared with that caused by the loss of even a single p53 allele. Different studies have reported that loss of p21 can accelerate, delay or have no impact on tumorigenesis. In an attempt to resolve this controversy, we examined whether loss of p21-mediated cell cycle arrest cooperates with PUMA deficiency in accelerating lymphoma development in Eμ-Myc mice (overexpressing c-MYC in B-lymphoid cells). We found that Eμ-Myc mice lacking both p21 and PUMA (Eμ-Myc;Puma(-/-);p21(-/-)) developed lymphoma at a rate comparable to Eμ-Myc;Puma(-/-) animals, notably with considerably longer latency than Eμ-Myc;p53(+/-)mice. Loss of p21 had no impact on the numbers, cycling or survival of pre-leukemic Eμ-Myc B-lymphoid cells, even when PUMA was lost concomitantly. These results demonstrate that even in the context of deregulated c-MYC expression, p53 must suppress tumor development by activating processes apart from, or in addition to, PUMA

  12. Targeting human c-Myc promoter duplex DNA with actinomycin D by use of multi-way analysis of quantum-dot-mediated fluorescence resonance energy transfer

    DEFF Research Database (Denmark)

    Gholami, Somayeh; Kompany Zare, Mohsen

    2013-01-01

    investigated by use of 2D-photoluminescence emission (2D-PLE), and the resulting data were subjected to analysis by use of convenient and powerful multi-way approaches. Fluorescence measurements were performed by use of the quantum dot (QD)-conjugated c-Myc promoter. Intercalation of 7AAD within duplex base...... important advantage over univariate classical methods of enabling us to investigate the source of variance in the fluorescence signal of the DNA-drug complex. It was established that hard trilinear decomposition analysis of FRET-measured data overcomes the problem of rank deficiency, enabling calculation of...... hybridization stability 1.0 x 10(8) mol(-1) L obtained were in good agreement with values reported in the literature. The analytical concentration of the QD-labeled DNA was determined by use of nonlinear fitting, without using external standard calibration samples. This study was a successful application of...

  13. Oridonin induces apoptosis and senescence in colorectal cancer cells by increasing histone hyperacetylation and regulation of p16, p21, p27 and c-myc

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    Zhao Ying-Zheng

    2010-11-01

    Full Text Available Abstract Background Oridonin, a tetracycline diterpenoid compound, has the potential antitumor activities. Here, we evaluate the antitumor activity and action mechanisms of oridonin in colorectal cancer. Methods Effects of oridonin on cell proliferation were determined by using a CCK-8 Kit. Cell cycle distribution was determined by flow cytometry. Apoptosis was examined by analyzing subdiploid population and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Senescent cells were determined by senescence-associated β-galactosidase activity analysis. Semi-quantitative RT-PCR was used to examine the changes of mRNA of p16, p21, p27 and c-myc. The concomitant changes of protein expression were analyzed with Western blot. Expression of AcH3 and AcH4 were examined by immunofluorescence staining and Western blots. Effects of oridonin on colony formation of SW1116 were examined by Soft Agar assay. The in vivo efficacy of oridonin was detected using a xenograft colorectal cancer model in nude mice. Results Oridonin induced potent growth inhibition, cell cycle arrest, apoptosis, senescence and colony-forming inhibition in three colorectal cancer cell lines in a dose-dependent manner in vitro. Daily i.p. injection of oridonin (6.25, 12.5 or 25 mg/kg for 28 days significantly inhibited the growth of SW1116 s.c. xenografts in BABL/C nude mice. With western blot and reverse transcription-PCR, we further showed that the antitumor activities of oridonin correlated with induction of histone (H3 and H4 hyperacetylation, activation of p21, p27 and p16, and suppression of c-myc expression. Conclusion Oridonin possesses potent in vitro and in vivo anti-colorectal cancer activities that correlated with induction of histone hyperacetylation and regulation of pathways critical for maintaining growth inhibition and cell cycle arrest. Therefore, oridonin may represent a novel therapeutic option in colorectal cancer treatment.

  14. Protein kinase A antagonist inhibits β-catenin nuclear translocation, c-Myc and COX-2 expression and tumor promotion in ApcMin/+ mice

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    Brudvik Kristoffer W

    2011-12-01

    Full Text Available Abstract Background The adenomatous polyposis coli (APC protein is part of the destruction complex controlling proteosomal degradation of β-catenin and limiting its nuclear translocation, which is thought to play a gate-keeping role in colorectal cancer. The destruction complex is inhibited by Wnt-Frz and prostaglandin E2 (PGE2 - PI-3 kinase pathways. Recent reports show that PGE2-induced phosphorylation of β-catenin by protein kinase A (PKA increases nuclear translocation indicating two mechanisms of action of PGE2 on β-catenin homeostasis. Findings Treatment of ApcMin/+ mice that spontaneously develop intestinal adenomas with a PKA antagonist (Rp-8-Br-cAMPS selectively targeting only the latter pathway reduced tumor load, but not the number of adenomas. Immunohistochemical characterization of intestines from treated and control animals revealed that expression of β-catenin, β-catenin nuclear translocation and expression of the β-catenin target genes c-Myc and COX-2 were significantly down-regulated upon Rp-8-Br-cAMPS treatment. Parallel experiments in a human colon cancer cell line (HCT116 revealed that Rp-8-Br-cAMPS blocked PGE2-induced β-catenin phosphorylation and c-Myc upregulation. Conclusion Based on our findings we suggest that PGE2 act through PKA to promote β-catenin nuclear translocation and tumor development in ApcMin/+ mice in vivo, indicating that the direct regulatory effect of PKA on β-catenin nuclear translocation is operative in intestinal cancer.

  15. Disturbance of Bcl-2, Bax, Caspase-3, Ki-67 and C-myc expression in acute and subchronic exposure to benzo(a)pyrene in cervix.

    Science.gov (United States)

    Gao, Meili; Li, Yongfei; Ji, Xiaoying; Xue, Xiaochang; Chen, Lan; Feng, Guodong; Zhang, Huqin; Wang, Huichun; Shah, Walayat; Hou, Zhanwu; Kong, Yu

    2016-03-01

    Epidemiological studies have demonstrated that cigarette smoking is an important cofactor or an independent risk factor for the development of cervical cancer. Benzo(a)pyrene (BaP) is one of the most potent tobacco smoke carcinogens in tobacco smoke. BaP induced DNA damage and over expression in p53 cervical tissue of mice as demonstrated in our previous study. Here we present the findings of exposure to BaP on the expression of Bcl-2, C-myc, Ki-67, Caspase-3 and Bax genes in mouse cervix. Acute intraperitoneal administration of BaP (12.5, 25, 50, 100mg/kg body weight) to ICR female mice induced a significant increase in Bcl-2, C-myc, Ki-67 mRNA and protein level till 72h except in Bcl-2 at 24h with 12.5, 25, 50mg/kg as well as at 48h with 12.5mg/kg body weight post treatment. A significant increase was also seen in Caspase-3 and Bax mRNA and protein level with peak level at 24h and gradual decrease till 72h, however, the expression of caspase-3 increased while that of Bax decreased with increasing dose of Bap after 24h. In sub chronic intraperitoneal and oral gavage administration of BaP (2.5, 5, 10mg/kg body weight), similar significant increase was observed for all the examined genes as compared to the control and vehicle groups, however the expression of Bax decreased in a dose dependent manner. The findings of this study will help in further understanding the molecular mechanism of BaP induced carcinogenesis of cervical cancer. PMID:26709117

  16. Preparation of 99Tcm labeled c-myc mRNA antisense peptide nucleic acid and its biodistribution in tumor-bearing nude mice

    International Nuclear Information System (INIS)

    Objective: The aim of this work was to study a 99Tcm labeling method for c-myc mRNA antisense peptide nucleic acid (PNA) fragments and the biodistribution of the labeled product in tumor- beating nude mice. Methods: A four amino acid sequence Gly-(D)-Ala-Gly-Gly [G-(D)-A-G-G] was used as a chelator. N-GAGG-Aba-GCATCGTCGCGG, a chelator-antisense PNA specific for the human c- myc oncogene mRNA initiation region, was synthesized, purified and characterized. N-GAGG-Aba-GCAT- GTCTGCGG, a chelator mismatched PNA, was synthesized and used as a control. G-(D)-A-G-G provided an N4 configuration for strong, efficient chelation of 99Tcm. The labeled PNA was identified with high performance liquid chromatography (HPLC) and the labeling yield and radiochemical purity were measured by paper chromatography. The biodistribution was studied with nude mice bearing colon carcinoma and the percentage activity of injected dose per gram of tissue (%ID/g) was calculated. ASA 6.12 was used for data analysis. Results: The results of HPLC and paper chromatography confirmed that 99Tcm was joined to the PNA or the mismatched PNA with a high radiochemical purity (> 95%). Both were stable in vitro or incubated with human fresh serum and were excreted through urine. Results of biodistribution studies showed that the highest radioactivity levels were in the kidneys and spleen. The radioactivity of 99Tcm labeled antisense PNA in tumor was high whereas that of 99Tcm labeled mismatch PNA was very low [(1.11% ± 0.12)% ID/g and (0.14 ± 0.02)% ID/g, respectively; t=14.75, P99Tcm by the method presented in this paper, with good yield, radiochemical purity and stability. It was an efficient method to label antisense PNA with 99Tcm. The product seemed to be a potential tumor imaging agent. (authors)

  17. Genetic dissimilarity between primary colorectal carcinomas and their lymph node metastases: ploidy, p53, bcl-2, and c-myc expression--a pilot study.

    Science.gov (United States)

    Zalata, Khaled Refaat; Elshal, Mohamed Farouk; Foda, Abd AlRahman Mohammad; Shoma, Ashraf

    2015-08-01

    The current paradigm of metastasis proposes that rare cells within primary tumors acquire metastatic capability via sequential mutations, suggesting that metastases are genetically dissimilar from their primary tumors. This study investigated the changes in the level of expression of a well-defined panel of cell proliferation, differentiation, and apoptosis markers between the primary colorectal cancer (CRC) and the corresponding synchronous lymph node (LN) metastasis from the same patients. DNA flow cytometry and immunostaining of p53, bcl-2, and c-myc were carried out on 36 cases of CRC radical resection specimens with their corresponding LN metastases. There was very low probability that the histological patterns of primary tumors and LN metastases are independent (p < 0.001). Metastatic tumors were significantly more diffusely positive for p53 than the primary tumors (p < 0.001). Conversely, primary tumors were significantly more diffusely positive for c-myc than metastatic tumors (p = 0.011). No significant difference was found between the LNs and the primary tumors in bcl-2 positivity (p = 0.538) and DNA aneuploidy (p = 0.35), with a tendency towards negative bcl-2 and less aneuploidy in LN metastases than primary tumors. In conclusion, LN metastatic colorectal carcinomas have a tendency of being less differentiated, with a higher incidence of diffuse p53 staining, lower incidence of bcl-2 staining, and less aneuploidy in comparison to their primary counterparts suggesting a more aggressive biological behavior, which could indicate the necessity for more aggressive adjuvant therapy. PMID:25840688

  18. PET/CT imaging of c-Myc transgenic mice identifies the genotoxic N-nitroso-diethylamine as carcinogen in a short-term cancer bioassay.

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    Katja Hueper

    Full Text Available BACKGROUND: More than 100,000 chemicals are in use but have not been tested for their safety. To overcome limitations in the cancer bioassay several alternative testing strategies are explored. The inability to monitor non-invasively onset and progression of disease limits, however, the value of current testing strategies. Here, we report the application of in vivo imaging to a c-Myc transgenic mouse model of liver cancer for the development of a short-term cancer bioassay. METHODOLOGY/PRINCIPAL FINDINGS: μCT and ¹⁸F-FDG μPET were used to detect and quantify tumor lesions after treatment with the genotoxic carcinogen NDEA, the tumor promoting agent BHT or the hepatotoxin paracetamol. Tumor growth was investigated between the ages of 4 to 8.5 months and contrast-enhanced μCT imaging detected liver lesions as well as metastatic spread with high sensitivity and accuracy as confirmed by histopathology. Significant differences in the onset of tumor growth, tumor load and glucose metabolism were observed when the NDEA treatment group was compared with any of the other treatment groups. NDEA treatment of c-Myc transgenic mice significantly accelerated tumor growth and caused metastatic spread of HCC in to lung but this treatment also induced primary lung cancer growth. In contrast, BHT and paracetamol did not promote hepatocarcinogenesis. CONCLUSIONS/SIGNIFICANCE: The present study evidences the accuracy of in vivo imaging in defining tumor growth, tumor load, lesion number and metastatic spread. Consequently, the application of in vivo imaging techniques to transgenic animal models may possibly enable short-term cancer bioassays to significantly improve hazard identification and follow-up examinations of different organs by non-invasive methods.

  19. Oridonin induces apoptosis and senescence in colorectal cancer cells by increasing histone hyperacetylation and regulation of p16, p21, p27 and c-myc

    International Nuclear Information System (INIS)

    Oridonin, a tetracycline diterpenoid compound, has the potential antitumor activities. Here, we evaluate the antitumor activity and action mechanisms of oridonin in colorectal cancer. Effects of oridonin on cell proliferation were determined by using a CCK-8 Kit. Cell cycle distribution was determined by flow cytometry. Apoptosis was examined by analyzing subdiploid population and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Senescent cells were determined by senescence-associated β-galactosidase activity analysis. Semi-quantitative RT-PCR was used to examine the changes of mRNA of p16, p21, p27 and c-myc. The concomitant changes of protein expression were analyzed with Western blot. Expression of AcH3 and AcH4 were examined by immunofluorescence staining and Western blots. Effects of oridonin on colony formation of SW1116 were examined by Soft Agar assay. The in vivo efficacy of oridonin was detected using a xenograft colorectal cancer model in nude mice. Oridonin induced potent growth inhibition, cell cycle arrest, apoptosis, senescence and colony-forming inhibition in three colorectal cancer cell lines in a dose-dependent manner in vitro. Daily i.p. injection of oridonin (6.25, 12.5 or 25 mg/kg) for 28 days significantly inhibited the growth of SW1116 s.c. xenografts in BABL/C nude mice. With western blot and reverse transcription-PCR, we further showed that the antitumor activities of oridonin correlated with induction of histone (H3 and H4) hyperacetylation, activation of p21, p27 and p16, and suppression of c-myc expression. Oridonin possesses potent in vitro and in vivo anti-colorectal cancer activities that correlated with induction of histone hyperacetylation and regulation of pathways critical for maintaining growth inhibition and cell cycle arrest. Therefore, oridonin may represent a novel therapeutic option in colorectal cancer treatment

  20. Alterations in TP53, cyclin D2, c-Myc, p21WAF1/CIP1 and p27KIP1 expression associated with progression in B-CLL

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    Antosz Halina

    2010-04-01

    Full Text Available B-cell chronic lymphocytic leukaemia (B-CLL originates from B lymphocytes that may differ in the activationlevel, maturation state or cellular subgroups in peripheral blood. Tumour progression in CLL B cells seems to result in gradualaccumulation of the clone of resting B lymphocytes in the early phases (G0/G1 of the cell cycle. The G1 phase isimpaired in B-CLL. We investigated the gene expression of five key cell cycle regulators: TP 53, c-Myc, cyclin D2,p21WAF1/CIP1 and p27KIP1, which primarily regulate the G1 phase of the cell cycle, or S-phase entry and ultimately controlthe proliferation and cell growth as well as their role in B-CLL progression. The study was conducted in peripheral bloodCLL lymphocytes of 40 previously untreated patients. Statistical analysis of correlations of TP53, cyclin D2, c-Myc,p21WAF1/CIP1 and p27KIP1 expressions in B-CLL patients with different Rai stages demonstrated that the progression of diseasewas accompanied by increases in p53, cyclin D2 and c-Myc mRNA expression. The expression of p27KIP1 was nearlystatistically significant whereas that of p21 WAF1/CIP1 showed no such correlation. Moreover, high expression levels of TP53and c-Myc genes were found to be closely associated with more aggressive forms of the disease requiring earlier therapy.

  1. Effect of Dihuang Guanshitong Granules on c-myc, TERT Protein Expression in Esophageal Cancer Rat Model after Radiotherapy%地黄管食通颗粒对放射治疗后食管癌模型大鼠c-myc,TERT表达的影响

    Institute of Scientific and Technical Information of China (English)

    王祥麒; 郑玉玲; 王俊涛; 韩倩倩

    2011-01-01

    观察地黄管食通颗粒对食管癌造模大鼠细胞凋亡及放疗后原癌基因( c-myc),端粒酶逆转录酶(TERT)蛋白表达的影响,从分子生物学角度分析其作用机制.方法 选用清洁级Wistar大鼠,除空白对照组(正常组)外,其余大鼠均以甲基戊基亚硝胺5 mg·kg -1sc,每周1次,连续18周,确定造模成功后,除模型组大鼠外,余造模大鼠均以戊巴比妥钠麻醉,钴60放射治疗机进行食管局部照射.末次照射24 h后,随机分为放疗组、地黄管食通高、中、低剂量组、六味地黄丸(阳性对照4.5g·kg-1)组,分别ig,连续35 d.应用TUNEL法检测对食管癌癌细胞凋亡的促进作用;免疫组化检测大鼠食管细胞中c-myc,TERT蛋白的表达.结果 ①TUNEL法检测各组均见有细胞凋亡,且药物治疗各组细胞凋亡指数明显增高,高剂量组细胞凋亡明显增多.②免疫组化结果显示c-myc蛋白在模型组、放疗组表达率及表达强度均明显增高,药物治疗组均有不同程度的降低,以高剂量组降低最明显(P<0.05),高剂量组与放疗组比较有统计学意义(P<0.05).③与放疗组比较,各药物组TERT蛋白表达均呈递减趋势,高、中、低剂量组有统计学意义(P<0.01,P<0.05).结论 诱导细胞凋亡是地黄管食通颗粒在体内杀伤食管癌细胞的作用机制之一,而这一作用机制与抑制c -myc,TERT蛋白的表达相关;该药物还可有效改善食管癌化疗后副作用,并预防复发.%Objective: To observe the effect of a combination of traditional Chinese herbs Dihuang Cuanshitong Granules on the rat model of esophageal cancer after rradiotherapy for inducing apoptosis and the c-myc, TERT protein expression. Method: Wistar rats were randomly divided into 2 groups. They were treated with MAN A 5 mg·kg-1 by subsutaneous injection except control group (the normal). After the model was successful, the model rats were treated with Intraperitoneal injection of sodium

  2. Opposite long-term regulation of c-Myc and p27Kip1 through overactivation of Raf-1 and the MEK/ERK module in proliferating human choroidal melanoma cells.

    Science.gov (United States)

    Lefevre, Gaëlle; Calipel, Armelle; Mouriaux, Frédéric; Hecquet, Christiane; Malecaze, François; Mascarelli, Frédéric

    2003-12-01

    Although there is no current evidence for ras gene mutation in choroidal melanoma, there is an increasing body of evidence indicating that deregulated intracellular signalling pathways are involved in choroidal melanoma pathogenesis. The various components of the linear Raf/MEK/ERK signalling pathway have been implicated in various tumours. We therefore investigated the role of Raf-1 and the MEK/ERK module in the proliferation of human normal choroidal melanocytes (NCM) and cells from the ocular choroidal melanoma (OCM-1) cell line. OCM-1 cells proliferated four times faster than NCM. High basal activation of the MEK/ERK module was observed in unstimulated OCM-1 cells, whereas rapid and persistent activation was detected after serum stimulation, throughout the 24-h period of culture. In contrast, the activation of MEK/ERK was barely detectable in unstimulated NCM and occurred late (6 h) after the stimulation of cell proliferation. Inhibition of Raf-1 and MEK1/2 activation by pharmacological approaches and of the production of Raf-1 and ERK1/2 by antisense oligonucleotide approaches demonstrated that Raf-1 and the MEK/ERK module controlled proliferation in OCM-1 cells, but not in NCM. OCM-1 cells produced very low levels of p27Kip1, whereas NCM produced constant, high levels of p27Kip1. The inhibition of Raf-1 or MEK1/2 induced a large increase in p27Kip1 in OCM-1 cells, associated with an arrest of cell proliferation. Levels of c-Myc production were high and constant in OCM-1 cells and low in NCM, in contrast to what was observed for p27Kip1. The inhibition of both Raf-1 and MEK1/2 induced a decrease in c-Myc production and downregulated c-Myc activity by preventing c-Myc phosphorylation in OCM-1 cells. We conclude that Raf-1 and the MEK/ERK module control the production of both p27Kip1 and c-Myc, and the activation of c-Myc for OCM-1 cell proliferation. PMID:14654778

  3. Genomic amplification patterns of human telomerase RNA gene and C-MYC in liquid-based cytological specimens used for the detection of high-grade cervical intraepithelial neoplasia

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    Chen Shaomin

    2012-04-01

    Full Text Available Abstract Background The amplification of oncogenes initiated by high-risk human papillomavirus (HPV infection is an early event in cervical carcinogenesis and can be used for cervical lesion diagnosis. We measured the genomic amplification rates and the patterns of human telomerase RNA gene (TERC and C-MYC in the liquid-based cytological specimens to evaluate the diagnostic characteristics for the detection of high-grade cervical lesions. Methods Two hundred and forty-three residual cytological specimens were obtained from outpatients aged 25 to 64 years at Qilu Hospital, Shandong University. The specimens were evaluated by fluorescence in situ hybridization (FISH using chromosome probes to TERC (3q26 and C-MYC (8q24. All of the patients underwent colposcopic examination and histological evaluation. A Chi-square test was used for categorical data analysis. Results In the normal, cervical intraepithelial neoplasia grade 1 (CIN1, grade 2 (CIN2, grade 3 (CIN3 and squamous cervical cancer (SCC cases, the TERC positive rates were 9.2%, 17.2%, 76.2%, 100.0% and 100.0%, respectively; the C-MYC positive rates were 20.7%, 31.0%, 71.4%, 81.8% and 100.0%, respectively. The TERC and C-MYC positive rates were higher in the CIN2+ (CIN2, CIN3 and SCC cases than in the normal and CIN1 cases (p p p > 0.05. Conclusions The TERC test is highly sensitive and is therefore suitable for cervical cancer screening. The C-MYC test is not suitable for cancer screening because of its lower sensitivity. The amplification patterns of TERC become more diverse and complex as the severity of cervical diseases increases, whereas for C-MYC, the amplification patterns are similar between the normal/CIN1 and CIN2+ groups. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1308004512669913.

  4. Generation of liver-specific TGF-α/c-Myc-overexpressing porcine induced pluripotent stem-like cells and blastocyst formation using nuclear transfer.

    Science.gov (United States)

    Park, Kyung-Mee; Lee, Joohyeong; Hussein, Kamal Hany; Hong, Seok-Ho; Yang, Se-Ran; Lee, Eunsong; Woo, Heung-Myong

    2016-05-01

    Transgenic porcine induced pluripotent stem (iPS) cells are attractive cell sources for the development of genetically engineered pig models, because they can be expanded without senescence and have the potential for multiple gene manipulation. They are also useful cell sources for disease modeling and treatment. However, the generation of transgenic porcine iPS cells is rare, and their embryonic development after nuclear transfer (NT) has not yet been reported. We report here the generation of liver-specific oncogenes (TGF-α/c-Myc)-overexpressing porcine iPS (T/M iPS)-like cells. They expressed stem cell characteristics and were differentiated into hepatocyte-like cells that express oncogenes. We also confirmed that NT embryos derived from T/M iPS-like cells successfully developed blastocysts in vitro. As an initial approach toward porcine transgenic iPS cell generation and their developmental competence after NT, this study provides foundations for the efficient generation of genetically modified porcine iPS cells and animal models. PMID:26725870

  5. 4EBP1/c-MYC/PUMA and NF-κB/EGR1/BIM pathways underlie cytotoxicity of mTOR dual inhibitors in malignant lymphoid cells.

    Science.gov (United States)

    Yun, Seongseok; Vincelette, Nicole D; Knorr, Katherine L B; Almada, Luciana L; Schneider, Paula A; Peterson, Kevin L; Flatten, Karen S; Dai, Haiming; Pratz, Keith W; Hess, Allan D; Smith, B Douglas; Karp, Judith E; Hendrickson, Andrea E Wahner; Fernandez-Zapico, Martin E; Kaufmann, Scott H

    2016-06-01

    The mammalian target of rapamycin (mTOR), a kinase that regulates proliferation and apoptosis, has been extensively evaluated as a therapeutic target in multiple malignancies. Rapamycin analogs, which partially inhibit mTOR complex 1 (mTORC1), exhibit immunosuppressive and limited antitumor activity, but sometimes activate survival pathways through feedback mechanisms involving mTORC2. Thus, attention has turned to agents targeting both mTOR complexes by binding the mTOR active site. Here we show that disruption of either mTOR-containing complex is toxic to acute lymphocytic leukemia (ALL) cells and identify 2 previously unrecognized pathways leading to this cell death. Inhibition of mTORC1-mediated 4EBP1 phosphorylation leads to decreased expression of c-MYC and subsequent upregulation of the proapoptotic BCL2 family member PUMA, whereas inhibition of mTORC2 results in nuclear factor-κB-mediated expression of the Early Growth Response 1 (EGR1) gene, which encodes a transcription factor that binds and transactivates the proapoptotic BCL2L11 locus encoding BIM. Importantly, 1 or both pathways contribute to death of malignant lymphoid cells after treatment with dual mTORC1/mTORC2 inhibitors. Collectively, these observations not only provide new insight into the survival roles of mTOR in lymphoid malignancies, but also identify alterations that potentially modulate the action of mTOR dual inhibitors in ALL. PMID:26917778

  6. miR-34a induces cellular senescence via modulation of telomerase activity in human hepatocellular carcinoma by targeting FoxM1/c-Myc pathway.

    Science.gov (United States)

    Xu, Xinsen; Chen, Wei; Miao, Runchen; Zhou, Yanyan; Wang, Zhixin; Zhang, Lingqiang; Wan, Yong; Dong, Yafeng; Qu, Kai; Liu, Chang

    2015-02-28

    Increasing evidence suggests that miRNAs can act as either tumor suppressors or oncogenes in carcinogenesis. In the present study, we identified the role of miR-34a in regulating telomerase activity, with subsequent effect on cellular senescence and viability. We found the higher expression of miR-34a was significantly correlated with the advanced clinicopathologic parameters in hepatocellular carcinoma. Furthermore, tumor tissues of 75 HCC patients demonstrated an inverse correlation between the miR-34a level and telomere indices (telomere length and telomerase activity). Transient introduction of miR-34a into HCC cell lines inhibited the telomerase activity and telomere length, which induced senescence-like phenotypes and affected cellular viability. We discovered that miR-34a potently targeted c-Myc and FoxM1, both of which were involved in the activation of telomerase reverse transcriptase (hTERT) transcription, essential for the sustaining activity of telomerase to avoid senescence. Taken together, our results demonstrate that miR-34a functions as a potent tumor suppressor through the modulation of telomere pathway in cellular senescence. PMID:25686834

  7. Elevated levels of a specific class of nuclear phosphoproteins in cells transformed with v-ras and v-mos oncogenes and by cotransfection with c-myc and polyoma middle T genes.

    OpenAIRE

    Giancotti, V; Pani, B.; D'Andrea, P; Berlingieri, M T; Di Fiore, P P; Fusco, A; Vecchio, G; Philp, R.; Crane-Robinson, C; Nicolas, R H

    1987-01-01

    Transformation of a rat thyroid epithelial cell line (FRTL5-C12) with Kirsten and Harvey murine sarcoma viruses (carrying the ras oncogenes) results in elevated levels of three perchloric acid-soluble nuclear phosphoproteins. These three proteins are also induced to high levels in the PC-C13 thyroid epithelial cell line when transformed by the myeloproliferative sarcoma virus (carrying the v-mos oncogene) and when transformed by transfection with the c-myc proto-oncogene followed by infection...

  8. Suppression of c-Myc is involved in multi-walled carbon nanotubes' down-regulation of ATP-binding cassette transporters in human colon adenocarcinoma cells

    International Nuclear Information System (INIS)

    Over-expression of ATP-binding cassette (ABC) transporters, a large family of integral membrane proteins that decrease cellular drug uptake and accumulation by active extrusion, is one of the major causes of cancer multi-drug resistance (MDR) that frequently leads to failure of chemotherapy. Carbon nanotubes (CNTs)-based drug delivery devices hold great promise in enhancing the efficacy of cancer chemotherapy. However, CNTs' effects on the ABC transporters remain under-investigated. In this study, we found that multiwalled carbon nanotubes (MWCNTs) reduced transport activity and expression of ABC transporters including ABCB1/Pgp and ABCC4/MRP4 in human colon adenocarcinoma Caco-2 cells. Proto-oncogene c-Myc, which directly regulates ABC gene expression, was concurrently decreased in MWCNT-treated cells and forced over-expression of c-Myc reversed MWCNTs' inhibitory effects on ABCB1 and ABCC4 expression. MWCNT-cell membrane interaction and cell membrane oxidative damage were observed. However, antioxidants such as vitamin C, β-mecaptoethanol and dimethylthiourea failed to antagonize MWCNTs' down-regulation of ABC transporters. These data suggest that MWCNTs may act on c-Myc, but not through oxidative stress, to down-regulate ABC transporter expression. Our findings thus shed light on CNTs' novel cellular effects that may be utilized to develop CNTs-based drug delivery devices to overcome ABC transporter-mediated cancer chemoresistance

  9. Suppression of c-Myc is involved in multi-walled carbon nanotubes' down-regulation of ATP-binding cassette transporters in human colon adenocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhaojing [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China); Xu, Yonghong [Institute of Ophthalmological Research, Department of Ophthalmology, Renmin Hospital of Wuhan University, 430060 Wuhan (China); Meng, Xiangning [School of Materials and Metallurgy, Northeastern University, Shenyang 110819 (China); Watari, Fumio [Department of Biomedical, Dental Materials and Engineering, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586 (Japan); Liu, Hudan, E-mail: hudanliu@hust.edu.cn [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China); Chen, Xiao, E-mail: mornsmile@yahoo.com [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China)

    2015-01-01

    Over-expression of ATP-binding cassette (ABC) transporters, a large family of integral membrane proteins that decrease cellular drug uptake and accumulation by active extrusion, is one of the major causes of cancer multi-drug resistance (MDR) that frequently leads to failure of chemotherapy. Carbon nanotubes (CNTs)-based drug delivery devices hold great promise in enhancing the efficacy of cancer chemotherapy. However, CNTs' effects on the ABC transporters remain under-investigated. In this study, we found that multiwalled carbon nanotubes (MWCNTs) reduced transport activity and expression of ABC transporters including ABCB1/Pgp and ABCC4/MRP4 in human colon adenocarcinoma Caco-2 cells. Proto-oncogene c-Myc, which directly regulates ABC gene expression, was concurrently decreased in MWCNT-treated cells and forced over-expression of c-Myc reversed MWCNTs' inhibitory effects on ABCB1 and ABCC4 expression. MWCNT-cell membrane interaction and cell membrane oxidative damage were observed. However, antioxidants such as vitamin C, β-mecaptoethanol and dimethylthiourea failed to antagonize MWCNTs' down-regulation of ABC transporters. These data suggest that MWCNTs may act on c-Myc, but not through oxidative stress, to down-regulate ABC transporter expression. Our findings thus shed light on CNTs' novel cellular effects that may be utilized to develop CNTs-based drug delivery devices to overcome ABC transporter-mediated cancer chemoresistance.

  10. Transcriptome Analysis of WHV/c-myc Transgenic Mice Implicates Cytochrome P450 Enzyme 17A1 as a Promising Biomarker for Hepatocellular Carcinoma.

    Science.gov (United States)

    Wang, Feng; Huang, Jian; Zhu, Zhu; Ma, Xiao; Cao, Li; Zhang, Yongzhi; Chen, Wei; Dong, Yang

    2016-09-01

    Early detection of hepatocellular carcinoma (HCC) is critical for successful treatment and favorable prognosis. To identify novel HCC biomarkers, we used the WHV/c-myc transgenic (Tg) mice, an animal model of hepatocarcinogenesis. By analyzing their gene expression profiling, we investigated differentially expressed genes in livers of wild-type and Tg mice. The cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17A1), a hepatic P450 enzyme, was revealed to be overexpressed in the liver tissues of Tg mice at both preneoplastic and neoplastic stages. Mouse-to-human validation demonstrated that CYP17A1 mRNA and protein were also significantly increased in human HCC tissues compared with paired nontumor tissues (P = 0.00041 and 0.00011, respectively). Immunohistochemical studies showed that CYP17A1 was overexpressed in 67% (58 of 87) of HCC, and strong staining of CYP17A1 was observed in well-differentiated HCCs. Consistent with this, the median serum levels of CYP17A1 were also significantly higher in patients with HCC (140.2 ng/mL, n = 776) compared with healthy controls (31.4 ng/mL, n = 366) and to those with hepatitis B virus (57.5 ng/mL, n = 160), cirrhosis (46.1 ng/mL, n = 147), lung cancer (27.4 ng/mL, n = 109), and prostate cancer (42.1 ng/mL, n = 130; all P AFP-negative HCC cases. Altogether, through mouse-to-human search and validation, we found that CYP17A1 is overexpressed in HCCs and it has great potentiality as a noninvasive marker for HCC detection. These results provide a rationale for the future development and clinical application of CYP17A1 measurement to diagnose HCC more precisely. Cancer Prev Res; 9(9); 739-49. ©2016 AACR. PMID:27339169

  11. Pokemon和c-myc在结直肠癌中的表达及临床意义%Expressions of Pokemon and c-myc in colorectal cancer and their clinical significance

    Institute of Scientific and Technical Information of China (English)

    郭柏华; 杨章林; 董国钢; 王笑凌; 班雨

    2015-01-01

    Objective To investigate the expressions of Pokemon and c-myc in colorectal cancer,colorectal adenomas and normal colorectal mucosa tissues,and demonstrate its relationship with clinicopathological features and prognosis in patients with colorectal cancer.Methods The specimens were taken from colorectal cancer tissue of 86 patients,colorectal adenomas tissue of 60 patients,and 40 normal colorectal mucosa tissue.The expressions of Pokemon and c-myc protein were detected by immunohistochemistry,and the expressions of Pokemon and c-myc gene were detected by reverse transcription polymerase chain reaction (RT-PCR).The correlation between the expressions of Pokemon and c-myc,and clinicopathological features was analyzed.Results The positive expression rates of Pokemon and c-myc protein in colorectal cancer tissue were significantly higher than those in colorectal adenomas tissue and normal colorectal mucosa tissue:69.8% (60/86) vs.13.3% (8/60) and 5.0% (2/40),73.3% (63/86) vs.15.0% (9/60) and 2.5%(1/40),and the expression levels of Pokemon and c-myc gene in colorectal cancer tissue were significantly higher than those in colorectal adenomas tissue and normal colorectal mucosa tissue:0.915 ±0.247 vs.0.358 ±0.102 and 0.277 ±0.085,1.272 ±0.360 vs.0.398 ± 0.153 and 0.255 ±0.097,there were statistical differences (P < 0.05).The expression levels of Pokemon and c-myc gene in colorectal cancer tissue had a close correlation with the degree of infiltration,histological differentiation,lymph node metastasis,distant metastasis and Dukes stage,there were statistical differences (P < 0.05),but had no correlation with the sex,age,and tumor diameter (P > 0.05).Conclusions The expression levels of Pokemon and c-myc are higher in colorectal cancer tissue,and the expressions are related to the clinicopathological features of colorectal cancer.The expression levels of Pokemon and c-myc may predict the prognosis in patients with colorectal cancer.%目的 检

  12. Pokemon mRNA在乳腺癌中的表达及与c- myc相关性分析%Expression of Pokemon mRNA in breast carcinoma and its relationship to c-myc

    Institute of Scientific and Technical Information of China (English)

    付朝江; 崔明; 徐衍; 王应霞

    2011-01-01

    目的:探讨人乳腺癌中原癌基因c-myc和Pokemon mRNA在乳腺癌组织中的表达及其与乳腺癌发生、转移的相关性.方法:收集浸润性导管癌组织、癌旁乳腺组织、正常乳腺组织各45、20和20例,用原位杂交法检测Pokemon mRNA表达,并用免疫组织化学法检测浸润性导管癌c-myc表达,并进行统计分析.结果:乳腺癌细胞质Pokemon mRNA的表达率为71.2%(37/45),显著高于癌旁正常乳腺组织40%(8/20)、乳腺增生组织25%(5/20), 三者有显著性差异 (P<0.05),细胞质c-myc阳性率分别为86.67%、60.0%、50.0%,三者有显著性差异(P<0.05).细胞质Pokemon mRNA表达与乳腺癌淋巴结转移、组织学分级相关(P<0.05).细胞质c-myc表达与乳腺癌腋窝淋巴结转移相关(P<0.05).45例乳腺癌细胞质Pokemon mRNA与c-myc表达呈正相关(γ=0.585 ,P<0.05).结论:Pokemon mRNA的表达可能在乳腺导管癌的组织发生中起关键作用,c-myc的过度表达可能与乳腺癌Pokemon基因转录激活有关.%Objective: To explore the expression and interaction of Pokemon mRNA and proto - oncogene c - myc in the course of carcinogenesis and metastasis of breast cancer.Methods : The expression of Pokemon mRNA was examined by in situhybridization in 45 cases of breast cancer,20 cases of adjacent noncancerous breast tissue and 20 cases of mammary gland hyperplasia,The expression of c - myc was examined by immunohistochemistry in 45 cases of carcinoma.Results:The rate of strong positive plasma Pokemon mRNA and c - myc expression was significandy higher in breast cancer than in adjacent noncancerous breast tissue and mammary gland hyperplasia ( P < 0.05 ) , the rates of strong positive plasma Pokemon expression were 71.2% ( 37/45 ) ,40% ( 8/20) , 25 % ( 5/20) ;86.67% 、60.0% 、50.0% , respectively.The positive expreasion of Pokemon mRNA and c - myc in breast cancer was strongly related to lympb nodemetastasis(P <0.05) .The expre8aion of Pokemon m

  13. A mouse strain defective in both T cells and NK cells has enhanced sensitivity to tumor induction by plasmid DNA expressing both activated H-Ras and c-Myc.

    Directory of Open Access Journals (Sweden)

    Li Sheng-Fowler

    Full Text Available As part of safety studies to evaluate the risk of residual cellular DNA in vaccines manufactured in tumorigenic cells, we have been developing in vivo assays to detect and quantify the oncogenic activity of DNA. We generated a plasmid expressing both an activated human H-ras gene and murine c-myc gene and showed that 1 µg of this plasmid, pMSV-T24-H-ras/MSV-c-myc, was capable of inducing tumors in newborn NIH Swiss mice. However, to be able to detect the oncogenicity of dominant activated oncogenes in cellular DNA, a more sensitive system was needed. In this paper, we demonstrate that the newborn CD3 epsilon transgenic mouse, which is defective in both T-cell and NK-cell functions, can detect the oncogenic activity of 25 ng of the circular form of pMSV-T24-H-ras/MSV-c-myc. When this plasmid was inoculated as linear DNA, amounts of DNA as low as 800 pg were capable of inducing tumors. Animals were found that had multiple tumors, and these tumors were independent and likely clonal. These results demonstrate that the newborn CD3 epsilon mouse is highly sensitive for the detection of oncogenic activity of DNA. To determine whether it can detect the oncogenic activity of cellular DNA derived from four human tumor-cell lines (HeLa, A549, HT-1080, and CEM, DNA (100 µg was inoculated into newborn CD3 epsilon mice both in the presence of 1 µg of linear pMSV-T24-H-ras/MSV-c-myc as positive control and in its absence. While tumors were induced in 100% of mice with the positive-control plasmid, no tumors were induced in mice receiving any of the tumor DNAs alone. These results demonstrate that detection of oncogenes in cellular DNA derived from four human tumor-derived cell lines in this mouse system was not possible; the results also show the importance of including a positive-control plasmid to detect inhibitory effects of the cellular DNA.

  14. S-Adenosylmethionine Inhibits the Growth of Cancer Cells by Reversing the Hypomethylation Status of c-myc and H-ras in Human Gastric Cancer and Colon Cancer

    OpenAIRE

    Luo, Jin; Li, Yan-Ni; Wang, Fei; Zhang, Wei-ming; Geng, Xin

    2010-01-01

    A global DNA hypomethylation might activate oncogene transcription, thus promoting carcinogenesis and tumor development. S-Adenosylmethionine (SAM) serves as a major methyl donor in biological transmethylation events. The object of this study is to explore the influence of SAM on the status of methylation at the promoter of the oncogenes c-myc, H-ras and tumor-suppressor gene p16 (INK4a), as well as its inhibitory effect on cancer cells. The results indicated that SAM treatment inhibited cell...

  15. Two-step stimulation of B lymphocytes to enter DNA synthesis: synergy between anti-immunoglobulin antibody and cytochalasin on expression of c-myc and a G1-specific gene.

    OpenAIRE

    Buckler, A J; Rothstein, T. L.; Sonenshein, G E

    1988-01-01

    Previously we demonstrated that stimulation of resting murine splenic B lymphocytes with goat anti-mouse immunoglobulin antibody (GaMIg) plus cytochalasin D (CD) led to DNA synthesis; GaMIg and CD added simultaneously, or GaMIg added before CD, induced this response (T. L. Rothstein, J. Immunol. 136:813-816, 1986). Cells similarly treated with GaMIg or CD alone did not enter S phase. Here we have measured the effects of this two-signal stimulation on the c-myc, 2F1, and gamma-actin genes. The...

  16. S-Adenosylmethionine Inhibits the Growth of Cancer Cells by Reversing the Hypomethylation Status of c-myc and H-ras in Human Gastric Cancer and Colon Cancer

    Directory of Open Access Journals (Sweden)

    Jin Luo, Yan-Ni Li, Fei Wang, Wei-Ming Zhang, Xin Geng

    2010-01-01

    Full Text Available A global DNA hypomethylation might activate oncogene transcription, thus promoting carcinogenesis and tumor development. S-Adenosylmethionine (SAM serves as a major methyl donor in biological transmethylation events. The object of this study is to explore the influence of SAM on the status of methylation at the promoter of the oncogenes c-myc, H-ras and tumor-suppressor gene p16 (INK4a, as well as its inhibitory effect on cancer cells. The results indicated that SAM treatment inhibited cell growth in gastric cancer cells and colon cancer cells, and the inhibition efficiency was significantly higher than that in the normal cells. Under standard growth conditions, C-myc and H-ras promoters were hypomethylated in gastric cancer cells and colon cancer cells. SAM treatment resulted in a heavy methylation of these promoters, which consequently downregulated mRNA and protein levels. In contrast, there was no significant difference in mRNA and protein levels of p16 (INK4a with and without SAM treatment. SAM can effectively inhibit the tumor cells growth by reversing the DNA hypomethylation on promoters of oncogenes, thus down-regulating their expression. With no influence on the expression of the tumor suppressor genes, such as P16, SAM could be used as a potential drug for cancer therapy.

  17. Vitamin K2 and cotylenin A synergistically induce monocytic differentiation and growth arrest along with the suppression of c-MYC expression and induction of cyclin G2 expression in human leukemia HL-60 cells.

    Science.gov (United States)

    Maniwa, Yasuhisa; Kasukabe, Takashi; Kumakura, Shunichi

    2015-08-01

    Although all-trans retinoic acid (ATRA) is a standard and effective drug used for differentiation therapy in acute promyelocytic leukemia, ATRA-resistant leukemia cells ultimately emerge during this treatment. Therefore, the development of new drugs or effective combination therapy is urgently needed. We demonstrate that the combined treatment of vitamin K2 and cotylenin A synergistically induced monocytic differentiation in HL-60 cells. This combined treatment also synergistically induced NBT-reducing activity and non-specific esterase-positive cells as well as morphological changes to monocyte/macrophage-like cells. Vitamin K2 and cotylenin A cooperatively inhibited the proliferation of HL-60 cells in short-term and long-term cultures. This treatment also induced growth arrest at the G1 phase. Although 5 µg/ml cotylenin A or 5 µM vitamin K2 alone reduced c-MYC gene expression in HL-60 cells to approximately 45% or 80% that of control cells, respectively, the combined treatment almost completely suppressed c-MYC gene expression. We also demonstrated that the combined treatment of vitamin K2 and cotylenin A synergistically induced the expression of cyclin G2, which had a positive effect on the promotion and maintenance of cell cycle arrest. These results suggest that the combination of vitamin K2 and cotylenin A has therapeutic value in the treatment of acute myeloid leukemia. PMID:26046133

  18. Overexpression of v-abl uniquely cooperates with c-myc dysregulation in induction of plasma cell tumors, bypassing the need for T-lymphocytic help and overcoming T-lymphocytic interference.

    Science.gov (United States)

    Weissinger, E M; Byrd, L G; Henderson, D W; Mushinski, J F

    1996-07-01

    We have investigated the effects of T lymphocytes on induction of mouse plasma cell tumors. We show that ABL-MYC, a plasmacytomagenic retrovirus that constitutively expresses v-abl and c-myc, is able to induce plasmacytomas in 100% of athymic BALB/c mice, with or without intraperitoneal pristane pretreatment. Other induction regimens are ineffective under these conditions, indicating that the combination of v-abl and c-myc oncogenes is uniquely able to transform plasma cells in mice that are deficient in T lymphocytes. Furthermore, in the absence of pristane, ABL-MYC-infected athymic congenics developed plasmacytomas in half the time required for euthymic BALB/c mice, suggesting that T lymphocytes can have a negative effect and can retard, but not totally inhibit, the outgrowth of plasmacytomas. This phenomenon could not be appreciated in other regimens of plasmacytoma induction, because only ABL-MYC is sufficient to induce plasmacytomas in athymic mice or in euthymic mice in the absence of pristane pretreatment. PMID:8690515

  19. Disruption of the CREBBP gene and decreased expression of CREB, NFκB p65, c-JUN, c-FOS, BCL2 and c-MYC suggest immune dysregulation.

    Science.gov (United States)

    Torres, Leuridan Cavalcante; Kulikowski, Leslie Domenici; Ramos, Patrícia Locosque; Sugayama, Sofia Mizuko Miura; Moreira-Filho, Carlos Alberto; Carneiro-Sampaio, Magda

    2013-08-01

    Genomic aberrations in the CREBBP (CREB-binding protein - CREBBP or CBP) gene such as point mutations, small insertions or exonic copy number changes are usually associated with Rubinstein-Taybi syndrome (RTs). In this study, the disruption of the CREBBP gene on chromosome 16p13.3, as revealed by CGH-array and FISH, suggests immune dysregulation in a patient with the Rubinstein Taybi syndrome (RTs) phenotype. Further investigation with Western blot techniques demonstrated decreased expression of CREB, NFκB, c-Jun, c-Fos, BCL2 and cMyc in peripheral blood mononuclear cells, thus indicating that the CREBBP gene is essential for the normal expression of these proteins and the regulation of immune responses. PMID:23643710

  20. The Phosphoinositide 3-Kinase p110α Isoform Regulates Leukemia Inhibitory Factor Receptor Expression via c-Myc and miR-125b to Promote Cell Proliferation in Medulloblastoma.

    Directory of Open Access Journals (Sweden)

    Fabiana Salm

    Full Text Available Medulloblastoma (MB is the most common malignant brain tumor in childhood and represents the main cause of cancer-related death in this age group. The phosphoinositide 3-kinase (PI3K pathway has been shown to play an important role in the regulation of medulloblastoma cell survival and proliferation, but the molecular mechanisms and downstream effectors underlying PI3K signaling still remain elusive. The impact of RNA interference (RNAi-mediated silencing of PI3K isoforms p110α and p110δ on global gene expression was investigated by DNA microarray analysis in medulloblastoma cell lines. A subset of genes with selectively altered expression upon p110α silencing in comparison to silencing of the closely related p110δ isoform was revealed. Among these genes, the leukemia inhibitory factor receptor α (LIFR α was validated as a novel p110α target in medulloblastoma. A network involving c-Myc and miR-125b was shown to be involved in the control of LIFRα expression downstream of p110α. Targeting the LIFRα by RNAi, or by using neutralizing reagents impaired medulloblastoma cell proliferation in vitro and induced a tumor volume reduction in vivo. An analysis of primary tumors revealed that LIFRα and p110α expression were elevated in the sonic hedgehog (SHH subgroup of medulloblastoma, indicating its clinical relevance. Together, these data reveal a novel molecular signaling network, in which PI3K isoform p110α controls the expression of LIFRα via c-Myc and miR-125b to promote MB cell proliferation.

  1. CyclinA、C-myc在皮肤瘢痕及瘢痕癌组织中的表达及意义%Expressions and Significance of CyclinA and C-myc in Skin Scar and Skin Scar Carcinoma

    Institute of Scientific and Technical Information of China (English)

    郭瑞珍; 周开梅; 王燕

    2011-01-01

    目的 探讨CyclinA、C-myc在皮肤病理性瘢痕和瘢痕癌组织中的表达及意义.方法以病理性皮肤瘢痕、皮肤瘢痕癌组织为研究对象,以正常皮肤组织为对照.采用免疫组织化学(SP法)分别检测CyclinA、C-myc蛋白的表达,采用核酸分子原位杂交法检测CyclinA mRNA的表达,所有数据输入计算机后运用SPSS 16.0软件包进行统计学分析.结果 (1)CyclinA、CyclinA mRNA在正常皮肤和皮肤瘢痕上皮中的表达呈阴性或弱阳性,在瘢痕癌组织中呈强阳性.瘢痕癌组的表达(平均吸光度和阳性面积)与正常皮肤组及皮肤瘢痕组比较,差异均有统计学意义(P<0.01);但正常皮肤组与瘢痕组比较,差异无统计学意义(P>0.05).(2)C-myc蛋白在正常皮肤中的表达呈弱阳性,在皮肤瘢痕上皮中呈阳性,在瘢痕癌组织中呈强阳性.且两两比较差异均有统计学意义(P<0.05).(3)相关分析显示,在皮肤瘢痕癌中,CyclinA与CyclinA mRNA(r=0.766,P<0.01)、CyclinA与C-myc蛋白(r=0.804,P<0.01)的表达均呈正相关.结论(1)CyclinA及其mRNA、C-myc的高表达,可能与皮肤瘢痕癌的发生有关;(2)C-myc蛋白的高表达与皮肤瘢痕上皮癌变有相关性.(3)在瘢痕癌中CyclinA同时存在蛋白水平和基因水平的异常表达.%Objective To study the expressions and significance of CyclinA and C-myc in skin Scar and skin Scar Carcinoma. Methods We compared pathological skin scar tissues and skin scar carcinoma tissues with normal skin tissues. The expression of CyclinA and C-myc proteins were detected by the immu-nohistochemical method of SP. And the expression of CyclinA mRNA was detected by in situ hybridization. All data were input into the computer and statistically analyzed with SPSS (16. 0) software. Results (1) CyclinA and its mRNA showed strong positive expression in scar carcinoma tissues, negative or weakly positive expression in normal skin epidermis and pathological skin scar epithelium

  2. Effect of TGF-β1 on cell proliferation and c-myc expression in Burkitt lymphoma cell line%TGF-β1对Burkitt淋巴瘤细胞增殖及c-myc表达的影响

    Institute of Scientific and Technical Information of China (English)

    李柱虎; Lee Mija

    2006-01-01

    目的:探讨TGF-β1对Burkitt淋巴瘤细胞生长的抑制作用和对c-myc基因及蛋白表达的影响.方法:于Burkitt淋巴瘤细胞株Jiyoye中加入5ng/mL TGF-β1做为实验组,不加TGF-β1做为对照组,分别培养24、48和72 h,用MTT、RT-PCR及Westem blot方法检测细胞生存率、c-myc mRNA及蛋白的表达水平.结果:经TGF-β1处理24、48和72 h的Jiyoye细胞生存率分别为(80.5±3.14)%、(70.5±3.77)%和(56.4±3.36)%,与对照组相比均显著降低(t=8.788 0,P=0.012 7;t=13.570 9,P=0.005 4;t=22.500 6,P=0.019 7).经TGF-β1处理的Jiyoye细胞随时间的延长生存率降低,72 h时的生存率与24h相比差异有统计学意义,t=8.186 2,P=0.001 2;c-myc mRNA及蛋白的表达水平也明显变化,24 h开始下降,48和72 h时明显受抑制,与对照组相比差异有统计学意义,P=0.000 0.结论:TGF-β1可呈时间依赖性抑制Jiyoye细胞的生长,其机制可能与抑制c-myc基因及蛋白的表达有关.

  3. Complex Biological Systems Analysis of Cell Cycling Models in Carcinogenesis: I. The essential roles of modifications in the c-Myc, TP53/p53, p27 and hTERT modules in Cancer Initiation and Progression

    CERN Document Server

    Prisecaru, V I

    2004-01-01

    A new approach to the integration of results from a modular, complex biological systems analysis of nonlinear dynamics in cell cycling network transformations that are leading to carcinogenesis is proposed. Carcinogenesis is a complex process that involves dynamically inter-connected biomolecules in the intercellular, membrane, cytosolic, nuclear and nucleolar compartments that form numerous inter-related pathways referred to as networks. One such network module contains the cell cyclins whose functions are essential to cell cycling and division. Cyclins are proteins that also link to several critical pro-apoptotic and other cell cycling/division components, such as: c-Myc, p27, the tumor suppressor gene TP53 and its product-- the p53 protein with key roles in controlling DNA repair, inducing apoptosis and activating p21 (which can depress cell cyclins if activated), mdm2(with its biosynthesis activated by p53 and also, in its turn, inhibiting p53), p21, the Thomsen-Friedenreich antigen(T- antigen),Rb,Bax, Ba...

  4. 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

    Oncogenes of the myc family c-raf-1 and K-ras have been reported to modulate radiosensitivity. We examined the possible relationship between in vivo radiosensitivity to single-dose irradiation with 3-10 Gy, and activity of these proto-oncogenes in 2 sets of small-cell lung cancer (SCLC) xenografts......-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 to modulate radiosensitivity. Thus, factors other than activation of the examined proto-oncogenes must be involved in causing the differences in radiosensitivity found in the SCLC xenografts. Possible long-term effects of irradiation on proto-oncogene expression was examined in xenografts of GLC...

  5. Triphala Extract Suppresses Proliferation and Induces Apoptosis in Human Colon Cancer Stem Cells via Suppressing c-Myc/Cyclin D1 and Elevation of Bax/Bcl-2 Ratio

    Directory of Open Access Journals (Sweden)

    Ramakrishna Vadde

    2015-01-01

    Full Text Available Colon cancer is the second leading cause of cancer related deaths in the USA. Cancer stem cells (CSCs have the ability to drive continued expansion of the population of malignant cells. Therefore, strategies that target CSCs could be effective against colon cancer and in reducing the risk of relapse and metastasis. In this study, we evaluated the antiproliferative and proapoptotic effects of triphala, a widely used formulation in Indian traditional medicine, on HCT116 colon cancer cells and human colon cancer stem cells (HCCSCs. The total phenolic content, antioxidant activity, and phytochemical composition (LC-MS-MS of methanol extract of triphala (MET were also measured. We observed that MET contains a variety of phenolics including naringin, quercetin, homoorientin, and isorhamnetin. MET suppressed proliferation independent of p53 status in HCT116 and in HCCSCs. MET also induced p53-independent apoptosis in HCCSCs as indicated by elevated levels of cleaved PARP. Western blotting data suggested that MET suppressed protein levels of c-Myc and cyclin D1, key proteins involved in proliferation, and induced apoptosis through elevation of Bax/Bcl-2 ratio. Furthermore, MET inhibited HCCSCs colony formation, a measure of CSCs self-renewal ability. Anticancer effects of triphala observed in our study warrant future studies to determine its efficacy in vivo.

  6. Detection of gene amplification in MYCN, C-MYC, MYCL1, ERBB2, EGFR, AKT2, and human papilloma virus in samples from cervical smear normal cytology, intraepithelial cervical neoplasia (CIN I, II, III, and cervical cancer

    Directory of Open Access Journals (Sweden)

    Dabeiba Adriana García

    2011-06-01

    Full Text Available Introducción: El cáncer cervical es el segundo cáncer más importante en mujeres a nivel mundial y es la segunda causa de muerte por cáncer en mujeres. Se ha demostrado que el proceso de carcinogénesis cervical presenta componentes tanto genéticos como epigenéticos y medio ambientales. En la actualidad, hay gran interés en la búsqueda de marcadores moleculares asociados con la progresión de esta enfermedad, uno de los posibles mecanismos y que además está poco estudiado en cáncer cervical es la amplificación génica de algunos oncogenes como la familia MYC, EGFR y AKT entre otros. Objetivos: Detectar la amplificación génica de MYCN, C-MYC, MYCL1, ERBB2, EGFR y AKT2 además de la presencia del virus de papiloma humano en cepillados cervicales en mujeres con citología normal o con neoplasia intraepitelial cervical (NIC I, II y III o con cáncer cervical. Métodos: Se genotipificó mediante reverse line blot (RLB el virus de papiloma humano (VPH y se determinó el estado de amplificación génica de los genes mencionados mediante PCR en tiempo real utilizando sondas taqman. Resultados: El VPH se encontró presente en 4% de las pacientes con citología normal, en 48% en NIC I, 63.6% en NIC II, 64% en NIC III y 70.8% en cáncer cervical. Los genes MYCN, MYCL1 y ERBB2 mostraron mayor amplificación en lesiones de alto grado y cáncer con diferencias estadísticamente significativas  a las lesiones de bajo grado y citología normal, en 39.1%, 34.7% y 30.4% respectivamente. Además, se encontraron amplificados los genes C-MYC, EGFR y AKT2, en muestras de pacientes con cáncer cervical, en 12%, 18% y 13% respectivamente. Sin embargo, no se observaron diferencias estadísticamente significativas con respecto a las lesiones de alto y bajo grado y citología normal. Conclusión: En las lesiones de alto grado como en cáncer cervical, se encuentra mayor prevalencia del virus al igual que se detectan mayor cantidad de alteraciones gen

  7. The research of the influence of Pingyangmycin on c-myc and Ras-P21 protein expression in penile cancer%平阳霉素对阴茎癌组织c-myc及Ras-P21蛋白表达影响的研究

    Institute of Scientific and Technical Information of China (English)

    王志超; 戴洪双; 刘文龙; 李效忠; 乔忠杰

    2014-01-01

    目的:探讨应用平阳霉素化疗对阴茎癌组织蛋白c-myc、Ras-P21表达的影响及意义。方法收集1995—2005年间阴茎鳞状细胞癌患者100例,按照术前是否进行化疗分为两组,其中化疗组50例,术前应用平阳霉素化疗7天,并在化疗后行阴茎部分切除术+改良方法的腹股沟淋巴结清扫术;对照组50例,未进行化疗而直接行阴茎部分切除术改良方法的腹股沟淋巴结清扫术。应用免疫组化法( SP)对两组的100例阴茎癌组织标本进行c-myc、Ras-P21蛋白产物检测。应用χ2检验对数据进行统计分析。结果化疗组50例阴茎癌标本中c-myc、Ras-P21表达阳性率分别为30%、27%。对照组50例阴茎癌标本中,c-myc、Ras-P21表达阳性率分别为52%、48%。经χ2检验,化疗组与对照组的c-myc、Ras-P21表达阳性率的差异具有统计学意义(P<0.05)。结论应用平阳霉素化疗后阴茎癌组织中c-myc、Ras-P21蛋白的表达明显下降。%Objective To evaluate the influence and significance of Pingyangmycin chemotherapy on the c-myc and Ras-P21 protein expression in penile cancer .Methods A total of 100 penile squamous cell carci-noma cases was retrospectively studied and divided into two groups .Data were obtained from 1995 to 2005 .In the chemotherapy group ,50 cases of patients were selected to perform preoperative chemotherapy before surgery .The patients were treated by Pingyangmycin .After 7 times of medication ,partial excision of penis plus improved ingui-nal lymph node dissection was performed .In the control group ,50 cases of patients were selected for partial exci-sion of penis plus improved inguinal lymph node dissection directly without any pre -operative chemotherapy .All pathology specimens were detected of c -myc and Ras-P21 protein expression by immunohistochemical staining assay.Theχ2 test was used for the statistical analysis .Results In

  8. Epstein–Barr virus growth-transformed cells are converted to malignancy following transfection of a 1.3-kb CATR1 antisense construct independent of a change in the level of c-myc expression followed by a 8;14 chromosomal translocation

    OpenAIRE

    Li, Dawei; Sun, Xiao Li; Casto, Bruce; Fang, Jin; Theil, Karl; Glaser, Ronald; Milo, George

    1998-01-01

    The AGLCL Epstein–Barr virus (EBV) growth-transformed cell line is incapable of inducing tumors in nude mice. When the cells were transfected with a 1.3-kb CATR1 antisense cDNA construct, progressively growing lymphomas could be induced in nude mice. Chromosome analysis of the parental, transfected, and tumor cells revealed that a chromosomal translocation t(8;14)(q24.1;q32) had occurred in the transfected cells and was retained in cells derived from tumors. Moreover, enhanced c-myc expressio...

  9. Research of influence of Pingyangmycin neoajuvant chemotherapy on c-myc, Ras-P21, and P53 protein expression in penile cancer%平阳霉素新辅助化疗对阴茎癌组织c-myc、Ras-P21、P53蛋白表达影响的研究

    Institute of Scientific and Technical Information of China (English)

    徐磊; 刘文龙; 王志超; 乔忠杰

    2014-01-01

    Objective To evaluate the influence and significance of Pingyangmycin neoajuvant chemotherapy on the c-myc, Ras-P21 and P53 protein expression in penile cancer on. Methods The Data of 100 patiens with penile squamous cell carcinoma were obtained in the Department of Urology, the Tumor Hospital of Harbin Medical University, from 1995 to 2005, and they were divided into two groups according to whether given the neoajuvant chemotherapy before the surgery or not. 50 patients in the neoajuvant group were given Pingyangmycin preoperative chemotherapy for 7 days before surgery, after the chemotherapy, partial excision of penis plus improved inguinal lymph node dissection was per-formed. 50 patients in the control group were given partial excision of penis plus improved inguinal lymph node dissec-tion directly without any pre-operative chemotherapy. All pathology specimens were detected of c-myc, Ras-P21, P53 protein product expression by immunohistochemical staining assay. Results In neoajuvant chemotherapy group, the pos-itive expression rates of c-myc, Ras-P21, P53 were 30%, 27%, 23%,respectively. While in control group, the positive expression rates of c-myc, Ras-P21, P53 were 52%, 48%, 50%, the differences were statistically significant (P<0.05). Conclusion The c-myc, Ras-P21, P53 protein expressions are significantly decreased in the tissue of Pingyangmycin neoajuvant chemotherapy of penile cancer, Pingyangmycin neoajuvant chemotherapy may decrease the degree of malig-nancy of penile cancer.%目的:探讨应用平阳霉素新辅助化疗对阴茎癌组织基因蛋白c-myc、Ras-P21、P53表达的影响及意义。方法收集哈尔滨医科大学附属肿瘤医院泌尿外科1995~2005年罹患阴茎鳞状细胞癌的住院患者100例,按照术前是否进行辅助化疗分为两组,其中新辅助化疗组50例,术前应用平阳霉素化疗7 d,化疗后行阴茎部分切除术,并行双侧腹股沟淋巴结改良清扫术;对照组50例,直接行

  10. Role of arsenic trioxide induced apoptosis in Burkitt lymphoma cell line Raji and influence on C-myc expression%三氧化二砷对Burkitt淋巴瘤细胞株Raji凋亡的诱导作用及C-myc表达的影响

    Institute of Scientific and Technical Information of China (English)

    张继青; 钟雷; 李进娥

    2015-01-01

    目的 探讨三氧化二砷(As2O3)对Burkitt淋巴瘤细胞袜Raji凋亡的诱导作用及C-myc表这的影响.方法 通过噻唑蓝比色法检测观察As2 O3对Raji细胞增殖的影响,流式细胞仪观察As2O3对Raji细胞凋亡的诱导作用,逆转录聚合酶链式反应(RT-PCR)法检测As2O3对C-myc mRNA表达的影响.结果 As2O3对Raji细胞生长有抑制作用,呈剂量和时间依赖关系(P<0.01);As2O3对Raji细胞有诱导凋亡作用,呈剂量和时间依赖关系(P<0.01);随着As2O3浓度升高,C-myc的表达水平明显下降(P<0.01).结论 As2O3对Burkitt淋巴瘤细胞株Raji具有增殖抑制和诱导凋亡作用,其作用机制可能与C-myc表达水平明显下降有关.

  11. 跑台运动训练对脑缺血损伤大鼠热休克蛋白70及C-MYC表达的影响%Effects of treadmill training on the expression of HSP70 and C-MYC in the brains of rats with focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    刘德山; 刘楠; 张逸仙; 杜厚伟; 陈荣华

    2010-01-01

    目的 探讨跑台运动训练对局灶性脑缺血大鼠神经功能恢复和脑缺血组织中热休克蛋白70(HSP70)及C-MYC表达的影响.方法 将42只清洁级成年雄性SD大鼠分为假手术组6只、模型组18只、运动组18只.模型组、运动组大鼠采用改良的Longs线栓法制备大脑中动脉闭塞(MCAO)脑缺血模型,运动组于造模成功后24 h采用跑台训练器进行运动训练,每周6 d,共2周,其余2组则置于普通笼内饲养,期间可自由活动、进食.采用修正的神经行为学评分方法评价模型组和运动组大鼠MCAO脑缺血后第3,7,14天的神经功能,并断头取脑,采用逆转录-多聚酶链反应(RT-PCR)法、免疫组织化学和Western blot法检测脑缺血组织中HSP70、C-MYC的表达.结果 运动组大鼠脑缺血第7,14天神经功能评分均明显优于模型组(P<0.05或0.01);运动组大鼠脑缺血第7,14天HSF70和C-MYC表达较模型组增强(P<0.05或0.01).结论 运动训练可促进脑缺血大鼠神经功能恢复,其机制可能与上调脑缺血组织中HSP70及C-MYC表达有关.%Objective To observe the effects of treadmill training on the recovery of neurological function and the expression of HSP70 and C-MYC in the brains of rats with focal cerebral ischemia. Methods Forty-two male adult Sprague-Dawley rats were randomly divided into a sham group ( n =6), a model group (n =18) and a treadmill exercise group (n=18). Focal cerebral ischemia was induced by right middle cerebral artery occlusion (MCAO) in the model group and exercise group using a modified version of Longa's method. The rats in the treadmill exercise group were given treadmill training 6 d per week for 2 weeks after 24 h of MCAO. By contrast, the rats in the sham group and the model group were reared in standard cages. Before the rats were sacrificed at the 3rd, 7th and 14th d after MCAO, their neurological functions were tested using modified neurological severity scores ( mNSS) , and the mRNA and

  12. Mapping the conformational epitope of a neutralizing antibody (AcV1) directed against the AcMNPV GP64 protein

    International Nuclear Information System (INIS)

    The envelope glycoprotein GP64 of Autographa californica nucleopolyhedrovirus (AcMNPV) is necessary and sufficient for the acid-induced membrane fusion activity that is required for fusion of the budded virus (BV) envelope and the endosome membrane during virus entry. Infectivity of the budded virus (BV) is neutralized by AcV1, a monoclonal antibody (MAb) directed against GP64. Prior studies indicated that AcV1 recognizes a conformational epitope and does not inhibit virus attachment to the cell, but instead inhibits entry at a step following virus attachment. We found that AcV1 recognition of GP64 was lost upon exposure of GP64 to low pH (pH 4.5) and restored by returning GP64 to pH 6.2. In addition, the AcV1 epitope was lost upon denaturation of GP64 in SDS, but the AcV1 epitope was restored by refolding the protein in the absence of SDS. Using truncated GP64 proteins expressed in insect cells, we mapped the AcV1 epitope to a 24 amino acid region in the central variable domain of GP64. When sequences within the mapped AcV1 epitope were substituted with a c-Myc epitope and the resulting construct was used to replace wt GP64 in recombinant AcMNPV viruses, the modified GP64 protein appeared to function normally. However, an anti-c-Myc monoclonal antibody did not neutralize infectivity of those viruses. Because binding of the c-Myc MAb to the same site in the GP64 sequence did not result in neutralization, these studies suggest that AcV1 neutralization may result from a specific structural constraint caused by AcV1 binding and not simply by steric hindrance caused by antibody binding at this position in GP64

  13. Wnt signaling and c-Myc in intestinal epithelium

    OpenAIRE

    Muncan, V.

    2007-01-01

    constantly produce cells from a stem cell reservoir that give rise to proliferating transit amplifying cells, which subsequently differentiate and are positioned in their proper compartments. This process has to be under stringent control to ensure life-long tissue homeostasis. It has now become clear that the same signaling pathways that are important during embryonic development control selfreneving tissues. Canonical Wnt signaling plays a key role in regulating intestinal tissue homeostasi...

  14. Mapping out Map Libraries

    Directory of Open Access Journals (Sweden)

    Ferjan Ormeling

    2008-09-01

    Full Text Available Discussing the requirements for map data quality, map users and their library/archives environment, the paper focuses on the metadata the user would need for a correct and efficient interpretation of the map data. For such a correct interpretation, knowledge of the rules and guidelines according to which the topographers/cartographers work (such as the kind of data categories to be collected, and the degree to which these rules and guidelines were indeed followed are essential. This is not only valid for the old maps stored in our libraries and archives, but perhaps even more so for the new digital files as the format in which we now have to access our geospatial data. As this would be too much to ask from map librarians/curators, some sort of web 2.0 environment is sought where comments about data quality, completeness and up-to-dateness from knowledgeable map users regarding the specific maps or map series studied can be collected and tagged to scanned versions of these maps on the web. In order not to be subject to the same disadvantages as Wikipedia, where the ‘communis opinio’ rather than scholarship, seems to be decisive, some checking by map curators of this tagged map use information would still be needed. Cooperation between map curators and the International Cartographic Association ( ICA map and spatial data use commission to this end is suggested.

  15. Linkage study of nonsyndromic cleft lip with or without cleft palate using candidate genes and mapped polymorphic markers

    Energy Technology Data Exchange (ETDEWEB)

    Stein, J.D.; Nelson, L.D.; Conner, B.J. [Univ. of Texas, Houston (United States)] [and others

    1994-09-01

    Nonsyndromic cleft lip with or without cleft palate (CL(P)) involves fusion or growth failure of facial primordia during development. Complex segregation analysis of clefting populations suggest that an autosomal dominant gene may play a role in this common craniofacial disorder. We have ascertained 16 multigenerational families with CL(P) and tested linkage to 29 candidate genes and 139 mapped short tandem repeat markers. The candidate genes were selected based on their expression in craniofacial development or were identified through murine models. These include: TGF{alpha}, TGF{beta}1, TGF{beta}2, TGF{beta}3, EGF, EGFR, GRAS, cMyc, FGFR, Jun, JunB, PDFG{alpha}, PDGF{beta}, IGF2R, GCR Hox7, Hox8, Hox2B, twirler, 5 collagen and 3 extracellular matrix genes. Linkage was tested assuming an autosomal dominant model with sex-specific decreased penetrance. Linkage to all of the candidate loci was excluded in 11 families. RARA was tested and was not informative. However, haplotype analysis of markers flanking RARA on 17q allowed exclusion of this candidate locus. We have previously excluded linkage to 61 STR markers in 11 families. Seventy-eight mapped short tandem repeat markers have recently been tested in 16 families and 30 have been excluded. The remaining are being analyzed and an exclusion map is being developed based on the entire study results.

  16. Map Projection

    CERN Document Server

    Ghaderpour, Ebrahim

    2014-01-01

    In this paper, we introduce some known map projections from a model of the Earth to a flat sheet of paper or map and derive the plotting equations for these projections. The first fundamental form and the Gaussian fundamental quantities are defined and applied to obtain the plotting equations and distortions in length, shape and size for some of these map projections.

  17. Harmonic Maps and Biharmonic Maps

    OpenAIRE

    Hajime Urakawa

    2015-01-01

    This is a survey on harmonic maps and biharmonic maps into (1) Riemannian manifolds of non-positive curvature, (2) compact Lie groups or (3) compact symmetric spaces, based mainly on my recent works on these topics.

  18. Brain mapping

    Directory of Open Access Journals (Sweden)

    Blaž Koritnik

    2004-08-01

    Full Text Available Cartography of the brain ("brain mapping" aims to represent the complexities of the working brain in an understandable and usable way. There are four crucial steps in brain mapping: (1 acquiring data about brain structure and function, (2 transformation of data into a common reference, (3 visualization and interpretation of results, and (4 databasing and archiving. Electrophysiological and functional imaging methods provide information about function of the human brain. A prerequisite for multisubject, multidimensional and multimodal mapping is transformation of individual images to match a standard brain template. To produce brain maps, color, contours, and other visual cues are used to differentiate metabolic rates, electrical field potentials, receptor densities, and other attributes of structure or function. Databases are used to organize and archive data records. By relating the maps to cognitive functions and psychological models, brain mapping offers a prerequisite for the understanding of organizational principles of the human brain.

  19. Affective Maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    Recently, in human geography there has been a considerable attention paid to retheorising maps; less as a product and more as practice. This refers to the notion that rather than reading maps as fixed representations, digital mapping is by nature a dynamic, performative, and participatory practice....... In particular, mapping environmental damage, endangered species, and human made disasters has become one of the focal point of affective knowledge production. These ‘more-than-humangeographies’ practices include notions of species, space and territory, and movement towards a new political ecology...

  20. Alterations of c-Myc and c-erbB-2 genes in ovarian tumours

    OpenAIRE

    Pastor Tibor; Popović Branka; Gvozdenović Ana; Boro Aleksandar; Petrović Bojana; Novaković Ivana; Puzović Dragana; Luković Ljiljana; Milašin Jelena

    2009-01-01

    Introduction. According to clinical and epidemiological studies, ovarian cancer ranks fifth in cancer deaths among women. The causes of ovarian cancer remain largely unknown but various factors may increase the risk of developing it, such as age, family history of cancer, childbearing status etc. This cancer results from a succession of genetic alterations involving oncogenes and tumour suppressor genes, which have a critical role in normal cell growth regulation. Mutations and/or overexpress...

  1. Pokemon,c-myc and breast tumor%Pokemon、c-myc与乳腺肿瘤

    Institute of Scientific and Technical Information of China (English)

    付朝江; 崔明

    2009-01-01

    Pokemon(POK erythroid ontogenic factor)蛋白,即POK红系髓性致癌因子,是POK转录抑制物家族的一个成员,为ZBTB7基因所编码的产物.Pokemon蛋白作为转录因子参与一些细胞基因转录的调节,并在细胞分化过程中发挥着关键、多效性的功能.近来发现,Pokemon和c-myc在乳腺肿瘤致癌转化过程中发挥着至关重要的作用,并与乳腺肿瘤的发生密切相关.c-myc原癌基因编码核内DNA结合蛋白,调节其它基因的转录.其基因、mRNA及编码蛋白在多种肿瘤组织中均有异常.c-myc蛋白主要是通过促进cychnE/CDK2复合物的活性来调控G1期细胞进程的.

  2. Nuclear topography of the c-myc gene transcript during enterocytic cell differentiation

    Czech Academy of Sciences Publication Activity Database

    Harničarová, Andrea; Kozubek, Stanislav; Bártová, Eva

    s. 61-61. [EMBO Workshop 2006. 05.05.2006-08.05.2006, Praha] R&D Projects: GA MŠk(CZ) LC535 Institutional research plan: CEZ:AV0Z50040507 Keywords : RNA -DNA FISH * nuclear topography * differentiation Subject RIV: BO - Biophysics

  3. Cognitive maps

    DEFF Research Database (Denmark)

    Minder, Bettina; Laursen, Linda Nhu; Lassen, Astrid Heidemann

    2014-01-01

    . Conceptual clustering is used to analyse and order information according to concepts or variables from within the data. The cognitive maps identified are validated through the comments of some of the same experts. The study presents three cognitive maps and respective world-views explaining how the design...

  4. Causal mapping

    DEFF Research Database (Denmark)

    Rasmussen, Lauge Baungaard

    2006-01-01

    The lecture note explains how to use the causal mapping method as well as the theoretical framework aoosciated to the method......The lecture note explains how to use the causal mapping method as well as the theoretical framework aoosciated to the method...

  5. CALS Mapping

    DEFF Research Database (Denmark)

    Collin, Ib; Nielsen, Povl Holm; Larsen, Michael Holm

    1998-01-01

    To enhance the industrial applications of CALS, CALS Center Danmark has developed a cost efficient and transparent assessment, CALS Mapping, to uncover the potential of CALS - primarily dedicated to small and medium sized enterprises. The idea behind CALS Mapping is that the CALS State of the...... enterprise is, when applied in a given organisation modified with respect to the industry regarded, hence irrelevant measure parameters are eliminated to avoid redundancy. This assessment of CALS Mapping, quantify the CALS potential of an organisation with the purpose of providing decision support to the top...

  6. Participatory maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    towards a new political ecology. This type of digital cartographies has been highlighted as the ‘processual turn’ in critical cartography, whereas in related computational journalism it can be seen as an interactive and iterative process of mapping complex and fragile ecological developments. This paper......There has recently been considerable attention paid to digital, spatial visualisations in digital journalism and technology studies; less as a product and more as practice. This refers to the notion that rather than reading maps as fixed representations, digital mapping is by nature a dynamic...... is defined as a digitally created affective (map)space within which journalistic practice can be seen as dynamic, performative interactions between journalists, ecosystems, space, and species....

  7. Brain mapping

    OpenAIRE

    Blaž Koritnik

    2004-01-01

    Cartography of the brain ("brain mapping") aims to represent the complexities of the working brain in an understandable and usable way. There are four crucial steps in brain mapping: (1) acquiring data about brain structure and function, (2) transformation of data into a common reference, (3) visualization and interpretation of results, and (4) databasing and archiving. Electrophysiological and functional imaging methods provide information about function of the human brain. A prere...

  8. Noise map

    OpenAIRE

    Němcová, Michaela

    2015-01-01

    The aim of this paper is to introduce the measurement of noise and create a noise map in a geographic information system. The first part is focused on describing the physical properties of sound in space, atmospheric and physiological acoustics. It also deals with the physiological effects of noise on the human body and technology needed for measure and process noise. Other part describes the structure of a geographic information system and noise map. The last part is about the practical crea...

  9. Rethinking maps

    OpenAIRE

    Kitchin, Rob; Dodge, Martin

    2007-01-01

    In this paper we argue that cartography is profitably conceived as a processual, rather than representational, science. Building on recent analysis concerning the philosophical underpinnings of cartography we question the ontological security of maps, contending that it is productive to rethink cartography as ontogenetic in nature; that is maps emerge through practices and have no secure ontological status. Drawing on the concepts of transduction and technicity we contend that ...

  10. Mapping Deeply

    Directory of Open Access Journals (Sweden)

    Denis Wood

    2015-08-01

    Full Text Available This is a description of an avant la lettre deep mapping project carried out by a geographer and a number of landscape architecture students in the early 1980s. Although humanists seem to take the “mapping” in deep mapping more metaphorically than cartographically, in this neighborhood mapping project, the mapmaking was taken literally, with the goal of producing an atlas of the neighborhood. In this, the neighborhood was construed as a transformer, turning the stuff of the world (gas, water, electricity into the stuff of individual lives (sidewalk graffiti, wind chimes, barking dogs, and vice versa. Maps in the central transformer section of the atlas were to have charted this process in action, as in one showing the route of an individual newspaper into the neighborhood, then through the neighborhood to a home, and finally, as trash, out of the neighborhood in a garbage truck; though few of these had been completed when the project concluded in 1986. Resurrected in 1998 in an episode on Ira Glass’ This American Life, the atlas was finally published, as Everything Sings: Maps for a Narrative Atlas, in 2010 (and an expanded edition in 2013.

  11. Parametric mapping

    Science.gov (United States)

    Branch, Allan C.

    1998-01-01

    Parametric mapping (PM) lies midway between older and proven artificial landmark based guidance systems and yet to be realized vision based guidance systems. It is a simple yet effective natural landmark recognition system offering freedom from the need for enhancements to the environment. Development of PM systems can be inexpensive and rapid and they are starting to appear in commercial and industrial applications. Together with a description of the structural framework developed to generically describe robot mobility, this paper illustrates clearly the parts of any mobile robot navigation and guidance system and their interrelationships. Among other things, the importance of the richness of the reference map, and not necessarily the sensor map, is introduced, the benefits of dynamic path planners to alleviate the need for separate object avoidance, and the independence of the PM system to the type of sensor input is shown.

  12. Appendix 2: Maps

    OpenAIRE

    2015-01-01

    Map 1. The border towns of Zabaykalsk (Russia) and Manzhouli (China). Map created by Philip Stickler. Map 2. Legendary and historical Khori Buryat migrations. Map created by Philip Stickler. Map 3. Buryat emigrations in the 20th century. Map created by Philip Stickler. Map 4. Numerous demarcation lines supplement the Sino-Russian international boundary. Map created by Philip Stickler.

  13. Radioelement mapping

    International Nuclear Information System (INIS)

    A high quality geochemical database is pertinent to a wide range of investigations in the earth and life sciences, and should be considered as an essential component of environmental knowledge. Natural radioactive elements associated with radioactive raw materials, the radiation environment and their health impact, form part of such a comprehensive geochemical database. Databases on radioelement mapping have been increasingly used and updated in several countries for the exploration of uranium and thorium raw materials for nuclear fuels, environmental geochemical studies and the assessment of the radiation environment. The demand for radioelement databases is expected to grow over the next decade as new applications for them are foreseen. To this end, the IAEA invited a group of experts to investigate the issues and draft a report on the current state of radioelement mapping and the development of a global radioelement baseline. In the past, based on gamma surveys for uranium exploration and field gamma spectrometry, the IAEA took a leading role in facilitating the development of methodologies and standards for the quantitative estimation of radioelement concentrations and for the geochemical mapping of radioelements.. The need for approved methodologies and standards for radioelement mapping was identified at an IAEA panel meeting in 1972. This led to IAEA technical meetings in 1973 and 1974 and the publication of the proceedings of an IAEA symposium entitled Exploration for Uranium Ore Deposits. In subsequent years, calibration standards and procedures were developed for radiometric field equipment. The standards were based on geological reference materials for laboratory gamma ray spectrometers issued by the IAEA. The information on the standards and the equipment has been documented in detail in IAEA technical reports: Preparation and Certification of IAEA Gamma ray Spectrometry Reference Materials RGU-1, RGTh-1 and RGK-1, report IAEA/RL/148 (1987); and

  14. Mapping filmmaking

    DEFF Research Database (Denmark)

    Gilje, Øystein; Frølunde, Lisbeth; Lindstrand, Fredrik;

    2010-01-01

    This chapter concerns mapping patterns in regards to how young filmmakers (age 15 – 20) in the Scandinavian countries learn about filmmaking. To uncover the patterns, we present portraits of four young filmmakers who participated in the Scandinavian research project Making a filmmaker. The focus is...

  15. Mapping Resilience

    DEFF Research Database (Denmark)

    Carruth, Susan

    2015-01-01

    relationship between resilience and energy planning, suggesting that planning in, and with, time is a core necessity in this domain. It then reviews four examples of graphically mapping with time, highlighting some of the key challenges, before tentatively proposing a graphical language to be employed by...

  16. Energetic map

    International Nuclear Information System (INIS)

    This report explains the energetic map of Uruguay as well as the different systems that delimits political frontiers in the region. The electrical system importance is due to the electricity, oil and derived , natural gas, potential study, biofuels, wind and solar energy

  17. MAPPING INNOVATION

    DEFF Research Database (Denmark)

    Thuesen, Christian Langhoff; Koch, Christian

    2011-01-01

    By adopting a theoretical framework from strategic niche management research (SNM) this paper presents an analysis of the innovation system of the Danish Construction industry. The analysis shows a multifaceted landscape of innovation around an existing regime, built around existing ways of working...... and developed over generations. The regime is challenged from various niches and the socio-technical landscape through trends as globalization. Three niches (Lean Construction, BIM and System Deliveries) are subject to a detailed analysis showing partly incompatible rationales and various degrees of innovation...... potential. The paper further discusses how existing policymaking operates in a number of tensions one being between government and governance. Based on the concepts from SNM the paper introduces an innovation map in order to support the development of meta-governance policymaking. By mapping some...

  18. Mapping Participation

    OpenAIRE

    Hood, Beverley

    2013-01-01

    Mapping/Tracking is a participatory, collaborative project, exploring GPS tracking via mobile devices as a performative drawing material, blending technology and creativity. Using the Forth Valley Royal Hospital and the surrounding forest as a canvas, the project is a collaboration between artist, lecturer and researcher Beverley Hood, visual artist Sharon Quigley, audio-visual artist Emma Bowen and participants of the Abrupt Encounters program. “Abrupt Encounters is a new live arts program d...

  19. $\\lambda$-perfect maps

    OpenAIRE

    Namdari, M.; Siavoshi, M. A.

    2015-01-01

    The $\\lambda$-perfect maps, a generalization of perfect maps (continuous closed maps with compact fibers) are presented. Using $P_\\lambda$-spaces and the concept of $\\lambda$-compactness some results regarding $\\lambda$-perfect maps will be investigated.

  20. Map viewer design and web mapping

    OpenAIRE

    Zupan Vrenko, Dunja

    2013-01-01

    This dissertation focuses on map viewers and the maps as a part of map viewer's design. Special attention was paid to the limitations affecting both seniors and colour-vision-impaired users. The first, general analysis focuses on providing basic information of the selected map viewers and web maps subjects of further analyses. The second analysis is of the visibility and perception of a web map’s/map viewer’s elements and map viewer’s manipulation, the emphasis is on the visual perception of ...

  1. Photon mapping

    OpenAIRE

    Nečas, Ondřej

    2009-01-01

    V rámci této práce byla provedena praktická implementace algoritmu photon mapping. Pro dosažení kvalitnějšího výstupu byly zkoumány některé základní a pokročilejší metody globálního osvětlení. Tyto náročné algoritmy jsou často prakticky nepoužitelné a je nutná jejich optimalizace. Základem praktické implementace je optimalizace raytraceru. Vzorky nepřímého difuzního osvětlení počítané metodou Monte Carlo je možné mezi sebou interpolovat s použitím vhodné techniky....

  2. Projective mapping

    DEFF Research Database (Denmark)

    Dehlholm, Christian; Brockhoff, Per B.; Bredie, Wender Laurentius Petrus

    2012-01-01

    will include the applied framework, semantic restrictions, the choice of type of assessors and the validation of product separations. The applied framework concerns the response surface as presented to the assessor in different shapes, e.g. rectangular, square or round. Semantic restrictions are a part...... of the assessor instructions and influence heavily the product placements and the descriptive vocabulary (Dehlholm et.al., 2012b). The type of assessors performing the method influences results with an extra aspect in Projective Mapping compared to more analytical tests, as the given spontaneous...... perceptions are much dependent on the assessor’s way of thinking. Furthermore, a suggestion for validating product separations is proposed for the case where Multiple Factor Analysis is chosen for data analysis (Dehlholm, Brockhoff & Bredie, 2012a)....

  3. Human Mind Maps

    Science.gov (United States)

    Glass, Tom

    2016-01-01

    When students generate mind maps, or concept maps, the maps are usually on paper, computer screens, or a blackboard. Human Mind Maps require few resources and little preparation. The main requirements are space where students can move around and a little creativity and imagination. Mind maps can be used for a variety of purposes, and Human Mind…

  4. National Pipeline Mapping System: Map Tool

    Data.gov (United States)

    Department of Transportation — The NPMS Public Map Viewer allows the general public to view maps of transmission pipelines, LNG plants, and breakout tanks in one selected county. Distribution and...

  5. Fuzzy Cognitive Maps and Neutrosophic Cognitive Maps

    OpenAIRE

    Vasantha, Kandasamy; Smarandache, Florentin

    2003-01-01

    In this book we study the concepts of Fuzzy Cognitive Maps (FCMs) and their Neutrosophic analogue, the Neutrosophic Cognitive Maps (NCMs).Fuzzy Cognitive Maps are fuzzy structures that strongly resemble neural networks, and they have powerful and far-reaching consequences as a mathematical tool for modeling complex systems. Neutrosophic Cognitive Maps are generalizations of FCMs, and their unique feature is the ability to handle indeterminacy in relations between two concepts thereby bringing...

  6. Maps & minds : mapping through the ages

    Science.gov (United States)

    U.S. Geological Survey

    1984-01-01

    Throughout time, maps have expressed our understanding of our world. Human affairs have been influenced strongly by the quality of maps available to us at the major turning points in our history. "Maps & Minds" traces the ebb and flow of a few central ideas in the mainstream of mapping. Our expanding knowledge of our cosmic neighborhood stems largely from a small number of simple but grand ideas, vigorously pursued.

  7. Biharmonic Riemannian maps

    OpenAIRE

    Sahin, Bayram

    2010-01-01

    We give necessary and sufficient conditions for Riemannian maps to be biharmonic. We also define pseudo umbilical Riemannian maps as a generalization of pseudo-umbilical submanifolds and show that such Riemannian maps put some restrictions on the base manifolds.

  8. Lunar Map Catalog

    Data.gov (United States)

    National Aeronautics and Space Administration — The Lunar Map Catalog includes various maps of the moon's surface, including Apollo landing sites; earthside, farside, and polar charts; photography index maps;...

  9. Mapping the Heart

    Science.gov (United States)

    Hulse, Grace

    2012-01-01

    In this article, the author describes how her fourth graders made ceramic heart maps. The impetus for this project came from reading "My Map Book" by Sara Fanelli. This book is a collection of quirky, hand-drawn and collaged maps that diagram a child's world. There are maps of her stomach, her day, her family, and her heart, among others. The…

  10. USGS Map Indices Overlay Map Service from The National Map

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — The USGS Map Indices service from The National Map (TNM) consists of 1x1 Degree, 30x60 Minute (100K), 15 Minute (63K), 7.5 Minute (24K), and 3.75 Minute grid...

  11. 7. Annex II: Maps

    OpenAIRE

    Aeberli, Annina

    2012-01-01

    Map 1: States of South Sudan UN OCHA (2012) Republic of South Sudan – States, as of 15 July 2012, Reliefweb http://reliefweb.int/map/south-sudan-republic/republic-south-sudan-states-15-july-2012-reference-map, accessed 31 July 2012. Map 2: Counties of South Sudan UN OCHA (2012) Republic of South Sudan – Counties, as of 16 July 2012, Reliefweb http://reliefweb.int/map/south-sudan-republic/republic-south-sudan-counties-16-july-2012-reference-map, accessed 31 July 2012. Map 3: Eastern Equato...

  12. VEGETATION MAPPING IN WETLANDS

    Directory of Open Access Journals (Sweden)

    F. PEDROTTI

    2004-01-01

    Full Text Available The current work examines the main aspects of wetland vegetation mapping, which can be summarized as analysis of the ecological-vegetational (ecotone gradients; vegetation complexes; relationships between vegetation distribution and geomorphology; vegetation of the hydrographic basin lo which the wetland in question belongs; vegetation monitoring with help of four vegetation maps: phytosociological map of the real and potential vegetation, map of vegetation dynamical tendencies, map of vegetation series.

  13. -Deformed nonlinear maps

    Indian Academy of Sciences (India)

    Ramaswamy Jaganathan; Sudeshna Sinha

    2005-03-01

    Motivated by studies on -deformed physical systems related to quantum group structures, and by the elements of Tsallis statistical mechanics, the concept of -deformed nonlinear maps is introduced. As a specific example, a -deformation procedure is applied to the logistic map. Compared to the canonical logistic map, the resulting family of -logistic maps is shown to have a wider spectrum of interesting behaviours, including the co-existence of attractors – a phenomenon rare in one-dimensional maps.

  14. Map Projection Transitions

    OpenAIRE

    Nedjeljko Frančula; Miljenko Lapaine

    2013-01-01

    Map Projection Transitions is a very successful web application about map projections. The web page (http://www.jasondavies.com/maps/transition) pre­sents a world map with graticule and country borders in the oblique Aitoff projection, with the South Pole. The map is not static, but animated. The South Pole moves toward the bottom and Earth rotates around its poles. The animation lasts five seconds, after which the projection changes and movement continues for five seconds, after which the pr...

  15. Simple thematic mapping

    OpenAIRE

    Maurizio Pisati

    2004-01-01

    Thematic maps illustrate the spatial distribution of one or more variables of interest within a given geographic unit. In a sense, a thematic map is the spatial analyst's equivalent to the scatterplot in nonspatial analysis. This paper presents the tmap package, a set of Stata programs designed to draw five kinds of thematic maps: choropleth, proportional symbol, deviation, dot, and label maps. The first three kinds of maps are intended to depict area data, the fourth is suitable for represen...

  16. Expression of the c-myc oncogene under control of an immunoglobulin enhancer in E mu-myc transgenic mice.

    OpenAIRE

    Alexander, W S; Schrader, J W; Adams, J. M.

    1987-01-01

    Transgenic mice bearing a cellular myc oncogene coupled to the immunoglobulin heavy-chain enhancer (E mu) exhibit perturbed B-lymphocyte development and succumb to B lymphoid tumors. To investigate how the enhancer has affected myc expression, we analyzed the structure and abundance of myc transcripts in tissues of prelymphomatous mice and in the lymphomas. Expression of the E mu-myc transgene appeared to be confined largely to B lymphoid cells, being dominant in bone marrow, spleen, and lymp...

  17. Conserved features of cancer cells define their sensitivity of HAMLET-induced death; c-Myc and glycolysis

    OpenAIRE

    Storm, Petter; Puthia, Manoj Kumar; Aits, Sonja; Urbano, Alexander; Northen, Trent; Powers, Scott; Bowen, Ben; Chao, Yinxia; Reindl, Wolfgang; Lee, Do Yup; Sullivan, Nancy Liu; Zhang, Jianping; Trulsson, Maria; Yang, Henry; Watson, James

    2011-01-01

    HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small hairpin RNA inhibition, proteomic ...

  18. Nanoparticles Targeted With NGR Motif Deliver c-myc siRNA and Doxorubicin for Anticancer Therapy

    OpenAIRE

    Chen, Yunching; Wu, Jinzi J.; Huang, Leaf

    2010-01-01

    We have designed a PEGylated LPD (liposome-polycation-DNA) nanoparticle for systemic, specific, and efficient delivery of small interfering RNA (siRNA) into solid tumors in mice by modification with NGR (aspargine–glycine–arginine) peptide, targeting aminopeptidase N (CD13) expressed in the tumor cells or tumor vascular endothelium. LPD-PEG-NGR efficiently delivered siRNA to the cytoplasm and downregulated the target gene in the HT-1080 cells but not CD13− HT-29 cells, whereas nanoparticles c...

  19. Triptolide suppresses proliferation, hypoxia-inducible factor-1α and c-Myc expression in pancreatic cancer cells.

    Science.gov (United States)

    Ding, Xiaoling; Zhou, Xiaorong; Jiang, Bo; Zhao, Qun; Zhou, Guoxiong

    2015-09-01

    Triptolide (TL) is known to suppress the proliferation of a number of pancreatic cancer cell lines in vitro. Marked antitumor effects were also observed in a xenograft model of pancreatic cancer. Hypoxia‑inducible factor‑1α (HIF‑1α) is highly expressed in pancreatic cancer cells lines. The present study therefore tested the hypothesis that suppression of HIF‑1α is associated with the antitumor activity of TL. Quantitative polymerase chain reaction and western blot analysis were used to determine the level of gene expression. A xenograft tumor model of pancreatic cancer was established in athymic nude mice and the tumor size was measured to evaluate the outcome of TL treatment. Immunohistochemistry was used to detect the expression of HIF‑1α and vascular endothelial growth factor (VEGF), and to assess microvessel density. Microarray was used to investigate gene expression in pancreatic cancer cells following TL treatment. The expression of HIF‑1α was shown to be reduced in pancreatic cell lines following treatment with TL, and this effect occurred in a dose‑dependent manner. In a xenograft model of pancreatic cancer, reduced levels of HIF‑1α were also observed in mice that were treated with TL. Furthermore, the expression of VEGF, which is a direct target of HIF‑1α, was also suppressed, and the microvessel density of tumor tissues was consequently reduced. A microarray analysis of gene expression was performed in order to investigate the potential mechanisms underlying the antitumor activity of TL. The results showed that 11 genes, including c‑Myc, SOX9 and Ets2, were downregulated at an early stage following treatment with TL. A recent study indicated that overexpression of c‑Myc in colon cancer cells promotes increased expression of HIF‑1α and VEGF. Therefore, TL may suppress HIF‑1α through a c‑Myc‑dependent mechanism, which is involved in antitumor effects in mouse models of pancreatic cancer. PMID:26094625

  20. The long non-coding RNA PARROT is an upstream regulator of c-Myc and affects proliferation and translation

    OpenAIRE

    Vucicevic, D.; Gehre, M; Dhamija, S.; Friis-Hansen, L.; Meierhofer, D; Sauer, S; Orom, U.A.

    2016-01-01

    Long non-coding RNAs are important regulators of gene expression and signaling pathways. The expression of long ncRNAs is dysregulated in cancer and other diseases. The identification and characterization of long ncRNAs is often challenging due to their low expression level and localization to chromatin. Here, we identify a functional long ncRNA, PARROT (Proliferation Associated RNA and Regulator Of Translation) transcribed by RNA polymerase II and expressed at a relatively high level in a nu...

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

    NARCIS (Netherlands)

    Rustgi, A.K.; Dyson, N.; Bernards, R.A.

    1991-01-01

    The proteins encoded by the myc gene family are involved is the control of cell proliferation and differentiation, and aberrant expression of myc proteins has been implicated in the genesis of a variety of neoplasms. In the carboxyl terminus, myc proteins have two domains that encode a basic domain/

  2. Google Maps: You Are Here

    Science.gov (United States)

    Jacobsen, Mikael

    2008-01-01

    Librarians use online mapping services such as Google Maps, MapQuest, Yahoo Maps, and others to check traffic conditions, find local businesses, and provide directions. However, few libraries are using one of Google Maps most outstanding applications, My Maps, for the creation of enhanced and interactive multimedia maps. My Maps is a simple and…

  3. Web Mapping Using Logo on Map

    OpenAIRE

    Ximing Hou; Hao Shi

    2013-01-01

    The newly proposed Logo on Map (LoM) system consists of three modules: picture extraction module (PEM), logo matching module (LMM) and web mapping module (WMM). Since the first two modules were covered in our previous paper, the third module WMM is described here to present a complete LoM system. Current research is focused on geo-location distribution of brands on Google Maps. Pictures taken by ordinary people are extracted using Picture Extraction Module (PEM). The pictures cont...

  4. The Fractal Nature of Maps and Mapping

    OpenAIRE

    Jiang, Bin

    2014-01-01

    A fractal can be simply understood as a set or pattern in which there are far more small things than large ones, e.g., far more small geographic features than large ones on the earth surface, or far more large-scale maps than small-scale maps for a geographic region. This paper attempts to argue and provide evidence for the fractal nature of maps and mapping. It is the underlying fractal structure of geographic features, either natural or human-made, that make reality mappable, large-scale ma...

  5. Web Mapping Using Logo on Map

    Directory of Open Access Journals (Sweden)

    Ximing Hou

    2013-01-01

    Full Text Available The newly proposed Logo on Map (LoM system consists of three modules: picture extraction module(PEM, logo matching module (LMM and web mapping module (WMM. Since the first two modules werecovered in our previous paper, the third module WMM is described here to present a complete LoM system.Current research is focused on geo-location distribution of brands on Google Maps. Pictures taken byordinary people are extracted using Picture Extraction Module (PEM. The pictures containing relevantlogos are obtained via Logo Matching Module (LMM. Brand distributions are overlaid on Google Maps.In this paper, GPS and brands are briefly described, and the implementation of Web Mapping Module(WMM based on Google Maps API is detailed. Then several experiments are carried out on the selectedtop brands. Finally the LMM-pictures are mapped on the Google Maps and the geographical distributionsof the brands are visualised. Brand uniqueness is discussed and conclusion is drawn that with uniquebrand names web mapping can visually reflect the real economic activities of a company in the world.

  6. Web Mapping Using Logo on Map

    Directory of Open Access Journals (Sweden)

    Ximing Hou

    2012-12-01

    Full Text Available The newly proposed Logo on Map (LoM system consists of three modules: picture extraction module (PEM, logo matching module (LMM and web mapping module (WMM. Since the first two modules were covered in our previous paper, the third module WMM is described here to present a complete LoM system. Current research is focused on geo-location distribution of brands on Google Maps. Pictures taken by ordinary people are extracted using Picture Extraction Module (PEM. The pictures containing relevant logos are obtained via Logo Matching Module (LMM. Brand distributions are overlaid on Google Maps. In this paper, GPS and brands are briefly described, and the implementation of Web Mapping Module (WMM based on Google Maps API is detailed. Then several experiments are carried out on the selected top brands. Finally the LMM-pictures are mapped on the Google Maps and the geographical distributions of the brands are visualised. Brand uniqueness is discussed and conclusion is drawn that with unique brand names web mapping can visually reflect the real economic activities of a company in the world.

  7. Phantom maps and chromatic phantom maps

    OpenAIRE

    Christensen, J. Daniel; Hovey, Mark

    1998-01-01

    In the first part, we determine conditions on spectra X and Y under which either every map from X to Y is phantom, or no nonzero maps are. We also address the question of whether such all or nothing behaviour is preserved when X is replaced with V smash X for V finite. In the second part, we introduce chromatic phantom maps. A map is n-phantom if it is null when restricted to finite spectra of type at least n. We define divisibility and finite type conditions which are suitable for studying n...

  8. Mapping with Drupal

    CERN Document Server

    Palazzolo, Alan

    2011-01-01

    Build beautiful interactive maps on your Drupal website, and tell engaging visual stories with your data. This concise guide shows you how to create custom geographical maps from top to bottom, using Drupal 7 tools and out-of-the-box modules. You'll learn how mapping works in Drupal, with examples on how to use intuitive interfaces to map local events, businesses, groups, and other custom data. Although building maps with Drupal can be tricky, this book helps you navigate the system's complexities for creating sophisticated maps that match your site design. Get the knowledge and tools you ne

  9. Mapping in the cloud

    CERN Document Server

    Peterson, Michael P

    2014-01-01

    This engaging text provides a solid introduction to mapmaking in the era of cloud computing. It takes students through both the concepts and technology of modern cartography, geographic information systems (GIS), and Web-based mapping. Conceptual chapters delve into the meaning of maps and how they are developed, covering such topics as map layers, GIS tools, mobile mapping, and map animation. Methods chapters take a learn-by-doing approach to help students master application programming interfaces and build other technical skills for creating maps and making them available on the Internet. Th

  10. Some Semi - Equivelar Maps

    CERN Document Server

    Upadhyay, Ashish K; Maity, Dipendu

    2011-01-01

    Semi-Equivelar maps are generalizations of Archimedean Solids (as are equivelar maps of the Platonic solids) to the surfaces other than $2-$Sphere. We classify some semi equivelar maps on surface of Euler characteristic -1 and show that none of these are vertex transitive. We establish existence of 12-covered triangulations for this surface. We further construct double cover of these maps to show existence of semi-equivelar maps on the surface of double torus. We also construct several semi-equivelar maps on the surfaces of Euler characteristics -8 and -10 and on non-orientable surface of Euler characteristics -2.

  11. Active Fire Mapping Program

    Science.gov (United States)

    Active Fire Mapping Program Current Large Incidents (Home) New Large Incidents Fire Detection Maps MODIS Satellite Imagery VIIRS Satellite Imagery Fire Detection GIS Data Fire Data in Google Earth ...

  12. Riparian Wetlands: Mapping

    Science.gov (United States)

    Riparian wetlands are critical systems that perform functions and provide services disproportionate to their extent in the landscape. Mapping wetlands allows for better planning, management, and modeling, but riparian wetlands present several challenges to effective mapping due t...

  13. Recovery Action Mapping Tool

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Recovery Action Mapping Tool is a web map that allows users to visually interact with and query actions that were developed to recover species listed under the...

  14. Invariants for Parallel Mapping

    Institute of Scientific and Technical Information of China (English)

    YIN Yajun; WU Jiye; FAN Qinshan; HUANG Kezhi

    2009-01-01

    This paper analyzes the geometric quantities that remain unchanged during parallel mapping (i.e., mapping from a reference curved surface to a parallel surface with identical normal direction). The second gradient operator, the second class of integral theorems, the Gauss-curvature-based integral theorems, and the core property of parallel mapping are used to derive a series of parallel mapping invadants or geometri-cally conserved quantities. These include not only local mapping invadants but also global mapping invari-ants found to exist both in a curved surface and along curves on the curved surface. The parallel mapping invadants are used to identify important transformations between the reference surface and parallel surfaces. These mapping invadants and transformations have potential applications in geometry, physics, biome-chanics, and mechanics in which various dynamic processes occur along or between parallel surfaces.

  15. MapBook

    Data.gov (United States)

    National Aeronautics and Space Administration — Beginning with the systematic mapping of the lunar surface more than three decades ago, this database contains over 1600 maps of the planets and satellites of the...

  16. Letter of Map Revision

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The National Flood Hazard Layer (NFHL) data incorporates all Digital Flood Insurance Rate Map(DFIRM) databases published by FEMA, and any Letters Of Map Revision...

  17. Mapping Medicare Disparities Tool

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CMS Office of Minority Health has designed an interactive map, the Mapping Medicare Disparities Tool, to identify areas of disparities between subgroups of...

  18. NAIP Status Maps Gallery

    Data.gov (United States)

    Farm Service Agency, Department of Agriculture — NAIP Status Maps Gallery. These maps illustrate what aerial imagery collection is planned, whats been collected, when it is available and how it is available. These...

  19. NGS Survey Control Map

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NGS Survey Control Map provides a map of the US which allows you to find and display geodetic survey control points stored in the database of the National...

  20. Branched polynomial covering maps

    DEFF Research Database (Denmark)

    Hansen, Vagn Lundsgaard

    1999-01-01

    A Weierstrass polynomial with multiple roots in certain points leads to a branched covering map. With this as the guiding example, we formally define and study the notion of a branched polynomial covering map. We shall prove that many finite covering maps are polynomial outside a discrete branch...... set. Particular studies are made of branched polynomial covering maps arising from Riemann surfaces and from knots in the 3-sphere....

  1. Branched polynomial covering maps

    DEFF Research Database (Denmark)

    Hansen, Vagn Lundsgaard

    2002-01-01

    A Weierstrass polynomial with multiple roots in certain points leads to a branched covering map. With this as the guiding example, we formally define and study the notion of a branched polynomial covering map. We shall prove that many finite covering maps are polynomial outside a discrete branch...... set. Particular studies are made of branched polynomial covering maps arising from Riemann surfaces and from knots in the 3-sphere. (C) 2001 Elsevier Science B.V. All rights reserved....

  2. Reading Angles in Maps

    Science.gov (United States)

    Izard, Véronique; O'Donnell, Evan; Spelke, Elizabeth S.

    2014-01-01

    Preschool children can navigate by simple geometric maps of the environment, but the nature of the geometric relations they use in map reading remains unclear. Here, children were tested specifically on their sensitivity to angle. Forty-eight children (age 47:15-53:30 months) were presented with fragments of geometric maps, in which angle sections…

  3. Statistical Mapping by Computer.

    Science.gov (United States)

    Utano, Jack J.

    The function of a statistical map is to provide readers with a visual impression of the data so that they may be able to identify any geographic characteristics of the displayed phenomena. The increasingly important role played by the computer in the production of statistical maps is manifested by the varied examples of computer maps in recent…

  4. Diffusion Based Photon Mapping

    DEFF Research Database (Denmark)

    Schjøth, Lars; Fogh Olsen, Ole; Sporring, Jon

    2007-01-01

    . To address this problem we introduce a novel photon mapping algorithm based on nonlinear anisotropic diffusion. Our algorithm adapts according to the structure of the photon map such that smoothing occurs along edges and structures and not across. In this way we preserve the important illumination...... features, while eliminating noise. We call our method diffusion based photon mapping....

  5. Diffusion Based Photon Mapping

    DEFF Research Database (Denmark)

    Schjøth, Lars; Olsen, Ole Fogh; Sporring, Jon

    2006-01-01

    . To address this problem we introduce a novel photon mapping algorithm based on nonlinear anisotropic diffusion. Our algorithm adapts according to the structure of the photon map such that smoothing occurs along edges and structures and not across. In this way we preserve the important illumination...... features, while eliminating noise. We call our method diffusion based photon mapping....

  6. Oil Exploration Mapping

    Science.gov (United States)

    1994-01-01

    After concluding an oil exploration agreement with the Republic of Yemen, Chevron International needed detailed geologic and topographic maps of the area. Chevron's remote sensing team used imagery from Landsat and SPOT, combining images into composite views. The project was successfully concluded and resulted in greatly improved base maps and unique topographic maps.

  7. OpenStreetMap, the Wikipedia Map

    Directory of Open Access Journals (Sweden)

    Gunther Maier

    2014-12-01

    Full Text Available This paper presents OpenStreetMap and closely related software as a resource for spatial economic research. The paper demonstrates how information can be extracted from OpenStreetMap, how it can be used as a geographical interface in web-based communication, and illustrates the value of the tools by use of a specific application, the WU campus GIS.

  8. $2^n-$rational maps

    OpenAIRE

    Kassotakis, Pavlos; Nieszporski, Maciej; Damianou, Pantelis

    2015-01-01

    We present a natural extension of the notion of nondegenerate rational maps (quadrirational maps) to arbitrary dimensions. We refer to these maps as $2^n-$rational maps. In this note we construct a rich family of $2^n-$rational maps. These maps by construction are involutions and highly symmetric in the sense that the maps and their companion maps have the same functional form.

  9. Open Land Use Map

    Directory of Open Access Journals (Sweden)

    T. Mildorf

    2014-12-01

    Full Text Available Open Land Use Map is an initiative that has been started by the Plan4business project and that will be extended as part of the SDI4Apps project in the future. This service aims to create an improved worldwide land use map. The initial map will be prepared using the CORINE Land Cover, Global Cover dataset and Open Street Map. Contributors, mainly volunteers, will able to change the geometry and assign up-to-date land use according to the HILUCS specification. For certain regions more detailed datasets, if available, will be used as an update of the Open Land Use Map. The product is treated as Open Data and users will be able to download the data in a specified format and for a selected area. The paper introduces the technical and business aspects of Open Land Use Map app including the integration and harmonisation tools, sustainability plan and apps that accompany the entire platform.

  10. Map Projection Transitions

    Directory of Open Access Journals (Sweden)

    Nedjeljko Frančula

    2013-06-01

    Full Text Available Map Projection Transitions is a very successful web application about map projections. The web page (http://www.jasondavies.com/maps/transition pre­sents a world map with graticule and country borders in the oblique Aitoff projection, with the South Pole. The map is not static, but animated. The South Pole moves toward the bottom and Earth rotates around its poles. The animation lasts five seconds, after which the projection changes and movement continues for five seconds, after which the projection changes again. Names of projections appear in a separate window. There are a total of 56 projections. The South Pole eventually becomes invisible and the North Pole appears at the top. Various parts of Earth appear in the center of the map by rotating around the poles.

  11. Classification of Lipschitz mappings

    CERN Document Server

    Piasecki, Lukasz

    2013-01-01

    The Lipschitz Condition Nonlinear spectral radius Uniformly lipschitzian mappings Basic Facts on Banach Spaces Convexity The operator norm Dual spaces, reexivity, the weak, and weak* topologiesMean Lipschitz Condition Nonexpansive and mean nonexpansive mappings in Banach spaces General case On the Lipschitz Constants for Iterates of Mean Lipschitzian Mappings A bound for Lipschitz constants of iterates A bound for the constant k∞(T)Moving averages in Bana

  12. Diametrically Contractive Multivalued Mappings

    Directory of Open Access Journals (Sweden)

    S. Dhompongsa

    2007-06-01

    Full Text Available Diametrically contractive mappings on a complete metric space are introduced by V. I. Istratescu. We extend and generalize this idea to multivalued mappings. An easy example shows that our fixed point theorem is more applicable than a former one obtained by H. K. Xu. A convergence theorem of Picard iteratives is also provided for multivalued mappings on hyperconvex spaces, thereby extending a Proinov's result.

  13. Geography Education Through Maps

    OpenAIRE

    N. Demiralp

    2007-01-01

    Geography studies the relationship between human and the earth and pay attention to space, place and environment. In its simplest definition, maps are language and communication tools in transferring knowledge of an area in the science of geography which studies the space. Thus teaching and teaching how to use maps is quite important. This is not valid just for all matters of geography education; they can be used at any point, level, age or grade in teaching. This is because map reading invol...

  14. Mind mapping management

    OpenAIRE

    Pugalendhi, Subburethina Bharathi; Nakkeeran, Senthil kumar

    2011-01-01

    A mind map is a diagram used to represent words, ideas, tasks, or other items linked to and arranged around a central key word or idea. Mind maps are used to generate, visualize, structure, and classify ideas, and as an aid to studying and organizing information, solving problems, making decisions, and writing. The fundamentals of mind map are arranged naturally according to the importance of the concepts, and are classified into groupings, branches, or areas, with the goal of representing se...

  15. Heat Capacity Mapping Mission

    Science.gov (United States)

    Nilsson, C. S.; Andrews, J. C.; Scully-Power, P.; Ball, S.; Speechley, G.; Latham, A. R. (Principal Investigator)

    1980-01-01

    The Tasman Front was delineated by airborne expendable bathythermograph survey; and an Heat Capacity Mapping Mission (HCMM) IR image on the same day shows the same principal features as determined from ground-truth. It is clear that digital enhancement of HCMM images is necessary to map ocean surface temperatures and when done, the Tasman Front and other oceanographic features can be mapped by this method, even through considerable scattered cloud cover.

  16. Obesity Prevalence Maps

    Science.gov (United States)

    ... Breastfeeding Micronutrient Malnutrition State and Local Programs Adult Obesity Prevalence Maps Recommend on Facebook Tweet Share Compartir Obesity Prevalence in 2015 Varies Across States and Territories ...

  17. Vegetation Fuel Mapping

    Directory of Open Access Journals (Sweden)

    A. V. Volokitina

    2014-12-01

    Full Text Available All vegetation sites as objects of burning are structural complexes of various fuels. Especially complex are forest biogeoceonoses. For practical use, pyrological characteristics of vegetation are reflected on plans and maps showing both general one-sided estimations with site descriptions (for example, their fire hazard and detailed multi-sided characteristics of all compounds in the vegetation fuel complexes. The latter become basic maps for obtaining various pyrological estimations and are called vegetation fuel maps. Vegetation fuel (VF mapping can be made using two methodological approaches: first, by distinguishing pyrological vegetation categories as standard complexes; second, by individually characterizing each vegetation site in terms of VF. Obviously, the standard VF characteristic of sites can be only approximate and rough, since the possible number of studied site categories is limited. For large-scale mapping, the detailed individual characteristic of vegetation sites in terms of VF is more preferable and precise but more expensive. Therefore, historically, the first approach to VF mapping got its development, i. e. distinguishing and mapping of certain vegetation categories with standard characteristics. Foreign and Russian methodical approaches to vegetation fuel (VF classification and mapping are considered. Examples of VF mapping at different scales and guidelines for their use are given.

  18. Multi-moment maps

    DEFF Research Database (Denmark)

    Swann, Andrew Francis; Madsen, Thomas Bruun

    2012-01-01

    We introduce a notion of moment map adapted to actions of Lie groups that preserve a closed three-form. We show existence of our multi-moment maps in many circumstances, including mild topological assumptions on the underlying manifold. Such maps are also shown to exist for all groups whose second...... and third Lie algebra Betti numbers are zero. We show that these form a special class of solvable Lie groups and provide a structural characterisation. We provide many examples of multi-moment maps for different geometries and use them to describe manifolds with holonomy contained in G(2) preserved by...

  19. On Nearly Euclidean Thurston Maps

    OpenAIRE

    Saenz Maldonado, Edgar Arturo

    2012-01-01

    Nearly Euclidean Thurston maps are simple generalizations of rational Lattes maps. A Thurston map is called nearly Euclidean if its local degree at each critical point is 2 and it has exactly four postcritical points. We investigate when such a map has the property that the associated pullback map on Teichmuller space is constant. We also show that no Thurston map of degree 2 has constant pullback map.

  20. On circle map coupled map lattice

    OpenAIRE

    2003-01-01

    The circle map in one and two dimensions is studied. Both its stability and synchronization, using a bounded control and persistence, are discussed. This work is expected to be applicable in ecology where spatial effects are known to be important. Also, it will be relevant to systems where delay effects are not negligible.

  1. Lyman Alpha Mapping Project (LAMP) Brightness Maps

    Science.gov (United States)

    Retherford, Kurt D.; Gladstone, G.; Stern, S.; Egan, A. F.; Miles, P. F.; Parker, J. W.; Greathouse, T. K.; Davis, M. W.; Slater, D. C.; Kaufmann, D. E.; Versteeg, M. H.; Feldman, P. D.; Hurley, D. M.; Pryor, W. R.; Hendrix, A. R.

    2010-10-01

    The Lyman Alpha Mapping Project (LAMP) is an ultraviolet (UV) spectrograph on the Lunar Reconnaissance Orbiter (LRO) that is designed to map the lunar albedo at far-UV wavelengths. LAMP primarily measures interplanetary Hydrogen Lyman-alpha sky-glow and far-UV starlight reflected from the night-side lunar surface, including permanently shadowed regions (PSRs) near the poles. Dayside observations are also obtained. Brightness maps sorted by wavelength (including the Lyman-alpha wavelength of 121.6 nm) are reported for the polar regions, with a few regions of interest reported in more detail. LAMP's spectral range of 58 nm to 196 nm includes a water ice spectral feature near 160 nm, which provides a diagnostic tool for detecting water on the lunar surface that is complementary to recent discoveries using infrared and radio frequency techniques. Progress towards producing far-UV albedo maps and searching for water ice signatures will be reported. We'll discuss how LAMP data may address questions regarding how water is formed on the moon, transported through the lunar atmosphere, and deposited in the PSRs.

  2. Map of Nasca Geoglyphs

    Science.gov (United States)

    Hanzalová, K.; Pavelka, K.

    2013-07-01

    The Czech Technical University in Prague in the cooperation with the University of Applied Sciences in Dresden (Germany) work on the Nasca Project. The cooperation started in 2004 and much work has been done since then. All work is connected with Nasca lines in southern Peru. The Nasca project started in 1995 and its main target is documentation and conservation of the Nasca lines. Most of the project results are presented as WebGIS application via Internet. In the face of the impending destruction of the soil drawings, it is possible to preserve this world cultural heritage for the posterity at least in a digital form. Creating of Nasca lines map is very useful. The map is in a digital form and it is also available as a paper map. The map contains planimetric component of the map, map lettering and altimetry. Thematic folder in this map is a vector layer of the geoglyphs in Nasca/Peru. Basis for planimetry are georeferenced satellite images, altimetry is created from digital elevation model. This map was created in ArcGis software.

  3. Simplifying Massive Contour Maps

    DEFF Research Database (Denmark)

    Arge, Lars; Deleuran, Lasse Kosetski; Mølhave, Thomas; Revsbæk, Morten; Truelsen, Jakob

    2012-01-01

    We present a simple, efficient and practical algorithm for constructing and subsequently simplifying contour maps from massive high-resolution DEMs, under some practically realistic assumptions on the DEM and contours.......We present a simple, efficient and practical algorithm for constructing and subsequently simplifying contour maps from massive high-resolution DEMs, under some practically realistic assumptions on the DEM and contours....

  4. Managing Vocabulary Mapping Services

    OpenAIRE

    Che, Chengjian; Monson, Kent; Poon, Kasey B.; Shakib, Shaun C.; Lau, Lee Min

    2005-01-01

    The efficient management and maintenance of large-scale and high-quality vocabulary mapping is an operational challenge. The 3M Health Information Systems (HIS) Healthcare Data Dictionary (HDD) group developed an information management system to provide controlled mapping services, resulting in improved efficiency and quality maintenance.

  5. Mapping Mutations on Phylogenies

    DEFF Research Database (Denmark)

    Nielsen, Rasmus

    2005-01-01

    This chapter provides a short review of recent methodologies developed for mapping mutations on phylogenies. Mapping of mutations, or character changes in general, using the maximum parsimony principle has been one of the most powerful tools in phylogenetics, and it has been used in a variety of...

  6. Diffusion Based Photon Mapping

    DEFF Research Database (Denmark)

    Schjøth, Lars; Sporring, Jon; Fogh Olsen, Ole

    2008-01-01

    . To address this problem, we introduce a photon mapping algorithm based on nonlinear anisotropic diffusion. Our algorithm adapts according to the structure of the photon map such that smoothing occurs along edges and structures and not across. In this way, we preserve important illumination features...

  7. Map-A-Planet

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — The Map-A-Planet website allows users to create and download custom image maps of planets and satellites from a variety of missions in an easy to use web interface

  8. Multivariate Nonnegative Quadratic Mappings

    NARCIS (Netherlands)

    Luo, Z-Q; Sturm, J.F.; Zhang, S.

    2003-01-01

    In this paper we study several issues related to the characterization of speci c classes of multivariate quadratic mappings that are nonnegative over a given domain, with nonnegativity de ned by a pre-speci ed conic order.In particular, we consider the set (cone) of nonnegative quadratic mappings de

  9. Android Mapping Application

    Directory of Open Access Journals (Sweden)

    Abdalwhab Bakheet

    2014-04-01

    Full Text Available Location-aware and mapping applications have gone f rom a desirable feature to an essential part of any smart phone. Whether a user is checking into a social network, looking for a pharmacy in the middle of the night, or located in somewhere and needs help, the key is always the same: location. In this project, an Android mapping application is developed. The application is able to display the map of the whole world while online or, display a pre-downloaded map while offline, track the user’s location, display a compass to determine north, send the user’s location to others in case of emergency using SMS, receive and interpret received location from the message, display it on the map, and notify the user by the reception of the location. The application was developed using agile methodol ogy. It, met its objectives and successfully passed 91% of the final system test, recording that some limitations were discovered, the application needs further testing and can be implem ented for particular company or university using their own maps or editing the maps in OSM (op en street maps.

  10. Mine mapping and layout

    Energy Technology Data Exchange (ETDEWEB)

    Williams, W.R.

    1983-01-01

    This book provides a study aid to mine engineering students combining graphical techniques of mine mapping, mine design, and mine layout, as well as supplemental techniques needed for adequate mine design. The book reviews cartographic techniques, the fundamentals of plane surveying, standard drafting room practices, guidelines for mine map symbolization and production, mine entry nomenclature, and details of topographic map production. Supplemental techniques include methods of achieving functional performance in the layout of a mine, statistical mapping of exploratory data, and techniques of descriptive geometry. Designs of ventilation, transportation, drainage, and electrical supply systems of mines are discussed in the final chapters. An appendix discusses mine mapping symbols. 105 references, 234 figures, 16 tables.

  11. Anisotropic progressive photon mapping

    Science.gov (United States)

    Liu, XiaoDan; Zheng, ChangWen

    2014-01-01

    Progressive photon mapping solves the memory limitation problem of traditional photon mapping. It gives the correct radiance with a large passes, but it converges slowly. We propose an anisotropic progressive photon mapping method to generate high quality images with a few passes. During the rendering process, different from standard progressive photon mapping, we store the photons on the surfaces. At the end of each pass, an anisotropic method is employed to compute the radiance of each eye ray based on the stored photons. Before move to a new pass, the photons in the scene are cleared. The experiments show that our method generates better results than the standard progressive photon mapping in both numerical and visual qualities.

  12. Iconicity as structure mapping.

    Science.gov (United States)

    Emmorey, Karen

    2014-09-19

    Linguistic and psycholinguistic evidence is presented to support the use of structure-mapping theory as a framework for understanding effects of iconicity on sign language grammar and processing. The existence of structured mappings between phonological form and semantic mental representations has been shown to explain the nature of metaphor and pronominal anaphora in sign languages. With respect to processing, it is argued that psycholinguistic effects of iconicity may only be observed when the task specifically taps into such structured mappings. In addition, language acquisition effects may only be observed when the relevant cognitive abilities are in place (e.g. the ability to make structural comparisons) and when the relevant conceptual knowledge has been acquired (i.e. information key to processing the iconic mapping). Finally, it is suggested that iconicity is better understood as a structured mapping between two mental representations than as a link between linguistic form and human experience. PMID:25092669

  13. Application of ecological mapping

    International Nuclear Information System (INIS)

    The US Fish and Wildlife Service has initiated the production of a comprehensive ecological inventory map series for use as a major new planning tool. Important species data along with special land use designations are displayed on 1:250,000 scale topographic base maps. Sets of maps have been published for the Atlantic and Pacific coastal areas of the United States. Preparation of a map set for the Gulf of Mexico is underway at the present time. Potential application of ecological inventory map series information to a typical land disposal facility could occur during the narrowing of the number of possible disposal sites, the design of potential disposal site studies of ecological resources, the preparation of the environmental report, and the regulatory review of license applications. 3 figures, 3 tables

  14. Mental Mapping: A Classroom Strategy

    Science.gov (United States)

    Solomon, Les

    1978-01-01

    Examines potential uses of mental maps in the classroom by reviewing research efforts, providing an example of the differences between mental maps of two student groups, and suggesting how to use mental maps in the geography curriculum. Mental mapping (or cognitive mapping) refers to individuals' processes of collecting, storing, and retrieving…

  15. Conformal Maps, Biharmonic Maps, and the Warped Product

    OpenAIRE

    Seddik Ouakkas; Djelloul Djebbouri

    2016-01-01

    In this paper we study some properties of conformal maps between equidimensional manifolds, we construct new example of non-harmonic biharmonic maps and we characterize the biharmonicity of some maps on the warped product manifolds.

  16. Removable singularities and bubbling of harmonic maps and biharmonic maps

    OpenAIRE

    Nakauchi, Nabumitsu; Urakawa, Hajime

    2009-01-01

    By using Moser's iteration technique, we show some removable singularity theorem of the tension field for biharmonic maps into manifolds of non-positive curvature, and the bubbling theorem of biharmonic maps and also harmonic maps.

  17. Color on emergency mapping

    Science.gov (United States)

    Jiang, Lili; Qi, Qingwen; Zhang, An

    2007-06-01

    There are so many emergency issues in our daily life. Such as typhoons, tsunamis, earthquake, fires, floods, epidemics, etc. These emergencies made people lose their lives and their belongings. Every day, every hour, even every minute people probably face the emergency, so how to handle it and how to decrease its hurt are the matters people care most. If we can map it exactly before or after the emergencies; it will be helpful to the emergency researchers and people who live in the emergency place. So , through the emergency map, before emergency is occurring we can predict the situation, such as when and where the emergency will be happen; where people can refuge, etc. After disaster, we can also easily assess the lost, discuss the cause and make the lost less. The primary effect of mapping is offering information to the people who care about the emergency and the researcher who want to study it. Mapping allows the viewers to get a spatial sense of hazard. It can also provide the clues to study the relationship of the phenomenon in emergency. Color, as the basic element of the map, it can simplify and clarify the phenomenon. Color can also affects the general perceptibility of the map, and elicits subjective reactions to the map. It is to say, structure, readability, and the reader's psychological reactions can be affected by the use of color.

  18. Blind Friendly Maps

    OpenAIRE

    Červenka, Petr; Břinda, Karel; Seifert, Radek; Hofman, Petr

    2016-01-01

    Space concept of the surrounding area is one of the most important preconditions of the independent mobility and orientation of the blind people. Tactile maps are considered to be the most appropriate source of spatial information. One of the main problems of the tactile maps usage is their problematic accessibility for the blind users since they are not available in time and with up-to-date content. The map production is a matter of tedious manual work and a result of expensive and time-cons...

  19. Map: Geospatial paradigm

    Directory of Open Access Journals (Sweden)

    Ikonović Vesna

    2006-01-01

    Full Text Available There are different definitions of map. There is no one which is accepted in whole world or at least from the most cartographers. In the paper it will be given several definitions which are, at the best way, (according to the author’s opinion reflecting essence of map as a model of reality. Map as a universal meaning of researching can’t serve only for representing particular geospace (spatial system or some its element, or to give only clear view about geographical dispersion of objects, phenomena and processes, but have to make possible studying the patterns of that dispersion, as well as their mutual connections and conditions.

  20. DOT Official County Highway Map

    Data.gov (United States)

    Minnesota Department of Natural Resources — The County Highway Map theme is a scanned and rectified version of the original MnDOT County Highway Map Series. The cultural features on some of these maps may be...

  1. Combinatorial properties of Newton maps

    OpenAIRE

    Lodge, Russell; Mikulich, Yauhen; Schleicher, Dierk

    2015-01-01

    This paper presents a combinatorial model for postcritically finite Newton maps (rational maps that arise from applying Newton's method to complex polynomials). This model is a first step towards a combinatorial classification of postcritically finite Newton maps.

  2. Northern Hemisphere Synoptic Weather Maps

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Daily Series of Synoptic Weather Maps. Part I consists of plotted and analyzed daily maps of sea-level and 500-mb maps for 0300, 0400, 1200, 1230, 1300, and 1500...

  3. Irreducibility properties of Keller maps

    OpenAIRE

    de Bondt, Michiel; Yan, Dan

    2013-01-01

    Jedrzejewicz showed that a polynomial map over a field of characteristic zero is invertible, if and only if the corresponding endomorphism maps irreducible polynomials to irreducible polynomials. Furthermore, he showed that a polynomial map over a field of characteristic zero is a Keller map, if and only if the corresponding endomorphism maps irreducible polynomials to square-free polynomials. We show that the latter endomorphism maps other square-free polynomials to square-free polynomials a...

  4. Interest rates mapping

    CERN Document Server

    Kanevski, M; Pozdnoukhov, A; Timonin, V

    2007-01-01

    The present study deals with the analysis and mapping of Swiss franc interest rates. Interest rates depend on time and maturity, defining term structure of the interest rate curves (IRC). In the present study IRC are considered in a two-dimensional feature space - time and maturity. Geostatistical models and machine learning algorithms (multilayer perceptron and Support Vector Machines) were applied to produce interest rate maps. IR maps can be used for the visualisation and patterns perception purposes, to develop and to explore economical hypotheses, to produce dynamic asses-liability simulations and for the financial risk assessments. The feasibility of an application of interest rates mapping approach for the IRC forecasting is considered as well.

  5. The CPD Maps System

    Data.gov (United States)

    Department of Housing and Urban Development — CPD Maps includes data on the locations of existing CDBG, HOME, public housing and other HUD-funded community assets, so that users can view past investments...

  6. Public Waters Inventory Maps

    Data.gov (United States)

    Minnesota Department of Natural Resources — This theme is a scanned and rectified version of the Minnesota DNR - Division of Waters "Public Waters Inventory" (PWI) maps. DNR Waters utilizes a small scale...

  7. TOXMAP®: Environmental Health Maps

    Data.gov (United States)

    U.S. Department of Health & Human Services — TOXMAP® is a Geographic Information System (GIS) that uses maps of the United States and Canada to help users visually explore data primarily from the EPA's Toxics...

  8. Haz-Map

    Data.gov (United States)

    U.S. Department of Health & Human Services — Haz-Map is an occupational health database designed for health and safety professionals and for consumers seeking information about the adverse effects of workplace...

  9. Marketplace Enrollment Maps

    Data.gov (United States)

    U.S. Department of Health & Human Services — The maps show the distribution of consumers in a state who enrolled in marketplace plans through federally facilitated, partnership, and supported state-based...

  10. MUTYH Associated Polyposis (MAP)

    DEFF Research Database (Denmark)

    Poulsen, Marie Louise Mølgaard; Bisgaard, M L

    2008-01-01

    MUTYH Associated Polyposis (MAP), a Polyposis predisposition caused by biallelic mutations in the Base Excision Repair (BER) gene MUTYH, confers a marked risk of colorectal cancer (CRC). The MAP phenotype is difficult to distinguish from other hereditary CRC syndromes. Especially from Familial...... Adenomatous Polyposis (FAP) and to a lesser extend Lynch Syndrome, which are caused by germline mutations in the APC and Mismatch Repair (MMR) genes, respectively.Here we review research findings regarding MUTYH interactions, genotypic and phenotypic characteristics of MAP, as well as surveillance and...... treatment of the disease. The applied papers, published between 1/1 2002- 1/2 2008, were found through PubMed.The exact role of MUTYH in CRC tumorgenesis is still uncertain, although MAP tumors show distinct molecular features, including somatic G:C>T:A transversions in the APC gene. Furthermore...

  11. National Coastal Mapping Program

    Data.gov (United States)

    Army Corps of Engineers, Department of the Army, Department of Defense — The U. S. Army Corps of Engineers (USACE) National Coastal Mapping Program (NCMP) is designed to provide high-resolution elevation and imagery data along U.S....

  12. Daily Weather Maps

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Several different government offices have published the Daily weather maps over its history. The publication has also gone by different names over time. The U.S....

  13. Mapping the HISS Dipole

    International Nuclear Information System (INIS)

    The principal component of the Bevalac HISS facility is a large super-conducting 3 Tesla dipole. The facility's need for a large magnetic volume spectrometer resulted in a large gap geometry - a 2 meter pole tip diameter and a 1 meter pole gap. Obviously, the field required detailed mapping for effective use as a spectrometer. The mapping device was designed with several major features in mind. The device would measure field values on a grid which described a closed rectangular solid. The grid would be a regular with the exact measurement intervals adjustable by software. The device would function unattended over the long period of time required to complete a field map. During this time, the progress of the map could be monitored by anyone with access to the HISS VAX computer. Details of the mechanical, electrical, and control design follow

  14. MetaMap

    Data.gov (United States)

    U.S. Department of Health & Human Services — MetaMap is a highly configurable application developed by the Lister Hill National Center for Biomedical Communications at the National Library of Medicine (NLM) to...

  15. International Map Year 2015

    OpenAIRE

    Miljenko Lapaine; Dražen Tutić

    2012-01-01

    The International Cartographic Association (ICA) decided to establish the International Map Year (IMY) during the year 2015. The working group was formed and terms of reference accepted by the ICA Executive Committee.

  16. NOS Bathymetric Maps

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This collection of bathymetric contour maps which represent the seafloor topography includes over 400 individual titles and covers US offshore areas including...

  17. FLOODPLAIN MAPPING, Bandera, TEXAS

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — The Floodplain Mapping/Redelineation study deliverables depict and quantify the flood risks for the study area. The primary risk classifications used are the...

  18. Programming with Hierarchical Maps

    DEFF Research Database (Denmark)

    Ørbæk, Peter

    This report desribes the hierarchical maps used as a central data structure in the Corundum framework. We describe its most prominent features, ague for its usefulness and briefly describe some of the software prototypes implemented using the technology....

  19. PDS Planetary Maps API

    Data.gov (United States)

    National Aeronautics and Space Administration — We are developing a set of NASA Extensions to the Google Maps API—and soon to other frameworks such as OpenLayers as well—that will make these platforms more useful...

  20. Mapping the EEZ

    Digital Repository Service at National Institute of Oceanography (India)

    De, S.; Shashikumar, K.

    The National Institute of Oceanography (NIO), Goa, India is trying to map the entire exclusive economic zone (EEZ) of the country, which will be boon for defence, communication, navigation and oceanographic research....

  1. Stochasticity in the Josephson map

    International Nuclear Information System (INIS)

    The Josephson map describes nonlinear dynamics of systems characterized by standard map with the uniform external bias superposed. The intricate structures of the phase space portrait of the Josephson map are examined on the basis of the tangent map associated with the Josephson map. Numerical observation of the stochastic diffusion in the Josephson map is examined in comparison with the renormalized diffusion coefficient calculated by the method of characteristic function. The global stochasticity of the Josephson map occurs at the values of far smaller stochastic parameter than the case of the standard map. (author)

  2. Complete Quasiconvex Mappings in Polydisc

    Institute of Scientific and Technical Information of China (English)

    LIU Tai-shun; ZHANG Wen-jun

    2006-01-01

    In this paper,a class of biholomorphic mappings called complete quasiconvex mappings is introduced and studied in bounded convex Reinhardt domains of Cn.Through a detailed analysis of the analytic characterization for this class of mappings,it is shown that this class of mappings contains the convex mappings and is also a subset of the class of starlike mappings.In the special case of the polydisc,a decomposition theorem is established for the complete quasiconvex mappings,which in turn is used to derive an improved sufficient condition for the convex mappings.

  3. Random mapping statistics

    OpenAIRE

    Flajolet, Philippe; Odlyzko, Andrew M.

    1989-01-01

    Random mappings from a finite set into itself are either a heuristic or an exact model for a variety of applications in random number generation, computational number theory, cryptography, and the analysis of algorithms at large. This paper introduces a general framework in which the analysis of about twenty characteristic parameters of random mappings is carried out. These parameters are studied systematically through the use of generating functions and singularity analysis. In particular, a...

  4. Mapping brains without coordinates

    OpenAIRE

    Kötter, Rolf; Wanke, Egon

    2005-01-01

    Brain mapping has evolved considerably over the last century. While most emphasis has been placed on coordinate-based spatial atlases, coordinate-independent parcellation-based mapping is an important technique for accessing the multitude of structural and functional data that have been reported from invasive experiments, and provides for flexible and efficient representations of information. Here, we provide an introduction to motivations, concepts, techniques and implications of coordinate-...

  5. Dynamic perceptual mapping

    OpenAIRE

    Greenacre, Michael

    2009-01-01

    Perceptual maps have been used for decades by market researchers to illuminate them about the similarity between brands in terms of a set of attributes, to position consumers relative to brands in terms of their preferences, or to study how demographic and psychometric variables relate to consumer choice. Invariably these maps are two-dimensional and static. As we enter the era of electronic publishing, the possibilities for dynamic graphics are opening up. We demonstrate the u...

  6. Ogallala Aquifer Mapping Program

    International Nuclear Information System (INIS)

    A computerized data file has been established which can be used efficiently by the contour-plotting program SURFACE II to produce maps of the Ogallala aquifer in 17 counties of the Texas Panhandle. The data collected have been evaluated and compiled into three sets, from which SURFACE II can generate maps of well control, aquifer thickness, saturated thickness, water level, and the difference between virgin (pre-1942) and recent (1979 to 1981) water levels. 29 figures, 1 table

  7. Sri Lanka Malaria Maps

    OpenAIRE

    Hoek Wim; Gunawardena Dissanayake M; Briët Olivier JT; Amerasinghe Felix P

    2003-01-01

    Abstract Background Despite a relatively good national case reporting system in Sri Lanka, detailed maps of malaria distribution have not been publicly available. Methods In this study, monthly records over the period 1995 – 2000 of microscopically confirmed malaria parasite positive blood film readings, at sub-district spatial resolution, were used to produce maps of malaria distribution across the island. Also, annual malaria trends at district resolution were displayed for the period 1995 ...

  8. Maps of Computer Science

    CERN Document Server

    Fried, Daniel

    2013-01-01

    We describe a practical approach for visual exploration of research papers. Specifically, we use the titles of papers from the DBLP database to create what we call maps of computer science (MoCS). Words and phrases from the paper titles are the cities in the map, and countries are created based on word and phrase similarity, calculated using co-occurrence. With the help of heatmaps, we can visualize the profile of a particular conference or journal over the base map. Similarly, heatmap profiles can be made of individual researchers or groups such as a department. The visualization system also makes it possible to change the data used to generate the base map. For example, a specific journal or conference can be used to generate the base map and then the heatmap overlays can be used to show the evolution of research topics in the field over the years. As before, individual researchers or research groups profiles can be visualized using heatmap overlays but this time over the journal or conference base map. Fin...

  9. MAPS of Cancer

    Science.gov (United States)

    Gray, Lincoln

    1998-01-01

    Our goal was to produce an interactive visualization from a mathematical model that successfully predicts metastases from head and neck cancer. We met this goal early in the project. The visualization is available for the public to view. Our work appears to fill a need for more information about this deadly disease. The idea of this project was to make an easily interpretable visualization based on what we call "functional maps" of disease. A functional map is a graphic summary of medical data, where distances between parts of the body are determined by the probability of disease, not by anatomical distances. Functional maps often beat little resemblance to anatomical maps, but they can be used to predict the spread of disease. The idea of modeling the spread of disease in an abstract multidimensional space is difficult for many people. Our goal was to make the important predictions easy to see. NASA must face this problem frequently: how to help laypersons and professionals see important trends in abstract, complex data. We took advantage of concepts perfected in NASA's graphics libraries. As an analogy, consider a functional map of early America. Suppose we choose travel times, rather than miles, as our measures of inter-city distances. For Abraham Lincoln, travel times would have been the more meaningful measure of separation between cities. In such a map New Orleans would be close to Memphis because of the Mississippi River. St. Louis would be close to Portland because of the Oregon Trail. Oklahoma City would be far from Little Rock because of the Cheyenne. Such a map would look puzzling to those of us who have always seen physical maps, but the functional map would be more useful in predicting the probabilities of inter-site transit. Continuing the analogy, we could predict the spread of social diseases such as gambling along the rivers and cattle rustling along the trails. We could simply print the functional map of America, but it would be more interesting

  10. Geologic mapping of Vesta

    Science.gov (United States)

    Yingst, R. A.; Mest, S. C.; Berman, D. C.; Garry, W. B.; Williams, D. A.; Buczkowski, D.; Jaumann, R.; Pieters, C. M.; De Sanctis, M. C.; Frigeri, A.; Le Corre, L.; Preusker, F.; Raymond, C. A.; Reddy, V.; Russell, C. T.; Roatsch, T.; Schenk, P. M.

    2014-11-01

    We report on a preliminary global geologic map of Vesta, based on data from the Dawn spacecraft's High-Altitude Mapping Orbit (HAMO) and informed by Low-Altitude Mapping Orbit (LAMO) data. This map is part of an iterative mapping effort; the geologic map has been refined with each improvement in resolution. Vesta has a heavily-cratered surface, with large craters evident in numerous locations. The south pole is dominated by an impact structure identified before Dawn's arrival. Two large impact structures have been resolved: the younger, larger Rheasilvia structure, and the older, more degraded Veneneia structure. The surface is also characterized by a system of deep, globe-girdling equatorial troughs and ridges, as well as an older system of troughs and ridges to the north. Troughs and ridges are also evident cutting across, and spiraling arcuately from, the Rheasilvia central mound. However, no volcanic features have been unequivocally identified. Vesta can be divided very broadly into three terrains: heavily-cratered terrain; ridge-and-trough terrain (equatorial and northern); and terrain associated with the Rheasilvia crater. Localized features include bright and dark material and ejecta (some defined specifically by color); lobate deposits; and mass-wasting materials. No obvious volcanic features are evident. Stratigraphy of Vesta's geologic units suggests a history in which formation of a primary crust was followed by the formation of impact craters, including Veneneia and the associated Saturnalia Fossae unit. Formation of Rheasilvia followed, along with associated structural deformation that shaped the Divalia Fossae ridge-and-trough unit at the equator. Subsequent impacts and mass wasting events subdued impact craters, rims and portions of ridge-and-trough sets, and formed slumps and landslides, especially within crater floors and along crater rims and scarps. Subsequent to the formation of Rheasilvia, discontinuous low-albedo deposits formed or were

  11. Conformal mappings and CR mappings on the Engel group

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    We show that conformal mappings between the Engel groups are CR or anti-CR mappings. This reduces the determination of conformal mappings to a problem in the theory of several complex analysis.The result about the group of CR automorphisms is used to determine the identity component of the group of conformal mappings on the Engel group.

  12. Generating continuous mappings with Lipschitz mappings

    OpenAIRE

    Cichon, J; Mitchell, James David; Morayne, M.

    2007-01-01

    If X is a metric space, then C-X and L-X denote the semigroups of continuous and Lipschitz mappings, respectively, from X to itself. The relative rank of C-X modulo L-X is the least cardinality of any set U\\L-X where U generates C-X. For a large class of separable metric spaces X we prove that the relative rank of C-X modulo L-X is uncountable. When X is the Baire space N-N, this rank is N-1. A large part of the paper emerged from discussions about the necessity of the assumptions imposed on ...

  13. Insurance flood maps

    International Nuclear Information System (INIS)

    Dear Client, in half an hour you will be hit by a flood, please get ready. Your insurance company. Such a phone call or SMS could only mean two things: drunk friends or an insurance company using a flood map. In the second case, the best thing to do on receiving such a message is to act quickly. The advantage of flood maps do not necessarily have to start at the moment a flood becomes an immediate threat. The primary role of flood maps is to allow for a fairer calculation of insurance rates. Insurance companies can save on re-insurance costs as if the risk level is predictable re-insurance companies may offer better rates. The three largest insurance companies: Allianz - Slovenska poistovna, Kooperativa and Ceska poistovna Slovensko have begun introducing flood maps. These three companies control about 75% of the market. And if competition does not force other market participants to adopt the same approach, re-insurance companies certainly will. They will charge more for a less specifically defined risk level. So far insurance companies have not encountered this pressure, re-insurance companies are helping them set up the flood maps and in the coming years flood maps will become a common tool. Then the pressure will be there: if a insurance company uses a different calculation method, the final price may differ greatly from the competition's. If the price is higher, the company will lose clients and if the price is much lower, the risk has probably not been calculated correctly and the insurance company may suffer substantial losses in the event of a major flood. In short, the investment of several million Sk in a flood map is essential

  14. Touch the map!: designing interactive maps for visually impaired people

    OpenAIRE

    Brock, Anke

    2013-01-01

    Visually impaired people face important challenges related to orientation and mobility. Accessible geographic maps are helpful for travel preparation. Historically, raised-line paper maps have been used, but these maps possess significant limitations. However, recent technological advances have enabled the design of accessible interactive maps that overcome these limitations. This paper presents the development of an accessible interactive map prototype based on the cycle of participatory des...

  15. Mappings for the Semantic Web

    OpenAIRE

    Gómez-Pérez, A.; Ramos, JA

    2008-01-01

    Mappings usually relate two similar knowledge aware resources. Mapping examples abound in thesauri, databases, and ontologies. Additionally, mapping systems can relate two different knowledge resources, such as databases and ontologies. All these mappings are operationally different and are sometimes named differently— for example, correspondences, semantic bridges, transformations, semantic relations, functions, conversions, and domain-method relations

  16. Mapping the University Learning Environment.

    Science.gov (United States)

    Mitchell, Alice A.; And Others

    The perceptual mapping technique was used to solicit University of Maryland college freshmen's perceptions of the campus environment. In perceptual mapping respondents are provided with a map of an indoor or outdoor location and their feelings or perceptions about areas on the map are solicited. During this study students participating in regular…

  17. Counting One-Vertex Maps

    OpenAIRE

    Orbanic, Alen; Petkovsek, Marko; Pisanski, Tomaz; Potocnik, Primoz

    2008-01-01

    The number of distinct maps (pre-maps) with a single vertex and valence $d$ is computed for any value of $d$. The types of maps (pre-maps) that we consider depend on whether the underlaying graph (pre-graph) is signed or unsigned and directed or undirected.

  18. Web Interactive Campus Map

    Directory of Open Access Journals (Sweden)

    Marylene S. Eder

    2015-03-01

    Full Text Available Abstract Interactive campus map is a web based application that can be accessed through a web browser. With the Google Map Application Programming Interface availability of the overlay function has been taken advantage to create custom map functionalities. Collection of building points were gathered for routing and to create polygons which serves as a representation of each building. The previous campus map provides a static visual representation of the campus. It uses legends building name and its corresponding building number in providing information. Due to its limited capabilities it became a realization to the researchers to create an interactive campus map.Storing data about the building room and staff information and university events and campus guide are among the primary features that this study has to offer. Interactive Web-based Campus Information System is intended in providing a Campus Information System.It is open to constant updates user-friendly for both trained and untrained users and capable of responding to all needs of users and carrying out analyses. Based on the data gathered through questionnaires researchers analyzed the results of the test survey and proved that the system is user friendly deliver information to users and the important features that the students expect.

  19. Mapping sequences by parts

    Directory of Open Access Journals (Sweden)

    Guziolowski Carito

    2007-09-01

    Full Text Available Abstract Background: We present the N-map method, a pairwise and asymmetrical approach which allows us to compare sequences by taking into account evolutionary events that produce shuffled, reversed or repeated elements. Basically, the optimal N-map of a sequence s over a sequence t is the best way of partitioning the first sequence into N parts and placing them, possibly complementary reversed, over the second sequence in order to maximize the sum of their gapless alignment scores. Results: We introduce an algorithm computing an optimal N-map with time complexity O (|s| × |t| × N using O (|s| × |t| × N memory space. Among all the numbers of parts taken in a reasonable range, we select the value N for which the optimal N-map has the most significant score. To evaluate this significance, we study the empirical distributions of the scores of optimal N-maps and show that they can be approximated by normal distributions with a reasonable accuracy. We test the functionality of the approach over random sequences on which we apply artificial evolutionary events. Practical Application: The method is illustrated with four case studies of pairs of sequences involving non-standard evolutionary events.

  20. Sri Lanka Malaria Maps

    Directory of Open Access Journals (Sweden)

    van der Hoek Wim

    2003-07-01

    Full Text Available Abstract Background Despite a relatively good national case reporting system in Sri Lanka, detailed maps of malaria distribution have not been publicly available. Methods In this study, monthly records over the period 1995 – 2000 of microscopically confirmed malaria parasite positive blood film readings, at sub-district spatial resolution, were used to produce maps of malaria distribution across the island. Also, annual malaria trends at district resolution were displayed for the period 1995 – 2002. Results The maps show that Plasmodium vivax malaria incidence has a marked variation in distribution over the island. The incidence of Plasmodium falciparum malaria follows a similar spatial pattern but is generally much lower than that of P. vivax. In the north, malaria shows one seasonal peak in the beginning of the year, whereas towards the south a second peak around June is more pronounced. Conclusion This paper provides the first publicly available maps of both P. vivax and P. falciparum malaria incidence distribution on the island of Sri Lanka at sub-district resolution, which may be useful to health professionals, travellers and travel medicine professionals in their assessment of malaria risk in Sri Lanka. As incidence of malaria changes over time, regular updates of these maps are necessary.

  1. Maps, immersions and permutations

    CERN Document Server

    Coquereaux, Robert

    2015-01-01

    We consider the problem of counting and of listing topologically inequivalent "planar" {4-valent} maps with a single component and a given number n of vertices. This enables us to count and to tabulate immersions of a circle in a sphere (spherical curves), extending results by Arnold and followers. Different options where the circle and/or the sphere are/is oriented are considered in turn, following Arnold's classification of the different types of symmetries. We also consider the case of bicolourable and bicoloured maps or immersions, where faces are bicoloured. Our method extends to immersions of a circle in a higher genus Riemann surface. There the bicolourability is no longer automatic and has to be assumed. We thus have two separate countings in non zero genus, that of bicolourable maps and that of general maps. We use a classical method of encoding maps in terms of permutations, on which the constraints of "one-componentness" and of a given genus may be applied. Depending on the orientation issue and on...

  2. The World Stress Map

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Knowledge of the stress field in the Earth's crust is a key issue for the understanding of geodynamic processes,seismic hazard assessment, and stability of underground openings such as waste disposals, tunnels, mines or wells, and reservoir management. The World Stress Map project is a collaborative project of academia,industry and governmental organizations that aims to understand the states and sources of tectonic stresses in the Earth's crust. We present the Worm Stress Map at 1:46,000,000 scale as a result of more than two decades of international collaboration. The map reveals that the first-order pattern of stress is of plate-wide scale, indicating that plate boundary forces are the major control of the stress orientations and the tectonic regime.

  3. Comparative wear mapping techniques

    DEFF Research Database (Denmark)

    Alcock, J.; Sørensen, Ole Toft; Jensen, S.; Kjeldsteen, P.

    Pin-on-disc tests of tungsten carbide pins against silicon carbide discs were performed and wear rate, mechanism and friction maps constructed. Correlations were observed between the wear mode and the friction of the pin-disc interface, and between the qualitative incidence of disruptive wear...... mechanisms and the wear rate. A microploughing wear mechanism was most prevalent at low test loads, but co-existing multiple mechanisms were observed at many velocity-load combinations. Three separate regimes of frictional behaviour were observed over the test length. Standard wear maps were found to be...... inadequate as aids to inter-wear test comparison. Methods of measuring the severity and prevalence of wear mechanisms, to produce 'quantitative mechanism maps' are required....

  4. Mapping Atrial Fibrillation: 2015 Update

    OpenAIRE

    Chirag R. Barbhayia; Saurabh Kumar; Gregory F. Michaud

    2015-01-01

    Atrial fibrillation requires a trigger that initiates the arrhythmia and substrate that favors perpetuation. Cardiac mapping is necessary to locate triggers and substrate so that an ablation strategy can be optimized. The most commonly used cardiac mapping approach is isochronal or activation mapping, which aims to create a spatial model of electrical wavefront propagation. Historically, activation mapping has been successful for mapping point source and single or double wave reentrant arr...

  5. Proportional Symbol Mapping in R

    OpenAIRE

    Susumu Tanimura; Chusi Kuroiwa; Tsutomu Mizota

    2006-01-01

    Visualization of spatial data on a map aids not only in data exploration but also in communication to impart spatial conception or ideas to others. Although recent carto-graphic functions in R are rapidly becoming richer, proportional symbol mapping, which is one of the common mapping approaches, has not been packaged thus far. Based on the theories of proportional symbol mapping developed in cartography, the authors developed some functions for proportional symbol mapping using R, including ...

  6. Map usage in virtual environments

    OpenAIRE

    Cevik, Helsin

    1998-01-01

    Approved for public release; distribution is unlimited. It is neither practical nor efficient to represent virtual maps as we do for paper maps in the real world due to major differences in hardware and software capabilities and requirements. Instead, we can determine the parameters that affect virtual map representation and that help to construct a mental map, and then manipulate these parameters in order to increase the effectiveness of map representation as an aid in performing navigati...

  7. Mapping your competitive position.

    Science.gov (United States)

    D'Aveni, Richard A

    2007-11-01

    A price-benefit positioning map helps you see, through your customers' eyes, how your product compares with all its competitors in a market. You can draw such a map quickly and objectively, without having to resort to costly, time-consuming consumer surveys or subjective estimates of the excellence of your product and the shortcomings of all the others. Creating a positioning map involves three steps: First, define your market to include everything your customers might consider to be your product's competitors or substitutes. Second, track the price your customers actually pay (wholesale or retail? bundled or unbundled?) and identify what your customers see as your offering's primary benefit. This is done through regression analysis, determining which of the product's attributes (as described objectively by rating services, government agencies, R&D departments, and the like) explains most of the variance in its price. Third, draw the map by plotting on a graph the position of every product in the market you've selected according to its price and its level of primary benefit, and draw a line that runs through the middle of the points. What you get is a picture of the competitive landscape of your market, where all the products above the line command a price premium owing to some secondary benefit customers value, and all those below the line are positioned to earn market share through lower prices and reduced secondary benefits. Using examples as varied as Harley-Davidson motorcycles, Motorola cell phones, and the New York restaurant market, Tuck professor D'Aveni demonstrates some of the many ways the maps can be used: to locate unoccupied or less-crowded spaces in highly competitive markets, for instance, or to identify opportunities created through changes in the relationship between the primary benefit and prices. The maps even allow companies to anticipate--and counter-- rivals' strategies. R eprint RO711G PMID:18159791

  8. Computer vision mapping system

    International Nuclear Information System (INIS)

    This paper describes a system capable of accurately mapping the pipe layout (including the associated components) in an existing nuclear power plant. The system processes the images taken by a laser range finder and creates a 3D model of the existing pipe system. Accurate mapping of the geometry, location, and orientation of pipe routes as well as components will permit both the generation of the 3D CAD database and validation of as-built plants with pre-existing CAD databases. (author)

  9. Graphene Conductance Uniformity Mapping

    DEFF Research Database (Denmark)

    Buron, Jonas Christian Due; Petersen, Dirch Hjorth; Bøggild, Peter;

    2012-01-01

    We demonstrate a combination of micro four-point probe (M4PP) and non-contact terahertz time-domain spectroscopy (THz-TDS) measurements for centimeter scale quantitative mapping of the sheet conductance of large area chemical vapor deposited graphene films. Dual configuration M4PP measurements......, demonstrated on graphene for the first time, provide valuable statistical insight into the influence of microscale defects on the conductance, while THz-TDS has potential as a fast, non-contact metrology method for mapping of the spatially averaged nanoscopic conductance on wafer-scale graphene with scan times......, dominating the microscale conductance of the investigated graphene film....

  10. Comparative wear mapping techniques

    DEFF Research Database (Denmark)

    Alcock, J.; Sørensen, Ole Toft; Jensen, S.; Kjeldsteen, P.

    Pin surfaces were analysed by laser profilometry. Two roughness parameters, R(a) and the fractal dimension, were investigated as a first step towards methods of quantitative wear mechanism mapping. Both parameters were analysed for their relationship to the severity and prevalence of a mechanism....... Three-dimensional maps of R(a), fractal dimension, average slope and average inter-deviation spacing were produced, It was found that whilst mechanistic information for multiple mechanisms was contained within R(a) and fractal dimension, without further quantitative knowledge of the surface, the...

  11. Learning Bing maps API

    CERN Document Server

    Sinani, Artan

    2013-01-01

    This is a practical, hands-on guide with illustrative examples, which will help you explore the vast universe of Bing maps.If you are a developer who wants to learn how to exploit the numerous features of Bing Maps then this book is ideal for you. It can also be useful for more experienced developers who wish to explore other areas of the APIs. It is assumed that you have some knowledge of JavaScript, HTML, and CSS. For some chapters a working knowledge of .Net and Visual Studio is also needed.

  12. Accretion Stream Mapping

    CERN Document Server

    Vrielmann, S; Vrielmann, Sonja; Schwope, Axel D.

    1998-01-01

    We present a new mapping algorithm, the Accretion Stream Mapping, which uses the complete emission-line light curve to derive spatially resolved intensity distributions along the stream on a surface created as a duodecadon shaped tube. We successfully test this method on artificial data and then applied it to emission line light curves in Hbeta, Hgamma and HeII 4686 of the magnetic CV HU Aqr. We find Balmer emission near the threading point in the stream facing the white dwarf and Helium emission all over the magnetic part of the stream.

  13. Some Combined Relations between Contractive Mappings, Kannan Mappings, Reasonable Expansive Mappings, and -Stability

    Directory of Open Access Journals (Sweden)

    De la Sen M

    2009-01-01

    Full Text Available In recent literature concerning fixed point theory for self-mappings in metric spaces , there are some new concepts which can be mutually related so that the inherent properties of each one might be combined for such self-mappings. Self-mappings can be referred to, for instance, as Kannan-mappings, reasonable expansive mappings, and Picard -stable mappings. Some relations between such concepts subject either to sufficient, necessary, or necessary and sufficient conditions are obtained so that in certain self-mappings can exhibit combined properties being inherent to each of its various characterizations.

  14. 2004 Alaska Lidar Mapping

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The data sets are generated using the OPTECH ALTM 70 kHz LIDAR system mounted onboard AeroMap's twin-engine Cessna 320 aircraft. Classified data sets such as this...

  15. Extending Lipschitz mappings continuously

    Czech Academy of Sciences Publication Activity Database

    Kopecká, Eva

    2012-01-01

    Roč. 18, č. 2 (2012), s. 167-177. ISSN 1425-6908 Institutional support: RVO:67985840 Keywords : Lipschitz mapping * Hilbert space * extension Subject RIV: BA - General Mathematics http://www.degruyter.com/view/j/jaa.2012.18.issue-2/jaa-2012-0011/jaa-2012-0011.xml

  16. Mapping digital media: Netherlands

    OpenAIRE

    Waal, de, P.R.; Leurdijk, A.; Nordeman, L.; Poell, T.

    2012-01-01

    The Mapping Digital Media project examines the global opportunities and risks created by the transition from traditional to digital media. Covering 60 countries, the project examines how these changes affect the core democratic service that any media system should provide: news about political, economic, and social affairs.

  17. eMAPS

    CERN Multimedia

    Human Resources Department

    2005-01-01

    Starting with the 2005 performance appraisal and advancement exercise (MAPS), the paper version of the annual appraisal report has been replaced by an electronic EDH version - eMAPS (see Weekly Bulletin 48/2004). As announced in Weekly Bulletin 2/2005, information sessions to explain the features of eMAPS using EDH have been arranged as follows: 18 January 2005: Main Auditorium (500-1-001) from 14:00 to 15:30. 20 January 2005: AB Auditorium II (864-1-D02) from 14:00 to 15:30. 24 January 2005: AT Auditorium (30-7-018) from 10:00 to 11:30. The changeover to an electronic appraisal report is designed to reduce the administrative workload involving, e.g. photocopying, tracing and filing paper copies, while allowing staff members and their hierarchy access to the report form at the appropriate times. There is no change in the procedure for the annual interview and the advancement exercise, though Administrative Circular No 26 (Rev. 5) has been updated to take account of the introduction of eMAPS. The content...

  18. Mapping Joint Action.

    Science.gov (United States)

    Slawski, Carl

    The flow diagrams in this document provide cognitive maps to aid in synthesizing diverse areas of knowledge in a special brand of field theory. A model is presented which highlights the domains of structural functionalism (with concepts of cultural, personal and societal systems) and symbolic interactionism (with the concepts of self, sentiments…

  19. Statistical parametric mapping (SPM)

    OpenAIRE

    Flandin, G.; Friston, K.J.

    2008-01-01

    Statistical parametric mapping is the application of Random Field Theory to make inferences about the topological features of statistical processes that are continuous functions of space or time. It is usually used to identify regionally specific effects (e.g., brain activations) in neuroimaging data to characterize functional anatomy and disease-related changes.

  20. Personal Food System Mapping

    Science.gov (United States)

    Wilsey, David; Dover, Sally

    2014-01-01

    Personal food system mapping is a practical means to engage community participants and educators in individualized and shared learning about food systems, decisions, and behaviors. Moreover, it is a useful approach for introducing the food system concept, which is somewhat abstract. We developed the approach to capture diversity of personal food…

  1. Learning maps -- Application

    International Nuclear Information System (INIS)

    The paper consists of a series of slides used in the presentation. They summarize the Root Learning Map process which is a tool that allows a company to modify its culture to improve productivity by allowing employees to have a vested interest in the outcome of the company. Educating the employees about different aspects of the organization is a major part of the process

  2. Mapping the Literature

    DEFF Research Database (Denmark)

    Boulus-Rødje, Nina

    2012-01-01

    As the utilization of various e-voting technologies has notably increased in the past few years, so has the amount of publications on experiences with these technologies. This article, will, therefore map the literature while highlighting some of the important topics discussed within the field of e...

  3. Bisimulation and open maps

    DEFF Research Database (Denmark)

    Joyal, André; Nielsen, Mogens; Winskel, Glynn

    1993-01-01

    Goltz and van Glabeek (1989). A tie-up with open maps in a (pre)topos brings to light a promising new model, presheaves on categories of pomsets, into which the usual category of labeled event structures embeds fully and faithfully. As an indication of its promise, this new presheaf model has refinement...

  4. Photogrammetry and Digital Mapping

    DEFF Research Database (Denmark)

    Frederiksen, Poul

    1998-01-01

    Technical tour to Lithuania, Poland and Estonia for 13 technical staff and managers of State Land Service, HQ, Latvia. Focus on technical aspects and management of geographical data for map production and administration. Visits to state and local government organisations and newly established...

  5. Mapping the Field

    DEFF Research Database (Denmark)

    Goerres, Achim; Vanhuysse, Pieter

    2012-01-01

    Whereas the call for a political science based study of older people and ageing is not new (Cutler 1977; Heclo 1988), relatively little unified progress has been made so far. This chapter maps the field of generational politics and introduces our edited volume "Ageing Populations in Post...

  6. "Total Deposition (TDEP) Maps"

    Science.gov (United States)

    The presentation provides an update on the use of a hybrid methodology that relies on measured values from national monitoring networks and modeled values from CMAQ to produce of maps of total deposition for use in critical loads and other ecological assessments. Additionally, c...

  7. Secured Ontology Mapping

    Directory of Open Access Journals (Sweden)

    Manjula Shenoy.K

    2012-11-01

    Full Text Available Today’s market evolution and high volatility of business requirements put an increasing emphasis on theability for systems to accommodate the changes required by new organizational needs while maintainingsecurity objectives satisfiability. This is all the more true in case of collaboration and interoperabilitybetween different organizations and thus between their information systems. Ontology mapping has beenused for interoperability and several mapping systems have evolved to support the same. Usual solutionsdo not take care of security. That is almost all systems do a mapping of ontologies which are unsecured.We have developed a system for mapping secured ontologies using graph similarity concept. Here we giveno importance to the strings that describe ontology concepts ,properties etc. Because these strings may beencrypted in the secured ontology. Instead we use the pure graphical structure to determine mappingbetween various concepts of given two secured ontologies. The paper also gives the measure of accuracyof experiment in a tabular form in terms of precision, recall and F-measure.

  8. STOCHASTIC FLOWS OF MAPPINGS

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In this paper, the stochastic flow of mappings generated by a Feller convolution semigroup on a compact metric space is studied. This kind of flow is the generalization of superprocesses of stochastic flows and stochastic diffeomorphism induced by the strong solutions of stochastic differential equations.

  9. Mapping Global Citizenship

    Science.gov (United States)

    Stein, Sharon

    2015-01-01

    The demand to cultivate global citizenship is frequently invoked as central to colleges' and universities' internationalization efforts. However, the term "global citizenship" remains undertheorized in the context of U.S. higher education. This article maps and engages three common global citizenship positions--entrepreneurial, liberal…

  10. SS05 - Mind Mapping

    OpenAIRE

    Rachman, Alwy; Rapi, Amrin

    2011-01-01

    Dunia kampus adalah dunia akademis. Dunia akademis adalah dunia gagasan (dunia ide) yang terhubung dengan ilmu pengetahuan. Menjadi mahasiswa baru ibarat memasuki tahap awal dari satu dunia sebagaimana di atas, sebuah dunia yang sarat dengan informasi dari berbagai disiplin pengetahuan. Oleh karenanya, memetakan pikiran dan gagasan (mind mapping) adalah keterampilan yang diperlukan bagi siapa saja yang berhubungan dengan dunia pikiran dan gagasan.

  11. Bisimulation from Open Maps

    DEFF Research Database (Denmark)

    Joyal, André; Nielsen, Mogens; Winskel, Glynn

    1996-01-01

    van Glabeek and Goltz. A tie-up with open maps in a (pre)topos, as they appear in the work of Joyal and Moerdijk, brings to light a new model, presheaves on categories of pomsets, into which the usual category of labelled event structures embeds fully and faithfully. As an indication of its promise...

  12. Mapping the Slavic languages

    Czech Academy of Sciences Publication Activity Database

    Kloferová, Stanislava

    Vol. 2. Berlin - New York: de Gruyter, 2010 - (Lameli, A.; Kehrein, R.; Rabanus, S.), s. 317-333 ISBN 978-3-11-019609-2 Institutional research plan: CEZ:AV0Z90610518 Keywords : Slavic language s * dialects * linguistic map * linguistic atlas Subject RIV: AI - Linguistics

  13. Covariance mapping techniques

    Science.gov (United States)

    Frasinski, Leszek J.

    2016-08-01

    Recent technological advances in the generation of intense femtosecond pulses have made covariance mapping an attractive analytical technique. The laser pulses available are so intense that often thousands of ionisation and Coulomb explosion events will occur within each pulse. To understand the physics of these processes the photoelectrons and photoions need to be correlated, and covariance mapping is well suited for operating at the high counting rates of these laser sources. Partial covariance is particularly useful in experiments with x-ray free electron lasers, because it is capable of suppressing pulse fluctuation effects. A variety of covariance mapping methods is described: simple, partial (single- and multi-parameter), sliced, contingent and multi-dimensional. The relationship to coincidence techniques is discussed. Covariance mapping has been used in many areas of science and technology: inner-shell excitation and Auger decay, multiphoton and multielectron ionisation, time-of-flight and angle-resolved spectrometry, infrared spectroscopy, nuclear magnetic resonance imaging, stimulated Raman scattering, directional gamma ray sensing, welding diagnostics and brain connectivity studies (connectomics). This review gives practical advice for implementing the technique and interpreting the results, including its limitations and instrumental constraints. It also summarises recent theoretical studies, highlights unsolved problems and outlines a personal view on the most promising research directions.

  14. Computerized Star Map.

    Science.gov (United States)

    Shooman, Andrew

    1982-01-01

    A program written for the 16K Level II TRS-80 computer that prints a star map, using various mathematical formulas to compute positions of the stars and the moon and displays them on terminals, is discussed. Some relevant astronomical background and terminology are covered in order to aid understanding. (MP)

  15. FriendsMap

    OpenAIRE

    Bombí Fernández, Bernat

    2012-01-01

    En esta memoria se explica detalladamente el proceso de elaboración de una aplicación para iPhone y iPad. Nombrada FriendsMap, ésta aplicación permite a los usuarios localizar a sus amigos gracias a la geolocalización.

  16. Mapping the Universe.

    Science.gov (United States)

    Landy, S. D.

    1999-06-01

    Galaxies congregate into clusters, clusters amass into superclusters and so on - at every observed scale, as astronomers build maps of the sky, they find matter organized into clumps. Yet taken as a whole, the texture of the universe is smooth, in keeping with theory. A new "music of the spheres" may explain how ordered structures emerged from the original smooth chaos.

  17. Bathymetry Offshore of Point Reyes Map Map Area, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the bathymetry and shaded-relief maps of the Offshore of Point Reyes map area, California. Raster data file is included in...

  18. Bathymetry Hillshade Offshore of Point Reyes Map Map Area, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the bathymetry and shaded-relief maps of the Offshore of Point Reyes map area, California. Raster data file is included in...

  19. Contours Offshore of Point Reyes Map Map Area, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the bathymetric contours for several seafloor maps of the Offshore of Point Reyes map area, California. The vector data file...

  20. USGS Imagery Only Base Map Service from The National Map

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — USGS Imagery Only is a tile cache base map of orthoimagery in The National Map visible to the 1:18,000 zoom scale. Orthoimagery data typically are high resolution...

  1. Mapping Future Education and Training: Group Concept Mapping Study

    OpenAIRE

    Stoyanov, Slavi; HOOGVELD Bert; Kirschner, Paul A.

    2010-01-01

    Stoyanov, S., Hoogveld, A. W. M., & Kirschner, P. A. (2010). Mapping Future Education and Training: Group Concept Mapping Study. Heerlen, The Netherlands: Open University of the Netherlands; EU Forlic project.

  2. Map format for mobile robot map-based autonomous navigation

    OpenAIRE

    Corominas Murtra, Andreu; Mirats-Tur, Josep M.

    2007-01-01

    This technical report defines the spatial representation and the map file format used in a mobile robot map-based autonomous navigation system designed to be deployed in urban areas. After a discussion about common requirements of spatial representations for map-based mobile robot autonomous navigation, a proposed environment model that fulfills previously discussed requirements is formally presented. An example of a map representing an outdoor area of an university campus of about 10000m2 is...

  3. Nonunique tangent maps at isolated singularities of harmonic maps

    OpenAIRE

    White, Brian

    1991-01-01

    Shoen and Uhlenbeck showed that ``tangent maps'' can be defined at singular points of energy minimizing maps. Unfortunately these are not unique, even for generic boundary conditions. Examples are discussed which have isolated singularities with a continuum of distinct tangent maps.

  4. On exposed positive maps: Robertson and Breuer-Hall maps

    OpenAIRE

    Chruściński, Dariusz

    2011-01-01

    It is well known that so called Breuer-Hall positive maps used in entanglement theory are optimal. We show that these maps possess much more subtle property --- they are exposed. As a byproduct it proves that a Robertson map in the algebra of 4 x 4 complex matrices is not only extreme, which was already shown by Robertson, but also exposed.

  5. NEPR Geographic Zone Map 2015

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This geographic zone map was created by interpreting satellite and aerial imagery, seafloor topography (bathymetry model), and the new NEPR Benthic Habitat Map...

  6. The mappings of degree 1

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available The maps of the form f( x = ∑ i=1 n a i ⋅x⋅ b i , called 1-degree maps, are introduced and investigated. For noncommutative algebras and modules over them 1-degree maps give an analogy of linear maps and differentials. Under some conditions on the algebra 𝒜 , contractibility of the group of 1-degree isomorphisms is proved for the module l 2 ( 𝒜 . It is shown that these conditions are fulfilled for the algebra of linear maps of a finite-dimensional linear space. The notion of 1-degree map gives a possibility to define a nonlinear Fredholm map of l 2 ( 𝒜 and a Fredholm manifold modelled by l 2 ( 𝒜 . 1-degree maps are also applied to some problems of Markov chains.

  7. Map projections cartographic information systems

    CERN Document Server

    Grafarend, Erik W

    2006-01-01

    Offers a review of map projections (sphere, ellipsoidal, rotational surfaces) and of the geodetic datum transformations, in the context of Geographical Information Systems (GIS). This book also includes the reviews of computer vision and remote sensing space projective mappings.

  8. Linear maps respecting unitary conjugation

    OpenAIRE

    Bhat, B V Rajarama

    2011-01-01

    We characterize linear maps on von Neumann algebras which leave every unital subalgebra invariant. We use this characterization to determine linear maps which respect unitary conjugation, answering a question of M. S. Moslehian.

  9. NEPR Benthic Habitat Map 2015

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This benthic habitat map was created from a semi-automated habitat mapping process, using a combination of bathymetry, satellite imagery, aerial imagery and...

  10. North America Synoptic Weather Maps

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Series of Synoptic Weather Maps. Maps contains a surface analysis comprised of plotted weather station observations, isobars indicating low and high-pressure...

  11. Knowledge Map of Facilities Management

    DEFF Research Database (Denmark)

    Nenonen, Suvi; Jensen, Per Anker; Lindahl, Göran

    2014-01-01

    profession, research and education. The knowledge map aims to contrast perspectives on how to map interdisciplinary research. Design/methodology/approach The Knowledge map is based on classification of 83 articles, including volume 2013 of Facilities (40 articles) and of Journal of Facilities Management (21...... articles) and all volumes (2010-2013) of International Journal of Facility Management (22 articles), except 2013, issue 3. Findings . The Knowledge map integrates eight different disciplines. Management is still the dominant discipline followed by engineering. Originality/value . Based on knowledge maps......Purpose This paper aims to draft a knowledge map of the fragmented and multidisciplinary research of and relevant to FM. Facilities management knowledge map is a tool for presenting what relevant data and knowledge, a.k.a. knowledge, resides in different disciplines. Knowledge mapping is a step...

  12. Graphene mobility mapping

    DEFF Research Database (Denmark)

    Buron, Jonas Christian Due; Pizzocchero, Filippo; Jepsen, Peter Uhd;

    2015-01-01

    Carrier mobility and chemical doping level are essential figures of merit for graphene, and large-scale characterization of these properties and their uniformity is a prerequisite for commercialization of graphene for electronics and electrodes. However, existing mapping techniques cannot directly...... assess these vital parameters in a non-destructive way. By deconvoluting carrier mobility and density from non-contact terahertz spectroscopic measurements of conductance in graphene samples with terahertz-transparent backgates, we are able to present maps of the spatial variation of both quantities over...... graphene indicates dominance by charged scatterers. Unexpectedly, significant variations in mobility rather than doping are the cause of large conductance inhomogeneities, highlighting the importance of statistical approaches when assessing large-area graphene transport properties....

  13. Copenhagen Sonic Experience Map

    DEFF Research Database (Denmark)

    Kreutzfeldt, Jacob

    2011-01-01

    In the wake of present European interest for mapping urban noise, it seems increasingly relevant to investigate the multiple ways in which sound intersects with the everyday experiences of urban citizens. Focusing on the polluting effects of infrastructural noise, the EU-initiated project...... of assessment and management of environmental noise brings forth the disturbing and potentially damaging effect of environmental sound.1 But as maps of coloured streets start to circulate, and real estate prices drop in designated blue and red areas,2 it is worth remembering that sound itself is not a killer....... The challenge for planners, designers, and architects is to deal with the auditory not only as pollution but also as an integrated part of urban experience, promoting fellowship and liveliness as well as distress....

  14. Fire PSA for MAPS

    International Nuclear Information System (INIS)

    Full text: Fire hazard has been identified as one of the major contributors to a plant's operational risk. As a result of several fire incidences at nuclear power plants, internal fire is included in level 1 probabilistic safety assessment (PSA) studies of nuclear power plants (NPPs). This activity is termed as fire risk analysis or fire PSA. In this context, fire PSA studies were initiated for Madras Atomic Power Station (MAPS). Fire PSA extends the consequence analysis of a fire event towards core damage, in case of nuclear power plants. The paper summarises and gives an overview of the fire PSA procedure performed for MAPS. It highlights the issues associated with the collection of data and information needed for fire modelling. An estimate of the contribution of fire to core damage frequency (CDF) has been obtained

  15. AGN Reverberation Mapping

    CERN Document Server

    Bentz, Misty C

    2015-01-01

    Reverberation mapping is now a well-established technique for investigating spatially-unresolved structures in the nuclei of distant galaxies with actively-accreting supermassive black holes. Structural parameters for the broad emission-line region, with angular sizes of microarcseconds, can be constrained through the substitution of time resolution for spatial resolution. Many reverberation experiments over the last 30 years have led to a practical understanding of the requirements necessary for a successful program. With reverberation measurements now in hand for 60 active galaxies, and more on the horizon, we are able to directly constrain black hole masses, derive scaling relationships that allow large numbers of black hole mass estimates throughout the observable Universe, and begin investigating the detailed geometry and kinematics of the broad line region. Reverberation mapping is therefore one of the few techniques available that will allow a deeper understanding of the physical mechanisms involved in...

  16. MAPS Appraisal Report Form

    CERN Multimedia

    HR Department

    2005-01-01

    As announced in Weekly Bulletin 48/2004, from now onwards, the paper MAPS appraisal report form has been replaced by an electronic form, which is available via EDH (on the EDH desktop under Other Tasks / HR & Training) No changes have been made to the contents of the form. Practical information will be available on the web page http://cern.ch/ais/projs/forms/maps/info.htm, and information meetings will be held on the following dates: 18 January 2005: MAIN AUDITORIUM (500-1-001) from 14:00 to 15:30. 20 January 2005: AB AUDITORIUM II (864-1-D02) from14:00 to 15:30. 24 January 2005: AT AUDITORIUM (30-7-018) from 10:00 to 11:30. Human Resources Department Tel. 73566

  17. Maps and statistics

    International Nuclear Information System (INIS)

    This document provides, supplying by more than 54 maps and tables, statistics on the petroleum industry and market. It covers the mine sites near Paris, in Aquitaine (France) and in north sea; the reserves; the petroleum and natural gas production in north sea; the refinery capacities; the petroleum production in CIS, North Africa, Egypt, Middle-East; the drilling activities; the turn over of petroleum, gas, para-petroleum, petrochemical industry and the industrialists; the refining in France; the chemical industry in France

  18. Mapping and Contact Zones

    DEFF Research Database (Denmark)

    Moberg, Bergur Rønne

    En undersøgelse af kortlægningsperspektiver - sted og rum - i Jørgen-Frantz Jacobsens Barbara og William Heinesens De fortabte Spillemænd med afsæt i Bakhtins kronotop-begreb og Foucaults begreb heterotopia. Analysen er koncentreret om konvergensen mellem blikket indefra og udefra og argumenterer...... herudfra for en netværkende form for mapping. Kortlægningsperspektivet forklares siden ind i en center-periferi kontekst, som forklares kulturgeografisk og postkolonialt....

  19. The grief map

    Science.gov (United States)

    Monteiro, L. H. A.

    2014-12-01

    Grieving is a natural human reaction to a significant loss. According to a psychiatric model, this process is characterized by a typical sequence of psychological changes. Here, I propose a discrete-time dynamical system, called the grief map, in order to represent the grieving process. The corresponding bifurcation diagram, which exhibits stationary, periodic, and chaotic behavior, is related to the stages of this sorrowful journey occurring during about 12 months post-loss.

  20. MAP user's manual copyright

    International Nuclear Information System (INIS)

    The program MITMAP represents a set of general purpose, two- dimensional, finite element programs for the calculation of magnetic fields. It consists of the program MAP and MAP2DJ. The two programs are used to solve different electromagnetic problems, but they have a common set of subrountines for pre- and postprocessing. Originally separate programs, they have been combined to make modification easier. The manuals, however, will remain separate. The program MAP is described in this manual. MAP is applicable to the class of problems with two-dimensional-planar or axisymmetric - geometries, in which the current density and the magnetic vector potential have only a single nonvanishing component. The single component is associated with the direction that is perpendicular to the plane of the problem and is invariant with respect to that direction. Maxwell's equations can be reduced to a solver diffusion equation in terms of the single, nonvanishing component of the magnetic vector potential for planar problems and to a single component of a vector potential for planar problems and to a single component of a vector diffusion equation for axisymmetric problems. The magnetic permeability appears in the governing equation. The permeability may be a function of the magnetic flux density. In addition, any electrically conducting material present will have eddy currents induced by a time varying magnetic field. These eddy currents must be included in the solution process. This manual provides a description of the structure of the input data and output for the program. There are several example problems presented that illustrate the major program features. Appendices are included that contain a derivation of the governing equations and the application of the finite element method to the solution of the equations

  1. Mapping the Literature

    DEFF Research Database (Denmark)

    Boulus-Rødje, Nina

    2012-01-01

    As the utilization of various e-voting technologies has notably increased in the past few years, so has the amount of publications on experiences with these technologies. This article, will, therefore map the literature while highlighting some of the important topics discussed within the field of e......-voting. Particular attention will be paid to non-technical dimensions, including socio-cultural, organizational and political dimensions of these implementations....

  2. Map of the Moon

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China releases data about the Moon collected its first lunar probe China has finished the full map of the Moon based on data obtained by its lunar probe Chang ’e 1,said Ouyang Ziyuan,chief scientist of China’s lunar exploration program and an academician at the Chinese Academy of Sciences (CAS),at a press conference about the scientific achievements made by Chang’e 1 on July 16,2010.

  3. Mapping the cytoskeletal prestress

    OpenAIRE

    Park, Chan Young; Tambe, Dhananjay; Alencar, Adriano M.; Trepat, Xavier; Zhou, En Hua; Millet, Emil; Butler, James P.; Fredberg, Jeffrey J.

    2010-01-01

    Cell mechanical properties on a whole cell basis have been widely studied, whereas local intracellular variations have been less well characterized and are poorly understood. To fill this gap, here we provide detailed intracellular maps of regional cytoskeleton (CSK) stiffness, loss tangent, and rate of structural rearrangements, as well as their relationships to the underlying regional F-actin density and the local cytoskeletal prestress. In the human airway smooth muscle cell, we used micro...

  4. Surface Mapping using Quadcopter

    OpenAIRE

    Haugen, Kenneth Eide

    2014-01-01

    This thesis studies the use of unmanned aerial vehicles to perform ice managementin the Arctic Ocean by gathering information about and physically control the iceenvironment. Such a system is needed for safety reasons as marine operations aremoving further north. In order to gather information about the ice environment, aUAV will be used for surface mapping. The quadcopter Parrot AR. Drone 2.0 will be used as a testbed for implementing proposed strategies for guidance, navigation and control ...

  5. Skyrmions from Harmonic Maps

    OpenAIRE

    Zakrzewski, Wojtek

    2000-01-01

    We describe some relations between solitonic solutions of various models in different dimensions. We present some examples and then concentrate on some of our recent work (performed in collaboration with Ioannidou and Piette) \\cite{IPZ} \\cite{us2} which shows how some harmonic maps from S2 to CPN-1 can be used to find nontrivial spherically symmetric static solutions of the SU(N) Skyrme model in 3 dimensions and to generate some of its low energy field configurations.

  6. Knowledge Map of Facilities Management

    OpenAIRE

    Nenonen, Suvi; Jensen, Per Anker; Lindahl, Göran

    2014-01-01

    Purpose This paper aims to draft a knowledge map of the fragmented and multidisciplinary research of and relevant to FM. Facilities management knowledge map is a tool for presenting what relevant data and knowledge, a.k.a. knowledge, resides in different disciplines. Knowledge mapping is a step in creating an inventory of knowledge (i.e. the knowledge base) and developing/improving the processes of knowledge sharing in research, education and practice. Theory Knowledge mapping is discussed in...

  7. System of automated map design

    International Nuclear Information System (INIS)

    Preprint 'System of automated map design' contains information about the program shell for construction of territory map, performing level line drawing of arbitrary two-dimension field (in particular, the radionuclide concentration field). The work schedule and data structures are supplied, as well as data on system performance. The preprint can become useful for experts in radioecology and for all persons involved in territory pollution mapping or multi-purpose geochemical mapping. (author)

  8. Teaching and assessing mind maps

    OpenAIRE

    Jennifer Wright

    2011-01-01

    The purpose of literacy interventions in higher education is to develop students’ competencies so they could cope with the literacy demands of their academic studies. One such competency is mind mapping. The literature provides strong arguments that mind mapping provides students with valuable organisational and heuristic tools and offers guidelines on how to draw mind maps. The issue of assessing mind maps is, however, generally absent. This paper explores the characteristics of effective mi...

  9. Algebraic entropy for algebraic maps

    International Nuclear Information System (INIS)

    We propose an extension of the concept of algebraic entropy, as introduced by Bellon and Viallet for rational maps, to algebraic maps (or correspondences) of a certain kind. The corresponding entropy is an index of the complexity of the map. The definition inherits the basic properties from the definition of entropy for rational maps. We give an example with positive entropy, as well as two examples taken from the theory of Bäcklund transformations. (letter)

  10. Forest Fire Mapping

    Science.gov (United States)

    1990-01-01

    The Fire Logistics Airborne Mapping Equipment (FLAME) system, mounted in a twin-engine and airplane operated by the U.S. Forest Service (USFS) of the U.S. Department of Agriculture (USDA), is an airborne instrument for detecting and pinpointing forest fires that might escape ground detection. The FLAME equipment rack includes the operator interface, a video monitor, the system's control panel and film output. FLAME's fire detection sensor is an infrared line scanner system that identifies fire boundaries. Sensor's information is correlated with the aircraft's position and altitude at the time the infrared imagery is acquired to fix the fire's location on a map. System can be sent to a fire locale anywhere in the U.S. at the request of a regional forester. USFS felt a need for a more advanced system to deliver timely fire information to fire management personnel in the decade of the 1990s. The Jet Propulsion Laboratory (JPL) conducted a study, jointly sponsored by NASA and USDA, on what advanced technologies might be employed to produce an end-to-end thermal infrared fire detection and mapping system. That led to initiation of the Firefly system, currently in development at JPL and targeted for operational service beginning in 1992. Firefly will employ satellite-reference position fixing and provide performance superior to FLAME.

  11. Mapping in inertial frames

    Energy Technology Data Exchange (ETDEWEB)

    Arunasalam, V.

    1989-05-01

    World space mapping in inertial frames is used to examine the Lorentz covariance of symmetry operations. It is found that the Galilean invariant concepts of simultaneity (S), parity (P), and time reversal symmetry (T) are not Lorentz covariant concepts for inertial observers. That is, just as the concept of simultaneity has no significance independent of the Lorentz inertial frame, likewise so are the concepts of parity and time reversal. However, the world parity (W) (i.e., the space-time reversal symmetry (P-T)) is a truly Lorentz covariant concept. Indeed, it is shown that only those mapping matrices M that commute with the Lorentz transformation matrix L (i.e., (M,L) = 0) are the ones that correspond to manifestly Lorentz covariant operations. This result is in accordance with the spirit of the world space Mach's principle. Since the Lorentz transformation is an orthogonal transformation while the Galilean transformation is not an orthogonal transformation, the formal relativistic space-time mapping theory used here does not have a corresponding non-relativistic counterpart. 12 refs.

  12. Mapping in inertial frames

    International Nuclear Information System (INIS)

    World space mapping in inertial frames is used to examine the Lorentz covariance of symmetry operations. It is found that the Galilean invariant concepts of simultaneity (S), parity (P), and time reversal symmetry (T) are not Lorentz covariant concepts for inertial observers. That is, just as the concept of simultaneity has no significance independent of the Lorentz inertial frame, likewise so are the concepts of parity and time reversal. However, the world parity (W) [i.e., the space-time reversal symmetry (P-T)] is a truly Lorentz covariant concept. Indeed, it is shown that only those mapping matrices M that commute with the Lorentz transformation matrix L (i.e., [M,L] = 0) are the ones that correspond to manifestly Lorentz covariant operations. This result is in accordance with the spirit of the world space Mach's principle. Since the Lorentz transformation is an orthogonal transformation while the Galilean transformation is not an orthogonal transformation, the formal relativistic space-time mapping theory used here does not have a corresponding non-relativistic counterpart. 12 refs

  13. Mapping Israel/Palestine

    Directory of Open Access Journals (Sweden)

    Christine Leuenberger

    2012-01-01

    studies and the sociology of knowledge in order to analyze the social context of map-making and the content and structure of maps. The focus is on how and why British, American, and Arab online news outlets depict the contested territories of Israel and the Palestinian Territories in often varied and inconsistent ways. Certain online news sources have been accused of political biases concerning the Israeli-Palestinian conflict, which arguably translates into particular maps and map layers being included in news stories. Rather than they are being a direct and pre-determined link between map-choice and politics, however, I argue that map-making can be understood as a form of ‘situated’ practice. In other words, the newsroom brings together various actors, materials, technologies and resources that enable and constrain certain activities. It is therefore local cultures, social and interactional contingencies, and institutional and political circumstances that impact map-making and explain how and why maps may converge with or diverge from politics at any given time and place. At the same time, the choice of certain maps and map layers in terms of their focus, content, design, and detail is inevitably selective and can hereby become politically meaningful. It is thus the various textual and visual signifiers and the contextual information included in a map that can become politics by other means. Moreover, the types and sources of news stories and their maps are also co-determined by power politics, the structural inequities between the state of Israel and a Palestinian state-in-the-making, and their respective ease of access to public relations infrastructures that can reach the public at large.

  14. The MAP Propulsion Subsystem

    Science.gov (United States)

    Davis, Gary T.; Bauer, Frank H. (Technical Monitor)

    2002-01-01

    This paper describes the requirements, design, integration, test, performance, and lessons learned of NASA's Microwave Anisotropy Probe (MAP) propulsion subsystem. MAP was launched on a Delta-II launch vehicle from NASA's Kennedy Space Center on June 30, 2001. Due to instrument thermal stability requirements, the Earth-Sun L2 Lagrange point was selected for the mission orbit. The L2 trajectory incorporated phasing loops and a lunar gravity assist. The propulsion subsystem's requirements are to manage momentum, perform maneuvers during the phasing loops to set up the lunar swingby, and perform stationkeeping at L2 for 2 years. MAP's propulsion subsystem uses 8 thrusters which are located and oriented to provide attitude control and momentum management about all axes, and delta-V in any direction without exposing the instrument to the sun. The propellant tank holds 72 kg of hydrazine, which is expelled by unregulated blowdown pressurization. Thermal management is complex because no heater cycling is allowed at L2. Several technical challenges presented themselves during I and T, such as in-situ weld repairs and in-situ bending of thruster tubes to accommodate late changes in the observatory CG. On-orbit performance has been nominal, and all phasing loop, mid-course correction, and stationkeeping maneuvers have been successfully performed to date.

  15. Making maps a visual guide to map design for GIS

    CERN Document Server

    Krygier, John

    2011-01-01

    Acclaimed for its innovative use of visual material, this book is engaging, clear, and compelling-exactly how an effective map should be. Nearly every page is organized around maps and other figures (many in full color) that illustrate all aspects of map making, including instructive examples of both good and poor design choices. The book covers everything from locating and processing data to making decisions about layout, symbols, color, and type. Readers are invited to think critically about both the technical features and social significance of maps as they learn to create better maps of t

  16. The Global Trachoma Mapping Project

    Directory of Open Access Journals (Sweden)

    Anthony W Solomon

    2014-04-01

    Full Text Available In the largest disease-mapping project ever conducted, health workers trained by the Global Trachoma Mapping Project have already examined the eyelids of more than 1 million people in nearly 1,000 districts since December 2012. The data collected are being used to create the first truly complete global map of trachoma and trichiasis, due in March 2015.

  17. Using Playground Maps for Movement

    Science.gov (United States)

    Colvin, A. Vonnie

    2016-01-01

    Many schools now decorate their outside hard surface areas with maps. These maps provide color and excitement to a playground and are a terrific teaching tool for geography. But these maps can easily be integrated into physical education as well to promote both physical activity as well as knowledge of geography. The purpose of this article is to…

  18. Genetic algorithms for map labeling

    NARCIS (Netherlands)

    Dijk, Steven Ferdinand van

    2002-01-01

    Map labeling is the cartographic problem of placing the names of features (for example cities or rivers) on the map. A good labeling has no intersections between labels. Even basic versions of the problem are NP-hard. In addition, realistic map-labeling problems deal with many cartographic constr

  19. The Map to LOINC Project

    OpenAIRE

    Khan, Agha N.; Russell, Dorothy; Moore, Catherine; Rosario, Arnulfo C.; Griffith, Stanley P.; Bertolli, Jeanne

    2003-01-01

    We describe a pilot project to standardize local laboratory test names to Logical Observation Identifier Names and Codes (LOINC) at five Indian Health Service (IHS) medical facilities. An automated mapping tool was developed to assign LOINC codes. The laboratory test names not mapped to LOINC by the mapping tool were assigned LOINC codes manually. The results achieved matched current benchmarks.

  20. A guide of patent map

    International Nuclear Information System (INIS)

    This book introduces application and characteristic of patent information, types of patent information data and research of patent information, arrangement of patent information and patent map, analysis of patent information, necessity, writing period arrangement way of patent map, cases of patent map on selection of task of research and development, system of research and development and application, examples of PM such as MAP by year, application, technique, Inventor, and claim point map and computerization like data arrangement of PM patent, collection of analysis range and item analysis of patent, cases and written reports on patent analysis.

  1. Timed bisimulation and open maps

    DEFF Research Database (Denmark)

    Hune, Thomas; Nielsen, Mogens

    Open maps have been used for defining bisimulations for a range of models, but none of these have modelled real-time. We define a category of timed transition systems, and use the general framework of open maps to obtain a notion of bisimulation. We show this to be equivalent to the standard notion...... of timed bisimulation. Thus the abstract results from the theory of open maps apply, e.g. the existence of canonical models and characteristic logics. Here, we provide an alternative proof of decidability of bisimulation for finite timed transition systems in terms of open maps, and illustrate the...... use of open maps in presenting bisimulations....

  2. Proportional Symbol Mapping in R

    Directory of Open Access Journals (Sweden)

    Susumu Tanimura

    2006-01-01

    Full Text Available Visualization of spatial data on a map aids not only in data exploration but also in communication to impart spatial conception or ideas to others. Although recent carto-graphic functions in R are rapidly becoming richer, proportional symbol mapping, which is one of the common mapping approaches, has not been packaged thus far. Based on the theories of proportional symbol mapping developed in cartography, the authors developed some functions for proportional symbol mapping using R, including mathematical and perceptual scaling. An example of these functions demonstrated the new expressive power and options available in R, particularly for the visualization of conceptual point data.

  3. Mapping the human protein interactome

    Institute of Scientific and Technical Information of China (English)

    Daniel Figeys

    2008-01-01

    Interactions are the essence of all biomolecules because they cannot fulfill their roles without interacting with other molecules. Hence, mapping the interactions of biomolecules can be useful for understanding their roles and functions. Furthermore, the development of molecular based systems biology requires an understanding of the biomolecular interactions. In recent years, the mapping of protein-protein interactions in different species has been reported, but few reports have focused on the large-scale mapping of protein-protein interactions in human. Here, we review the developments in protein interaction mapping and we discuss issues and strategies for the mapping of the human protein interactome.

  4. Teaching and assessing mind maps

    Directory of Open Access Journals (Sweden)

    Jennifer Wright

    2011-08-01

    Full Text Available The purpose of literacy interventions in higher education is to develop students’ competencies so they could cope with the literacy demands of their academic studies. One such competency is mind mapping. The literature provides strong arguments that mind mapping provides students with valuable organisational and heuristic tools and offers guidelines on how to draw mind maps. The issue of assessing mind maps is, however, generally absent. This paper explores the characteristics of effective mind maps, their benefits and importance at all levels of education, as well as the issue of whether or not they should be assessed. It seems that too little attention has been paid to the value of mind mapping in higher education; and that the assessment of mind maps requires further debate by those with an interest in creative teaching at tertiary level.

  5. Online Exhibits & Concept Maps

    Science.gov (United States)

    Douma, M.

    2009-12-01

    Presenting the complexity of geosciences to the public via the Internet poses a number of challenges. For example, utilizing various - and sometimes redundant - Web 2.0 tools can quickly devour limited time. Do you tweet? Do you write press releases? Do you create an exhibit or concept map? The presentation will provide participants with a context for utilizing Web 2.0 tools by briefly highlighting methods of online scientific communication across several dimensions. It will address issues of: * breadth and depth (e.g. from narrow topics to well-rounded views), * presentation methods (e.g. from text to multimedia, from momentary to enduring), * sources and audiences (e.g. for experts or for the public, content developed by producers to that developed by users), * content display (e.g. from linear to non-linear, from instructive to entertaining), * barriers to entry (e.g. from an incumbent advantage to neophyte accessible, from amateur to professional), * cost and reach (e.g. from cheap to expensive), and * impact (e.g. the amount learned, from anonymity to brand awareness). Against this backdrop, the presentation will provide an overview of two methods of online information dissemination, exhibits and concept maps, using the WebExhibits online museum (www.webexhibits.org) and SpicyNodes information visualization tool (www.spicynodes.org) as examples, with tips on how geoscientists can use either to communicate their science. Richly interactive online exhibits can serve to engage a large audience, appeal to visitors with multiple learning styles, prompt exploration and discovery, and present a topic’s breadth and depth. WebExhibits, which was among the first online museums, delivers interactive information, virtual experiments, and hands-on activities to the public. While large, multidisciplinary exhibits on topics like “Color Vision and Art” or “Calendars Through the Ages” require teams of scholars, user interface experts, professional writers and editors

  6. Probability mapping of contaminants

    International Nuclear Information System (INIS)

    Exhaustive characterization of a contaminated site is a physical and practical impossibility. Descriptions of the nature, extent, and level of contamination, as well as decisions regarding proposed remediation activities, must be made in a state of uncertainty based upon limited physical sampling. The probability mapping approach illustrated in this paper appears to offer site operators a reasonable, quantitative methodology for many environmental remediation decisions and allows evaluation of the risk associated with those decisions. For example, output from this approach can be used in quantitative, cost-based decision models for evaluating possible site characterization and/or remediation plans, resulting in selection of the risk-adjusted, least-cost alternative. The methodology is completely general, and the techniques are applicable to a wide variety of environmental restoration projects. The probability-mapping approach is illustrated by application to a contaminated site at the former DOE Feed Materials Production Center near Fernald, Ohio. Soil geochemical data, collected as part of the Uranium-in-Soils Integrated Demonstration Project, have been used to construct a number of geostatistical simulations of potential contamination for parcels approximately the size of a selective remediation unit (the 3-m width of a bulldozer blade). Each such simulation accurately reflects the actual measured sample values, and reproduces the univariate statistics and spatial character of the extant data. Post-processing of a large number of these equally likely statistically similar images produces maps directly showing the probability of exceeding specified levels of contamination (potential clean-up or personnel-hazard thresholds)

  7. Schema matching and mapping

    CERN Document Server

    Bellahsene, Zohra; Rahm, Erhard

    2011-01-01

    Requiring heterogeneous information systems to cooperate and communicate has now become crucial, especially in application areas like e-business, Web-based mash-ups and the life sciences. Such cooperating systems have to automatically and efficiently match, exchange, transform and integrate large data sets from different sources and of different structure in order to enable seamless data exchange and transformation. The book edited by Bellahsene, Bonifati and Rahm provides an overview of the ways in which the schema and ontology matching and mapping tools have addressed the above requirements

  8. Pseudomythological Constellation Maps

    Directory of Open Access Journals (Sweden)

    Andres Kuperjanov

    2006-01-01

    Full Text Available The objective of the article is to observe how the description of the starry sky has developed by looking at the sky map as a mental composition, a symbolic system that enables orientation in the sky on the basis of a specific integral narrative. The article observes the different ways in which such narratives have emerged and the astromythological essence of these stories. The author attempts to evaluate the nature and development of the different layers of constellations in folk astronomy.

  9. Radial Rydberg wavepacket maps

    Science.gov (United States)

    Zeibel, J. G.; Jones, R. R.

    2001-04-01

    Picosecond laser pulses have been used to excite radial Rydberg wavepackets in Ca. Time-delayed, unipolar, `half-cycle' electric field pulses are used to probe the evolution of the wavepackets as a continuous function of binding energy. The data provide three-dimensional maps of wavepacket recurrence probability versus binding energy versus time. A rescaling of the energy and time coordinate axes allows the visualization of the distinct difference between the initial oscillations of the wavepacket and those that occur at integer and fractional revivals.

  10. Journal of Maps

    Directory of Open Access Journals (Sweden)

    Nedjeljko Frančula

    2009-12-01

    Full Text Available Journal of Maps (JoM (http://www.journalofmaps.com počeo je izlaziti 2005. godine isključivo kao elektronički časopis. Izdavač je School of Earth Sciences and Geography, Kingston University, UK. Budući da ne izlazi u tiskanom izdanju, časopis nema uobičajene sveske. Svescima se, ipak, mogu smatrati članci srodne tematike koji se objavljuju tri puta godišnje – u travnju, kolovozu i prosincu.

  11. Mapping Wind Energy Controversies

    DEFF Research Database (Denmark)

    Munk, Anders Kristian

    As part the Wind2050 project funded by the Danish Council for Strategic Research we have mapped controversies on wind energy as they unfold online. Specifically we have collected two purpose built datasets, a web corpus containing information from 758 wind energy websites in 6 different countries......, and a smaller social media corpus containing information from 14 Danish wind energy pages on Facebook. These datasets have been analyzed to answer questions like: How do wind proponents and opponents organize online? Who are the central actors? And what are their matters of concern? The purpose of...

  12. Mapping the brain

    International Nuclear Information System (INIS)

    With powerful new technologies such as positron tomography and superconducting quantum interference device that peer through the skull and see the brain at work, neuroscientists seek the wellsprings of thoughts and emotions, the genesis of intelligence and language. A functional map of the brain is thus obtained and its challenge is to move beyond brain structure to create a detailed diagram of which part do what. For that the brain's cartographers rely on a variety of technologies such as positron tomography and superconducting quantum interference devices. Their performances and uses are briefly reviewed. ills

  13. STRONGLY MINIMAL g* -CONTINUOUS MAPS AND STRONGLY MINIMAL g** -CONTINUOUS MAPS IN MINIMAL SPACES

    OpenAIRE

    E.Subha,; A.Pushpalatha

    2010-01-01

    In this paper, we introduce and study the concepts of a new class of maps, namely strongly minimal continuous maps, strongly minimal g*-continuous maps, strongly minimal g**-continuous maps which includes the class of continuous maps.

  14. Mapping geomorphology: A journey from paper maps, through computer mapping to GIS and Virtual Reality

    Science.gov (United States)

    Vitek, John D.; Giardino, John R.; Fitzgerald, Jeffrey W.

    1996-07-01

    Maps are integral components of research in geomorphology and Quaternary geology. Visual presentation of the spatial and temporal distribution of a phenomenon often provides clues to the process(es) that generated the phenomenon. Compiling information on maps, interpreting spatial patterns, and using standard topographic maps were fundamental parts of the undergraduate experience. Why have such experiences been slowly disappearing from undergraduate curricula? How are geology majors taught map scale, map projections, and the pitfalls associated with the display of spatial information? Neglect in preserving the mapping tradition places the geology major at a disadvantage. The use of maps and mapping is undergoing a renaissance; use in the classroom has a bright future because of digital scanning, computer cartography, geographic information systems (GIS), and virtual reality. Pen and ink techniques should be relegated to museums. Pencil sketches can be scanned and perfect products generated every time. These techniques, however, do not eliminate the need for basic map knowledge such as scale, projections, and generalization. What assumptions about map projections have been built into the software? How are spatial data and attribute data integrated into the resultant map in a geographic information system (GIS)? Because the application of virtual reality to geomorphic processes looms on the horizon, geologists must recognize how the current spatial revolution can help with the assessment of geologic phenomena and teach students to function with the new technology.

  15. ANNUAL INTERVIEWS (MAPS)

    CERN Multimedia

    Human Resources Division

    2002-01-01

    The calendar for the 2002/2003 annual interview programme is confirmed as normally from 15 November 2002 to 15 February 2002 as foreseen in Administrative Circular N° 26 (rev. 2). However, where it is preferred to be as close as possible to 12 months since the last interview, supervisors and staff concerned may agree to the interview taking place up to 15 March 2003. This may also be necessary due to the roles of different supervisors resulting from the particular situations of divisional re-restructurings and detachments this year. The report form template is as last year available on the HR Division Website. A banner on the internal homepage leads directly to the page with the form. In collaboration with AS Division, the MAPS form including the personal data for the first page can be generated via the Human Resources Toolkit (HRT) application. For this exercise each staff member can now generate his/her own MAPS form. Information about how to do this is available here. Human Resources Division Tel. ...

  16. Quantitive DNA Fiber Mapping

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Chun-Mei; Wang, Mei; Greulich-Bode, Karin M.; Weier, Jingly F.; Weier, Heinz-Ulli G.

    2008-01-28

    Several hybridization-based methods used to delineate single copy or repeated DNA sequences in larger genomic intervals take advantage of the increased resolution and sensitivity of free chromatin, i.e., chromatin released from interphase cell nuclei. Quantitative DNA fiber mapping (QDFM) differs from the majority of these methods in that it applies FISH to purified, clonal DNA molecules which have been bound with at least one end to a solid substrate. The DNA molecules are then stretched by the action of a receding meniscus at the water-air interface resulting in DNA molecules stretched homogeneously to about 2.3 kb/{micro}m. When non-isotopically, multicolor-labeled probes are hybridized to these stretched DNA fibers, their respective binding sites are visualized in the fluorescence microscope, their relative distance can be measured and converted into kilobase pairs (kb). The QDFM technique has found useful applications ranging from the detection and delineation of deletions or overlap between linked clones to the construction of high-resolution physical maps to studies of stalled DNA replication and transcription.

  17. Karst Map of Puerto Rico

    Science.gov (United States)

    Aleman-Gonzalez, Wilma B., (compiler)

    2010-01-01

    This map is a digital compilation, combining the mapping of earlier geologists. Their work, cited on the map, contains more detailed descriptions of karst areas and landforms in Puerto Rico. This map is the basis for the Puerto Rico part of a new national karst map currently being compiled by the U.S. Geological Survey. In addition, this product is a standalone, citable source of digital karst data for Puerto Rico. Nearly 25 percent of the United States is underlain by karst terrain, and a large part of that area is undergoing urban and industrial development. Accurate delineations of karstic rocks are needed at scales suitable for national, State, and local maps. The data on this map contribute to a better understanding of subsidence hazards, groundwater contamination potential, and cave resources as well as serve as a guide to topical research on karst. Because the karst data were digitized from maps having a different scale and projection from those on the base map used for this publication, some karst features may not coincide perfectly with physiographic features portrayed on the base map.

  18. Statistical methods in physical mapping

    International Nuclear Information System (INIS)

    One of the great success stories of modern molecular genetics has been the ability of biologists to isolate and characterize the genes responsible for serious inherited diseases like fragile X syndrome, cystic fibrosis and myotonic muscular dystrophy. This dissertation concentrates on constructing high-resolution physical maps. It demonstrates how probabilistic modeling and statistical analysis can aid molecular geneticists in the tasks of planning, execution, and evaluation of physical maps of chromosomes and large chromosomal regions. The dissertation is divided into six chapters. Chapter 1 provides an introduction to the field of physical mapping, describing the role of physical mapping in gene isolation and ill past efforts at mapping chromosomal regions. The next two chapters review and extend known results on predicting progress in large mapping projects. Such predictions help project planners decide between various approaches and tactics for mapping large regions of the human genome. Chapter 2 shows how probability models have been used in the past to predict progress in mapping projects. Chapter 3 presents new results, based on stationary point process theory, for progress measures for mapping projects based on directed mapping strategies. Chapter 4 describes in detail the construction of all initial high-resolution physical map for human chromosome 19. This chapter introduces the probability and statistical models involved in map construction in the context of a large, ongoing physical mapping project. Chapter 5 concentrates on one such model, the trinomial model. This chapter contains new results on the large-sample behavior of this model, including distributional results, asymptotic moments, and detection error rates. In addition, it contains an optimality result concerning experimental procedures based on the trinomial model. The last chapter explores unsolved problems and describes future work

  19. Statistical methods in physical mapping

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, D.O. [Univ. of California, Berkeley, CA (United States)

    1995-05-01

    One of the great success stories of modern molecular genetics has been the ability of biologists to isolate and characterize the genes responsible for serious inherited diseases like fragile X syndrome, cystic fibrosis and myotonic muscular dystrophy. This dissertation concentrates on constructing high-resolution physical maps. It demonstrates how probabilistic modeling and statistical analysis can aid molecular geneticists in the tasks of planning, execution, and evaluation of physical maps of chromosomes and large chromosomal regions. The dissertation is divided into six chapters. Chapter 1 provides an introduction to the field of physical mapping, describing the role of physical mapping in gene isolation and ill past efforts at mapping chromosomal regions. The next two chapters review and extend known results on predicting progress in large mapping projects. Such predictions help project planners decide between various approaches and tactics for mapping large regions of the human genome. Chapter 2 shows how probability models have been used in the past to predict progress in mapping projects. Chapter 3 presents new results, based on stationary point process theory, for progress measures for mapping projects based on directed mapping strategies. Chapter 4 describes in detail the construction of all initial high-resolution physical map for human chromosome 19. This chapter introduces the probability and statistical models involved in map construction in the context of a large, ongoing physical mapping project. Chapter 5 concentrates on one such model, the trinomial model. This chapter contains new results on the large-sample behavior of this model, including distributional results, asymptotic moments, and detection error rates. In addition, it contains an optimality result concerning experimental procedures based on the trinomial model. The last chapter explores unsolved problems and describes future work.

  20. 18 CFR 154.106 - Map.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Map. 154.106 Section....106 Map. (a) The map must show the general geographic location of the company's principal pipeline... on a single map. In addition, a separate map should be provided for each zone. (b) (c) The map...