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Sample records for anchorage independent growth

  1. SATB2 expression increased anchorage-independent growth and cell migration in human bronchial epithelial cells

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    Wu, Feng; Jordan, Ashley; Kluz, Thomas [Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States); Shen, Steven [Center for Health Informatics and Bioinformatics, New York University Langone Medical Center, New York, NY 10016 (United States); Sun, Hong; Cartularo, Laura A. [Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States); Costa, Max, E-mail: Max.Costa@nyumc.org [Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States)

    2016-02-15

    The special AT-rich sequence-binding protein 2 (SATB2) is a protein that binds to the nuclear matrix attachment region of the cell and regulates gene expression by altering chromatin structure. In our previous study, we reported that SATB2 gene expression was induced in human bronchial epithelial BEAS-2B cells transformed by arsenic, chromium, nickel and vanadium. In this study, we show that ectopic expression of SATB2 in the normal human bronchial epithelial cell-line BEAS-2B increased anchorage-independent growth and cell migration, meanwhile, shRNA-mediated knockdown of SATB2 significantly decreased anchorage-independent growth in Ni transformed BEAS-2B cells. RNA sequencing analyses of SATB2 regulated genes revealed the enrichment of those involved in cytoskeleton, cell adhesion and cell-movement pathways. Our evidence supports the hypothesis that SATB2 plays an important role in BEAS-2B cell transformation. - Highlights: • We performed SATB2 overexpression in the BEAS-2B cell line. • We performed SATB2 knockdown in a Ni transformed BEAS-2B cell line. • SATB2 induced anchorage-independent growth and increased cell migration. • SATB2 knockdown significantly decreased anchorage-independent growth. • We identified alterations in gene involved in cytoskeleton, cell adhesion.

  2. SATB2 expression increased anchorage-independent growth and cell migration in human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Wu, Feng; Jordan, Ashley; Kluz, Thomas; Shen, Steven; Sun, Hong; Cartularo, Laura A.; Costa, Max

    2016-01-01

    The special AT-rich sequence-binding protein 2 (SATB2) is a protein that binds to the nuclear matrix attachment region of the cell and regulates gene expression by altering chromatin structure. In our previous study, we reported that SATB2 gene expression was induced in human bronchial epithelial BEAS-2B cells transformed by arsenic, chromium, nickel and vanadium. In this study, we show that ectopic expression of SATB2 in the normal human bronchial epithelial cell-line BEAS-2B increased anchorage-independent growth and cell migration, meanwhile, shRNA-mediated knockdown of SATB2 significantly decreased anchorage-independent growth in Ni transformed BEAS-2B cells. RNA sequencing analyses of SATB2 regulated genes revealed the enrichment of those involved in cytoskeleton, cell adhesion and cell-movement pathways. Our evidence supports the hypothesis that SATB2 plays an important role in BEAS-2B cell transformation. - Highlights: • We performed SATB2 overexpression in the BEAS-2B cell line. • We performed SATB2 knockdown in a Ni transformed BEAS-2B cell line. • SATB2 induced anchorage-independent growth and increased cell migration. • SATB2 knockdown significantly decreased anchorage-independent growth. • We identified alterations in gene involved in cytoskeleton, cell adhesion.

  3. Barium promotes anchorage-independent growth and invasion of human HaCaT keratinocytes via activation of c-SRC kinase.

    Science.gov (United States)

    Thang, Nguyen Dinh; Yajima, Ichiro; Kumasaka, Mayuko Y; Ohnuma, Shoko; Yanagishita, Takeshi; Hayashi, Rumiko; Shekhar, Hossain U; Watanabe, Daisuke; Kato, Masashi

    2011-01-01

    Explosive increases in skin cancers have been reported in more than 36 million patients with arsenicosis caused by drinking arsenic-polluted well water. This study and previous studies showed high levels of barium as well as arsenic in the well water. However, there have been no reports showing a correlation between barium and cancer. In this study, we examined whether barium (BaCl(2)) may independently have cancer-related effects on human precancerous keratinocytes (HaCaT). Barium (5-50 µM) biologically promoted anchorage-independent growth and invasion of HaCaT cells in vitro. Barium (5 µM) biochemically enhanced activities of c-SRC, FAK, ERK and MT1-MMP molecules, which regulate anchorage-independent growth and/or invasion. A SRC kinase specific inhibitor, protein phosphatase 2 (PP2), blocked barium-mediated promotion of anchorage-independent growth and invasion with decreased c-SRC kinase activity. Barium (2.5-5 µM) also promoted anchorage-independent growth and invasion of fibroblasts (NIH3T3) and immortalized nontumorigenic melanocytes (melan-a), but not transformed cutaneous squamous cell carcinoma (HSC5 and A431) and malignant melanoma (Mel-ret) cells, with activation of c-SRC kinase. Taken together, our biological and biochemical findings newly suggest that the levels of barium shown in drinking well water independently has the cancer-promoting effects on precancerous keratinocytes, fibroblast and melanocytes in vitro.

  4. Elevated p21-Activated Kinase 2 Activity Results in Anchorage-Independent Growth and Resistance to Anticancer Drug–Induced Cell Death

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    Jerry W. Marlin

    2009-03-01

    Full Text Available p21-Activated kinase 2 (PAK-2 seems to be a regulatory switch between cell survival and cell death signaling. We have shown previously that activation of full-length PAK-2 by Rac or Cdc42 stimulates cell survival, whereas caspase activation of PAK-2 to the proapoptotic PAK-2p34 fragment is involved in the cell death response. In this study, we present a role of elevated activity of full-length PAK-2 in anchorage-independent growth and resistance to anticancer drug–induced apoptosis of cancer cells. Hs578T human breast cancer cells that have low levels of PAK-2 activity were more sensitive to anticancer drug–induced apoptosis and showed higher levels of caspase activation of PAK-2 than MDA-MB435 and MCF-7 human breast cancer cells that have high levels of PAK-2 activity. To examine the role of elevated PAK-2 activity in breast cancer, we have introduced a conditionally active PAK-2 into Hs578T human breast cells. Conditional activation of PAK-2 causes loss of contact inhibition and anchorage-independent growth of Hs578T cells. Furthermore, conditional activation of PAK-2 suppresses activation of caspase 3, caspase activation of PAK-2, and apoptosis of Hs578T cells in response to the anticancer drug cisplatin. Our data suggest a novel mechanism by which full-length PAK-2 activity controls the apoptotic response by regulating levels of activated caspase 3 and thereby its own cleavage to the proapoptotic PAK-2p34 fragment. As a result, elevated PAK-2 activity interrupts the apoptotic response and thereby causes anchorage-independent survival and growth and resistance to anticancer drug–induced apoptosis.

  5. A genetic screen for anchorage-independent proliferation in mammalian cells identifies a membrane-bound neuregulin.

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    Davide Danovi

    2010-07-01

    Full Text Available Anchorage-independent proliferation is a hallmark of oncogenic transformation and is thought to be conducive to proliferation of cancer cells away from their site of origin. We have previously reported that primary Schwann cells expressing the SV40 Large T antigen (LT are not fully transformed in that they maintain a strict requirement for attachment, requiring a further genetic change, such as oncogenic Ras, to gain anchorage-independence. Using the LT-expressing cells, we performed a genetic screen for anchorage-independent proliferation and identified Sensory and Motor Neuron Derived Factor (SMDF, a transmembrane class III isoform of Neuregulin 1. In contrast to oncogenic Ras, SMDF induced enhanced proliferation in normal primary Schwann cells but did not trigger cellular senescence. In cooperation with LT, SMDF drove anchorage-independent proliferation, loss of contact inhibition and tumourigenicity. This transforming ability was shared with membrane-bound class III but not secreted class I isoforms of Neuregulin, indicating a distinct mechanism of action. Importantly, we show that despite being membrane-bound signalling molecules, class III neuregulins transform via a cell intrinsic mechanism, as a result of constitutive, elevated levels of ErbB signalling at high cell density and in anchorage-free conditions. This novel transforming mechanism may provide new targets for cancer therapy.

  6. Protein disulfide isomerases in the endoplasmic reticulum promote anchorage-independent growth of breast cancer cells.

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    Wise, Randi; Duhachek-Muggy, Sara; Qi, Yue; Zolkiewski, Michal; Zolkiewska, Anna

    2016-06-01

    Metastatic breast cancer cells are exposed to stress of detachment from the extracellular matrix (ECM). Cultured breast cancer cells that survive this stress and are capable of anchorage-independent proliferation form mammospheres. The purpose of this study was to explore a link between mammosphere growth, ECM gene expression, and the protein quality control system in the endoplasmic reticulum (ER). We compared the mRNA and protein levels of ER folding factors in SUM159PT and MCF10DCIS.com breast cancer cells grown as mammospheres versus adherent conditions. Publicly available gene expression data for mammospheres formed by primary breast cancer cells and for circulating tumor cells (CTCs) were analyzed to assess the status of ECM/ER folding factor genes in clinically relevant samples. Knock-down of selected protein disulfide isomerase (PDI) family members was performed to examine their roles in SUM159PT mammosphere growth. We found that cells grown as mammospheres had elevated expression of ECM genes and ER folding quality control genes. CTC gene expression data for an index patient indicated that upregulation of ECM and ER folding factor genes occurred at the time of acquired therapy resistance and disease progression. Knock-down of PDI, ERp44, or ERp57, three members of the PDI family with elevated protein levels in mammospheres, in SUM159PT cells partially inhibited the mammosphere growth. Thus, breast cancer cell survival and growth under detachment conditions require enhanced assistance of the ER protein folding machinery. Targeting ER folding factors, in particular members of the PDI family, may improve the therapeutic outcomes in metastatic breast cancer.

  7. PAX2 regulates ADAM10 expression and mediates anchorage-independent cell growth of melanoma cells.

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    Sophia Boyoung Lee

    Full Text Available PAX transcription factors play an important role during development and carcinogenesis. In this study, we investigated PAX2 protein levels in melanocytes and melanoma cells by Western Blot and immunofluorescence analysis and characterized the role of PAX2 in the pathogenesis of melanoma. In vitro we found weak PAX2 protein expression in keratinocytes and melanocytes. Compared to melanocytes increased PAX2 protein levels were detectable in melanoma cell lines. Interestingly, in tissue sections of melanoma patients nuclear PAX2 expression strongly correlated with nuclear atypia and the degree of prominent nucleoli, indicating an association of PAX2 with a more atypical cellular phenotype. In addition, with chromatin immunoprecipitation assay, PAX2 overexpression and PAX2 siRNA we present compelling evidence that PAX2 can regulate ADAM10 expression, a metalloproteinase known to play important roles in melanoma metastasis. In human tissue samples we found co-expression of PAX2 and ADAM10 in melanocytes of benign nevi and in melanoma cells of patients with malignant melanoma. Importantly, the downregulation of PAX2 by specific siRNA inhibited the anchorage independent cell growth and decreased the migratory and invasive capacity of melanoma cells. Furthermore, the downregulation of PAX2 abrogated the chemoresistance of melanoma cells against cisplatin, indicating that PAX2 expression mediates cell survival and plays important roles during melanoma progression.

  8. Induction of anchorage-independent growth in primary human cells exposed to protons or HZE ions separately or in dual exposures.

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    Sutherland, B M; Cuomo, N C; Bennett, P V

    2005-10-01

    Travelers on space missions will be exposed to a complex radiation environment that includes protons and heavy charged particles. Since protons are present at much higher levels than are heavy ions, the most likely scenario for cellular radiation exposure will be proton exposure followed by a hit by a heavy ion. Although the effects of individual ion species on human cells are being investigated extensively, little is known about the effects of exposure to both radiation types. One useful measure of mammalian cell damage is induction of the ability to grow in a semi-solid agar medium highly inhibitory to the growth of normal human cells, termed neoplastic transformation. Using primary human cells, we evaluated induction of soft-agar growth and survival of cells exposed to protons only or to heavy charged particles (600 MeV/nucleon silicon) only as well as of cells exposed to protons followed after a 4-day interval by silicon ions. Both ions alone efficiently transformed the human cells to anchorage-independent growth. Initial experiments indicate that the dose responses for neoplastic transformation of cells exposed to protons and then after 4 days to silicon ions appear similar to that of cells exposed to silicon ions alone.

  9. Spheroid Culture of Head and Neck Cancer Cells Reveals an Important Role of EGFR Signalling in Anchorage Independent Survival.

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    Braunholz, Diana; Saki, Mohammad; Niehr, Franziska; Öztürk, Merve; Borràs Puértolas, Berta; Konschak, Robert; Budach, Volker; Tinhofer, Ingeborg

    2016-01-01

    In solid tumours millions of cells are shed into the blood circulation each day. Only a subset of these circulating tumour cells (CTCs) survive, many of them presumable because of their potential to form multi-cellular clusters also named spheroids. Tumour cells within these spheroids are protected from anoikis, which allows them to metastasize to distant organs or re-seed at the primary site. We used spheroid cultures of head and neck squamous cell carcinoma (HNSCC) cell lines as a model for such CTC clusters for determining the role of the epidermal growth factor receptor (EGFR) in cluster formation ability and cell survival after detachment from the extra-cellular matrix. The HNSCC cell lines FaDu, SCC-9 and UT-SCC-9 (UT-SCC-9P) as well as its cetuximab (CTX)-resistant sub-clone (UT-SCC-9R) were forced to grow in an anchorage-independent manner by coating culture dishes with the anti-adhesive polymer poly-2-hydroxyethylmethacrylate (poly-HEMA). The extent of apoptosis, clonogenic survival and EGFR signalling under such culture conditions was evaluated. The potential of spheroid formation in suspension culture was found to be positively correlated with the proliferation rate of HNSCC cell lines as well as their basal EGFR expression levels. CTX and gefitinib blocked, whereas the addition of EGFR ligands promoted anchorage-independent cell survival and spheroid formation. Increased spheroid formation and growth were associated with persistent activation of EGFR and its downstream signalling component (MAPK/ERK). Importantly, HNSCC cells derived from spheroid cultures retained their clonogenic potential in the absence of cell-matrix contact. Addition of CTX under these conditions strongly inhibited colony formation in CTX-sensitive cell lines but not their resistant subclones. Altogether, EGFR activation was identified as crucial factor for anchorage-independent survival of HNSCC cells. Targeting EGFR in CTC cluster formation might represent an attractive anti

  10. Cellular Dichotomy Between Anchorage-Independent Growth Responses to bFGF and TA Reflects Molecular Switch in Commitment to Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Waters, Katrina M.; Tan, Ruimin; Opresko, Lee K.; Quesenberry, Ryan D.; Bandyopadhyay, Somnath; Chrisler, William B.; Weber, Thomas J.

    2009-11-01

    We have investigated gene expression patterns underlying reversible and irreversible anchorage-independent growth (AIG) phenotypes to identify more sensitive markers of cell transformation for studies directed at interrogating carcinogenesis responses. In JB6 mouse epidermal cells, basic fibroblast growth factor (bFGF) induces an unusually efficient and reversible AIG response, relative to 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced AIG which is irreversible. The reversible and irreversible AIG phenotypes are characterized by largely non-overlapping global gene expression profiles. However, a subset of differentially expressed genes were identified as common to reversible and irreversible AIG phenotypes, including genes regulated in a reciprocal fashion. Hepatic leukemia factor (HLF) and D-site albumin promoter-binding protein (DBP) were increased in both bFGF and TPA soft agar colonies and selected for functional validation. Ectopic expression of human HLF and DBP in JB6 cells resulted in a marked increase in TPA- and bFGF-regulated AIG responses. HLF and DBP expression were increased in soft agar colonies arising from JB6 cells exposed to gamma radiation and in a human basal cell carcinoma tumor tissue, relative to paired non-tumor tissue. Subsequent biological network analysis suggests that many of the differentially expressed genes that are common to bFGF- and TPA-dependent AIG are regulated by c-Myc, SP-1 and HNF-4 transcription factors. Collectively, we have identified a potential molecular switch that mediates the transition from reversible to irreversible AIG.

  11. Enhanced caveolin-1 expression increases migration, anchorage-independent growth and invasion of endometrial adenocarcinoma cells

    International Nuclear Information System (INIS)

    Diaz-Valdivia, Natalia; Bravo, Denisse; Huerta, Hernán; Henriquez, Soledad; Gabler, Fernando; Vega, Margarita; Romero, Carmen; Calderon, Claudia; Owen, Gareth I.; Leyton, Lisette; Quest, Andrew F. G.

    2015-01-01

    Caveolin-1 (CAV1) has been implicated both in tumor suppression and progression, whereby the specific role appears to be context dependent. Endometrial cancer is one of the most common malignancies of the female genital tract; however, little is known about the role of CAV1 in this disease. Here, we first determined by immunohistochemistry CAV1 protein levels in normal proliferative human endometrium and endometrial tumor samples. Then using two endometrial cancer cell lines (ECC: Ishikawa and Hec-1A) we evaluated mRNA and protein levels of CAV1 by real time qPCR and Western blot analysis, respectively. The role of CAV1 expression in ECC malignancy was further studied by either inducing its expression in endometrial cancer cells with the tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate (4β-TPA) or decreasing expression using short-hairpin RNA constructs, and then evaluating the effects of these changes on ECC proliferation, transmigration, matrigel invasion, and colony formation in soft agar. Immunohistochemical analysis of endometrial epithelia revealed that substantially higher levels of CAV1 were present in endometrial tumors than the normal proliferative epithelium. Also, in Ishikawa and Hec-1A endometrial cancer cells CAV1 expression was readily detectable. Upon treatment with 4β-TPA CAV1 levels increased and coincided with augmented cell transmigration, matrigel invasion, as well as colony formation in soft agar. Reduction of CAV1 expression using short-hairpin RNA constructs ablated these effects in both cell types whether treated or not with 4β-TPA. Alternatively, CAV1 expression appeared not to modulate significantly proliferation of these cells. Our study shows that elevated CAV1, observed in patients with endometrial cancer, is linked to enhanced malignancy of endometrial cancer cells, as evidenced by increased migration, invasion and anchorage-independent growth. The online version of this article (doi:10.1186/s12885-015-1477-5) contains

  12. Cell cycle control by components of cell anchorage

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    Gad, Annica

    2005-01-01

    Extracellular factors, such as growth factors and cell anchorage to the extracellular matrix, control when and where cells may proliferate. This control is abolished when a normal cell transforms into a tumour cell. The control of cell proliferation by cell anchorage was elusive and less well studied than the control by growth factors. Therefore, we aimed to clarify at what points in the cell cycle and through which molecular mechanisms cell anchorage controls cell cycle pro...

  13. Diacylglycerol kinase α mediates 17-β-estradiol-induced proliferation, motility, and anchorage-independent growth of Hec-1A endometrial cancer cell line through the G protein-coupled estrogen receptor GPR30.

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    Filigheddu, Nicoletta; Sampietro, Sara; Chianale, Federica; Porporato, Paolo E; Gaggianesi, Miriam; Gregnanin, Ilaria; Rainero, Elena; Ferrara, Michele; Perego, Beatrice; Riboni, Francesca; Baldanzi, Gianluca; Graziani, Andrea; Surico, Nicola

    2011-12-01

    Increased levels of endogenous and/or exogenous estrogens are one of the well known risk factors of endometrial cancer. Diacylglycerol kinases (DGKs) are a family of enzymes which phosphorylate diacylglycerol (DAG) to produce phosphatidic acid (PA), thus turning off and on DAG-mediated and PA-mediated signaling pathways, respectively. DGK α activity is stimulated by growth factors and oncogenes and is required for chemotactic, proliferative, and angiogenic signaling in vitro. Herein, using either specific siRNAs or the pharmacological inhibitor R59949, we demonstrate that DGK α activity is required for 17-β-estradiol (E2)-induced proliferation, motility, and anchorage-independent growth of Hec-1A endometrial cancer cell line. Impairment of DGK α activity also influences basal cell proliferation and growth in soft agar of Hec-1A, while it has no effects on basal cell motility. Moreover, we show that DGK α activity induced by E2, as well as its observed effects, are mediated by the G protein-coupled estrogen receptor GPR30 (GPER). These findings suggest that DGK α may be a potential target in endometrial cancer therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. XIAP BIR domain suppresses miR-200a expression and subsequently promotes EGFR protein translation and anchorage-independent growth of bladder cancer cell

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    Chao Huang

    2017-01-01

    Full Text Available Abstract Background The X-linked inhibitor of apoptosis protein (XIAP is a well-known potent apoptosis suppressor and also participates in cancer cell biological behaviors, therefore attracting great attentions as a potential antineoplastic therapeutic target for past years. Anti-IAP therapy is reported to be closely related to epidermal growth factor receptor (EGFR expression level. However, whether and how XIAP modulates EGFR expression remains largely unknown. Methods Human XIAP was knockdown with short-hairpin RNA in two different bladder cancer cell lines, T24T and UMUC3. Two XIAP mutants, XIAP ∆BIR (deletion of N-terminal three BIR domains and XIAP ∆RING (deletion of C-terminal RING domain and keeping the function of BIR domains, were generated to determine which domain is involved in regulating EGFR. Results We found here that lacking of XIAP expression resulted in a remarkable suppression of EGFR expression, consequently leading to the deficiency of anchorage-independent cell growth. Further study demonstrated that BIR domain of XIAP was crucial for regulating the EGFR translation by suppressing the transcription and expression of miR-200a. Mechanistic studies indicated that BIR domain activated the protein phosphatase 2 (PP2A activity by decreasing the phosphorylation of PP2A at Tyr307 in its catalytic subunit, PP2A-C. Such activated PP2A prevented the deviant phosphorylation and activation of MAPK kinases/MAPKs, their downstream effector c-Jun, and in turn inhibiting transcription of c-Jun-regulated the miR-200a. Conclusions Our study uncovered a novel function of BIR domain of XIAP in regulating the EGFR translation, providing significant insight into the understanding of the XIAP overexpression in the cancer development and progression, further offering a new theoretical support for using XIAP BIR domain and EGFR as targets for cancer therapy.

  15. Bone anchorage: When and why?

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    Ahmet Nejat Erverdi

    2015-01-01

    Full Text Available Anchorage is the most important concept in biomechanics of orthodontics. In contemporary orthodontics, bone anchorage is a magic tool, which decreased the indication for extraoral appliances greatly and at the same time achieving stationary anchorage became possible. However, the indication for bone anchorage has to be clarified carefully. Skeletal open-bite treatment, effective molar distalization, Class III treatment by using chin anchorage, and space closure in severe minimal anchorage cases are some examples for bone anchorage supported orthodontic treatment. Here, we discussed three necessary usages of bone anchorage for different treatment modalities.

  16. Role of postreplication repair in transformation of human fibroblasts to anchorage independence

    International Nuclear Information System (INIS)

    Boyer, J.C.; Kaufmann, W.K.; Cordeiro-Stone, M.

    1991-01-01

    Cellular capacity for postreplication repair (PRR) and sensitivity to transformation to anchorage independence (AI) were quantified in normal foreskin and xeroderma pigmentosum (XP) variant fibroblasts after treatment with UV or benzo(a)pyrene-diol-epoxide I (BPDE-I). PRR is defined here as a collection of pathways that facilitate the replication of DNA damaged by genotoxic agents. It is recognized biochemically as the process by which nascent DNA grows longer than the average distance between two lesions in the DNA template. PRR refers more directly to the elimination of gaps in the daughter-strand DNA by mechanisms which remain to be determined for human cells, but which may include translesion replication and recombination. PRR was measured in diploid human fibroblasts by analysis of the dose kinetics for inhibition of DNA strand growth in carcinogen-treated cells. Logarithmically growing foreskin fibroblasts (NHF1) displayed D0 values of 4.3 J/m 2 and 0.14 microM for the inhibition of DNA synthesis in active replicons by UV and BPDE-I, respectively. XP variant cells (CRL1162) exhibited corresponding D0 values of 1.5 J/m 2 and 0.16 microM. The increased sensitivity to inhibition of DNA replication by UV in these XP variant fibroblasts (2.9-fold greater than normal) was mirrored by an enhanced frequency of transformation to AI. XP variant fibroblasts (CRL1162) were 3.2 times more sensitive to transformation to AI by UV than were the normal foreskin fibroblasts. As predicted by the PRR studies, both cell types exhibited similar frequencies of AI colonies induced by BPDE-I. Apparent thresholds were observed for induction of AI by UV (normal fibroblasts, 2.7 J/m 2 ; XP variant fibroblasts, 0.3 J/m 2 ) and BPDE-I (both, 0.05 microM)

  17. Bone anchorage: When and why?

    OpenAIRE

    Ahmet Nejat Erverdi

    2015-01-01

    Anchorage is the most important concept in biomechanics of orthodontics. In contemporary orthodontics, bone anchorage is a magic tool, which decreased the indication for extraoral appliances greatly and at the same time achieving stationary anchorage became possible. However, the indication for bone anchorage has to be clarified carefully. Skeletal open-bite treatment, effective molar distalization, Class III treatment by using chin anchorage, and space closure in severe minimal anchorage cas...

  18. Characterization of mutagen-activated cellular oncogenes that confer anchorage independence to human fibroblasts and tumorigenicity to NIH 3T3 cells: Sequence analysis of an enzymatically amplified mutant HRAS allele

    International Nuclear Information System (INIS)

    Stevens, C.W.; Manoharan, T.H.; Fahl, W.E.

    1988-01-01

    Treatment of diploid human fibroblasts with an alkylating mutagen has been shown to induce stable, anchorage-independent cell populations at frequencies consistent with an activating mutation. After treatment of human foreskin fibroblasts with the mutagen benzo[α]pyrene (±)anti-7,8-dihydrodiol 9,10-epoxide and selection in soft agar, 17 anchorage-independent clones were isolated and expanded, and their cellular DNA was used to cotransfect NIH 3T3 cells along with pSV2neo. DNA from 11 of the 17 clones induced multiple NIH 3T3 cell tumors in recipient nude mice. Southern blot analyses showed the presence of human Alu repetitive sequences in all of the NIH 3T3 tumor cell DNAs. Intact, human HRAS sequences were observed in 2 of the 11 tumor groups, whereas no hybridization was detected when human KRAS or NRAS probes were used. Slow-migrating ras p21 proteins, consistent with codon 12 mutations, were observed in the same two NIH 3T3 tumor cell groups that contained the human HRAS bands. Genomic DNA from one of these two human anchorage-independent cell populations (clone 21A) was used to enzymatically amplify a portion of exon 1 of the HRAS gene. The results demonstrate that exposure of normal human cells to a common environmental mutagen yields HRAS GC → TA codon 12 transversions that have been commonly observed in human tumors

  19. 78 FR 11099 - Safety Zone Within the Lower Portion of Anchorage #9, Mantua Creek Anchorage; Paulsboro, NJ

    Science.gov (United States)

    2013-02-15

    ... 1625-AA00 Safety Zone Within the Lower Portion of Anchorage 9, Mantua Creek Anchorage; Paulsboro, NJ... temporary safety zone around the southern one-third of Anchorage 9 (Mantua Creek Anchorage), below position 39[deg] 51.573 N-075[deg] 13.557 W due to dredging operations. The Dredge Florida will be working...

  20. WNT10B functional dualism: beta-catenin/Tcf-dependent growth promotion or independent suppression with deregulated expression in cancer.

    Science.gov (United States)

    Yoshikawa, Hirohide; Matsubara, Kenichi; Zhou, Xiaoling; Okamura, Shu; Kubo, Takahiko; Murase, Yaeko; Shikauchi, Yuko; Esteller, Manel; Herman, James G; Wei Wang, Xin; Harris, Curtis C

    2007-11-01

    We found aberrant DNA methylation of the WNT10B promoter region in 46% of primary hepatocellular carcinoma (HCC) and 15% of colon cancer samples. Three of 10 HCC and one of two colon cancer cell lines demonstrated low or no expression, and 5-aza-2'deoxycytidine reactivated WNT10B expression with the induction of demethylation, indicating that WNT10B is silenced by DNA methylation in some cancers, whereas WNT10B expression is up-regulated in seven of the 10 HCC cell lines and a colon cancer cell line. These results indicate that WNT10B can be deregulated by either overexpression or silencing in cancer. We found that WNT10B up-regulated beta-catenin/Tcf activity. However, WNT10B-overexpressing cells demonstrated a reduced growth rate and anchorage-independent growth that is independent of the beta-catenin/Tcf activation, because mutant beta-catenin-transduced cells did not suppress growth, and dominant-negative hTcf-4 failed to alleviate the growth suppression by WNT10B. Although WNT10B expression alone inhibits cell growth, it acts synergistically with the fibroblast growth factor (FGF) to stimulate cell growth. WNT10B is bifunctional, one function of which is involved in beta-catenin/Tcf activation, and the other function is related to the down-regulation of cell growth through a different mechanism. We suggest that FGF switches WNT10B from a negative to a positive cell growth regulator.

  1. Is skeletal anchorage changing the limit of orthodontics?

    DEFF Research Database (Denmark)

    Melsen, Birte

    2007-01-01

    The limits for orthodontic treatment are often set by the lack of suitable anchorage. The mini-implant is used where conventional anchorage cannot be applied; not as a replacement for conventional anchorage. In patients with lack of teeth and reduced periodontium, skeletal anchorage allows...... and can be loaded immediately. The course will be addressed the following topics: Are the mini-implants replacing conventional anchorage? Why are orthodontic mini-implants necessary? The development of the skeletal anchorage systems The biological basis for the skeletal anchorage systems...... The characteristics of the different skeletal anchorage systems The insertion procedure The indications for the use of orthodontic mini-implants Treatment planning in relation to the use of mini-implants Case presentations...

  2. [Skeletal anchorage in the past, today and tomorrow].

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    Melsen, Birte; Dalstra, Michel

    2017-03-01

    Skeletal anchorage was not introduced as an alternative to conventional anchorage modalities. The first skeletal anchorage was a ligature through a hole in the infrazygomatic crest. This was replaced by surgical screws and finally the TADs, which were optimized with respect to the material and morphology, were developed. A bracket-like head allows for the use of the mini-implant as indirect anchorage, but should not be a tool for lost control resulting from badly planned biomechanics or failing compliance. Skeletal anchorage should serve as an adjunct to correct biomechanics, to enable treatments that could not be performed prior to the introduction of skeletal anchorage. The aim of this study was to test the hypothesis that temporary anchorage mini-screws help maintain bone density, height and width of alveolar processes in the extraction sites, and thus prevent the thinning of the alveolar ridge usually observed. In adult patients with degenerated dentitions the application of skeletal anchorage can allow for the displacement of teeth where no anchorage units are present, but also for the redevelopment and maintenance of atrophic alveolar bone. The basis for the optimal use of skeletal anchorage is that the correct line of action for the desired tooth displacement is defined and the necessary force system constructed either with the skeletal anchorage as direct or as indirect anchorage. After a period, during which osseointegrated implants were used as anchorage for tooth movement and bone maintenance, it was accepted that the mini-implants could serve also as anchorage for skeletal displacements avoiding loading of teeth. © EDP Sciences, SFODF, 2017.

  3. Orthodontic Anchorage Implants: State-of-the-art

    DEFF Research Database (Denmark)

    Melsen, Birte

    2007-01-01

    The limits of an orthodontic treatment are often set by the lack of suitable anchorage. The mini-implant is used where conventional anchorage cannot be applied and not as a replacement for conventional anchorage. In patients with lack of teeth and reduced periodontium, skeletal anchorage allows...... will improve the reconstruction possibilities. The mini-implant has widened the orthodontic possibilities....

  4. Inhibition of connective tissue growth factor (CTGF/CCN2) in gallbladder cancer cells leads to decreased growth in vitro.

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    Garcia, Patricia; Leal, Pamela; Ili, Carmen; Brebi, Priscilla; Alvarez, Hector; Roa, Juan C

    2013-06-01

    Gallbladder cancer (GBC) is an aggressive neoplasm associated with late diagnosis, unsatisfactory treatment and poor prognosis. Previous work showed that connective tissue growth factor (CTGF) expression is increased in this malignancy. This matricellular protein plays an important role in various cellular processes and its involvement in the tumorigenesis of several human cancers has been demonstrated. However, the precise function of CTGF expression in cancer cells is yet to be determined. The aim of this study was to evaluate the CTGF expression in gallbladder cancer cell lines, and its effect on cell viability, colony formation and in vitro cell migration. CTGF expression was evaluated in seven GBC cell lines by Western blot assay. Endogenous CTGF expression was downregulated by lentiviral shRNA directed against CTGF mRNA in G-415 cells, and the effects on cell viability, anchorage-independent growth and migration was assessed by comparing them to scrambled vector-transfected cells. Knockdown of CTGF resulted in significant reduction in cell viability, colony formation and anchorage-independent growth (P cancer may confer a growth advantage for neoplastic cells. © 2013 The Authors. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.

  5. Inhibition of Estrogen-induced Growth of Breast Cancer by Targeting Mitochondrial Oxidants

    National Research Council Canada - National Science Library

    Roy, Deodutta; Felty, Quentin; Kunkle, Brian

    2008-01-01

    ...) Anchorage-independent cell growth, and (c) tumor spheroid formation using new 3D HuBiogel bioassay whether estrogen induced conversion of normal cells to transformed cells is inhibited by treatment with antioxidants, over expression of MnSOD...

  6. Friction and anchorage loading revisited.

    Science.gov (United States)

    Dholakia, Kartik D

    2012-01-01

    Contemporary concepts of sliding mechanics explain that friction is inevitable. To overcome this frictional resistance, excess force is required to retract the tooth along the archwire (ie, individual retraction of canines, en masse retraction of anterior teeth), in addition to the amount of force required for tooth movement. The anterior tooth retraction force, in addition to excess force (to overcome friction), produces reciprocal protraction force on molars, thereby leading to increased anchorage loading. However, this traditional concept was challenged in recent literature, which was based on the finite element model, but did not bear correlation to the clinical scenario. This article will reinforce the fact that clinically, friction increases anchorage loading in all three planes of space, considering the fact that tooth movement is a quasistatic process rather than a purely continuous or static one, and that conventional ways of determining the effects of static or dynamic friction on anchorage load cannot be applied to clinical situations (which consist of anatomical resistance units and a complex muscular force system). The article does not aim to quantify friction and its effect on the amount of anchorage load. Rather, a new perspective regarding the role of various additional factors (which is not explained by contemporary concept) that may influence friction and anchorage loading is provided..

  7. Performance of Sequoyah Containment Anchorage System

    International Nuclear Information System (INIS)

    Fanous, F.; Greimann, L.; Wassef, W.; Bluhm, D.

    1993-01-01

    Deformation of a steel containment anchorage system during a severe accident may result in a leakage path at the containment boundaries. Current design criteria are based on either ductile or brittle failure modes of headed bolts that do not account for factors such as cracking of the containment basemat or deformation of the anchor bolt that may affect the behavior of the containment anchorage system. The purpose of this study was to investigate the performance of a typical ice condenser containment's anchorage system. This was accomplished by analyzing the Sequoyah Containment Anchorage System. Based on a strength of materials approach and assuming that the anchor bolts are resisting the uplift caused by the internal pressure, one can estimate that the failure of the anchor bolts would occur at a containment pressure of 79 psig. To verify these results and to calibrate the strength of materials equation, the Sequoyah containment anchorage system was analyzed with the ABAQUS program using a three-dimensional, finite-element model. The model included portions of the steel containment building, shield building, anchor bolt assembly, reinforced concrete mat and soil foundation material

  8. Anchorage Areas

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — An anchorage area is a place where boats and ships can safely drop anchor. These areas are created in navigable waterways when ships and vessels require them for...

  9. PHTS, a novel putative tumor suppressor, is involved in the transformation reversion of HeLaHF cells independently of the p53 pathway

    International Nuclear Information System (INIS)

    Yu Dehua; Fan, Wufang; Liu, Guohong; Nguy, Vivian; Chatterton, Jon E.; Long Shilong; Ke, Ning; Meyhack, Bernd; Bruengger, Adrian; Brachat, Arndt; Wong-Staal, Flossie; Li, Qi-Xiang

    2006-01-01

    HeLaHF is a non-transformed revertant of HeLa cells, likely resulting from the activation of a putative tumor suppressor(s). p53 protein was stabilized in this revertant and reactivated for certain transactivation functions. Although p53 stabilization has not conclusively been linked to the reversion, it is clear that the genes in p53 pathway are involved. The present study confirms the direct role of p53 in HeLaHF reversion by demonstrating that RNAi-mediated p53 silencing partially restores anchorage-independent growth potential of the revertant through the suppression of anoikis. In addition, we identified a novel gene, named PHTS, with putative tumor suppressor properties, and showed that this gene is also involved in HeLaHF reversion independently of the p53 pathway. Expression profiling revealed that PHTS is one of the genes that is up-regulated in HeLaHF but not in HeLa. It encodes a putative protein with CD59-like domains. RNAi-mediated PHTS silencing resulted in the partial restoration of transformation (anchorage-independent growth) in HeLaHF cells, similar to that of p53 gene silencing, implying its tumor suppressor effect. However, the observed increased transformation potential by PHTS silencing appears to be due to an increased anchorage-independent proliferation rate rather than suppression of anoikis, unlike the effect of p53 silencing. p53 silencing did not affect PHTS gene expression, and vice versa, suggesting PHTS may function in a new and p53-independent tumor suppressor pathway. Furthermore, over-expression of PHTS in different cancer cell lines, in addition to HeLa, reduces cell growth likely via induced apoptosis, confirming the broad PHTS tumor suppressor properties

  10. Effectiveness of 3 methods of anchorage reinforcement for maximum anchorage in adolescents: A 3-arm multicenter randomized clinical trial.

    Science.gov (United States)

    Sandler, Jonathan; Murray, Alison; Thiruvenkatachari, Badri; Gutierrez, Rodrigo; Speight, Paul; O'Brien, Kevin

    2014-07-01

    The objective of this 3-arm parallel randomized clinical trial was to compare the effectiveness of temporary anchorage devices (TADs), Nance button palatal arches, and headgear for anchorage supplementation in the treatment of patients with malocclusions that required maximum anchorage. This trial was conducted between August 2008 and February 2013 in 2 orthodontic departments in the United Kingdom. The study included 78 patients (ages, 12-18 years; mean age, 14.2 years) who needed maximum anchorage. Eligibility criteria included no active caries, exemplary oral hygiene, and maximum anchorage required. The primary outcome was mesial molar movement during the period in which anchorage supplementation was required. The secondary outcomes were duration of anchorage reinforcement, number of treatment visits, number of casual and failed appointments, total treatment time, dento-occlusal change, and patients' perceptions of the method of anchorage supplementation. Treatment allocation was implemented by contacting via the Internet the randomization center at the University of Nottingham, Clinical Trials Unit. The randomization was based on a computer-generated pseudo-random code with random permuted blocks of randomly varying size. A research assistant who was blinded to the group allocation recorded all data. The patients were randomly allocated to receive anchorage supplementation with TADs, a Nance button on a palatal arch, or headgear. They were all treated with maxillary and mandibular preadjusted edgewise fixed appliances with 0.022-in slot prescription brackets. They were followed until orthodontic treatment was complete. Seventy-eight patients were randomized in a 1:1:1 ratio among the 3 groups. The baseline characteristics were similar in the groups, and they were treated for an average of 27.4 months (SD, 7.1 months); 71 completed orthodontic treatment. The data were analyzed on a per-protocol basis and showed no differences in the effectiveness of anchorage

  11. 29 CFR 1926.755 - Column anchorage.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 8 2010-07-01 2010-07-01 false Column anchorage. 1926.755 Section 1926.755 Labor... (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Steel Erection § 1926.755 Column anchorage. (a) General requirements for erection stability. (1) All columns shall be anchored by a minimum of 4 anchor...

  12. Procedures adopted by orthodontists for space closure and anchorage control.

    Science.gov (United States)

    Monini, André da Costa; Gandini Júnior, Luiz Gonzaga; dos Santos-Pinto, Ary; Maia, Luiz Guilherme Martins; Rodrigues, Willian Caetano

    2013-01-01

    The aim of this study was to identify the procedures adopted by Brazilian orthodontists in the following situations: extraction space closure, anchorage control in case of necessary anchorage for group A and frequency of skeletal anchorage use, especially in the upper jaw. A questionnaire was sent to the e-mail address of all dentists registered in the Brazilian Federal Council of Dentistry. The results showed that most Brazilian orthodontists usually perform extraction space closure by means of sliding mechanics. The use of palatal bar, inclusion of second molars in the archwire and space closure performed in two phases are the most used techniques for anchorage control in the upper jaw. The skeletal anchorage is referenced by 36.5% of specialists as a routine practice for the upper arch anchorage. There is a wide variety of procedures adopted by Brazilian orthodontists for orthodontic space closure and anchorage control.

  13. Experimental evidence of pharmacological management of anchorage in Orthodontics: A systematic review

    Science.gov (United States)

    Fernández-González, Felipe José; Cañigral, Aránzazu; Balbontín-Ayala, Felipe; Gonzalo-Orden, José Manuel; de Carlos, Felix; Cobo, Teresa; Fernández-Vázquez, Jose Pedro; Sánchez-Lasheras, Fernando; Vega, José Antonio

    2015-01-01

    Introduction: Orthodontic anchorage is one of the most challenging aspects of Orthodontics. Preventing undesired movement of teeth could result in safer and less complicated orthodontic treatment. Recently, several reviews have been published about the effects of different molecules on bone physiology and the clinical side effects in Orthodontics. However, the effects of local application of these substances on the rate of orthodontic tooth movement have not been assessed. Objectives: The aim of this research was to analyze the scientific evidence published in the literature about the effects of different molecules on orthodontic anchorage. Methods: The literature was systematically reviewed using PubMed/Medline, Scopus and Cochrane databases from 2000 up to July 31st, 2014. Articles were independently selected by two different researchers based on previously established inclusion and exclusion criteria, with a concordance Kappa index of 0.86. The methodological quality of the reviewed papers was performed. Results: Search strategy identified 270 articles. Twenty-five of them were selected after application of inclusion/exclusion criteria, and only 11 qualified for final analysis. Molecules involved in orthodontic anchorage were divided into three main groups: osteoprotegerin (OPG), bisphosphonates (BPs) and other molecules (OMs). Conclusions: Different drugs are able to alter the bone remodeling cycle, influencing osteoclast function and, therefore, tooth movement. Thus, they could be used in order to provide maximal anchorage while preventing undesired movements. OPG was found the most effective molecule in blocking the action of osteoclasts, thereby reducing undesired movements. PMID:26560822

  14. Procedures adopted by orthodontists for space closure and anchorage control

    Directory of Open Access Journals (Sweden)

    André da Costa Monini

    2013-12-01

    Full Text Available OBJECTIVE: The aim of this study was to identify the procedures adopted by Brazilian orthodontists in the following situations: extraction space closure, anchorage control in case of necessary anchorage for group A and frequency of skeletal anchorage use, especially in the upper jaw. METHOD: A questionnaire was sent to the e-mail address of all dentists registered in the Brazilian Federal Council of Dentistry. RESULTS: The results showed that most Brazilian orthodontists usually perform extraction space closure by means of sliding mechanics. The use of palatal bar, inclusion of second molars in the archwire and space closure performed in two phases are the most used techniques for anchorage control in the upper jaw. The skeletal anchorage is referenced by 36.5% of specialists as a routine practice for the upper jaw anchorage. CONCLUSIONS: There is a wide variety of procedures adopted by Brazilian orthodontists for orthodontic space closure and anchorage control.

  15. TERRAIN, Anchorage, Alaska

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — The Anchorage AOI consists of seven areas. These areas were to be collected to the 'highest' accuracy requirement. Ground Control is collected throughout the AOI for...

  16. On decisive factors of liner anchorage behaviour

    International Nuclear Information System (INIS)

    Bucchardt, F.; Weber, M.; Yazdi, F.

    1984-01-01

    Design of reinforced and prestressed containments for nuclear power plants in the FRG shall be guided by DIN 25459; this also includes the structural behaviour of the liner. While the containment safety analysis is a more global matter, the liner and especially the liner anchorage behaviour concentrates on local effects which need a more refined local area description. Due to the predominant stiffness of the concrete structure liner failure analysis are performed by decoupling the steel membrane which is then only supported by anchorage springs. A comprehensive nonlinear analytical study is carried out to examine the anchorage behaviour. (Author) [pt

  17. Efficacy of the Nance appliance as an anchorage-reinforcement method.

    Science.gov (United States)

    Al-Awadhi, Ebrahim A; Garvey, Therese M; Alhag, Mohamed; Claffey, Noel M; O'Connell, Brian

    2015-03-01

    The Nance appliance is widely considered to be an efficient method of anchorage reinforcement; however, much of the perceived advantage is based on clinical judgment. The aim of this study was to assess the amounts of anchorage loss and desired tooth movement associated with the Nance appliance. The mandibular arches of 7 beagle dogs were used. The first and third premolars were extracted. Reference miniscrews were placed at the first premolar sites as stable references to measure the amounts of anchorage loss and desired tooth movement. Four beagles were fitted with custom-made Nance appliances on the fourth premolars and orthodontic bands on the second premolars (Nance group). Three beagles were fitted with orthodontic bands on the second and fourth premolars with no anchorage reinforcement (control group). The second premolars were retracted over 15 weeks in both groups. The amounts of second premolar movement (desired tooth movement) and fourth premolar movement (anchorage loss) were recorded at 5, 10, and 15 weeks. The percentages of desired tooth movement and anchorage loss to the total space closure were calculated. The mean desired tooth movement was significantly more in the Nance group than in the control group at 10 weeks (P appliance did not provide absolute anchorage, but there was significantly less anchorage loss with it than in the control group. The majority of anchorage loss occurred during the first 10 weeks in the Nance group. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  18. Paradigm shifts in orthodontic treatment with mini-implant anchorage

    Directory of Open Access Journals (Sweden)

    Johnny Joung-Lin Liaw

    2015-01-01

    Full Text Available After the applications of mini-implant anchorage, the envelope of orthodontic treatment was expanded and some treatment modes were changed because of more predictable tooth movement with empowered anchorage. The author tried to share his experience of TADs applications for clarifying the paradigm shifts of orthodontic treatment assisted with the mini-implant anchorage.

  19. Suppression of progranulin expression inhibits bladder cancer growth and sensitizes cancer cells to cisplatin

    OpenAIRE

    Buraschi, Simone; Xu, Shi-Qiong; Stefanello, Manuela; Moskalev, Igor; Morcavallo, Alaide; Genua, Marco; Tanimoto, Ryuta; Birbe, Ruth; Peiper, Stephen C.; Gomella, Leonard G.; Belfiore, Antonino; Black, Peter C.; Iozzo, Renato V.; Morrione, Andrea

    2016-01-01

    We have recently demonstrated a critical role for progranulin in bladder cancer. Progranulin contributes, as an autocrine growth factor, to the transformed phenotype by modulating Akt-and MAPK-driven motility, invasion and anchorage-independent growth. Progranulin also induces F-actin remodeling by interacting with the F-actin binding protein drebrin. In addition, progranulin is overexpressed in invasive bladder cancer compared to normal tissue controls, suggesting that progranulin might play...

  20. Suppression of progranulin expression inhibits bladder cancer growth and sensitizes cancer cells to cisplatin.

    Science.gov (United States)

    Buraschi, Simone; Xu, Shi-Qiong; Stefanello, Manuela; Moskalev, Igor; Morcavallo, Alaide; Genua, Marco; Tanimoto, Ryuta; Birbe, Ruth; Peiper, Stephen C; Gomella, Leonard G; Belfiore, Antonino; Black, Peter C; Iozzo, Renato V; Morrione, Andrea

    2016-06-28

    We have recently demonstrated a critical role for progranulin in bladder cancer. Progranulin contributes, as an autocrine growth factor, to the transformed phenotype by modulating Akt-and MAPK-driven motility, invasion and anchorage-independent growth. Progranulin also induces F-actin remodeling by interacting with the F-actin binding protein drebrin. In addition, progranulin is overexpressed in invasive bladder cancer compared to normal tissue controls, suggesting that progranulin might play a key role in driving the transition to the invasive phenotype of urothelial cancer. However, it is not established whether targeting progranulin could have therapeutic effects on bladder cancer. In this study, we stably depleted urothelial cancer cells of endogenous progranulin by shRNA approaches and determined that progranulin depletion severely inhibited the ability of tumorigenic urothelial cancer cells to migrate, invade and grow in anchorage-independency. We further demonstrate that progranulin expression is critical for tumor growth in vivo, in both xenograft and orthotopic tumor models. Notably, progranulin levels correlated with response to cisplatin treatment and were upregulated in bladder tumors. Our data indicate that progranulin may constitute a novel target for therapeutic intervention in bladder tumors. In addition, progranulin may serve as a novel biomarker for bladder cancer.

  1. Comparative photoelastic study of dental and skeletal anchorages in the canine retraction

    Directory of Open Access Journals (Sweden)

    Cristiane Aparecida de Assis Claro

    2014-01-01

    Full Text Available OBJECTIVE: To compare dental and skeletal anchorages in mandibular canine retraction by means of a stress distribution analysis. METHODS: A photoelastic model was produced from second molar to canine, without the first premolar, and mandibular canine retraction was simulated by a rubber band tied to two types of anchorage: dental anchorage, in the first molar attached to adjacent teeth, and skeletal anchorage with a hook simulating the mini-implant. The forces were applied 10 times and observed in a circular polariscope. The stresses located in the mandibular canine were recorded in 7 regions. The Mann-Whitney test was employed to compare the stress in each region and between both anchorage systems. The stresses in the mandibular canine periradicular regions were compared by the Kruskal-Wallis test. RESULTS: Stresses were similar in the cervical region and the middle third. In the apical third, the stresses associated with skeletal anchorage were higher than the stresses associated with dental anchorage. The results of the Kruskal-Wallis test showed that the highest stresses were identified in the cervical-distal, apical-distal, and apex regions with the use of dental anchorage, and in the apical-distal, apical-mesial, cervical-distal, and apex regions with the use of skeletal anchorage. CONCLUSIONS: The use of skeletal anchorage in canine retraction caused greater stress in the apical third than the use of dental anchorage, which indicates an intrusive component resulting from the direction of the force due to the position of the mini-implant and the bracket hook of the canine.

  2. FRP tendon anchorage in post-tensioned concrete structures

    DEFF Research Database (Denmark)

    Schmidt, Jacob Wittrup; Täljsten, Björn; Bennitz, Anders

    2008-01-01

    effective Young´s modulus and the high stress capacity in the linear elastic range of the material. The use of external tendons increases the requirements on the anchorage systems. This is in particular important when using un-bonded tendon systems, where the anchorage and deviators are the only force...... transfer points. The demand for high capacity anchorage tendons is fulfilled for steel tendons, but no competitive mechanical anchor has yet been developed for FRP tendon. A new small, reliable and more user friendly anchor has to be developed, before FRP tendons can be utilized with all of its capacity...

  3. Urinary transforming growth factors in neoplasia: separation of 125I-labeled transforming growth factor-alpha from epidermal growth factor in human urine

    International Nuclear Information System (INIS)

    Stromberg, K.; Hudgins, W.R.

    1986-01-01

    Purified human epidermal growth factor (hEGF) from urine promotes anchorage-independent cell growth in soft agar medium. This growth is enhanced by transforming growth factor-beta (TGF-beta), and is specifically inhibited by hEGF antiserum. Transforming growth factors of the alpha type (TGF-alpha), potentially present in normal human urine or urine from tumor-bearing patients, also promote anchorage-independent cell growth and compete with EGF for membrane receptor binding. Consequently, TGF-alpha cannot be distinguished from urinary hEGF by these two functional assays. Therefore, a technique for separation of TGF-alpha and related peptides from urinary EGF based on biochemical characteristics would be useful. Radioiodination of characterized growth factors [mouse EGF (mEGF), hEGF, and rat TGF-alpha (rTGF-alpha)], which were then separately added to human urine, was used to evaluate a resolution scheme that separates TGF-alpha from the high level of background hEGF present in human urine. Methyl bonded microparticulate silica efficiently adsorbed the 125 I-labeled mEGF, 125 I-labeled hEGF, and 125 I-labeled rTGF-alpha that were added to 24-h human urine samples. Fractional elution with acetonitrile (MeCN) of the adsorbed silica released approximately 70 to 80% of the 125 I-labeled mEGF and 125 I-labeled hEGF between 25 and 30% MeCN, and over 80% of the 125 I-labeled rTGF-alpha between 15 and 25% MeCN, with retention after dialysis of less than 0.2 and 1.7% of the original urinary protein, respectively. A single-step enrichment of about 400-fold for mEGF and hEGF, and 50-fold for rTGF-alpha were achieved rapidly. 125 I-labeled mEGF and 125 I-labeled hEGF eluted later than would be predicted on the basis of their reported molecular weight of approximately 6000, whereas 125 I-labeled rTGF-alpha eluted from Bio-Gel P-10 at an approximate molecular weight of 8000 to 9000

  4. Indian Board of Orthodontics case report: Orthodontic management of vertical excess using skeletal anchorage

    Directory of Open Access Journals (Sweden)

    Ajit J Kalia

    2016-01-01

    Full Text Available B.B., a 21-year-old girl, presented with the chief complaint of forwardly placed upper front teeth and gummy smile. Diagnosis revealed prognathic maxilla and average mandible, Class II skeletal base with vertical growth pattern, end-on molars and Class II canine relationship bilaterally, convex profile, potentially incompetent lips, gummy smile, and protrusive lower lip. The patient′s treatment plan was extraction of all first bicuspids and retraction using temporary anchorage devices. Anchorage was reinforced using microimplants in the maxillary arch and second molar banding in the mandibular arch. The implants were placed high up in the vestibule to have more of an intrusive component and to reduce gummy smile at the end of the treatment.

  5. A new non-metallic anchorage system for post-tensioning applications using CFRP tendons

    Science.gov (United States)

    Taha, Mahmoud Reda

    The objective of the work described in this thesis is to design, develop and test a new non-metallic anchorage system for post-tensioning applications using CFRP tendons. The use of a non-metallic anchorage system should eliminate corrosion and deterioration concerns in the anchorage zone. The development of a reliable non-metallic anchorage would provide an important contribution to this field of knowledge. The idea of the new anchorage is to hold the tendon through mechanical gripping. The anchorage consists of a barrel with a conical housing and four wedges. The anchorage components are made of ultra high performance concrete (UHPC) specially developed for the anchorage. Sixteen concrete mixtures with different casting and curing regimes were examined to develop four UHPC mixtures with compressive strengths in excess of 200 MPa. The UHPC mixtures showed very dense microstructures with some unique characteristics. To enhance the fracture toughness of the newly developed UHPC, analytical and experimental analyses were performed. Using 3 mm chopped carbon fibres, a significant increase in the fracture toughness of UHPC was achieved. The non-metallic anchorage was developed with the UHPC with enhanced fracture toughness. The barrel required careful wrapping with CFRP sheets to provide the confinement required to utilize the strength and toughness of the UHPC. Thirty-three anchorages were tested under both static and dynamic loading conditions. The non-metallic anchorage showed excellent mechanical performance and fulfilled the different requirements of a post-tensioning anchorage system. The development of the new non-metallic anchorage will widen the inclusion of CFRP tendons in post-tensioned concrete/masonry structures. The new system will offer the opportunity to exploit CFRP tendons effectively creating an innovative generation of corrosion-free, smart structures.

  6. Chlamydia induces anchorage independence in 3T3 cells and detrimental cytological defects in an infection model.

    Directory of Open Access Journals (Sweden)

    Andrea E Knowlton

    Full Text Available Chlamydia are gram negative, obligate intracellular bacterial organisms with different species causing a multitude of infections in both humans and animals. Chlamydia trachomatis is the causative agent of the sexually transmitted infection (STI Chlamydia, the most commonly acquired bacterial STI in the United States. Chlamydial infections have also been epidemiologically linked to cervical cancer in women co-infected with the human papillomavirus (HPV. We have previously shown chlamydial infection results in centrosome amplification and multipolar spindle formation leading to chromosomal instability. Many studies indicate that centrosome abnormalities, spindle defects, and chromosome segregation errors can lead to cell transformation. We hypothesize that the presence of these defects within infected dividing cells identifies a possible mechanism for Chlamydia as a cofactor in cervical cancer formation. Here we demonstrate that infection with Chlamydia trachomatis is able to transform 3T3 cells in soft agar resulting in anchorage independence and increased colony formation. Additionally, we show for the first time Chlamydia infects actively replicating cells in vivo. Infection of mice with Chlamydia results in significantly increased cell proliferation within the cervix, and in evidence of cervical dysplasia. Confocal examination of these infected tissues also revealed elements of chlamydial induced chromosome instability. These results contribute to a growing body of data implicating a role for Chlamydia in cervical cancer development and suggest a possible molecular mechanism for this effect.

  7. Finite element simulation and testing of ISW CFRP anchorage

    DEFF Research Database (Denmark)

    Schmidt, Jacob Wittrup; Goltermann, Per; Hertz, Kristian Dahl

    2013-01-01

    is modelled in the 3D finite Element program ABAQUS, just as digital image correlation (DIC) testing was performed to verify the finite element simulation. Also a new optimized design was produced to ensure that the finite element simulation and anchorage behaviour correlated well. It is seen....... This paper presents a novel mechanical integrated sleeve wedge anchorage which seem very promising when perusing the scope of ultimate utilization of CFRP 8mm rods (with a tension capacity of approximately 140kN). Compression transverse to the CFRP is evaluated to prevent premature failure. The anchorage...

  8. Comparison of anchorage reinforcement with temporary anchorage devices or a Herbst appliance during lingual orthodontic protraction of mandibular molars without maxillary counterbalance extraction.

    Science.gov (United States)

    Metzner, Rebecca; Schwestka-Polly, Rainer; Helms, Hans-Joachim; Wiechmann, Dirk

    2015-06-20

    Orthodontic protraction of mandibular molars without maxillary counterbalance extraction in cases of aplasia or extraction requires stable anchorage. Reinforcement may be achieved by using either temporary anchorage devices (TAD) or a fixed, functional appliance. The objective was to compare the clinical effectiveness of both methods by testing the null-hypothesis of no significant difference in velocity of space closure (in mm/month) between them. In addition, we set out to describe the quality of posterior space management and treatment-related factors, such as loss of anchorage (assessed in terms of proportions of gap closure by posterior protraction or anterior retraction), frequencies of incomplete space closure, and potential improvement in the sagittal canine relationship. Twenty-seven subjects (15 male/12 female) with a total of 36 sites treated with a lingual multi-bracket appliance were available for retrospective evaluation of the effects of anchorage reinforcement achieved with either a Herbst appliance (n(subjects) = 15; 7 both-sided/8 single-sided Herbst appliances; n(sites) = 22) or TADs (n(subjects )= 12; 2 both-sided; 10 single-sided; n(sites) = 14). Descriptive analysis was based on measurements using intra-oral photographs which were individually scaled to corresponding plaster casts and taken on insertion of anchorage mechanics (T1), following removal of anchorage mechanics (T2), and at the end of multi-bracket treatment (T3). The null-hypothesis was rejected: The rate of mean molar protraction was significantly faster in the Herbst-reinforced group (0.51 mm/month) than in the TAD group (0.35). While complete space closure by sheer protraction of posterior teeth was achieved in all Herbst-treated cases, space closure in the TAD group was achieved in 76.9% of subjects by sheer protraction of molars, and it was incomplete in 50% of cases (mean gap residues: 1 mm). Whilst there was a deterioration in the canine relationship towards

  9. Seismic verification of nuclear plant equipment anchorage

    International Nuclear Information System (INIS)

    Lepiece, M.; Van Vyve, J.

    1991-01-01

    More than 60% of the electrical power of Belgium is generated by seven PWR nuclear power plants. For three of them, the electro-mechanical equipment had to be reassessed after ten years of operation, because the seismic requirements were upgraded from 0.1 g to 0.17 g free field ground acceleration. The seismic requalification of the active equipment was a critical problem as the classical methods were too conservative. The approach based on the use of the past experience on the seismic behavior of nonnuclear equipment, chosen and developed by the SQUG, had to be transposed to the Belgian N.P.P. The decision of the accept-ability of equipment relies heavily on the aseismatic capacity of anchorage. The Electrical Power Research Institute (EPRI) developed the procedure and guideline for the demonstration of the aseismatic adequacy of equipment anchorage in a cost-effective and consistent manner, to support the decision by Seismic Review Team. The field inspection procedure to identify the type of fasteners and detect their possible defects and the verification procedure developed to calculate the aseismatic capacity of equipment anchorage on the strength of fasteners, the aseismatic capacity of anchorage and the comparison of the capacity with the demand are reported. (K.I.)

  10. Research on the Bond Anchorage Properties of Alkali-Activated Slag Cementitious Material

    Science.gov (United States)

    Zhu, J.; Zheng, W. Z.; Leng, Y. F.; Qin, C. Z.; Xu, Z. Z.

    2017-12-01

    By bond-anchorage property tests at 20°C ∼500°C, the distribution of shear stress between carbon fiber sheets and concrete at all levels of loading and anchorage lengths were measured, which means the bond lengths during CFRP sheets are pulled off at the same time when the concrete is torn and stripped were gotten. The failure modes were obtained. In addition, the failure loads were measured, and the calculated formulas of anchorage lengths were identified by fitting at high temperature. It can be seen that the anchorage lengths of carbon fiber sheets increase with increasing temperature at 20°C ∼100°C, the anchorage lengths of carbon fiber sheets decrease with increasing temperature at 100°C ∼500°C. Tests prove that AASCM has favorable high-temperature resistant and bond anchorage properties.

  11. Procedures adopted by orthodontists for space closure and anchorage control

    OpenAIRE

    Monini,André da Costa; Gandini Júnior,Luiz Gonzaga; Santos-Pinto,Ary dos; Maia,Luiz Guilherme Martins; Rodrigues,Willian Caetano

    2013-01-01

    OBJECTIVE: The aim of this study was to identify the procedures adopted by Brazilian orthodontists in the following situations: extraction space closure, anchorage control in case of necessary anchorage for group A and frequency of skeletal anchorage use, especially in the upper jaw. METHOD: A questionnaire was sent to the e-mail address of all dentists registered in the Brazilian Federal Council of Dentistry. RESULTS: The results showed that most Brazilian orthodontists usually perform extra...

  12. The benefit of differential moment concept in managing posterior anchorage and avoiding bite deepening

    Directory of Open Access Journals (Sweden)

    Harryanto Wijaya

    2012-09-01

    Full Text Available Background: Anchorage is one of the major concerns in orthodontic space closure. Various methods have been proposed to enhance posterior anchorage in space closure such as headgear, Nance holding appliance, and micro implant as temporary anchorage devices. However, several issues such as patient's compliance, appliance effectiveness, and cost of the device become many clinicians concern. The differential moment concept in segmented arch is a technique that requires no patient compliance but can effectively manage posterior anchorage and avoid bite deepening by careful application of forces and moments. Purpose: The purpose of this case report is to show the use of differential moment concept in segmented arch technique to manage posterior anchorage and to avoid bite deepening. Case: A 21 years old female patient with protrusive teeth as her chief complaint was treated using fixed orthodontic appliance. Case management: The treatment included four first bicuspid extraction and space closure utilizing differential moment concept in segmented arch. Conclusion: It can be concluded that application of differential moment concept in segmented arch technique is a non invasive, compliance independent, effective, and cost efficient method to manage posterior anchorage and to avoid bite deepening.latar belakang: Penjangkaran merupakan salah satu aspek yang sering kali menjadi masalah dalam penutupan ruang pada perawatan ortodonti. Berbagai metode disarankan untuk memperkuat penjangkaran posterior dalam penutupan ruang seperti headgear, piranti penahan Nance, dan implan mikro sebagai alat penjangkar sementara. Namun demikian, beberapa hal seperti kerjasama pasien, efektivitas piranti, dan biaya dari alat-alat tersebut sering menjadi perhatian/pertimbangan bagi klinisi. Konsep momen diferensial pada segmented arch adalah suatu cara yang efektif untuk memperkuat penjangkaran dan menghindari pendalaman gigitan tanpa memerlukan kerjasama pasien. tujuan

  13. Bioreactor design for successive culture of anchorage-dependent cells operated in an automated manner.

    Science.gov (United States)

    Kino-Oka, Masahiro; Ogawa, Natsuki; Umegaki, Ryota; Taya, Masahito

    2005-01-01

    A novel bioreactor system was designed to perform a series of batchwise cultures of anchorage-dependent cells by means of automated operations of medium change and passage for cell transfer. The experimental data on contamination frequency ensured the biological cleanliness in the bioreactor system, which facilitated the operations in a closed environment, as compared with that in flask culture system with manual handlings. In addition, the tools for growth prediction (based on growth kinetics) and real-time growth monitoring by measurement of medium components (based on small-volume analyzing machinery) were installed into the bioreactor system to schedule the operations of medium change and passage and to confirm that culture proceeds as scheduled, respectively. The successive culture of anchorage-dependent cells was conducted with the bioreactor running in an automated way. The automated bioreactor gave a successful culture performance with fair accordance to preset scheduling based on the information in the latest subculture, realizing 79- fold cell expansion for 169 h. In addition, the correlation factor between experimental data and scheduled values through the bioreactor performance was 0.998. It was concluded that the proposed bioreactor with the integration of the prediction and monitoring tools could offer a feasible system for the manufacturing process of cultured tissue products.

  14. Mini-Implants in the Anchorage Armamentarium: New Paradigms in the Orthodontics

    Directory of Open Access Journals (Sweden)

    Masaru Yamaguchi

    2012-01-01

    Full Text Available Paradigms have started to shift in the orthodontic world since the introduction of mini-implants in the anchorage armamentarium. Various forms of skeletal anchorage, including miniscrews and miniplates, have been reported in the literature. Recently, great emphasis has been placed on the miniscrew type of temporary anchorage device (TAD. These devices are small, are implanted with a relatively simple surgical procedure, and increase the potential for better orthodontic results. Therefore, miniscrews not only free orthodontists from anchorage-demanding cases, but they also enable clinicians to have good control over tooth movement in 3 dimensions. The miniplate type also produces significant improvements in treatment outcomes and has widened the spectrum of orthodontics. The purpose of this paper is to update clinicians on the current concepts and versatile uses and clinical applications of skeletal anchorage in orthodontics.

  15. Role for cER and Mmr1p in anchorage of mitochondria at sites of polarized surface growth in budding yeast.

    Science.gov (United States)

    Swayne, Theresa C; Zhou, Chun; Boldogh, Istvan R; Charalel, Joseph K; McFaline-Figueroa, José Ricardo; Thoms, Sven; Yang, Christine; Leung, Galen; McInnes, Joseph; Erdmann, Ralf; Pon, Liza A

    2011-12-06

    Mitochondria accumulate at neuronal and immunological synapses and yeast bud tips and associate with the ER during phospholipid biosynthesis, calcium homeostasis, and mitochondrial fission. Here we show that mitochondria are associated with cortical ER (cER) sheets underlying the plasma membrane in the bud tip and confirm that a deletion in YPT11, which inhibits cER accumulation in the bud tip, also inhibits bud tip anchorage of mitochondria. Time-lapse imaging reveals that mitochondria are anchored at specific sites in the bud tip. Mmr1p, a member of the DSL1 family of tethering proteins, localizes to punctate structures on opposing surfaces of mitochondria and cER sheets underlying the bud tip and is recovered with isolated mitochondria and ER. Deletion of MMR1 impairs bud tip anchorage of mitochondria without affecting mitochondrial velocity or cER distribution. Deletion of the phosphatase PTC1 results in increased Mmr1p phosphorylation, mislocalization of Mmr1p, defects in association of Mmr1p with mitochondria and ER, and defects in bud tip anchorage of mitochondria. These findings indicate that Mmr1p contributes to mitochondrial inheritance as a mediator of anchorage of mitochondria to cER sheets in the yeast bud tip and that Ptc1p regulates Mmr1p phosphorylation, localization, and function. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. 77 FR 43514 - Anchorage Regulations; Narragansett Bay and Rhode Island Sound, RI

    Science.gov (United States)

    2012-07-25

    ...-AA01 Anchorage Regulations; Narragansett Bay and Rhode Island Sound, RI AGENCY: Coast Guard, DHS... Narragansett Bay, Rhode Island, and adding an offshore anchorage in Rhode Island Sound south of Brenton Point... rulemaking (NPRM) entitled ``Anchorage Regulations; Narragansett Bay and Rhode Island Sound, RI,'' in the...

  17. Association of ultraviolet-induced retrovirus expression with anchorage-independent survival in rat embryo cells

    International Nuclear Information System (INIS)

    Suk, W.A.

    1985-01-01

    The authors have shown in the AI assay that the nontransforming retrovirus increases the differential in enhanced survival response in infected cultures. To more fully understand this aspect of the system, they examined the effect of UV irradiation on infected and uninfected FRE cells. In this communication the authors report that UV irradiation induces AI survival in infected and uninfected cells;in uninfected cells there is a concomitant induction of endogenous retrovirus expression. The AI survival of both cell lines was determined using a previously described procedure. Anchorage-dependent media control and solvent control cells, when suspended in medium above an agar base layer, showed a rapid decline in cell survival;however, cells that had been treated with carcinogen did not undergo the destructive process that took place in control cells, indicating specificity

  18. [Clinical effects of micro-implant and traditional anchorage in orthodontic treatments].

    Science.gov (United States)

    Qian, Yi; Zhou, Hua-Jie; Wu, Jian-Hua

    2017-06-01

    To analyze the value of micro-implant and traditional anchorage in the treatment of malocclusion. From Jan 2015 to Jan 2016, 20 cases with malocclusion were randomly divided into control group(10) and experimental group (10). A comparison was conducted between the control group, in which traditional anchorage was used and the experimental group, in which micro-implant anchorage was adopted. The data were analyzed with SPSS 17.0 software package. There was significant difference of U1-NA, L1-NB, U1-APg, U6-PtPNS between the 2 groups(PMicro-implant anchorage can improve overjet relation of the anterior teeth and effect of orthodontic treatment.

  19. Factors predisposing to maxillary anchorage loss: a retrospective study of 1403 cases.

    Directory of Open Access Journals (Sweden)

    Hong Su

    Full Text Available Anchorage loss is very disturbing for orthodontists and patients during orthodontic treatment, which usually results in bad treatment effects. Despite the same treatment strategy, different patients show different tendencies toward anchorage loss, which influences the treatment results and should preferably be predicted before the treatment is begun. However, relatively little research has been conducted on which patients are more likely to lose anchorage. The mesial tipping of the first molar marks the onset of anchorage loss, and changes in the angulation of the first molar are closely related to anchorage loss. This cross-sectional study aimed to determine how the mesiodistal angulation of the upper first molars changes during general orthodontic treatment and to identify the individual physiologic factors leading to these changes in a large sample of 1403 patients with malocclusion. The data indicate that the upper first molars tend to be tipped mesially during orthodontic treatment, and this constitutes a type of anchorage loss that orthodontists should consider carefully. Compared to treatment-related factors, patients' physiologic characteristics have a greater influence on changes in the angulation of the upper first molars during orthodontic treatment. The more distally tipped the upper first molars are before treatment, the more they will tip mesially during treatment. Mesial tipping of the upper first molars, and therefore, anchorage loss, is more likely to occur in adolescents, males, patients with class II malocclusion and patients who have undergone maxillary premolar extraction. This finding is of clinical significance to orthodontists who wish to prevent iatrogenic anchorage loss by tipping originally distally tipped upper molars forward, and provides a new perspective on anchorage during orthodontic treatment planning.

  20. The perlecan-interacting growth factor progranulin regulates ubiquitination, sorting, and lysosomal degradation of sortilin.

    Science.gov (United States)

    Tanimoto, Ryuta; Palladino, Chiara; Xu, Shi-Qiong; Buraschi, Simone; Neill, Thomas; Gomella, Leonard G; Peiper, Stephen C; Belfiore, Antonino; Iozzo, Renato V; Morrione, Andrea

    2017-12-01

    Despite extensive clinical and experimental studies over the past decades, the pathogenesis and progression to the castration-resistant stage of prostate cancer remains largely unknown. Progranulin, a secreted growth factor, strongly binds the heparin-sulfate proteoglycan perlecan, and counteracts its biological activity. We established that progranulin acts as an autocrine growth factor and promotes prostate cancer cell motility, invasion, and anchorage-independent growth. Progranulin was overexpressed in prostate cancer tissues vis-à-vis non-neoplastic tissues supporting the hypothesis that progranulin may play a key role in prostate cancer progression. However, progranulin's mode of action is not well understood and proteins regulating progranulin signaling have not been identified. Sortilin, a single-pass type I transmembrane protein of the Vps10 family, binds progranulin in neurons and targets progranulin for lysosomal degradation. Significantly, in DU145 and PC3 cells, we detected very low levels of sortilin associated with high levels of progranulin production and enhanced motility. Restoring sortilin expression decreased progranulin levels, inhibited motility and anchorage-independent growth and destabilized Akt. These results demonstrated a critical role for sortilin in regulating progranulin and suggest that sortilin loss may contribute to prostate cancer progression. Here, we provide the novel observation that progranulin downregulated sortilin protein levels independent of transcription. Progranulin induced sortilin ubiquitination, internalization via clathrin-dependent endocytosis and sorting into early endosomes for lysosomal degradation. Collectively, these results constitute a regulatory feed-back mechanism whereby sortilin downregulation ensures sustained progranulin-mediated oncogenesis. Copyright © 2017. Published by Elsevier B.V.

  1. Research on Anchorage Performance of Grouting Anchor Connection of Precast Concrete Structure

    Science.gov (United States)

    Wang, Donghui; Liu, Xudong; Wang, Sheng; Cao, Xixi

    2018-03-01

    The bonding of grouted anchor bars is one of the vertical connection forms of steel bars in fabricated concrete structures. The performance of grouted connection is mainly affected by the anchorage length and lap length of steel bars. The mechanisms of bond and anchorage between steel bar and concrete are analyzed, and the factors that influence the anchorage performance of steel bar are systematically summarized. Results show that the bond and anchorage performance of steel and concrete have been studied widely, but there are still shortcomings, and the connection forms need to be further improved.

  2. Application and Curative Effect of Micro-implant Anchorage in ...

    African Journals Online (AJOL)

    research hot spot in the Department of. Stomatology. Instead of taking teeth as the basis, as was previously the case, this new anchorage exerts the counteracting force of orthodontics on the jaw, thus completely avoiding the displacement of teeth. It solves a lot of problems existing in clinical anchorage. Micro - implant.

  3. Flexural Strengthening of RC Slabs with Prestressed CFRP Strips Using Different Anchorage Systems

    Directory of Open Access Journals (Sweden)

    José Sena-Cruz

    2015-10-01

    Full Text Available Externally Bonded Reinforcement (EBR technique has been widely used for flexural strengthening of concrete structures by using carbon fiber-reinforced polymers (CFRP. EBR technique offers several structural advantages when the CFRP material is prestressed. This paper presents an experimental and numerical study on reinforced (RC slabs strengthened in flexure with prestressed CFRP strips as a structural strengthening system. The strips are applied as an externally bonded reinforcement (EBR and anchored with either a mechanical or a gradient anchorage. The former foresees metallic anchorage plates fixed to the concrete substrate, while the latter is based on an accelerated epoxy resin curing followed by a segment-wise prestress force decrease at the strip ends. Both anchorage systems, in combination with different CFRP strip geometries, were subjected to static loading tests. It could be demonstrated that the composite strip’s performance is better exploited when prestressing is used, with slightly higher overall load carrying capacities for mechanical anchorages than for the gradient anchorage. The performed investigations by means of a cross-section analysis supported the experimental observation that in case a mechanical anchorage is used, progressive strip debonding changes the fully bonded configuration to an unbonded end-anchored system. The inclusion of defined debonding criteria for both the anchorage zones and free length between the anchorage regions allowed to precisely capture the ultimate loading forces.

  4. Molecular and functional analysis of anchorage independent, treatment-evasive neuroblastoma tumorspheres with enhanced malignant properties: A possible explanation for radio-therapy resistance.

    Science.gov (United States)

    Abou-Antoun, Tamara J; Nazarian, Javad; Ghanem, Anthony; Vukmanovic, Stanislav; Sandler, Anthony D

    2018-01-01

    Despite significant advances in cancer treatment and management, more than 60% of patients with neuroblastoma present with very poor prognosis in the form of metastatic and aggressive disease. Solid tumors including neuroblastoma are thought to be heterogeneous with a sub-population of stem-like cells that are treatment-evasive with highly malignant characteristics. We previously identified a phenomenon of reversible adaptive plasticity (RAP) between anchorage dependent (AD) cells and anchorage independent (AI) tumorspheres in neuroblastoma cell cultures. To expand our molecular characterization of the AI tumorspheres, we sought to define the comprehensive proteomic profile of murine AD and AI neuroblastoma cells. The proteomic profiles of the two phenotypic cell populations were compared to each other to determine the differential protein expression and molecular pathways of interest. We report exclusive or significant up-regulation of tumorigenic pathways expressed by the AI tumorspheres compared to the AD cancer cells. These pathways govern metastatic potential, enhanced malignancy and epithelial to mesenchymal transition. Furthermore, radio-therapy induced significant up-regulation of specific tumorigenic and proliferative proteins, namely survivin, CDC2 and the enzyme Poly [ADP-ribose] polymerase 1. Bio-functional characteristics of the AI tumorspheres were resistant to sutent inhibition of receptor tyrosine kinases (RTKs) as well as to 2.5 Gy radio-therapy as assessed by cell survival, proliferation, apoptosis and migration. Interestingly, PDGF-BB stimulation of the PDGFRβ led to transactivation of EGFR and VEGFR in AI tumorspheres more potently than in AD cells. Sutent inhibition of PDGFRβ abrogated this transactivation in both cell types. In addition, 48 h sutent treatment significantly down-regulated the protein expression of PDGFRβ, MYCN, SOX2 and Survivin in the AI tumorspheres and inhibited tumorsphere self-renewal. Radio-sensitivity in AI

  5. Syk Tyrosine Kinase Acts as a Pancreatic Adenocarcinoma Tumor Suppressor by Regulating Cellular Growth and Invasion

    OpenAIRE

    Layton, Tracy; Stalens, Cristel; Gunderson, Felizza; Goodison, Steve; Silletti, Steve

    2009-01-01

    We have identified the nonreceptor tyrosine kinase syk as a marker of differentiation/tumor suppressor in pancreatic ductal adenocarcinoma (PDAC). Syk expression is lost in poorly differentiated PDAC cells in vitro and in situ, and stable reexpression of syk in endogenously syk-negative Panc1 (Panc1/syk) cells retarded their growth in vitro and in vivo and reduced anchorage-independent growth in vitro. Panc1/syk cells exhibited a more differentiated morphology and down-regulated cyclin D1, ak...

  6. 77 FR 60081 - Anchorages; Captain of the Port Puget Sound Zone, WA

    Science.gov (United States)

    2012-10-02

    ...'31'' W. Thorndike Bay Emergency Explosives Anchorage. Coordinates would be revised to read: All... 048[deg]T to point of origin. (6) Thorndike Bay Emergency Explosives Anchorage. All waters in a...

  7. 78 FR 59914 - Foreign-Trade Zone 160-Anchorage, Alaska; Application for Reorganization Under Alternative Site...

    Science.gov (United States)

    2013-09-30

    ...: Site 1 (56.89 acres)--the Port of Anchorage and Port of Anchorage Industrial Park, 1075 Dock Rd., 1076... acres)--619 East Ship Creek Ave., Anchorage; Site 6 (12.2 acres)-- Douglas Management Company, 660...

  8. Insulin-Like Growth Factor-Independent Effects of Growth Hormone on Growth Plate Chondrogenesis and Longitudinal Bone Growth.

    Science.gov (United States)

    Wu, Shufang; Yang, Wei; De Luca, Francesco

    2015-07-01

    GH stimulates growth plate chondrogenesis and longitudinal bone growth directly at the growth plate. However, it is not clear yet whether these effects are entirely mediated by the local expression and action of IGF-1 and IGF-2. To determine whether GH has any IGF-independent growth-promoting effects, we generated (TamCart)Igf1r(flox/flox) mice. The systemic injection of tamoxifen in these mice postnatally resulted in the excision of the IGF-1 receptor (Igf1r) gene exclusively in the growth plate. (TamCart)Igf1r(flox/flox) tamoxifen-treated mice [knockout (KO) mice] and their Igf1r(flox/flox) control littermates (C mice) were injected for 4 weeks with GH. At the end of the 4-week period, the tibial growth and growth plate height of GH-treated KO mice were greater than those of untreated C or untreated KO mice. The systemic injection of GH increased the phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 5B in the tibial growth plate of the C and KO mice. In addition, GH increased the mRNA expression of bone morphogenetic protein-2 and the mRNA expression and protein phosphorylation of nuclear factor-κB p65 in both C and KO mice. In cultured chondrocytes transfected with Igf1r small interfering RNA, the addition of GH in the culture medium significantly induced thymidine incorporation and collagen X mRNA expression. In conclusion, our findings demonstrate that GH can promote growth plate chondrogenesis and longitudinal bone growth directly at the growth plate, even when the local effects of IGF-1 and IGF-2 are prevented. Further studies are warranted to elucidate the intracellular molecular mechanisms mediating the IGF-independent, growth-promoting GH effects.

  9. Anchorage Behaviors of Frictional Tieback Anchors in Silty Sand

    Science.gov (United States)

    Hsu, Shih-Tsung; Hsiao, Wen-Ta; Chen, Ke-Ting; Hu, Wen-Chi; Wu, Ssu-Yi

    2017-06-01

    Soil anchors are extensively used in geotechnical applications, most commonly serve as tieback walls in deep excavations. To investigate the anchorage mechanisms of this tieback anchor, a constitutive model that considers both strain hardening and softening and volume dilatancy entitled SHASOVOD model, and FLAC3D software are used to perform 3-D numerical analyses. The results from field anchor tests are compared with those calculated by numerical analyses to enhance the applicability of the numerical method. After the calibration, this research carried out the parameter studies by numerical analyses. The numerical results reveal that whether the yield of soil around an anchor develops to ground surface and/or touches the diaphragm wall depending on the overburden depth H and the embedded depth Z of an anchor, this study suggests the minimum overburden and embedded depths to avoid the yield of soils develop to ground surface and/or touch the diaphragm wall. When the embedded depth, overburden depth or fixed length of an anchor increases, the anchorage capacity also increases. Increasing fixed length should be the optimum method to increase the anchorage capacity for fixed length less than 20m. However, when the fixed length of an anchor exceeds 30 m, the increasing rate of anchorage capacity per fixed length decreases, and progressive yield occurs obviously between the fixed length and surrounding soil.

  10. 76 FR 59596 - Anchorage Regulations; Newport, RI

    Science.gov (United States)

    2011-09-27

    ... up to three cruise ships simultaneously in anchorage ``D''. For the convenience and safety of... standards (e.g., specifications of materials, performance, design, or operation; test methods; sampling...

  11. 77 FR 6010 - Anchorage Regulations; Newport, RI

    Science.gov (United States)

    2012-02-07

    ... anchor up to three cruise ships simultaneously in anchorage ``D''. For the convenience and safety of..., design, or operation; test methods; sampling procedures; and related management systems practices) that...

  12. Inspection Mechanism and Experimental Study of Prestressed Reverse Tension Method under PC Beam Bridge Anchorage

    Science.gov (United States)

    Peng, Zhang

    2018-03-01

    the prestress under anchorage is directly related to the structural security and performance of PC beam bridge. The reverse tension method is a kind of inspection which confirms the prestress by exerting reversed tension load on the exposed prestressing tendon of beam bridge anchoring system. The thesis elaborately expounds the inspection mechanism and mechanical effect of reverse tension method, theoretically analyzes the influential elements of inspection like tool anchorage deformation, compression of conjuncture, device glide, friction of anchorage loop mouth and elastic compression of concrete, and then presents the following formula to calculate prestress under anchorage. On the basis of model experiment, the thesis systematically studies some key issues during the reverse tension process of PC beam bridge anchorage system like the formation of stress-elongation curve, influential factors, judgment method of prestress under anchorage, variation trend and compensation scale, verifies the accuracy of mechanism analysis and demonstrates: the prestress under anchorage is less than or equal to 75% of the ultimate strength of prestressing tendon, the error of inspect result is less than 1%, which can meet with the demands of construction. The research result has provided theoretical basis and technical foundation for the promotion and application of reverse tension in bridge construction.

  13. Quantification of temperature effect on impedance monitoring via PZT interface for prestressed tendon anchorage

    Science.gov (United States)

    Huynh, Thanh-Canh; Kim, Jeong-Tae

    2017-12-01

    In this study, the quantification of temperature effect on impedance monitoring via a PZT interface for prestressed tendon-anchorage is presented. Firstly, a PZT interface-based impedance monitoring technique is selected to monitor impedance signatures by predetermining sensitive frequency bands. An analytical model is designed to represent coupled dynamic responses of the PZT interface-tendon anchorage system. Secondly, experiments on a lab-scaled tendon anchorage are described. Impedance signatures are measured via the PZT interface for a series of temperature and prestress-force changes. Thirdly, temperature effects on measured impedance responses of the tendon anchorage are estimated by quantifying relative changes in impedance features (such as RMSD and CCD indices) induced by temperature variation and prestress-force change. Finally, finite element analyses are conducted to investigate the mechanism of temperature variation and prestress-loss effects on the impedance responses of prestressed tendon anchorage. Temperature effects on impedance monitoring are filtered by effective frequency shift-based algorithm for distinguishing prestress-loss effects on impedance signatures.

  14. 76 FR 15246 - Anchorage Regulations; Narragansett Bay and Rhode Island Sound, RI

    Science.gov (United States)

    2011-03-21

    ...-AA01 Anchorage Regulations; Narragansett Bay and Rhode Island Sound, RI AGENCY: Coast Guard, DHS... Rhode Island Sound south of Brenton Point, Rhode Island, for use by vessels waiting to enter... Sound that under current informal practice is routinely used by mariners as an anchorage while waiting...

  15. The anchorage capacity of reinforcing bars at normal and high temperatures

    DEFF Research Database (Denmark)

    Hertz, Kristian Dahl

    1982-01-01

    of the cross-section. A simple method for calculating the resistance to splitting is proposed, and a test method for determining the bond strength is presented. Test results are shown from a series of 280 specimens exposed to various maximum temperatures, and a relation between the bond strength......The anchorage failure of reinforcing bars is analysed, and it is shown that two modes of failures are possible: splitting or bond failure. It is concluded that the anchorage capacity cannot be estimated by means of a standard specimen, since splitting failure is dependent upon the geometry...... and the ultimate limit stress of concrete under plane strain conditions is indicated. The influence of high temperatures upon the anchorage resistance is explained, and the theory is illustrated by examples....

  16. Improved anchorage of steel linings at WWER nuclear power plants

    International Nuclear Information System (INIS)

    Bouda, M.; Cepicky, J.

    1987-01-01

    Three variants were tested of anchoring the steel lining of special structures of nuclear power plants with WWER reactors, such as the containment, viz.: point anchorage with pins according to a Czechoslovak design, and two methods of linear anchorage according to a Soviet design and a design by the Institute for Industrial Construction of the GDR. Graphically shown are some results of the tests of the point anchorage with pins that showed the reliability of the method with respect to deformation and strain of the lining and of the anchoring elements at a lining temperature of up to 300 degC, which significantly exceeded the design-basis accident temperature of 150 degC. The advantages of the variant include a lower content of labour and an increased quality of welding jobs thanks to the application of the Nelson semi-automatic welding technique. (Z.M.). 10 figs., 7 refs

  17. Modification of evaluation response spectrum by ductility of equipment anchorage

    International Nuclear Information System (INIS)

    Choi, I. G.; Jun, Y. S.; Su, J. M.

    2003-01-01

    The failure mode of welded anchorage is assumed as brittle in the seismic capacity evaluation of nuclear power plant equipments. But the welded anchorage has some ductile capacity. This limited displacement capacity can cause the reduction of the effective frequency of high frequency equipments and the increase of the inelastic energy absorption capacity due to the nonlinear behavior. In this study, the uniform hazard spectrum for Korean nuclear power plant site was modified using the response spectrum reduction factor developed by EPRI. The spectral acceleration for various damping ratio was determined by the theoretical method based on the random vibration theory. In conclusion, the high frequency components of evaluation response spectra were greatly reduced due to the consideration of welded anchorage ductility. This reduced response spectra can be used for the development of in-structure response spectra used in the seismic capacity evaluation of high frequency equipments

  18. Peroxisome Proliferator-Activated Receptor-γ Inhibits Transformed Growth of Non-Small Cell Lung Cancer Cells through Selective Suppression of Snail

    Directory of Open Access Journals (Sweden)

    Rashmi Choudhary

    2010-03-01

    Full Text Available Work from our laboratory and others has demonstrated that activation of the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ inhibits transformed growth of non-small cell lung cancer (NSCLC cell lines in vitro and in vivo. We have demonstrated that activation of PPARγ promotes epithelial differentiation of NSCLC by increasing expression of E-cadherin, as well as inhibiting expression of COX-2 and nuclear factor-κB. The Snail family of transcription factors, which includes Snail (Snail1, Slug (Snail2, and ZEB1, is an important regulator of epithelial-mesenchymal transition, as well as cell survival. The goal of this study was to determine whether the biological responses to rosiglitazone, a member of the thiazolidinedione family of PPARγ activators, are mediated through the regulation of Snail family members. Our results indicate that, in two independent NSCLC cell lines, rosiglitazone specifically decreased expression of Snail, with no significant effect on either Slug or ZEB1. Suppression of Snail using short hairpin RNA silencing mimicked the effects of PPARγ activation, in inhibiting anchorage-independent growth, promoting acinar formation in three-dimensional culture, and inhibiting invasiveness. This was associated with the increased expression of E-cadherin and decreased expression of COX-2 and matrix metaloproteinases. Conversely, overexpression of Snail blocked the biological responses to rosiglitazone, increasing anchorage-independent growth, invasiveness, and promoting epithelial-mesenchymal transition. The suppression of Snail expression by rosiglitazone seemed to be independent of GSK-3 signaling but was rather mediated through suppression of extracellular signal-regulated kinase activity. These findings suggest that selective regulation of Snail may be critical in mediating the antitumorigenic effects of PPARγ activators.

  19. Implants for orthodontic anchorage

    Science.gov (United States)

    Zheng, Xiaowen; Sun, Yannan; Zhang, Yimei; Cai, Ting; Sun, Feng; Lin, Jiuxiang

    2018-01-01

    Abstract Implantanchorage continues to receive much attention as an important orthodontic anchorage. Since the development of orthodontic implants, the scope of applications has continued to increase. Although multiple reviews detailing implants have been published, no comprehensive evaluations have been performed. Thus, the purpose of this study was to comprehensively evaluate the effects of implants based on data published in review articles. An electronic search of the Cochrane Library, Medline, Embase, Ebsco and Sicencedirect for reviews with “orthodontic” and “systematic review or meta analysis” in the title, abstract, keywords, or full text was performed. A subsequent manual search was then performed to identify reviews concerning orthodontic implants. A manual search of the orthodontic journals American Journal of Orthodontics and Dentofacial Orthopedics (AJODO), European Journal of Orthodontics (EJO), and Angle Othodontist was also performed. Such systematic reviews that evaluated the efficacy and safety of orthodontic implants were used to indicate success rates and molar movements. A total of 23 reviews were included in the analysis. The quality of each review was assessed using a measurement tool for Assessment of Multiple Systematic Reviews (AMSTAR), and the review chosen to summarize outcomes had a quality score of >6. Most reviews were less than moderate quality. Success rates of implants ranged in a broad scope, and movement of the maxillary first molar was superior with implants compared with traditional anchorage. PMID:29595673

  20. Calculation of absorbed dose of anchorage-dependent cells from internal beta-rays irradiation

    International Nuclear Information System (INIS)

    Chen Jianwei; Huang Gang; Li Shijun

    2001-01-01

    Objective: To elicit the formula of internal dosimetry in anchorage-dependent cells by beta-emitting radionuclides from uniformly distributed volume sources. Methods: By means of the definition of absorbed dose and the MIRD (Medical International Radiation Dose) scheme the formula of internal dosimetry was reasonably deduced. Firstly, studying the systems of suspension culture cells. Then, taking account of the speciality of the systems of the anchorage-dependent cells and the directions of irradiation, the absorbed dose of anchorage -dependent cells was calculated by the accumulated radioactivity, beta-ray energy, and the volume of the cultured systems. Results: The formula of internal dosimetry of suspension culture cells and anchorage-dependent cells were achieved. At the same time, the formula of internal dosimetry of suspension culture cells was compared with that of MIRD and was confirmed accurate. Conclusion: The formula of internal dosimetry is concise, reliable and accurate

  1. Water quality and bathymetry of Sand Lake, Anchorage, Alaska

    Science.gov (United States)

    Donaldson, Donald E.

    1976-01-01

    Sand Lake, a dimictic lowland lake in Anchorage, Alaska, has recently become as urban lake. Analyses indicate that the lake is oligotrophic, having low dissolved solids and nutrient concentrations. Snowmelt runoff from an adjacent residential area, however, has a dissolved-solids concentration 10 times that of the main body of Sand Lake. Lead concentrations in the runoff exceed known values from other water in the ANchorage area, including water samples taken beneath landfills. The volume of the snowmelt runoff has not been measured. The data presented can be used as a baseline for water-resource management. (Woodard-USGS)

  2. Guidelines for evaluation of anchorage adequacy for safety-related equipment typically used on WWER-type NPPs

    International Nuclear Information System (INIS)

    Masopust, R.

    1999-01-01

    This report describes the criteria which should be met when the capacity evaluation of anchorage of safety related equipment is performed for the WWER type NPPs. It should be noted that these criteria were developed specifically for anchorage of WWER type equipment and components to the concrete or steel building structures and they cover different types of anchor bolts and other anchorage details which are typical just for the existing, constructed or reconstructed WWER type NPPs. The screening approach for verifying of equipment anchorage presented in this report is based on a combination of inspections, calculations, and engineering judgement

  3. Feasibility Verification of Mountable PZT-Interface for Impedance Monitoring in Tendon-Anchorage

    Directory of Open Access Journals (Sweden)

    Thanh-Canh Huynh

    2015-01-01

    Full Text Available This study has been motivated to numerically evaluate the performance of the mountable PZT-interface for impedance monitoring in tendon-anchorage. Firstly, electromechanical impedance monitoring and feature classification methods are outlined. Secondly, a structural model of tendon-anchorage subsystem with mountable PZT-interface is designed for impedance monitoring. Finally, the feasibility of the mountable PZT-interface is numerically examined. A finite element (FE model is designed for the lab-scaled tendon-anchorage. The FE model of the PZT-interface is tuned as its impedance signatures meet the experimental test results at the same frequency ranges and also with identical patterns. Equivalent model properties of the FE model corresponding to prestress forces inflicted on the lab-tested structure are identified from the fine-tuning practice.

  4. Downregulation of Akt1 Inhibits Anchorage-Independent Cell Growth and Induces Apoptosis in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xuesong Liu

    2001-01-01

    Full Text Available The serine/threonine kinases, Akti/PKBα, Akt2/PKBβ, and Akt3/PKBγ, play a critical role in preventing cancer cells from undergoing apoptosis. However, the function of individual Akt isoforms in the tumorigenicity of cancer cells is still not well defined. In the current study, we used an AM antisense oligonucleotide (AS to specifically downregulate Akti protein in both cancer and normal cells. Our data indicate that AM AS treatment inhibits the ability of MiaPaCa-2, H460, HCT-15, and HT1080 cells to grow in soft agar. The treatment also induces apoptosis in these cancer cells as demonstrated by FRCS analysis and a caspase activity assay. Conversely, Akti AS treatment has little effect on the cell growth and survival of normal human cells including normal human fibroblast (NHF, fibroblast from muscle (FBM, and mammary gland epithelial 184135 cells. In addition, AM AS specifically sensitizes cancer cells to typical chemotherapeutic agents. Thus, Akti is indispensable for maintaining the tumorigenicity of cancer cells. Inhibition of AM may provide a powerful sensitization agent for chemotherapy specifically in cancer cells.

  5. 33 CFR 166.200 - Shipping safety fairways and anchorage areas, Gulf of Mexico.

    Science.gov (United States)

    2010-07-01

    ... anchorage areas, Gulf of Mexico. 166.200 Section 166.200 Navigation and Navigable Waters COAST GUARD... the erection of structures therein to provide safe approaches through oil fields in the Gulf of Mexico... for Fairway Anchorages in the Gulf of Mexico. Structures may be placed within an area designated as a...

  6. Immunolocalization of transforming growth factor alpha in normal human tissues

    DEFF Research Database (Denmark)

    Christensen, M E; Poulsen, Steen Seier

    1996-01-01

    anchorage-independent growth of normal cells and was, therefore, considered as an "oncogenic" growth factor. Later, its immunohistochemical presence in normal human cells as well as its biological effects in normal human tissues have been demonstrated. The aim of the present investigation was to elucidate...... the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF......-alpha was found to be widely distributed in cells of normal human tissues derived from all three germ layers, most often in differentiated cells. In epithelial cells, three different kinds of staining patterns were observed, either diffuse cytoplasmic, cytoplasmic in the basal parts of the cells, or distinctly...

  7. Transcriptional and post-transcriptional upregulation of p27 mediates growth inhibition of isorhapontigenin (ISO) on human bladder cancer cells.

    Science.gov (United States)

    Jiang, Guosong; Huang, Chao; Li, Jingxia; Huang, Haishan; Wang, Jingjing; Li, Yawei; Xie, Fei; Jin, Honglei; Zhu, Junlan; Huang, Chuanshu

    2018-03-08

    There are few approved drugs available for the treatment of muscle-invasive bladder cancer (MIBC). Recently, we have demonstrated that isorhapontigenin (ISO), a new derivative isolated from the Chinese herb Gnetum cleistostachyum, effectively induces cell-cycle arrest at the G0/G1 phase and inhibits anchorage-independent cell growth through the miR-137/Sp1/cyclin D1 axis in human MIBC cells. Herein, we found that treatment of bladder cancer (BC) cells with ISO resulted in a significant upregulation of p27, which was also observed in ISO-treated mouse BCs that were induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Importantly, knockdown of p27 caused a decline in the ISO-induced G0-G1 growth arrest and reversed ISO suppression of anchorage-independent growth in BC cells. Mechanistic studies revealed that ISO promoted p27 expression at mRNA transcription level through increasing direct binding of forkhead box class O1 (FOXO1) to its promoter, while knockdown of FOXO1 attenuated ISO inhibition of BC cell growth. On the other hand, ISO upregulated the 3'-untranslated region (3'-UTR) activity of p27, which was accompanied by a reduction of miR-182 expression. In line with these observations, ectopic expression of miR-182 significantly blocked p27 3'-UTR activity, whereas mutation of the miR-182-binding site at p27 mRNA 3'-UTR effectively reversed this inhibition. Accordingly, ectopic expression of miR-182 also attenuated ISO upregulation of p27 expression and impaired ISO inhibition of BC cell growth. Our results not only provide novel insight into understanding of the underlying mechanism related to regulation of MIBC cell growth but also identify new roles and mechanisms underlying ISO inhibition of BC cell growth.

  8. Numerical Simulation and Experimental Validation of an Integrated Sleeve-Wedge Anchorage for CFRP Rods

    DEFF Research Database (Denmark)

    Schmidt, Jacob Wittrup; Smith, Scott T.; Täljsten, Björn

    2011-01-01

    . Recently, an integrated sleeve-wedge anchorage has been successfully developed specifically for CFRP rods. This paper in turn presents a numerical simulation of the newly developed anchorage using ABAQUS. The three-dimensional finite element (FE) model, which considers material non-linearity, uses...

  9. Image guided placement of temporary anchorage devices for tooth movement

    Energy Technology Data Exchange (ETDEWEB)

    Bahl-Palomo, L.; Bissada, N. [Case Western Reserve Univ. School of Dental Medicine, Dept. of Periodontics, Cleveland, OH (United States); Palomo, J.M.; Hans, M.G. [Case Western Reserve Univ. School of Dental Medicine, Dept. of Orthodontics, Cleveland, OH (United States)

    2007-06-15

    The aim of this project is to develop an image guided protocol for placement of a temporary anchorage device without surgically reflecting a mucoperiosteal flap. Eighteen orthodontic cases were selected for skeletal anchorage from the department of orthodontics at Case University. CBCT images of the subjects were taken using the Hitachi CB MercuRay system set at 15 mA, 120 kVp. CBCT images evaluated the ideal location for TAD placement in three dimensions. Horizontal and vertical linear measurements were taken from fixed dental landmarks to clearly define the location for placement. Transverse slices were used to evaluate the thickness of the buccal plate. Using the transverse view, the angle of insertion was determined such that the maximum buccal plate surface area would contact the screw. TADs were placed in the optimum location, with the most appropriate angle of insertion using a closed approach and with minimal local anesthesia and without flap elevation. Results: All TADs were placed without anatomic encroachment and enabled fixed orthodontic anchorage. (orig.)

  10. Image guided placement of temporary anchorage devices for tooth movement

    International Nuclear Information System (INIS)

    Bahl-Palomo, L.; Bissada, N.; Palomo, J.M.; Hans, M.G.

    2007-01-01

    The aim of this project is to develop an image guided protocol for placement of a temporary anchorage device without surgically reflecting a mucoperiosteal flap. Eighteen orthodontic cases were selected for skeletal anchorage from the department of orthodontics at Case University. CBCT images of the subjects were taken using the Hitachi CB MercuRay system set at 15 mA, 120 kVp. CBCT images evaluated the ideal location for TAD placement in three dimensions. Horizontal and vertical linear measurements were taken from fixed dental landmarks to clearly define the location for placement. Transverse slices were used to evaluate the thickness of the buccal plate. Using the transverse view, the angle of insertion was determined such that the maximum buccal plate surface area would contact the screw. TADs were placed in the optimum location, with the most appropriate angle of insertion using a closed approach and with minimal local anesthesia and without flap elevation. Results: All TADs were placed without anatomic encroachment and enabled fixed orthodontic anchorage. (orig.)

  11. The significance of fibroblast growth factors 8, 17, and 18 and the fibroblast growth factor receptor 4 for malignant behaviour of hepatocarcinoma cells

    International Nuclear Information System (INIS)

    Gauglhofer, C. L.

    2010-01-01

    at high levels in human hepatocytes, was found to be further upregulated in a subset of human HCC cases. Characterization of the FGFR4 genotype in healthy individuals and in patients suffering from premalignant liver disease or HCC showed that the presence of a SNP in codon 388 of FGFR4 (G388R polymorphism) predisposes for the development of liver malignancy. For mechanistic investigation either the wildtype or mutated form of FGFR4 was overexpressed in hepatocarcinoma cell lines. Wildtype FGFR4 had only minor effects on the growth of the cell lines but strongly enhanced anchorage-independent growth of cells and induced tumorigenicity in a non-tumorigenic cell line. Overexpression of the mutated receptor form had an even more pronounced effect on anchorage-independent growth, but did not affect tumorigenicity. Knockdown of endogenous FGFR4 expression by siRNA led to reduced clone formation capacity of hepatocarcinoma cell lines. Cells were also adenovirally infected with dominant-negative FGFR4 constructs being either kinase-dead or encoding for the soluble extracellular domain of FGFR4, which binds and neutralizes FGFR4-ligands. This led to reduced cell viability and anchorage-independent growth in vitro and lowered tumor formation in SCID mice. To conclude, FGFR4 contributes to the malignant behaviour of hepatocarcinoma cells and its effects may be aggravated by the G388R polymorphism. Therefore, downregulation of FGFR4 appears to be a promising approach for HCC therapy. (author) [de

  12. Thick-Walled Cylinder Theory Applied on a Conical Wedge Anchorage

    DEFF Research Database (Denmark)

    Bennitz, Anders; Grip, Niklas; Schmidt, Jacob Wittrup

    2011-01-01

    for further development of the anchorage.In this paper, we derive and examine an analytical model for the internal stresses and strains within the anchorage for a prescribed presetting distance. This model is derived from the theory of thick walled cylinders under the assumptions regarding plane stress...... and axial symmetry. We simplify the resulting system of ten nonlinear equations and derive a method for solving them numerically. A comparison of plotted results for three different angles on the wedge’s outer surface and six different presetting distances follows.These results are also compared to both axi...

  13. Inhibition of Curcumin on ZAKα Activity Resultant in Apoptosis and Anchorage-Independent Growth in Cancer Cells.

    Science.gov (United States)

    Lee, Jin-Sun; Wang, Tsu-Shing; Lin, Ming Cheng; Lin, Wei-Wen; Yang, Jaw-Ji

    2017-10-31

    Curcumin, a popular yellow pigment of the dietary spice turmeric, has been reported to inhibit cell growth and to induce apoptosis in a wide variety of cancer cells. Although numerous studies have investigated anticancer effects of curcumin, the precise molecular mechanism of action remains unidentified. Whereas curcumin mediates cell survival and apoptosis through mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling cascades, its impact on the upstream regulation of MAPK is unclear. The leucine-zipper and sterile-α motif kinase alpha (ZAKα), a mitogen-activated protein kinase kinase kinase (MAP3K), activates the c-Jun N-terminal kinase (JNK) and NF-κB pathway. This paper investigated the prospective involvement of ZAKα in curcumin-induced effects on cancer cells. Our results suggest that the antitumor activity of curcumin is mediated via a mechanism involving inhibition of ZAKα activity.

  14. Model-independent cosmological constraints from growth and expansion

    Science.gov (United States)

    L'Huillier, Benjamin; Shafieloo, Arman; Kim, Hyungjin

    2018-05-01

    Reconstructing the expansion history of the Universe from Type Ia supernovae data, we fit the growth rate measurements and put model-independent constraints on some key cosmological parameters, namely, Ωm, γ, and σ8. The constraints are consistent with those from the concordance model within the framework of general relativity, but the current quality of the data is not sufficient to rule out modified gravity models. Adding the condition that dark energy density should be positive at all redshifts, independently of its equation of state, further constrains the parameters and interestingly supports the concordance model.

  15. Orthodontic treatment with skeletal anchorage system

    Directory of Open Access Journals (Sweden)

    Arya Brahmanta

    2011-06-01

    Full Text Available Background: Correction of class I malocclusion with bimaxillary dental protrusion and unilateral free end right upper ridge in adult patient is one of difficult biomechanical case in orthodontics. Due to this case that needs proper anchorage for upper incisor retraction with missing teeth in the right posterior segment. Purpose: The aim of this study to find an effective therapy for correction of bimaxillary protrusion with unilateral free and ridge. Case: A female patient, 36 year old complaining for the difficulty of lip closure due to severe bimaxillary protrusion with incompetence lip. Case management: Firstly correction of the maxillary and mandibular incisor proclination were done by extraction of the mandibular first premolar, the maxillary second premolar on left side and finally placement of miniplates implant in the zygomatic process on right side as an absolut anchorage. Conclusion: Skeletal anchorage system (SAS can be considered as an effective therapy for corection of bimaxillary protrusion with unilateral free end ridge.Latar belakang: Koreksi dari maloklusi klas I dari penderita dewasa yang disertai protrusi bimaksiler dengan kehilangan gigi posterior pada regio kanan atas merupakan salah satu kasus sulit untuk dikerjakan terutama berhubungan dengan biomekanik pergerakan giginya dalam perawatan ortodonti. Tujuan: Tujuan dari penulisan artikel ini adalah untuk menemukan terapi yang efektif untuk perbaikan protrusi bimaksiler dan kehilangan gigi posterior pada satu sisi. Kasus: Seorang penderita wanita usia 35 tahun datang dengan keluhan utama kesulitan untuk menutup mulut oleh karena gigi rahang atas dan rahang bawahnya maju dan bibirnya tidak kompeten. Tatalaksana kasus: Koreksi pada gigi insisivus rahang atas dan insisivus rahang bawah yang protrusi dilakukan dengan melakukan pencabutan terlebih dahulu pada gigi premolar pertama dirahang bawah sisi kanan dan sisi kiri serta pencabutan pada gigi premolar kedua di rahang atas sisi

  16. 33 CFR 162.136 - Connecting waters from Lake Huron to Lake Erie; anchorage grounds.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Connecting waters from Lake Huron to Lake Erie; anchorage grounds. 162.136 Section 162.136 Navigation and Navigable Waters COAST GUARD... REGULATIONS § 162.136 Connecting waters from Lake Huron to Lake Erie; anchorage grounds. (a) In the Detroit...

  17. Behaviour of Prestressed CFRP Anchorages during and after Freeze-Thaw Cycle Exposure

    Directory of Open Access Journals (Sweden)

    Yunus Emre Harmanci

    2018-05-01

    Full Text Available The long-term performance of externally-bonded reinforcements (EBR on reinforced concrete (RC structures highly depends on the behavior of constituent materials and their interfaces to various environmental loads, such as temperature and humidity exposure. Although significant efforts have been devoted to understanding the effect of such conditions on the anchorage resistance of unstressed EBR, with or without sustained loading, the effect of a released prestressing has not been thoroughly investigated. For this purpose, a series of experiments has been carried out herein, with concrete blocks strengthened with carbon fiber-reinforced polymer (CFRP strips, both unstressed, as well as prestressed using the gradient anchorage. The gradient anchorage is a non-mechanical technique to anchor prestressed CFRP by exploiting the accelerated curing property of epoxy under higher temperatures and segment-wise prestress-force releasing. Subsequently, strengthened blocks are transferred into a chamber for exposure in dry freeze-thaw cycles (FTC. Following FTC exposure, the blocks are tested in a conventional lap-shear test setup to determine their residual anchorage resistance and then compared with reference specimens. Blocks were monitored during FTC by conventional and Fabry–Pérot-based fiber optic strain (FOS sensors and a 3D-digital image correlation (3D-DIC system during gradient application and lap-shear testing. Results indicate a reduction of residual anchorage resistance, stiffness and deformation capacity of the system after FTC and a change in the failure mode from concrete substrate to epoxy-concrete interface failure. It was further observed that all of these properties experienced a more significant reduction for prestressed specimens. These findings are presented with a complementary finite element model to shed more light onto the durability of such systems.

  18. Expression of a hyperactive androgen receptor leads to androgen-independent growth of prostate cancer cells.

    Science.gov (United States)

    Hsieh, Chen-Lin; Cai, Changmeng; Giwa, Ahmed; Bivins, Aaronica; Chen, Shao-Yong; Sabry, Dina; Govardhan, Kumara; Shemshedini, Lirim

    2008-07-01

    Cellular changes that affect the androgen receptor (AR) can cause prostate cancer to transition from androgen dependent to androgen independent, which is usually lethal. One common change in prostate tumors is overexpression of the AR, which has been shown to lead to androgen-independent growth of prostate cancer cells. This led us to hypothesize that expression of a hyperactive AR would be sufficient for androgen-independent growth of prostate cancer cells. To test this hypothesis, stable lune cancer prostate (LNCaP) cell lines were generated, which express a virion phosphoprotein (VP)16-AR hybrid protein that contains full-length AR fused to the strong viral transcriptional activation domain VP16. This fusion protein elicited as much as a 20-fold stronger transcriptional activity than the natural AR. Stable expression of VP16-AR in LNCaP cells yielded androgen-independent cell proliferation, while under the same growth conditions the parental LNCaP cells exhibited only androgen-dependent growth. These results show that expression of a hyperactive AR is sufficient for androgen-independent growth of prostate cancer cells. To study the molecular basis of this enhanced growth, we measured the expression of soluble guanylyl cyclase-alpha1 (sGCalpha1), a subunit of the sGC, an androgen-regulated gene that has been shown to be involved in prostate cancer cell growth. Interestingly, the expression of sGCalpha1 is androgen independent in VP16-AR-expressing cells, in contrast to its androgen-induced expression in control LNCaP cells. RNA(I)-dependent inhibition of sGCalpha1 expression resulted in significantly reduced proliferation of VP16-AR cells, implicating an important role for sGCalpha1 in the androgen-independent growth of these cells.

  19. ROCK1 and ROCK2 are Required for Non-Small Cell Lung Cancer Anchorage-Independent Growth and Invasion

    OpenAIRE

    Vigil, Dominico; Kim, Tai Young; Plachco, Ana; Garton, Andrew J.; Castaldo, Linda; Pachter, Jonathan A.; Dong, Hanqing; Chen, Xin; Tokar, Brianna; Campbell, Sharon L.; Der, Channing J.

    2012-01-01

    Evidence is emerging that the closely related ROCK1 and ROCK2 serine/threonine kinases support the invasive and metastatic growth of a spectrum of human cancer types. Therefore, inhibitors of ROCK are under preclinical development. However, a key step in their development involves the identification of genetic biomarkers that will predict ROCK inhibitor anti-tumor activity. One identified mechanism for ROCK activation in cancer involves the loss of function of the DLC1 tumor suppressor gene, ...

  20. Ground Water in the Anchorage Area, Alaska--Meeting the Challenges of Ground-Water Sustainability

    Science.gov (United States)

    Moran, Edward H.; Galloway, Devin L.

    2006-01-01

    Ground water is an important component of Anchorage's water supply. During the 1970s and early 80s when ground water extracted from aquifers near Ship Creek was the principal source of supply, area-wide declines in ground-water levels resulted in near record low streamflows in Ship Creek. Since the importation of Eklutna Lake water in the late 1980s, ground-water use has been reduced and ground water has contributed 14-30 percent of the annual supply. As Anchorage grows, given the current constraints on the Eklutna Lake water availability, the increasing demand for water could place an increasing reliance on local ground-water resources. The sustainability of Anchorage's ground-water resources challenges stakeholders to develop a comprehensive water-resources management strategy.

  1. Maxillary incisors changes during space closure with conventional and skeletal anchorage methods: a systematic review.

    Science.gov (United States)

    Jayaratne, Yasas Shri Nalaka; Uribe, Flavio; Janakiraman, Nandakumar

    2017-01-01

    The objective of this systematic review was to compare the antero-posterior, vertical and angular changes of maxillary incisors with conventional anchorage control techniques and mini-implant based space closure methods. The electronic databases Pubmed, Scopus, ISI Web of knowledge, Cochrane Library and Open Grey were searched for potentially eligible studies using a set of predetermined keywords. Full texts meeting the inclusion criteria as well as their references were manually searched. The primary outcome data (linear, angular, and vertical maxillary incisor changes) and secondary outcome data (overbite changes, soft tissue changes, biomechanical factors, root resorption and treatment duration) were extracted from the selected articles and entered into spreadsheets based on the type of anchorage used. The methodological quality of each study was assessed. Six studies met the inclusion criteria. The amount of incisor retraction was greater with buccally placed mini-implants than conventional anchorage techniques. The incisor retraction with indirect anchorage from palatal mini-implants was less when compared with buccally placed mini-implants. Incisor intrusion occurred with buccal mini-implants, whereas extrusion was seen with conventional anchorage. Limited data on the biomechanical variables or adverse effects such as root resorption were reported in these studies. More RCT's that take in to account relevant biomechanical variables and employ three-dimensional quantification of tooth movements are required to provide information on incisor changes during space closure.

  2. Use of miniplates as a method for orthodontic anchorage: a case report.

    Science.gov (United States)

    Peres, Fernando Gianzanti; Padovan, Luis Eduardo Marques; Kluppel, Leandro Eduardo; Albuquerque, Gustavo Calvalcanti; Souza, Paulo Cesar Ulson de; Claudino, Marcela

    2016-01-01

    Temporary anchorage devices (TADs) have been developed to be used as direct adjuncts in orthodontic treatment and have facilitated treatment of more complex orthodontic cases, including patients with dental impaction. This clinical case reports the applicability of TADs in the orthodontic treatment of a patient with impacted mandibular second molars. Surgical and orthodontic procedures related to the use of miniplates were also discussed in this study. The use of temporary anchorage devices, such as miniplates, can be suggested as an alternative to treat patients with impacted mandibular second molars.

  3. Electromechanical impedance-based health diagnosis for tendon and anchorage zone in a nuclear containment structure

    Science.gov (United States)

    Min, Jiyoung; Shim, Hyojin; Yun, Chung-Bang

    2012-04-01

    For a nuclear containment structure, the structural health monitoring is essential because of its high potential risk and grave social impact. In particular, the tendon and anchorage zone are to be monitored because they are under high tensile or compressive stress. In this paper, a method to monitor the tendon force and the condition of the anchorage zone is presented by using the impedance-based health diagnosis system. First, numerical simulations were conducted for cases with various loose tensile forces on the tendon as well as damages on the bearing plate and concrete structure. Then, experimental studies were carried out on a scaled model of the anchorage system. The relationship between the loose tensile force and the impedance-based damage index was analyzed by a regression analysis. When a structure gets damaged, the damage index increases so that the status of damage can be identified. The results of the numerical and experimental studies indicate a big potential of the proposed impedance-based method for monitoring the tendon and anchorage system.

  4. 75 FR 3641 - Television Broadcasting Services; Anchorage, AK

    Science.gov (United States)

    2010-01-22

    ... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 [DA 10-40; MB Docket No. 09-210; RM-11583] Television Broadcasting Services; Anchorage, AK AGENCY: Federal Communications Commission. ACTION: Final rule... review Act, see 5 U.S.C. 801(a)(1)(A). List of Subjects in 47 CFR Part 73 Television, Television...

  5. Comparative evaluation of sagittal anchorage loss in lingual and labial appliances during space closure: A pilot study

    Directory of Open Access Journals (Sweden)

    Shivanand Venkatesh

    2015-01-01

    Full Text Available Aim: The purpose of this investigation was to assess and compare the anchorage loss between labial and lingual appliance systems during space closure. Materials and Methods: Twenty subjects were part of the study among which 10 subjects (mean age 21 ± 3.6 years were treated using lingual appliance system (0.018" slot-STb™ and 10 subjects (mean age 19 ± 6.1 years were treated using labial preadjusted edgewise appliance system (0.018" slot-MBT™ . First premolar extractions were performed to enable retraction of anterior teeth. Lateral cephalometric radiographs were taken at two intervals, before starting space closure and after space closure that were connoted as T0 and T1 and were analyzed using the method described by Pancherz to measure anchorage loss. Intraclass correlation coefficient (ICC was used to evaluate intraexaminer reliability of the measurements. Student′s t-test was performed to verify any statistical significant correlation between the labial and lingual appliance systems. Statistical differences were determined at the 95% confidence level (P < 0.05. Results: The results showed that all ICC for lingual and labial group were ≥0.90 showing good repeatability of the measurements. Mean anchorage loss of 1.238 ± 0.17 mm in lingual appliance system and an anchorage loss of 2.06 ± 0.39 mm occurred with the labial appliance system. On the comparison between the two appliance systems, lingual appliance demonstrated a significantly lesser anchorage loss than did the labial appliance. Interpretation and Conclusion: This prospective study concludes with the fact that lingual appliance provided better anchorage control than labial appliance during space closure. Use of lingual appliance could be considered in critical anchorage cases when compared with labial appliance.

  6. MAXILLARY INCISORS CHANGES DURING SPACE CLOSURE WITH CONVENTIONAL AND SKELETAL ANCHORAGE METHODS: A SYSTEMATIC REVIEW

    Directory of Open Access Journals (Sweden)

    Yasas Shri Nalaka JAYARATNE

    2017-12-01

    Full Text Available Purpose: The objective of this systematic review was to compare the antero-posterior, vertical and angular changes of maxillary incisors with conventional anchorage control techniques and mini-implant based space closure methods. Materials and Methods: The electronic databases Pubmed, Scopus, ISI Web of knowledge, Cochrane Library and Open Grey were searched for potentially eligible studies using a set of predetermined keywords. Full texts meeting the inclusion criteria as well as their references were manually searched. The primary outcome data (linear, angular, and vertical maxillary incisor changes and secondary outcome data (overbite changes, soft tissue changes, biomechanical factors, root resorption and treatment duration were extracted from the selected articles and entered into spreadsheets based on the type of anchorage used. The methodological quality of each study was assessed. Results: Six studies met the inclusion criteria. The amount of incisor retraction was greater with buccally placed mini-implants than conventional anchorage techniques. The incisor retraction with indirect anchorage from palatal mini-implants was less when compared with buccally placed mini-implants. Incisor intrusion occurred with buccal mini-implants, whereas extrusion was seen with conventional anchorage. Limited data on the biomechanical variables or adverse effects such as root resorption were reported in these studies. Conclusion: More RCT’s that take in to account relevant biomechanical variables and employ three-dimensional quantification of tooth movements are required to provide information on incisor changes during space closure.

  7. The Plurality of Harbors at Caesarea: The Southern Anchorage in Late Antiquity

    Science.gov (United States)

    Ratzlaff, Alexandra; Galili, Ehud; Waiman-Barak, Paula; Yasur-Landau, Assaf

    2017-08-01

    The engineering marvel of Sebastos, or Portus Augusti as it was called in Late Antiquity (284-638 CE), dominated Caesarea's harbor center along modern Israel's central coast but it was only one part of a larger maritime complex. The Southern Anchorage provides a case study as one portion of the Caesarea complex, as well as a node within the regional network of anchorages and small harbors. Ceramics recovered from here show a high percentage of locally, and provincially, produced storage jars engaged in maritime trade. The ceramic evidence points towards an intensified regional trade or cabotage rather than favouring long distance trade from large port to port. Working out of these small harbors, opportunities arose for greater flexibility in specialization of commodities and materials passing through the network of subsidiary ports, contributing to a more diversified market economy. This analysis provides another example in the growing focus on how these simple and semi-modified anchorages in the Eastern Mediterranean were often the predominant economic networks connecting hinterland and coastal trade.

  8. Success rates of a skeletal anchorage system in orthodontics: A retrospective analysis.

    Science.gov (United States)

    Lam, Raymond; Goonewardene, Mithran S; Allan, Brent P; Sugawara, Junji

    2018-01-01

    To evaluate the premise that skeletal anchorage with SAS miniplates are highly successful and predictable for a range of complex orthodontic movements. This retrospective cross-sectional analysis consisted of 421 bone plates placed by one clinician in 163 patients (95 female, 68 male, mean age 29.4 years ± 12.02). Simple descriptive statistics were performed for a wide range of malocclusions and desired movements to obtain success, complication, and failure rates. The success rate of skeletal anchorage system miniplates was 98.6%, where approximately 40% of cases experienced mild complications. The most common complication was soft tissue inflammation, which was amenable to focused oral hygiene and antiseptic rinses. Infection occurred in approximately 15% of patients where there was a statistically significant correlation with poor oral hygiene. The most common movements were distalization and intrusion of teeth. More than a third of the cases involved complex movements in more than one plane of space. The success rate of skeletal anchorage system miniplates is high and predictable for a wide range of complex orthodontic movements.

  9. Premaxilla: an independent bone that can base therapeutics for middle third growth!

    Science.gov (United States)

    Trevizan, Mariana; Consolaro, Alberto

    2017-01-01

    Premaxilla, in its early descriptions, had the participation of Goethe. In our face, in a certain period of growth and development processes, premaxilla is an independent and, then, a semi-independent bone to finally be totally integrated to the maxilla. Formation of the premaxilla acts as a stabilization element inside the facial skeleton comparable to the cornerstone of a Roman arch and is closely related to the development of human face and its abnormal growth with characteristic malformations. Until when the premaxillary-maxillary suture remains open and offers opportunities to orthopedically influence facial growth to exert influence over facial esthetics and function? Contact with preliminary results in 1183 skulls from anatomic museums at USP, Unicamp and Unifesp led us to question therapeutic perspectives and its clinical applicability.

  10. Orthodontic space closure after first molar extraction without skeletal anchorage.

    Science.gov (United States)

    Jacobs, Collin; Jacobs-Müller, Claudia; Luley, Carolin; Erbe, Christina; Wehrbein, Heiner

    2011-03-01

    The aim of the study was an analysis of effects and side-effects during mesialization of second molars after extraction of the first permanent molars using the anterior dentition/premolars (PM) as an anchorage unit. A total of 35 patients were examined retrospectively who had undergone unilateral or bilateral first permanent molar extraction in the upper or lower arch due to carious lesions. Space closure was carried out in all cases through mesialization of the second molar using an elastic chain fixed to an edgewise stainless steel archwire and tying the anterior dentition/PM together with a continuous laceback ligature. Tooth movement was assessed from lateral cephalograms, orthopantomograms (OPGs) and images of the patient's study casts taken before and after the end of therapy. Space closure after first molar extractions by mesialization of the second molars without skeletal anchorage was largely achieved by bodily forward movement of the teeth, including a small tipping component or tooth-uprighting component when molars were already mesially inclined. Unilateral and bilateral mesialization of the second molars led to retrusion in the maxilla and mandible [(∆incl.=-3.6° (max., bil.), ∆incl.=-4.2° (mand., bil.)] and to translational retraction [(∆s=-2.3 mm (max., bil.), ∆s=-1.6 mm (mand., bil.)] of the incisors. Examination of the soft tissues revealed an increased posterior displacement of the upper and lower lips to the esthetic line [(∆s=-2.8 mm (max. bil.), ∆s=-2.2 mm (mand., bil.)]. In cases of unilateral mesialization less than 50% of the patients had a slight midline deviation in the mandible towards the extraction side. Side effects during mesialization of the second molars without skeletal anchorage in the anterior dentition/PM were observed primarily affecting the incisors integrated into the anterior anchorage unit. These side-effects resulted in posterior displacement of the soft tissues, including a change in profile. This must be

  11. Premaxilla: an independent bone that can base therapeutics for middle third growth!

    Directory of Open Access Journals (Sweden)

    Mariana Trevizan

    Full Text Available ABSTRACT Premaxilla, in its early descriptions, had the participation of Goethe. In our face, in a certain period of growth and development processes, premaxilla is an independent and, then, a semi-independent bone to finally be totally integrated to the maxilla. Formation of the premaxilla acts as a stabilization element inside the facial skeleton comparable to the cornerstone of a Roman arch and is closely related to the development of human face and its abnormal growth with characteristic malformations. Until when the premaxillary-maxillary suture remains open and offers opportunities to orthopedically influence facial growth to exert influence over facial esthetics and function? Contact with preliminary results in 1183 skulls from anatomic museums at USP, Unicamp and Unifesp led us to question therapeutic perspectives and its clinical applicability.

  12. Fatigue of cable anchorage of large cable stayed bridge; Daikibo shachokyo cable teichaku kozo no hiro

    Energy Technology Data Exchange (ETDEWEB)

    Endo, T.; Matsumoto, T. [Honshu-Shikoku Bridge Authority, Tokyo (Japan); Tsukahara, H. [Yokogawa Bridge Corp., Tokyo (Japan); Miki, C. [Tokyo Institute of Technology, Tokyo (Japan)

    1995-10-21

    Design considerations such as design schemes, the assemblage and welding of steel plates, and safety for fatigue of welded connections have to be taken for the cable anchorages of the steel cable stayed bridges. In this study, two full scale models, which have different shape of box anchorages welded to the web of the main girder, were made to investigate fatigue characteristics as well as assemblage of plate and gelding details. Finite element analyses for both test models and actual bridges here carried out to compare stress distribution. It was confirmed that the assemblage and welding of both types of box anchorage were attainable kith required quality and accuracy. According to the fatigue test, fatigue cracks originated from the weldings of the bearing plate to which the load from cable socket applied directly were caused by out-of-plane bending of the bearing plate. It was proved that the slight modifications of the details around the bearing plate resulted in sufficient fatigue strength in both types of anchorage. 1 ref., 23 figs., 2 tabs.

  13. Actomyosin organisation for adhesion, spreading, growth and movement in chick fibroblasts

    DEFF Research Database (Denmark)

    Couchman, J R; Rees, D A

    1979-01-01

    for anchorage-dependent growth, rather than facilitate their movement. The fibroblasts specialized for movement from the explants, though equally well spread, make contact with substratum through extensive areas of relatively unspecialized membrane, have less well developed stress fibres and a low growth rate....

  14. Anchorage of equipment - requirements and verification methods with emphasis on equipment of existing and constructed VVER-type nuclear power plants

    International Nuclear Information System (INIS)

    Masopust, R.

    1999-01-01

    Criteria and verification methods which are recommended for use in the capacity evaluation of anchorage of safety-related equipment at WWER-type nuclear power plants are presented. Developed in compliance with the relevant basic standards documents specifically for anchorage of WWER-type equipment components, the criteria and methods cover different types of anchor bolts and other anchorage elements which are typical of existing, constructed, or reconstructed WWER-type nuclear power plants

  15. 78 FR 44917 - Anchorage Regulations; Port of New York

    Science.gov (United States)

    2013-07-25

    ...-AA01 Anchorage Regulations; Port of New York AGENCY: Coast Guard, DHS. ACTION: Notice of proposed... New York. This action is necessary to facilitate safe navigation and provide safe and secure... this rule, call or email Mr. Jeff Yunker, Sector New York, Waterways Management Division, U.S. Coast...

  16. 75 FR 22323 - Anchorage Regulations; Port of New York

    Science.gov (United States)

    2010-04-28

    ...-AA01 Anchorage Regulations; Port of New York AGENCY: Coast Guard, DHS. ACTION: Supplemental notice of..., Coast Guard Sector New York, Waterways Management Division; telephone 718-354-4195, e-mail Jeff.M.Yunker... Purpose The Hudson River Pilots Association, through the Port of New York/ New Jersey Harbor Safety...

  17. Herbst appliance with skeletal anchorage versus dental anchorage in adolescents with Class II malocclusion: study protocol for a randomised controlled trial.

    Science.gov (United States)

    Batista, Klaus Barretto Dos Santos Lopes; Lima, Tatiana; Palomares, Nathália; Carvalho, Felipe de Assis; Quintão, Cátia; Miguel, José Augusto Mendes; Lin, Yin-Ling; Su, Ting-Li; O'Brien, Kevin

    2017-11-25

    The Herbst appliance is an orthodontic appliance that is used for the correction of class II malocclusion with skeletal discrepancies. Research has shown that this is effective. However, a potential harm is excessive protrusion of the lower front teeth. This is associated with gingival recession, loss of tooth support, and root resorption. This trial evaluates a method of reducing this problem. The study is a single-center, randomised, assessor-blinded, superiority clinical trial with parallel 1:1 allocation. Male and female young people (10-14 years old) with prominent front teeth (class II, division 1) will be treated in one orthodontic clinic. Group 1 will be treated with the conventional Herbst appliance with dental anchorage and group 2 with the Herbst appliance with indirect skeletal anchorage for 12 months. The primary objective will be to compare the proclination of the lower incisors between the Herbst appliance with dental anchorage and skeletal anchorage. Secondary objectives will be to evaluate the changes occurring between the groups in the mandible, maxilla, lower and upper molars, and in gingival recession and root resorption at the end of the treatment. Additionally, the young patient's experience using the appliances will be assessed. The primary outcome measure will be the amount of lower incisor proclination at the end of treatment. This will be assessed by cone-beam computed tomography (CBCT) superimposition. Secondary outcome measures will be the changes in the mandible, maxilla, lower and upper molars at the end of treatment assessed by tomography superimposition and the young patient's experience using the appliances assessed by self-reported questionnaires and semi-structured interviews. The randomisation method will be blocked randomisation, using software to generate a randomised list. The allocation concealment will be done in opaque envelopes numbered from 1 to 40 containing the treatment modality. The randomisation will be

  18. [Effects of ezrin silencing on pancreatic cancer cell line Panc-1].

    Science.gov (United States)

    Meng, Yun-xiao; Yu, Shuang-ni; Lu, Zhao-hui; Chen, Jie

    2012-12-01

    To explore the effects of ezrin silencing on pancreatic cancer cell line Panc-1. Pancreatic cancer cell line Panc-1 was transfected with ezrin silencing plasmid. The proliferation and the cell cycle status were determined by CCK-8 assay and flow cytometry analysis, respectively. Cellular membrane protrusions/microvilli formation were visualized by scanning election microscopy. Colony formation assay was used to determine the cell anchor-independent growth ability in vitro. Trans-filter migration and invasion assays were performed with 8 µm pore inserts in a 24-well BioCoat chamber with/without Matrigel. Ezrin silencing decreased cellular protrusions/microvilli formation, anchorage-independent growth, cell migration and invasion, but had no effects on cell proliferation in vitro and cell cycle, in pancreatic cancer cell line Panc-1. Ezrin expression affects the cellular protrusions/microvilli formation, anchorage-independent growth, cell migration and invasion in pancreatic cancer cell line Panc-1.

  19. FTY720 inhibits mesothelioma growth in vitro and in a syngeneic mouse model.

    Science.gov (United States)

    Szymiczek, Agata; Pastorino, Sandra; Larson, David; Tanji, Mika; Pellegrini, Laura; Xue, Jiaming; Li, Shuangjing; Giorgi, Carlotta; Pinton, Paolo; Takinishi, Yasutaka; Pass, Harvey I; Furuya, Hideki; Gaudino, Giovanni; Napolitano, Andrea; Carbone, Michele; Yang, Haining

    2017-03-15

    Malignant mesothelioma (MM) is a very aggressive type of cancer, with a dismal prognosis and inherent resistance to chemotherapeutics. Development and evaluation of new therapeutic approaches is highly needed. Immunosuppressant FTY720, approved for multiple sclerosis treatment, has recently raised attention for its anti-tumor activity in a variety of cancers. However, its therapeutic potential in MM has not been evaluated yet. Cell viability and anchorage-independent growth were evaluated in a panel of MM cell lines and human mesothelial cells (HM) upon FTY720 treatment to assess in vitro anti-tumor efficacy. The mechanism of action of FTY720 in MM was assessed by measuring the activity of phosphatase protein 2A (PP2A)-a major target of FTY720. The binding of the endogenous inhibitor SET to PP2A in presence of FTY720 was evaluated by immunoblotting and immunoprecipitation. Signaling and activation of programmed cell death were evaluated by immunoblotting and flow cytometry. A syngeneic mouse model was used to evaluate anti-tumor efficacy and toxicity profile of FTY720 in vivo. We show that FTY720 significantly suppressed MM cell viability and anchorage-independent growth without affecting normal HM cells. FTY720 inhibited the phosphatase activity of PP2A by displacement of SET protein, which appeared overexpressed in MM, as compared to HM cells. FTY720 promoted AKT dephosphorylation and Bcl-2 degradation, leading to induction of programmed cell death, as demonstrated by caspase-3 and PARP activation, as well as by cytochrome c and AIF intracellular translocation. Moreover, FTY720 administration in vivo effectively reduced tumor burden in mice without apparent toxicity. Our preclinical data indicate that FTY720 is a potentially promising therapeutic agent for MM treatment.

  20. 76 FR 20524 - Anchorage Regulations; Port of New York

    Science.gov (United States)

    2011-04-13

    ...-AA01 Anchorage Regulations; Port of New York AGENCY: Coast Guard, DHS. ACTION: Final rule. SUMMARY: The... Yunker, Coast Guard Sector New York, Waterways Management Division; telephone 718-354-4195, e-mail Jeff.M... New York in the Federal Register (74 FR 47906). We received one comment on the NPRM. No public meeting...

  1. Local application of zoledronate for maximum anchorage during space closure.

    Science.gov (United States)

    Ortega, Adam J A J; Campbell, Phillip M; Hinton, Robert; Naidu, Aparna; Buschang, Peter H

    2012-12-01

    Orthodontists have used various compliance-dependent physical means such as headgears and intraoral appliances to prevent anchorage loss. The aim of this study was to determine whether 1 local application of the bisphosphonate zoledronate could be used to prevent anchorage loss during extraction space closure in rats. Thirty rats had their maxillary left first molars extracted and their maxillary left second molars protracted into the extraction space with a 10-g nickel-titanium closing coil for 21 days. Fifteen control rats received a local injection of phosphate-buffered saline solution, and 15 experimental rats received 16 μg of the bisphosphonate zoledronate. Bisphosphonate was also delivered directly into the extraction site and left undisturbed for 5 minutes. Cephalograms and incremental thickness gauges were used to measure tooth movements. Tissues were analyzed by microcomputed tomography and histology. The control group demonstrated significant (P <0.05) tooth movements throughout the 21-day period. They showed significantly greater tooth movements than the experimental group beginning in the second week. The experimental group showed no significant tooth movement after the first week. The microcomputed tomography and histologic observations showed significant bone loss in the extraction sites and around the second molars of the controls. In contrast, the experimental group had bone preservation and bone fill. There was no evidence of bisphosphonate-associated osteonecrosis in any sample. A single small, locally applied dose of zoledronate provided maximum anchorage and prevented significant bone loss. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  2. Distinct spinning patterns gain differentiated loading tolerance of silk thread anchorages in spiders with different ecology.

    Science.gov (United States)

    Wolff, Jonas O; van der Meijden, Arie; Herberstein, Marie E

    2017-07-26

    Building behaviour in animals extends biological functions beyond bodies. Many studies have emphasized the role of behavioural programmes, physiology and extrinsic factors for the structure and function of buildings. Structure attachments associated with animal constructions offer yet unrealized research opportunities. Spiders build a variety of one- to three-dimensional structures from silk fibres. The evolution of economic web shapes as a key for ecological success in spiders has been related to the emergence of high performance silks and thread coating glues. However, the role of thread anchorages has been widely neglected in those models. Here, we show that orb-web (Araneidae) and hunting spiders (Sparassidae) use different silk application patterns that determine the structure and robustness of the joint in silk thread anchorages. Silk anchorages of orb-web spiders show a greater robustness against different loading situations, whereas the silk anchorages of hunting spiders have their highest pull-off resistance when loaded parallel to the substrate along the direction of dragline spinning. This suggests that the behavioural 'printing' of silk into attachment discs along with spinneret morphology was a prerequisite for the evolution of extended silk use in a three-dimensional space. This highlights the ecological role of attachments in the evolution of animal architectures. © 2017 The Author(s).

  3. Customized lingual bracket system and skeletal anchorage system for open bite correction

    Directory of Open Access Journals (Sweden)

    Toru Inami

    2016-01-01

    Full Text Available We treated a female patient with open bite and high-angle Class II Division 2 malocclusion using fully customized lingual appliances, orthodontic anchor screws (OAS, and a skeletal anchorage system (SAS. By carefully controlling torque, anchorage, and vertical skeletal and dental factors, we were able to obtain proper anterior coupling. Even after the retention phase of treatment, the occlusion was maintained, indicating that we provided proper treatment according to the properly designed treatment plan. This also indicates that cases with an extremely high level of difficulty, as in the present case with high-angle retrognathic mandible and open bite, can be treated by combining the Incognito appliance (a fully customized lingual bracket appliance with a SAS and OAS.

  4. The Role of a Novel Protease NES1 in Breast Cancer

    National Research Council Canada - National Science Library

    Band, Vimla

    2001-01-01

    ...). IVGG sequence is required for salt bridge formation. Transfection of NESl cDNA into NESl-negative breast cancer cell line suppressed the anchorage-independent growth and tumor formation in nude mice...

  5. Maxillary distraction osteogenesis in cleft lip and palate patients with skeletal anchorage.

    Science.gov (United States)

    Minami, Katsuhiro; Mori, Yoshihide; Tae-Geon, Kwon; Shimizu, Hidetaka; Ohtani, Miyuki; Yura, Yoshiaki

    2007-03-01

    Maxillary distraction osteogenesis with the rigid external distraction (RED) system has been used to treat cleft lip and palate (CLP) patients with severe maxillary hypoplasia. We introduce maxillary distraction osteogenesis for CLP patients with skeletal anchorage adapted on a stereolithographic model. Six maxillary deficiency CLP patients treated according to our CLP treatment protocol had undergone maxillary distraction osteogenesis. In all patients, computed tomography (CT) images were recorded preoperatively, and the data were transferred to a workstation. Three-dimensional skeletal structures were reconstructed with CT data sets, and a stereolithographic model was produced. On the stereolithographic model, miniplates were adapted to the surface of maxilla beside aperture piriforms. The operation performed involved a high Le Fort I osteotomy with pterygomaxillary disjunction. Miniplates were fixed to the maxillary segment with three or four screws and used for anchorage of the RED system. Retraction of the maxillary segment was initiated after 1 week. The accuracy of the stereolithographic models was enough to adapt the miniplates so that there was no need to readjust the plates during surgery. Postoperative cephalometric analysis showed that the direction of the retraction was almost parallel to the palatal plane, and dental compensation did not occur. We performed maxillary distraction osteogenesis with skeletal anchorage adapted on the stereolithographic models. Excellent esthetic outcome and skeletal advancement were achieved without dentoalveolar compensations.

  6. Anchorage strategies in geriatric hip fracture management

    Directory of Open Access Journals (Sweden)

    Knobe Matthias

    2016-12-01

    Full Text Available There is an enormous humanitarian and socioeconomic need to improve the quality and effectiveness of care for patients with hip fracture. To reduce mechanical complications in the osteosynthesis of proximal femoral fractures, improved fixation techniques have been developed including blade or screw-anchor devices, locked minimally invasive or cement augmentation strategies. However, despite numerous innovations and advances regarding implant design and surgical techniques, systemic and mechanical complication rates remain high. Treatment success depends on secure implant fixation in often-osteoporotic bone as well as on patient-specific factors (fracture stability, bone quality, comorbidity, and gender and surgeon-related factors (experience, correct reduction, and optimal screw placement in the head/neck fragment. For fracture fixation, the anchorage of the lag screw within the femoral head plays a crucial role depending on the implant’s design. Meta-analyses and randomized controlled studies demonstrate that there is a strong trend towards arthroplasty treating geriatric femoral neck fractures. However, for young adults as well as older patients with less compromised bone quality, or in undisplaced fractures, head-preserving therapy is preferred as it is less invasive and associated with good functional results. This review summarizes the evidence for the internal fixation of femoral neck fractures and trochanteric femoral fractures in elderly patients. In addition, biomechanical considerations regarding implant anchorage in the femoral head including rotation, migration, and femoral neck shortening are made. Finally, cement augmentation strategies for hip fracture implants are evaluated critically.

  7. Revisiting the stability of mini-implants used for orthodontic anchorage

    Directory of Open Access Journals (Sweden)

    Chung-Chen Jane Yao

    2015-11-01

    Conclusion: This study revealed that once the dental surgeon becomes familiar with the procedure, the stability of orthodontic mini-implants depends on the type of mini-implant, age of the patient, implantation site, and the healing time of the mini-implant. Miniplates are a more feasible anchorage system when miniscrews fail repeatedly.

  8. Loss of tumorigenic potential by human lung tumor cells in the presence of antisense RNA specific to the ectopically synthesized alpha subunit of human chorionic gonadotropin.

    Science.gov (United States)

    Rivera, R T; Pasion, S G; Wong, D T; Fei, Y B; Biswas, D K

    1989-06-01

    A clonal strain of human lung tumor cells in culture (ChaGo), derived from a bronchogenic carcinoma, synthesizes and secretes large amounts of alpha (alpha) and a comparatively lower level of beta (beta) subunit of the glycoprotein hormone, human chorionic gonadotropin (HCG). ChaGo cells lost their characteristic anchorage-independent growth phenotype in the presence of anti-alpha-HCG antibody. The effect of the antibody was partially reversed by addition of alpha-HCG to the culture medium. ChaGo cells were transfected with an expression vector (pRSV-anti-alpha-HCG), that directs synthesis of RNA complementary to alpha-HCG mRNA. The transfectants produced alpha-HCG antisense RNA which was associated with the reduced level of alpha-HCG. Transfectants also displayed several altered phenotypic properties, including altered morphology, less mitosis, reduced growth rate, loss of anchorage-independent growth, and loss of tumorigenicity in nude mice. Treatment of transfectants with 8,bromo-cAMP resulted in increased accumulation of alpha-HCG mRNA, no change in the level of alpha-HCG antisense RNA, release of the inhibition of [3H]thymidine incorporation, and restoration of anchorage-independent growth phenotype. The overexpression of c-myc, observed in ChaGo cells, was unaffected by the reduced level of alpha-HCG. These results suggest that ectopic synthesis of the alpha subunit of HCG plays a functional role in the transformation of these human lung cells.

  9. Rate-Independent Processes with Linear Growth Energies and Time-Dependent Boundary Conditions

    Czech Academy of Sciences Publication Activity Database

    Kružík, Martin; Zimmer, J.

    2012-01-01

    Roč. 5, č. 3 (2012), s. 591-604 ISSN 1937-1632 R&D Projects: GA AV ČR IAA100750802 Grant - others:GA ČR(CZ) GAP201/10/0357 Institutional research plan: CEZ:AV0Z10750506 Keywords : concentrations * oscillations * time - dependent boundary conditions * rate-independent evolution Subject RIV: BA - General Mathematics http://library.utia.cas.cz/separaty/2011/MTR/kruzik-rate-independent processes with linear growth energies and time - dependent boundary conditions.pdf

  10. Clinical application of micro-implant anchorage in initial orthodontic retraction.

    Science.gov (United States)

    Wahabuddin, Shaji; Mascarenhas, Rohan; Iqbal, Mahamad; Husain, Akhter

    2015-02-01

    Micro-implant is a device that is temporarily fixed to bone for the purpose of enhancing orthodontic anchorage either by supporting the teeth of the reactive unit or by obviating the need for the reactive unit altogether, and which is subsequently removed after use. The purpose of this study was to evaluate the clinical efficiency of micro-implants in reinforcing anchorage during the initial retraction of anterior teeth, check the rate of initial retraction for 8 weeks, and assess the stability of micro-implants during this period. Eighteen micro-implants were placed (10 in the maxilla and 8 in the mandible) and immediately loaded with 200-250 g of force using 9-mm closed coil Nitinol springs. The amount of space closure was measured every 2 weeks until the eighth week. Cephalometric measurements were made at the end of the study to evaluate anchor loss, if any. Micro-implant stability was also assessed. The rate of initial retraction in the maxilla at the end of 8 weeks was 1.65 mm/quadrant and 1.51 mm/quadrant in the mandible. The amount of retraction on the left side of the arches was 1.66 mm/quadrant and 1.49 mm/quadrant on the right side. The average initial retraction for both arches per month was 0.78 mm. An anchor loss of 0.1 mm (0.06%) was observed in the maxilla while no mandibular anchor loss was recorded. The rate of initial retraction observed in the maxilla was more than that achieved in the mandible. Initial retraction was also more on the left side of the arches. There was no anchor loss in the mandible. The micro-implant-reinforced anchorage was helpful in minimizing anchor loss and accepted heavy traction forces but did not bring about a faster rate of retraction.

  11. A novel anchorage technique for transnasal traction in rigid external maxillary distraction.

    Science.gov (United States)

    Varol, A; Basa, S

    2013-12-01

    We describe an effective technique for anchorage of transnasal traction in the management of maxillary rotation during external distraction. Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  12. Three-dimensional printing spiders: back-and-forth glue application yields silk anchorages with high pull-off resistance under varying loading situations.

    Science.gov (United States)

    Wolff, Jonas O; Herberstein, Marie E

    2017-02-01

    The anchorage of structures is a crucial element of construction, both for humans and animals. Spiders use adhesive plaques to attach silk threads to substrates. Both biological and artificial adhesive structures usually have an optimal loading angle, and are prone to varying loading situations. Silk anchorages, however, must cope with loading in highly variable directions. Here we show that the detachment forces of thread anchorages of orb-web spiders are highly robust against pulling in different directions. This is gained by a two-step back-and-forth spinning pattern during the rapid production of the adhesive plaque, which shifts the thread insertion point towards the plaque centre and forms a flexible tree root-like network of branching fibres around the loading point. Using a morphometric approach and a tape-and-thread model we show that neither area, nor width of the plaque, but the shift of the loading point towards the plaque centre has the highest effect on pull-off resistance. This is explained by a circular propagation of the delamination crack with a low peeling angle. We further show that silken attachment discs are highly directional and adjusted to provide maximal performance in the upstream dragline. These results show that the way the glue is applied, crucially enhances the toughness of the anchorage without the need of additional material intake. This work is a starting point to study the evolution of tough and universal thread anchorages among spiders, and to develop bioinspired 'instant' anchorages of thread- and cable-like structures to a broad bandwidth of substrates. © 2017 The Author(s).

  13. The Role of EMMPRIN in Tumor Angiogenesis and Metastasis

    National Research Council Canada - National Science Library

    Marieb, Erica

    2002-01-01

    .... Using a soft agar assay to assess anchorage-independent growth, increased expression of EMMPRIN stimulated 10-fold and 5-fold increases respectively in the number of colonies formed by MDA-MB-436 and MCF-7...

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

    Directory of Open Access Journals (Sweden)

    Rama Jasty

    2001-01-01

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

  15. PAK1 is a breast cancer oncogene that coordinately activates MAPK and MET signaling.

    Science.gov (United States)

    Shrestha, Y; Schafer, E J; Boehm, J S; Thomas, S R; He, F; Du, J; Wang, S; Barretina, J; Weir, B A; Zhao, J J; Polyak, K; Golub, T R; Beroukhim, R; Hahn, W C

    2012-07-19

    Activating mutations in the RAS family or BRAF frequently occur in many types of human cancers but are rarely detected in breast tumors. However, activation of the RAS-RAF-MEK-ERK MAPK pathway is commonly observed in human breast cancers, suggesting that other genetic alterations lead to activation of this signaling pathway. To identify breast cancer oncogenes that activate the MAPK pathway, we screened a library of human kinases for their ability to induce anchorage-independent growth in a derivative of immortalized human mammary epithelial cells (HMLE). We identified p21-activated kinase 1 (PAK1) as a kinase that permitted HMLE cells to form anchorage-independent colonies. PAK1 is amplified in several human cancer types, including 30--33% of breast tumor samples and cancer cell lines. The kinase activity of PAK1 is necessary for PAK1-induced transformation. Moreover, we show that PAK1 simultaneously activates MAPK and MET signaling; the latter via inhibition of merlin. Disruption of these activities inhibits PAK1-driven anchorage-independent growth. These observations establish PAK1 amplification as an alternative mechanism for MAPK activation in human breast cancer and credential PAK1 as a breast cancer oncogene that coordinately regulates multiple signaling pathways, the cooperation of which leads to malignant transformation.

  16. Randomized clinical trial comparing control of maxillary anchorage with 2 retraction techniques.

    Science.gov (United States)

    Xu, Tian-Min; Zhang, Xiaoyun; Oh, Hee Soo; Boyd, Robert L; Korn, Edward L; Baumrind, Sheldon

    2010-11-01

    The objective of this pilot randomized clinical trial was to investigate the relative effectiveness of anchorage conservation of en-masse and 2-step retraction techniques during maximum anchorage treatment in patients with Angle Class I and Class II malocclusions. Sixty-four growing subjects (25 boys, 39 girls; 10.2-15.9 years old) who required maximum anchorage were randomized to 2 treatment techniques: en-masse retraction (n = 32) and 2-step retraction (n = 32); the groups were stratified by sex and starting age. Each patient was treated by a full-time clinic instructor experienced in the use of both retraction techniques at the orthodontic clinic of Peking University School of Stomatology in China. All patients used headgear, and most had transpalatal appliances. Lateral cephalograms taken before treatment and at the end of treatment were used to evaluate treatment-associated changes. Differences in maxillary molar mesial displacement and maxillary incisor retraction were measured with the before and after treatment tracings superimposed on the anatomic best fit of the palatal structures. Differences in mesial displacement of the maxillary first molar were compared between the 2 treatment techniques, between sexes, and between different starting-age groups. Average mesial displacement of the maxillary first molar was slightly less in the en-masse group than in the 2-step group (mean, -0.36 mm; 95% CI, -1.42 to 0.71 mm). The average mesial displacement of the maxillary first molar for both treatment groups pooled (n = 63, because 1 patient was lost to follow-up) was 4.3 ± 2.1 mm (mean ± standard deviation). Boys had significantly more mesial displacement than girls (mean difference, 1.3 mm; P <0.03). Younger adolescents had significantly more mesial displacement than older adolescents (mean difference, 1.3 mm; P <0.02). Average mesial displacement of the maxillary first molar with 2-step retraction was slightly greater than that for en-masse retraction, but the

  17. A review on the technical basis for ACI 349 code revision to anchorage criteria

    International Nuclear Information System (INIS)

    Lee, N. H.; You, S. H.

    1999-01-01

    Anchors are widely used to attach structural and nonstructural elements to concrete in nuclear power plant construction. Anchorage to concrete in nuclear-related structure plant has been designed per ACI 349-90 Appendix B. However, a new criteria for anchorage based on the concrete capacity design(CCD) approach is ready for publication under the normal publication procedures by ACI 349 Code Committee. Both design procedures(ACI 349-90 and ACI 349-New) show rather different concrete capacities. Earlier comparable studies show that the CCD method is a more reliable predictor of concrete breakout than the 45-degree cone method(ACI 349-90), hence the CCD method adopted by ACI 349-New Code has been recommended. The philosophy of the current code is to design ductile fastenings, which requires a limit to guard against brittle concrete failure. On the other hand, the new code requires calculations for the concrete breakout strength, pullout strength, side-face blowout strength of fastener in tension, and concrete breakout strength, pryout strength of fastener in shear. Therefore, the new code can accurately predict the concrete failure capacity for different behavior of the anchorage system. In this review, the provisions of ACI 349-90 and ACI 349-New are compared to show the major differences with emphasis on the concrete breakout capacity

  18. Biofilm formation on surface characterized micro-implants for skeletal anchorage in orthodontics

    NARCIS (Netherlands)

    Chin, Yeen; Sandham, John; de Vries, Jacob; van der Mei, Henderina; Busscher, Hendrik

    Micro-implants are increasingly popular in clinical orthodontics to effect skeletal anchorage. However, biofilm formation on their surfaces and subsequent infection of peri-implant tissues can result in either exfoliation or surgical removal of these devices. The present study aimed to assess

  19. Impedance-Based Cable Force Monitoring in Tendon-Anchorage Using Portable PZT-Interface Technique

    Directory of Open Access Journals (Sweden)

    Thanh-Canh Huynh

    2014-01-01

    Full Text Available In this paper, a portable PZT interface for tension force monitoring in the cable-anchorage subsystem is developed. Firstly, the theoretical background of the impedance-based method is presented. A few damage evaluation approaches are outlined to quantify the variation of impedance signatures. Secondly, a portable PZT interface is designed to monitor impedance signatures from the cable-anchorage subsystem. One degree-of-freedom analytical model of the PZT interface is established to explain how to represent the loss of cable force from the change in the electromechanical impedance of the PZT interface as well as reducing the sensitive frequency band by implementing the interface device. Finally, the applicability of the proposed PZT-interface technique is experimentally evaluated for cable force-loss monitoring in a lab-scaled test structure.

  20. Induction of miR-137 by Isorhapontigenin (ISO) Directly Targets Sp1 Protein Translation and Mediates Its Anticancer Activity Both In Vitro and In Vivo.

    Science.gov (United States)

    Zeng, Xingruo; Xu, Zhou; Gu, Jiayan; Huang, Haishan; Gao, Guangxun; Zhang, Xiaoru; Li, Jingxia; Jin, Honglei; Jiang, Guosong; Sun, Hong; Huang, Chuanshu

    2016-03-01

    Our recent studies found that isorhapontigenin (ISO) showed a significant inhibitory effect on human bladder cancer cell growth, accompanied with cell-cycle G0-G1 arrest as well as downregulation of Cyclin D1 expression at transcriptional level via inhibition of Sp1 transactivation in bladder cancer cells. In the current study, the potential ISO inhibition of bladder tumor formation has been explored in a xenograft nude mouse model, and the molecular mechanisms underlying ISO inhibition of Sp1 expression and anticancer activities have been elucidated both in vitro and in vivo. Moreover, the studies demonstrated that ISO treatment induced the expression of miR-137, which in turn suppressed Sp1 protein translation by directly targeting Sp1 mRNA 3'-untranslated region (UTR). Similar to ISO treatment, ectopic expression of miR-137 alone led to G0-G1 cell growth arrest and inhibition of anchorage-independent growth in human bladder cancer cells, which could be completely reversed by overexpression of GFP-Sp1. The inhibition of miR-137 expression attenuated ISO-induced inhibition of Sp1/Cyclin D1 expression, induction of G0-G1 cell growth arrest, and suppression of cell anchorage-independent growth. Taken together, our studies have demonstrated that miR-137 induction by ISO targets Sp1 mRNA 3'-UTR and inhibits Sp1 protein translation, which consequently results in reduction of Cyclin D1 expression, induction of G0-G1 growth arrest, and inhibition of anchorage-independent growth in vitro and in vivo. Our results have provided novel insights into understanding the anticancer activity of ISO in the therapy of human bladder cancer. ©2016 American Association for Cancer Research.

  1. Opposing activities of the Ras and Hippo pathways converge on regulation of YAP protein turnover

    DEFF Research Database (Denmark)

    Hong, Xin; Nguyen, Thanh Hung; Chen, Qingfeng

    2014-01-01

    Cancer genomes accumulate numerous genetic and epigenetic modifications. Yet, human cellular transformation can be accomplished by a few genetically defined elements. These elements activate key pathways required to support replicative immortality and anchorage independent growth, a predictor...

  2. Mitochondrial clearance by the STK38 kinase supports oncogenic Ras-induced cell transformation

    Science.gov (United States)

    Bettoun, Audrey; Surdez, Didier; Vallerand, David; Gundogdu, Ramazan; Sharif, Ahmad A.D.; Gomez, Marta; Cascone, Ilaria; Meunier, Brigitte; White, Michael A.; Codogno, Patrice; Parrini, Maria Carla; Camonis, Jacques H.; Hergovich, Alexander

    2016-01-01

    Oncogenic Ras signalling occurs frequently in many human cancers. However, no effective targeted therapies are currently available to treat patients suffering from Ras-driven tumours. Therefore, it is imperative to identify downstream effectors of Ras signalling that potentially represent promising new therapeutic options. Particularly, considering that autophagy inhibition can impair the survival of Ras-transformed cells in tissue culture and mouse models, an understanding of factors regulating the balance between autophagy and apoptosis in Ras-transformed human cells is needed. Here, we report critical roles of the STK38 protein kinase in oncogenic Ras transformation. STK38 knockdown impaired anoikis resistance, anchorage-independent soft agar growth, and in vivo xenograft growth of Ras-transformed human cells. Mechanistically, STK38 supports Ras-driven transformation through promoting detachment-induced autophagy. Even more importantly, upon cell detachment STK38 is required to sustain the removal of damaged mitochondria by mitophagy, a selective autophagic process, to prevent excessive mitochondrial reactive oxygen species production that can negatively affect cancer cell survival. Significantly, knockdown of PINK1 or Parkin, two positive regulators of mitophagy, also impaired anoikis resistance and anchorage-independent growth of Ras-transformed human cells, while knockdown of USP30, a negative regulator of PINK1/Parkin-mediated mitophagy, restored anchorage-independent growth of STK38-depleted Ras-transformed human cells. Therefore, our findings collectively reveal novel molecular players that determine whether Ras-transformed human cells die or survive upon cell detachment, which potentially could be exploited for the development of novel strategies to target Ras-transformed cells. PMID:27283898

  3. Testing of large prestressing tendon end anchorage regions

    International Nuclear Information System (INIS)

    Johnson, T.E.

    1976-01-01

    Tests were performed on concrete end anchorage regions for prestressing tendons with ultimate strengths of approximately 8,900 kN. One test structure simulated a full scale concrete containment buttress and the other two test specimens were concrete blocks. The behavior of the test structure and specimens, when subjected to loading, was monitored by strain gages and dial gages. The testing illustrated that all of the amounts of reinforcing tested should be acceptable for the end anchor zones of large tendons presently used in prestressed concrete containment structures. (author)

  4. The significance of fibroblast growth factors 8, 17, and 18 and the fibroblast growth factor receptor 4 for malignant behaviour of hepatocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Gauglhofer, C L

    2010-07-01

    at high levels in human hepatocytes, was found to be further upregulated in a subset of human HCC cases. Characterization of the FGFR4 genotype in healthy individuals and in patients suffering from premalignant liver disease or HCC showed that the presence of a SNP in codon 388 of FGFR4 (G388R polymorphism) predisposes for the development of liver malignancy. For mechanistic investigation either the wildtype or mutated form of FGFR4 was overexpressed in hepatocarcinoma cell lines. Wildtype FGFR4 had only minor effects on the growth of the cell lines but strongly enhanced anchorage-independent growth of cells and induced tumorigenicity in a non-tumorigenic cell line. Overexpression of the mutated receptor form had an even more pronounced effect on anchorage-independent growth, but did not affect tumorigenicity. Knockdown of endogenous FGFR4 expression by siRNA led to reduced clone formation capacity of hepatocarcinoma cell lines. Cells were also adenovirally infected with dominant-negative FGFR4 constructs being either kinase-dead or encoding for the soluble extracellular domain of FGFR4, which binds and neutralizes FGFR4-ligands. This led to reduced cell viability and anchorage-independent growth in vitro and lowered tumor formation in SCID mice. To conclude, FGFR4 contributes to the malignant behaviour of hepatocarcinoma cells and its effects may be aggravated by the G388R polymorphism. Therefore, downregulation of FGFR4 appears to be a promising approach for HCC therapy. (author) [German] Das hepatozellulaere Karzinom (HCC), welches die haeufigste Form von primaerem Leberkrebs darstellt, ist die fuenft-haeufigste Krebserkrankung weltweit. Aufgrund der Tatsache, dass nur fruehe Stadien der Erkrankung erfolgreich behandelt werden koennen, ist HCC von einer hohen Mortalitaet gekennzeichnet. Die zugrundeliegenden Risikofaktoren wurden eingehend untersucht und es ist bekannt, dass sich ein Groayteil der Tumore als Folge von chronisch-entzuendlichen Lebererkrankungen

  5. Evaluating School Wellness Policy in Curbing Childhood Obesity in Anchorage, Alaska

    Science.gov (United States)

    Parsons, Wendy G.; Garcia, Gabriel M.; Hoffman, Pamela K.

    2014-01-01

    In 2006, the Anchorage School District implemented a school wellness policy to address the problem of obesity among its elementary-aged students. We assessed whether the addition of this policy is effective in protecting or preventing students from becoming overweight/obese over time. The methods involved following two cohorts of students for 5…

  6. Sortilin regulates progranulin action in castration-resistant prostate cancer cells.

    Science.gov (United States)

    Tanimoto, Ryuta; Morcavallo, Alaide; Terracciano, Mario; Xu, Shi-Qiong; Stefanello, Manuela; Buraschi, Simone; Lu, Kuojung G; Bagley, Demetrius H; Gomella, Leonard G; Scotlandi, Katia; Belfiore, Antonino; Iozzo, Renato V; Morrione, Andrea

    2015-01-01

    The growth factor progranulin is as an important regulator of transformation in several cellular systems. We have previously demonstrated that progranulin acts as an autocrine growth factor and stimulates motility, proliferation, and anchorage-independent growth of castration-resistant prostate cancer cells, supporting the hypothesis that progranulin may play a critical role in prostate cancer progression. However, the mechanisms regulating progranulin action in castration-resistant prostate cancer cells have not been characterized. Sortilin, a single-pass type I transmembrane protein of the vacuolar protein sorting 10 family, binds progranulin in neurons and negatively regulates progranulin signaling by mediating progranulin targeting for lysosomal degradation. However, whether sortilin is expressed in prostate cancer cells and plays any role in regulating progranulin action has not been established. Here, we show that sortilin is expressed at very low levels in castration-resistant PC3 and DU145 cells. Significantly, enhancing sortilin expression in PC3 and DU145 cells severely diminishes progranulin levels and inhibits motility, invasion, proliferation, and anchorage-independent growth. In addition, sortilin overexpression negatively modulates Akt (protein kinase B, PKB) stability. These results are recapitulated by depleting endogenous progranulin in PC3 and DU145 cells. On the contrary, targeting sortilin by short hairpin RNA approaches enhances progranulin levels and promotes motility, invasion, and anchorage-independent growth. We dissected the mechanisms of sortilin action and demonstrated that sortilin promotes progranulin endocytosis through a clathrin-dependent pathway, sorting into early endosomes and subsequent lysosomal degradation. Collectively, these results point out a critical role for sortilin in regulating progranulin action in castration-resistant prostate cancer cells, suggesting that sortilin loss may contribute to prostate cancer progression.

  7. Numerical implementation of multiple peeling theory and its application to spider web anchorages.

    Science.gov (United States)

    Brely, Lucas; Bosia, Federico; Pugno, Nicola M

    2015-02-06

    Adhesion of spider web anchorages has been studied in recent years, including the specific functionalities achieved through different architectures. To better understand the delamination mechanisms of these and other biological or artificial fibrillar adhesives, and how their adhesion can be optimized, we develop a novel numerical model to simulate the multiple peeling of structures with arbitrary branching and adhesion angles, including complex architectures. The numerical model is based on a recently developed multiple peeling theory, which extends the energy-based single peeling theory of Kendall, and can be applied to arbitrarily complex structures. In particular, we numerically show that a multiple peeling problem can be treated as the superposition of single peeling configurations even for complex structures. Finally, we apply the developed numerical approach to study spider web anchorages, showing how their function is achieved through optimal geometrical configurations.

  8. Early bone anchorage to micro- and nano-topographically complex implant surfaces in hyperglycemia.

    Science.gov (United States)

    Ajami, Elnaz; Bell, Spencer; Liddell, Robert S; Davies, John E

    2016-07-15

    The aim of this work was to investigate the effect of implant surface design on early bone anchorage in the presence of hyperglycemia. 108 Wistar rats were separated into euglycemic (EG) controls and STZ-treated hyperglycemic (HG) groups, and received bilateral femoral custom rectangular implants of two surface topographies: grit blasted (GB) and grit-blast with a superimposed calcium phosphate nanotopography (GB-DCD). The peri-implant bone was subjected to a tensile disruption test 5, 7, and 9days post-operatively (n=28/time point); the force was measured; and the residual peri-implant bone was observed by scanning electron microscopy (SEM). Disruption forces at 5days were not significantly different from zero for the GB implants (p=0.24) in either metabolic group; but were for GB+DCD implants in both metabolic groups (pmicro-surfaced implants showed significantly different disruption forces at all time points (e.g. >15N and implants, as all values were very low (implant bone showed compromised intra-fibrillar collagen mineralization in hyperglycemia, while inter-fibrillar and cement line mineralization remained unaffected. Enhanced bone anchorage to the implant surfaces was observed on the nanotopographically complex surface independent of metabolic group. The compromised intra-fibrillar mineralization observed provides a mechanism by which early bone mineralization is affected in hyperglycemia. It is generally accepted that the hyperglycemia associated with diabetes mellitus compromises bone quality, although the mechanism by which this occurs is unknown. Uncontrolled hyperglycemia is therefore a contra-indication for bone implant placement. It is also known that nano-topographically complex implant surfaces accelerate early peri-implant healing. In this report we show that, in our experimental model, nano-topographically complex surfaces can mitigate the compromised bone healing seen in hyperglycemia. Importantly, we also provide a mechanistic explanation for

  9. Epidermal growth factor receptor: an independent predictor of survival in astrocytic tumors given definitive irradiation

    International Nuclear Information System (INIS)

    An Zhu; Shaeffer, James; Leslie, Susan; Kolm, Paul; El-Mahdi, Anas M.

    1996-01-01

    Purpose: To determine whether the expression of epidermal growth factor receptor (EGFR) protein was predictive of patient survival independently of other prognostic factors in astrocytic tumors. Methods and Materials: Epidermal growth factor receptor protein expression was investigated immunohistochemically in formalin-fixed, paraffin-embedded surgical specimens of 55 glioblastoma multiforme, 14 anaplastic astrocytoma, and 2 astrocytomas given definitive irradiation. We evaluated the relationship of EGFR protein expression and tumor grade, histologic features, age at diagnosis, sex, patient survival, and recurrence-free survival. Results: The percentage of tumor cells which were EGFR positive related to reduced survival by Cox regression analysis in both univariate (p = 0.0424) and multivariate analysis (p = 0.0016). Epidermal growth factor receptor positivity was the only 1 of 11 clinical and histological variables associated with decreased recurrence-free survival by either univariate (p = 0.0353) or multivariate (p = 0.0182) analysis. Epidermal growth factor receptor protein expression was not related to patient age, sex, or histologic features. Conclusion: Epidermal growth factor receptor positivity was a significant and independent prognostic indicator for overall survival and recurrence-free survival for irradiated patients with astrocytic gliomas

  10. PPARγ-independent induction of growth arrest and apoptosis in prostate and bladder carcinoma

    International Nuclear Information System (INIS)

    Chaffer, Christine L; Thomas, David M; Thompson, Erik W; Williams, Elizabeth D

    2006-01-01

    Although PPARγ antagonists have shown considerable pre-clinical efficacy, recent studies suggest PPARγ ligands induce PPARγ-independent effects. There is a need to better define such effects to permit rational utilization of these agents. We have studied the effects of a range of endogenous and synthetic PPARγ ligands on proliferation, growth arrest (FACS analysis) and apoptosis (caspase-3/7 activation and DNA fragmentation) in multiple prostate carcinoma cell lines (DU145, PC-3 and LNCaP) and in a series of cell lines modelling metastatic transitional cell carcinoma of the bladder (TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1-B2). 15-deoxy-prostaglandin J 2 (15dPGJ2), troglitazone (TGZ) and to a lesser extent ciglitazone exhibited inhibitory effects on cell number; the selective PPARγ antagonist GW9662 did not reverse these effects. Rosiglitazone and pioglitazone had no effect on proliferation. In addition, TGZ induced G0/G1 growth arrest whilst 15dPGJ2 induced apoptosis. Troglitazone and 15dPGJ2 inhibit growth of prostate and bladder carcinoma cell lines through different mechanisms and the effects of both agents are PPARγ-independent

  11. Anchorage onto deciduous teeth: effectiveness of early rapid maxillary expansion in increasing dental arch dimension and improving anterior crowding

    OpenAIRE

    Mutinelli, Sabrina; Manfredi, Mario; Guiducci, Antonio; Denotti, Gloria; Cozzani, Mauro

    2015-01-01

    Background Anchorage onto permanent dentition is a common procedure in rapid maxillary expansion. However, replacing first permanent molars with the second deciduous molars seems to be an option to reduce some negative side effects during orthodontic treatment. The purpose of this study was to evaluate the dental effect of rapid maxillary expansion with anchorage exclusively onto deciduous teeth performed in the first period of transition. Methods Twenty patients with a lateral cross-bite tre...

  12. Internal structure of mandible around mandibular molar using computed tomography. Anatomical consideration of molar anchorage in orthodontic treatment

    International Nuclear Information System (INIS)

    Enomoto, Yutaka; Yamashita, Daisuke; Saito, Katsuhiko; Kasai, Kazutaka

    2008-01-01

    For establishment of fine occlusion, facial profile and oral function in orthodontic treatment, molar anchorage in teeth movement is important manner in extracted cases. The aims of this study were to investigate the relationship between facial morphology and internal structure of mandibular body in molar region by computer tomography, and to discuss about molar anchorage in orthodontic treatment. The data for this study were obtained from 35 modern male Japanese skulls (mean age; 27 year-old, ranged from 18 year-old to 47 year-old). Measurement variables were FMA, SN to mandibular plane angle, gonial angle, alveolar breadth, cortical bone thickness of buccal and lingual sides, and the distance between dental root and cortical bone. As a result, alveolar breadth and the distance between dental root and cortical bone were narrow in long facial type, on the contrary, these variables were wide in short facial type. The result suggested that these variables were considered important factors as molar anchorage in extracted cases. (author)

  13. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

    International Nuclear Information System (INIS)

    Jiang, Jiahua; Jedinak, Andrej; Sliva, Daniel

    2011-01-01

    Highlights: ► Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. ► CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. ► GDNT inhibits expression of CDC20 in breast cancer cells. ► GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. ► GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes—ganoderic and lucidenic acids—the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.

  14. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Jiahua; Jedinak, Andrej [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Sliva, Daniel, E-mail: dsliva@iuhealth.org [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN (United States); Indiana University Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. Black-Right-Pointing-Pointer CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. Black-Right-Pointing-Pointer GDNT inhibits expression of CDC20 in breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes-ganoderic and lucidenic acids-the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.

  15. [Treatment of adult bimaxillary arch protrusion with micro-implant anchorage].

    Science.gov (United States)

    Chen, Cheng; Zhang, Xiao-Rong

    2015-02-01

    In this study, micro-implants were used in 15 adult patients with mild and moderate bimaxillary arch protrusion or crowding. Cephalometric analysis was used to analyze hard and soft-tissues change before and after treatment, with the aim to investigate the effects of treatment on adult bimaxillary arch protrusion with micro-implant anchorage. Fifteen adult patients with mild and moderate bimaxillary arch protrusion were selected in this study. Micro-implants were inserted into the zygomaticoalveolar ridge of maxilla and the external oblique line of mandible. A NiTi coil spring was attached to the micro-implant to drag the whole upper and lower dentition for distal movement. Cephalometrics were taken before and after treatment, and the changes of soft and hard-tissue profile were studied. SPSS13.0 software package was used to analyze the data. (1)Sixty micro-implants remained stable.(2)SNA, SNB had no significant changes (P>0.05), and the relationship between the maxilla and the mandible did not change significantly. U1/NA, U1-NA, L1/NB, L1-NB and U1/L1 changes in hard tissue had significant difference in cephalometric measurement (PMicro-implant can provide not only excellent skeletal anchorage but also a novel way to distalize the whole dentition efficiently.

  16. Explaining the democratic anchorage of governance networks

    DEFF Research Database (Denmark)

    Skelcher, Chris; Klijn, Erik-Hans; Kübler, Daniel

    2011-01-01

    Advances in understanding the democratic anchorage of governance networks require carefully designed and contextually grounded empirical analysis that take into account contextual factors. The article uses a conjectural framework to study the impact of the national democratic milieu...... on the relationship between network governance and representative institutions in four European countries: the United Kingdom, Switzerland, the Netherlands, and Denmark. The article shows that the distinction between majoritarian and consensus democracy as well as the varying strength of voluntary associations...... are important contextual factors that help explain cross-national differences in the relationship between governance networks and representative institutions. We conclude that a context of weak associationalism in majoritarian democracies facilitates the instrumentalization of networks by government actors...

  17. Mini-placa como ancoragem ortodôntica: relato de caso Mini screw as orthodontic anchorage: case report

    Directory of Open Access Journals (Sweden)

    André Luiz Zétola

    2005-08-01

    ígida pode ser utilizada com bastante propriedade no tratamento ortodôntico qunado for requerida uma ancoragem máxima.It is needless to say that anchorage control is necessary to a successful orthodontic treatment. Without it, it would be impossible to obtain an ideal occlusion through orthodontic mechanics in the majority of cases. The utilization of rigid devices, originated from face traumatology and implant dentistry principles, to obtain rigid anchorage in orthodontics revolutionized the way of treating cases with an unsatisfactory prognosis. Specially in cases where a lot of anchorage is needed and it is difficult or impossible to get it. The objective of this article was to revise the literature related to the use of mini-screw implant systems, to report a case where it was utilized and to discuss some aspects related to the usage of rigid anchorage orthodontics. The rigid anchorage was used in a 39 year old female patient, who had the upper left molars with a relevant extrusion due to the absence of the lower left molars. Fixed appliances were placed on the upper arch with a TPA connecting the second bicuspids. The TPA was used to anchor the intrusion of the upper left molars. A quad-helix appliance was used to correct the upper right third molar crossbite. Since the orthodontic intrusion with only dental anchorage did not have a satisfactory result, an "L" shaped titanium plate was placed on the maxilla, at the apical region of the upper first and second left molars, with the purpose of obtaining a rigid orthodontic anchorage to intrude them. Elastics were used during five months with intrusive force,the obtained intrusion was 6 millimeters. After the removal of the appliance, upper and lower dental bleaching was made and final prosthesis were placed over the implants. Through the literature reviewed and the case reported, it can be concluded that rigid anchorage can be indicated in orthodontic treatments where there is lack of anchorage or the need of an absolute

  18. Comparison of rate of En masse retraction and anchorage loss in conventional labial appliance with labial and lingual force: A clinical study

    Directory of Open Access Journals (Sweden)

    Dilshad Quraishi

    2018-01-01

    Full Text Available Aims: The rate of en masse retraction and anchorage loss were compared between labial appliance with lingual force and conventional labial appliance. Subjects and Methods: The sample consists of 14 patients and they were divided into two groups. In Group 1 – labial appliance with lingual force, elastomeric chain was placed from the palatal surface of the canines to the palatal surface of the molars. In Group 2 – labial appliance with labial force, elastomeric chain was placed from the crimpable hook distal to lateral incisor to the molar tube hooks. The rate of en masse retraction and anchorage loss was calculated for both the groups during retraction in dental casts (R0, initial; R1, 4 weeks; R2, 8 weeks; and R3, 12 weeks. Statistical Analysis Used: Student's paired t-test. Results: The rate of retraction was faster and anchorage loss was lower with labial appliance with lingual force, i.e., Group 1. The difference of anchorage loss in Group 1 and Group 2 shows t = 4.824 and P value= 0.000, which is statistically highly significant. The difference of rate of retraction in Group 1 and Group 2 shows t = 3.573 and P value = 0.004, which is statistically signifcant. Conclusions: The rate of retraction was faster and anchorage loss was lower with labial appliance with lingual force, thus indicating that this new technique of space closure utilizes biomechanical advantage of lingual force in conventional labial appliance.

  19. Production of transforming growth factor α in human pancreatic cancer cells: evidence for a superagonist autocrine cycle

    International Nuclear Information System (INIS)

    Smith, J.J.; Derynck, R.; Korc, M.

    1987-01-01

    Previous work showed that cultured human pancreatic cancer cells overexpress the epidermal growth factor (EGF) receptor. In the present study, the authors sought to determine whether some of these cell lines produce transforming growth factor α (TGF-α). Utilizing a radiolabeled TGF-α cDNA in hybridization experiments, they determined that ASPC-1, T 3 M 4 , PANC-1, COLO-357, and MIA PaCa-2 cell lines expressed TGF-α mRNA. Serum-free medium conditioned by T 3 M 4 and ASPC-1 cells contained significant amounts of TGF-α protein. Although unlabeled TGF-α readily competed with 125 I-labeled EGF for binding, each cell line exhibited lower surface binding and internalization of 125 I-labeled TGF-α as compared to 125 I-labeled EGF. Both TGF-α and EGF significantly enhanced the anchorage-independent growth of PANC-1, T 3 M 4 , and ASPC-1 cells. However, TGF-α was 10- to 100-fold more potent than EGF. These findings suggest that the concomitant overexpression of EGF receptors and production of TGF-α may represent an efficient mechanism for certain cancer cells to obtain a growth advantage

  20. Enhanced carcinogenicity by coexposure to arsenic and iron and a novel remediation system for the elements in well drinking water.

    Science.gov (United States)

    Kumasaka, Mayuko Y; Yamanoshita, Osamu; Shimizu, Shingo; Ohnuma, Shoko; Furuta, Akio; Yajima, Ichiro; Nizam, Saika; Khalequzzaman, Md; Shekhar, Hossain U; Nakajima, Tamie; Kato, Masashi

    2013-03-01

    Various carcinomas including skin cancer are explosively increasing in arsenicosis patients who drink arsenic-polluted well water, especially in Bangladesh. Although well drinking water in the cancer-prone areas contains various elements, very little is known about the effects of elements except arsenic on carcinogenicity. In order to clarify the carcinogenic effects of coexposure to arsenic and iron, anchorage-independent growth and invasion in human untransformed HaCaT and transformed A431 keratinocytes were examined. Since the mean ratio of arsenic and iron in well water was 1:10 in cancer-prone areas of Bangladesh, effects of 1 μM arsenic and 10 μM iron were investigated. Iron synergistically promoted arsenic-mediated anchorage-independent growth in untransformed and transformed keratinocytes. Iron additionally increased invasion in both types of keratinocytes. Activities of c-SRC and ERK that regulate anchorage-independent growth and invasion were synergistically enhanced in both types of keratinocytes. Our results suggest that iron promotes arsenic-mediated transformation of untransformed keratinocytes and progression of transformed keratinocytes. We then developed a low-cost and high-performance adsorbent composed of a hydrotalcite-like compound for arsenic and iron. The adsorbent rapidly reduced concentrations of both elements from well drinking water in cancer-prone areas of Bangladesh to levels less than those in WHO health-based guidelines for drinking water. Thus, we not only demonstrated for the first time increased carcinogenicity by coexposure to arsenic and iron but also proposed a novel remediation system for well drinking water.

  1. Disimpaction of maxillary canines using temporary bone anchorage and cantilever springs.

    Science.gov (United States)

    Thebault, Benoit; Dutertre, Eric

    2015-03-01

    Impacted canines, particularly in the maxilla, are frequently encountered in orthodontic practice. Unfortunately, depending on their position, correction can often be difficult and sometimes unsuccessful. Thorough diagnosis along with orthodontic treatment combining bone-supported anchorage and cantilever springs appears, in our view, to offer the best solution to this tricky orthodontic challenge while limiting, as far as possible, the risk of failure. Copyright © 2015. Published by Elsevier Masson SAS.

  2. Epigenetic repression of regulator of G-protein signaling 2 promotes androgen-independent prostate cancer cell growth.

    Science.gov (United States)

    Wolff, Dennis W; Xie, Yan; Deng, Caishu; Gatalica, Zoran; Yang, Mingjie; Wang, Bo; Wang, Jincheng; Lin, Ming-Fong; Abel, Peter W; Tu, Yaping

    2012-04-01

    G-protein-coupled receptor (GPCR)-stimulated androgen-independent activation of androgen receptor (AR) contributes to acquisition of a hormone-refractory phenotype by prostate cancer. We previously reported that regulator of G-protein signaling (RGS) 2, an inhibitor of GPCRs, inhibits androgen-independent AR activation (Cao et al., Oncogene 2006;25:3719-34). Here, we show reduced RGS2 protein expression in human prostate cancer specimens compared to adjacent normal or hyperplastic tissue. Methylation-specific PCR analysis and bisulfite sequencing indicated that methylation of the CpG island in the RGS2 gene promoter correlated with RGS2 downregulation in prostate cancer. In vitro methylation of this promoter suppressed reporter gene expression in transient transfection studies, whereas reversal of this promoter methylation with 5-aza-2'-deoxycytidine (5-Aza-dC) induced RGS2 reexpression in androgen-independent prostate cancer cells and inhibited their growth under androgen-deficient conditions. Interestingly, the inhibitory effect of 5-Aza-dC was significantly reduced by an RGS2-targeted short hairpin RNA, indicating that reexpressed RGS2 contributed to this growth inhibition. Restoration of RGS2 levels by ectopic expression in androgen-independent prostate cancer cells suppressed growth of xenografts in castrated mice. Thus, RGS2 promoter hypermethylation represses its expression and unmasks a latent pathway for AR transactivation in prostate cancer cells. Targeting this reversible process may provide a new strategy for suppressing prostate cancer progression by reestablishing its androgen sensitivity. Copyright © 2011 UICC.

  3. Impact of a new gasoline benzene regulation on ambient air pollutants in Anchorage, Alaska

    Science.gov (United States)

    Yano, Yuriko; Morris, Stephen S.; Salerno, Christopher; Schlapia, Anne M.; Stichick, Mathew

    2016-05-01

    The purpose of this study was to quantify the impact of a new U.S. Environmental Protection Agency (EPA) standard that limits the amount of benzene allowed in gasoline on ambient benzene concentrations. This new standard, together with two companion regulations that limit cold-temperature automotive emissions and the permeability of portable fuel containers, was expected to lower the levels of ambient benzene and other volatile organic compounds (VOCs) nationwide. In this study the impact of the gasoline benzene standard was evaluated in Anchorage, Alaska in a two-phase ambient air monitoring study conducted before and after the new gasoline standard was implemented. Gasoline sold by Anchorage retailers was also evaluated in each phase to determine the content of benzene and other gasoline components. The average benzene content in Anchorage gasoline was reduced by 70%, from 5.05% (w/w) to 1.53% (w/w) following the implementation of the standard. The annual mean ambient benzene concentration fell by 51%, from 0.99 ppbv in Phase 1 to 0.49 ppbv in Phase 2. Analysis suggests the change in gasoline benzene content alone reduced benzene emissions by 46%. The changes in toluene, ethylbenzene, and xylene content in gasoline between Phase 1 and 2 were relatively small and the differences in the mean ambient concentrations of these compounds between phases were modest. Our results suggest that cold winter communities in high latitude and mountainous regions may benefit more from the gasoline benzene standard because of high benzene emissions resulting from vehicle cold start and a tendency to develop atmospheric stagnation conditions in the winter.

  4. Strontium ranelate improved tooth anchorage and reduced root resorption in orthodontic treatment of rats.

    Science.gov (United States)

    Kirschneck, Christian; Wolf, Michael; Reicheneder, Claudia; Wahlmann, Ulrich; Proff, Peter; Roemer, Piero

    2014-12-05

    The anchorage mechanisms currently used in orthodontic treatment have various disadvantages. The objective of this study was to determine the applicability of the osteoporosis medication strontium ranelate in pharmacologically induced orthodontic tooth anchorage. In 48 male Wistar rats, a constant orthodontic force of 0.25 N was reciprocally applied to the upper first molar and the incisors by means of a Sentalloy(®) closed coil spring for two to four weeks. 50% of the animals received strontium ranelate at a daily oral dosage of 900 mg per kilogramme of body weight. Bioavailability was determined by blood analyses. The extent of tooth movement was measured both optometrically and cephalometrically (CBCT). Relative alveolar gene expression of osteoclastic markers and OPG-RANKL was assessed by qRT-PCR and root resorption area and osteoclastic activity were determined in TRAP-stained histologic sections of the alveolar process. Compared to controls, the animals treated with strontium ranelate showed up to 40% less tooth movement after four weeks of orthodontic treatment. Gene expression and histologic analyses showed significantly less osteoclastic activity and a significantly smaller root resorption area. Blood analyses confirmed sufficient bioavailability of strontium ranelate. Because of its pharmacologic effects on bone metabolism, strontium ranelate significantly reduced tooth movement and root resorption in orthodontic treatment of rats. Strontium ranelate may be a viable agent for inducing tooth anchorage and reducing undesired root resorption in orthodontic treatment. Patients under medication of strontium ranelate have to expect prolonged orthodontic treatment times. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Pyruvate carboxylase is required for glutamine-independent growth of tumor cells

    Science.gov (United States)

    Cheng, Tzuling; Sudderth, Jessica; Yang, Chendong; Mullen, Andrew R.; Jin, Eunsook S.; Matés, José M.; DeBerardinis, Ralph J.

    2011-01-01

    Tumor cells require a constant supply of macromolecular precursors, and interrupting this supply has been proposed as a therapeutic strategy in cancer. Precursors for lipids, nucleic acids, and proteins are generated in the tricarboxylic acid (TCA) cycle and removed from the mitochondria to participate in biosynthetic reactions. Refilling the pool of precursor molecules (anaplerosis) is therefore crucial to maintain cell growth. Many tumor cells use glutamine to feed anaplerosis. Here we studied how “glutamine-addicted” cells react to interruptions of glutamine metabolism. Silencing of glutaminase (GLS), which catalyzes the first step in glutamine-dependent anaplerosis, suppressed but did not eliminate the growth of glioblastoma cells in culture and in vivo. Profiling metabolic fluxes in GLS-suppressed cells revealed induction of a compensatory anaplerotic mechanism catalyzed by pyruvate carboxylase (PC), allowing the cells to use glucose-derived pyruvate rather than glutamine for anaplerosis. Although PC was dispensable when glutamine was available, forcing cells to adapt to low-glutamine conditions rendered them absolutely dependent on PC for growth. Furthermore, in other cell lines, measuring PC activity in nutrient-replete conditions predicted dependence on specific anaplerotic enzymes. Cells with high PC activity were resistant to GLS silencing and did not require glutamine for survival or growth, but displayed suppressed growth when PC was silenced. Thus, PC-mediated, glucose-dependent anaplerosis allows cells to achieve glutamine independence. Induction of PC during chronic suppression of glutamine metabolism may prove to be a mechanism of resistance to therapies targeting glutaminolysis. PMID:21555572

  6. Root perforation associated with the use of a miniscrew implant used for orthodontic anchorage: a case report.

    Science.gov (United States)

    McCabe, P; Kavanagh, C

    2012-07-01

    To highlight one of the possible complications associated with the inter-radicular placement of orthodontic miniscrews. This case report describes the endodontic treatment and surgical repair of an iatrogenic root perforation involving a maxillary first molar tooth following the placement of an orthodontic miniscrew placed for anchorage purposes in the treatment of an adult patient. The orthodontic treatment plan was completed. The long-term follow-up shows a successful treatment outcome. Inter-radicular placement of orthodontic miniscrews is a valuable source of anchorage in the treatment of orthodontic patients. Root perforation is a possible complication from inter-radicular placement of orthodontic miniscrews. Root perforation can be successfully treated, but may involve apical surgery. © 2012 International Endodontic Journal.

  7. [Comparing the anchorage effects of micro-implant and J hook on treating patients with maxillary protrusion].

    Science.gov (United States)

    Wu, Xin; Liu, Guo-yuan; Jiang, Yong-lian

    2015-10-01

    To investigate the differences in anchorage effects between micro-implants and J hook in treating patients with Class II division 1 maxillary protrusion. Thirty-one cases of adult patients with Class II division 1 maxillary protrusion were treated. They were divided into 2 groups depending on their selection. The first group included 17 patients for micro-implant anchorage, who adopted micro-implant and sliding mechanism to close maxillary extraction space and depress the mandibular molar. The second group encompassed 14 cases for J hook, who adopted sliding mechanism, J hooks in high traction and Class II intermaxillary traction to close extraction space. X-ray lateral cephalometric radiographs were measured before and after treatment, and SPSS16.0 software package was employed to compare the differences in soft and hard tissue changes before and after treatment between 2 groups. There were statistically significant differences in SNB, ANB, MP-FH, U1-Y, U6-Y, L6-MP, NLA, and UL-Y between the 2 groups before and after treatment, while there was no significant difference in SNA, U1-SN, U1-X, and U6-X between the 2 groups. In treating patients with Class II division 1 maxillary protrusion, micro-implant has stronger anchorage effects than J hook, while at the same time depressing the mandibular molars, and making it more favorable to improve Class II faces.

  8. Skeletal anchorage in orthodontics : A review of various systems in animal and human studies

    NARCIS (Netherlands)

    Janssen, Krista I.; Raghoebar, Gerry M.; Vissink, Arjan; Sandham, John

    2008-01-01

    Purpose: The aim of the present investigation was to review and evaluate the current literature on skeletal bone anchorage in orthodontics with regard to success rates of the various systems. Materials and Methods: MEDLINE, PubMed, and Cochrane searches (period January 1966 to January 2006, English

  9. Down-regulation of Rab5 decreases characteristics associated with maintenance of cell transformation

    International Nuclear Information System (INIS)

    Silva, Patricio; Soto, Nicolás; Díaz, Jorge; Mendoza, Pablo; Díaz, Natalia; Quest, Andrew F.G.; Torres, Vicente A.

    2015-01-01

    The early endosomal protein Rab5 is highly expressed in tumor samples, although a causal relationship between Rab5 expression and cell transformation has not been established. Here, we report the functional effects of targeting endogenous Rab5 with specific shRNA sequences in different tumor cell lines. Rab5 down-regulation in B16-F10 cells decreased tumor formation by subcutaneous injection into C57/BL6 mice. Accordingly, Rab5 targeting in B16-F10 and A549, but not MDA-MB-231 cells was followed by decreased cell proliferation, increased apoptosis and decreased anchorage-independent growth. These findings suggest that Rab5 expression is required to maintain characteristics associated with cell transformation. - Highlights: • Rab5 is important to the maintenance of cell transformation characteristics. • Down-regulation of Rab5 decreases cell proliferation and increases apoptosis in different cancer cells. • Rab5 is required for anchorage-independent growth and tumorigenicity in-vivo

  10. Exploiting orthologue diversity for systematic detection of gain-of-function phenotypes

    Directory of Open Access Journals (Sweden)

    Cantarella Daniela

    2008-05-01

    Full Text Available Abstract Background Systematic search for genes whose gain-of-function by exogenous expression confers an advantage in cell-based selective screenings is a powerful method for unbiased functional exploration of the genome, and has the potential to disclose new targets for cancer therapy. A major limit of this approach resides in the labor-intensive cloning of resistant cells, identification of the integrated genes and validation of their ability to confer a selective advantage. Moreover, the selection has to be drastic and genes conferring a limited advantage are typically missed. Results We developed a new functional screening strategy based on transduction of mammalian cells of a given species with an expression library from another species, followed by one-shot quantitative tracing with DNA microarrays of all library-derived transcripts before and after selection. In this way, exogenous transcripts enriched after selection, and therefore likely to confer resistance, are readily detected. We transduced a retroviral cDNA expression library from mouse testis into human and canine cells, and optimized the use of commercial murine gene expression arrays for species-specific detection of library-derived transcripts. We then conducted a functional screening by growing library-transduced canine MDCK cells in suspension, to enrich for cDNAs conferring anchorage independence. Notably, these cells show partial resistance to loss of anchorage, and the selection can be of limited stringency, compromising approaches based on clonal selection or anyway requiring high stringency. Microarray analysis revealed reproducible enrichment after three weeks of growth on polyhema for seven genes, among which the Hras proto-oncogene and Sox5. When individually transduced into MDCK cells, Sox5 specifically promoted anchorage-independent growth, thereby confirming the validity and specificity of the approach. Conclusion The procedure described here brings substantial

  11. 1964 Great Alaska Earthquake: a photographic tour of Anchorage, Alaska

    Science.gov (United States)

    Thoms, Evan E.; Haeussler, Peter J.; Anderson, Rebecca D.; McGimsey, Robert G.

    2014-01-01

    On March 27, 1964, at 5:36 p.m., a magnitude 9.2 earthquake, the largest recorded earthquake in U.S. history, struck southcentral Alaska (fig. 1). The Great Alaska Earthquake (also known as the Good Friday Earthquake) occurred at a pivotal time in the history of earth science, and helped lead to the acceptance of plate tectonic theory (Cox, 1973; Brocher and others, 2014). All large subduction zone earthquakes are understood through insights learned from the 1964 event, and observations and interpretations of the earthquake have influenced the design of infrastructure and seismic monitoring systems now in place. The earthquake caused extensive damage across the State, and triggered local tsunamis that devastated the Alaskan towns of Whittier, Valdez, and Seward. In Anchorage, the main cause of damage was ground shaking, which lasted approximately 4.5 minutes. Many buildings could not withstand this motion and were damaged or collapsed even though their foundations remained intact. More significantly, ground shaking triggered a number of landslides along coastal and drainage valley bluffs underlain by the Bootlegger Cove Formation, a composite of facies containing variably mixed gravel, sand, silt, and clay which were deposited over much of upper Cook Inlet during the Late Pleistocene (Ulery and others, 1983). Cyclic (or strain) softening of the more sensitive clay facies caused overlying blocks of soil to slide sideways along surfaces dipping by only a few degrees. This guide is the document version of an interactive web map that was created as part of the commemoration events for the 50th anniversary of the 1964 Great Alaska Earthquake. It is accessible at the U.S. Geological Survey (USGS) Alaska Science Center website: http://alaska.usgs.gov/announcements/news/1964Earthquake/. The website features a map display with suggested tour stops in Anchorage, historical photographs taken shortly after the earthquake, repeat photography of selected sites, scanned documents

  12. Survivin inhibits anti-growth effect of p53 activated by aurora B

    International Nuclear Information System (INIS)

    Jung, Ji-Eun; Kim, Tae-Kyung; Lee, Joong-Seob; Oh, Se-Yeong; Kwak, Sungwook; Jin, Xun; Sohn, Jin-Young; Song, Min-Keun; Sohn, Young-Woo; Lee, Soo-Yeon; Pian, Xumin; Lee, Jang-Bo; Chung, Yong Gu; Choi, Young Ki; You, Seungkwon; Kim, Hyunggee

    2005-01-01

    Genomic instability and apoptosis evasion are hallmarks of cancer, but the molecular mechanisms governing these processes remain elusive. Here, we found that survivin, a member of the apoptosis-inhibiting gene family, and aurora B kinase, a chromosomal passenger protein, were co-overexpressed in the various glioblastoma cell lines and tumors. Notably, exogenous introduction of the aurora B in human BJ cells was shown to decrease cell growth and increase the senescence-associated β-galactosidase activity by activation of p53 tumor suppressor. However, aurora B overexpression failed to inhibit cell proliferation in BJ and U87MG cells transduced with dominant-negative p53 as well as in p53 -/- mouse astrocytes. Aurora B was shown to increase centrosome amplification in the p53 -/- astrocytes. Survivin was shown to induce anchorage-independent growth and inhibit anti-proliferation and drug-sensitive apoptosis caused by aurora B. Overexpression of both survivin and aurora B further accelerated the proliferation of BJ cells. Taken together, the present study indicates that survivin should accelerate tumorigenesis by inhibiting the anti-proliferative effect of p53 tumor suppressor that is activated by aurora B in normal and glioblastoma cells containing intact p53

  13. 77 FR 8252 - Adequacy Status of the Anchorage, Alaska, Carbon Monoxide Maintenance Plan for Transportation...

    Science.gov (United States)

    2012-02-14

    ... a SIP means that transportation activities will not produce new air quality violations, worsen... Anchorage, Alaska, Carbon Monoxide Maintenance Plan for Transportation Conformity Purposes AGENCY... Transportation & Public Facilities, and the U.S. Department of Transportation will be required to use [[Page 8253...

  14. Upregulated Expression of a Unique Gene by Hepatitis B x Antigen Promotes Hepatocellular Growth and Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Zhaorui Lian

    2003-05-01

    Full Text Available Hepatitis B x antigen (HBxAg is a trans-activating protein that may be involved in hepatocarcinogenesis, although few natural effectors of HBxAg that participate in this process have been identified. To identify additional effectors, whole cell RNA isolated from HBxAg-positive and HBxAg-negative HepG2 cells were compared by polymerase chain reaction select cDNA subtraction, and one clone, upregulated gene, clone 11 (URG11, was chosen for further characterization. Elevated levels of URG11 mRNA and protein were observed in HBxAg-positive compared to HBxAg-negative HepG2 cells. Costaining was observed in infected liver (P<.01. URG11 stimulated cell growth in culture (P<.01, anchorage-independent growth in soft agar (P<.001, and accelerated tumor formation (P<.01, and yielded larger tumors (P<.02 in SCID mice injected subcutaneously with HepG2 cells. These data suggest that URG11 is a natural effector of HBxAg that may promote the development of hepatocellular carcinoma.

  15. Anchorage failure of young trees in sandy soils is prevented by a rigid central part of the root system with various designs

    Science.gov (United States)

    Danquechin Dorval, Antoine; Meredieu, Céline; Danjon, Frédéric

    2016-01-01

    Background and Aims Storms can cause huge damage to European forests. Even pole-stage trees with 80-cm rooting depth can topple. Therefore, good anchorage is needed for trees to survive and grow up from an early age. We hypothesized that root architecture is a predominant factor determining anchorage failure caused by strong winds. Methods We sampled 48 seeded or planted Pinus pinaster trees of similar aerial size from four stands damaged by a major storm 3 years before. The trees were gathered into three classes: undamaged, leaning and heavily toppled. After uprooting and 3D digitizing of their full root architectures, we computed the mechanical characteristics of the main components of the root system from our morphological measurements. Key Results Variability in root architecture was quite large. A large main taproot, either short and thick or long and thin, and guyed by a large volume of deep roots, was the major component that prevented stem leaning. Greater shallow root flexural stiffness mainly at the end of the zone of rapid taper on the windward side also prevented leaning. Toppling in less than 90-cm-deep soil was avoided in trees with a stocky taproots or with a very big leeward shallow root. Toppled trees also had a lower relative root biomass – stump excluded – than straight trees. Conclusions It was mainly the flexural stiffness of the central part of the root system that secured anchorage, preventing a weak displacement of the stump. The distal part of the longest taproot and attached deep roots may be the only parts of the root system contributing to anchorage through their maximum tensile load. Several designs provided good anchorage, depending partly on available soil depth. Pole-stage trees are in-between the juvenile phase when they fail by toppling and the mature phase when they fail by uprooting. PMID:27456136

  16. Silver oxide-containing hydroxyapatite coating supports osteoblast function and enhances implant anchorage strength in rat femur.

    Science.gov (United States)

    Eto, Shuichi; Miyamoto, Hiroshi; Shobuike, Takeo; Noda, Iwao; Akiyama, Takayuki; Tsukamoto, Masatsugu; Ueno, Masaya; Someya, Shinsuke; Kawano, Shunsuke; Sonohata, Motoki; Mawatari, Masaaki

    2015-09-01

    Antibacterial silver with hydroxyapatite (Ag-HA) is a promising coating material for imparting antibacterial properties to implants. We previously reported that 3% (w/w) silver with HA (3% Ag-HA) has both antibacterial activity and osteoconductivity. In this study, we investigated the effects of Ag-HA on the in vitro osteoblast function and the in vivo anchorage strength and osteoconductivity of implants. Production of the osteoblast marker alkaline phosphatase, but not cytotoxicity, was observed in cells of the osteoblast cell line MC3T3-E1 cultured on the 3% Ag-HA-coated surface. These results were similar to those observed with silver-free HA coating. In contrast, a significant high level of cytotoxicity was observed when the cells were cultured on a 50% Ag-HA-coated surface. The anchorage strength of implants inserted into the femur of Sprague-Dawley (SD) rats was enhanced by coating the implants with 3% Ag-HA. On the 3% Ag-HA-coated surface, both metaphyseal and diaphyseal areas were largely covered with new bone and had adequate osteoconductivity. These results suggest that 3% Ag-HA, like conventional HA, promotes osteogenesis by supporting osteoblast viability and function and thereby contributes to sufficient anchorage strength of implants. Application of 3% Ag-HA, which combines the osteoconductivity of HA and the antibacterial activity of silver, to prosthetic joints will help prevent postoperative infections. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  17. Ground-water quality beneath solid-waste disposal sites at anchorage, Alaska

    Science.gov (United States)

    Zenone, Chester; Donaldson, D.E.; Grunwaldt, J.J.

    1975-01-01

    Studies at three solid-waste disposal sites in the Anchorage area suggest that differences in local geohydrologic conditions influence ground-water quality. A leachate was detected in ground water within and beneath two sites where the water table is very near land surface and refuse is deposited either at or below the water table in some parts of the filled areas. No leachate was detected in ground water beneath a third site where waste disposal is well above the local water table.

  18. Human Sarcoma growth is sensitive to small-molecule mediated AXIN stabilization.

    Directory of Open Access Journals (Sweden)

    Alessandra De Robertis

    Full Text Available Sarcomas are mesenchymal tumors showing high molecular heterogeneity, reflected at the histological level by the existence of more than fifty different subtypes. Genetic and epigenetic evidences link aberrant activation of the Wnt signaling to growth and progression of human sarcomas. This phenomenon, mainly accomplished by autocrine loop activity, is sustained by gene amplification, over-expression of Wnt ligands and co-receptors or epigenetic silencing of endogenous Wnt antagonists. We previously showed that pharmacological inhibition of Wnt signaling mediated by Axin stabilization produced in vitro and in vivo antitumor activity in glioblastoma tumors. Here, we report that targeting different sarcoma cell lines with the Wnt inhibitor/Axin stabilizer SEN461 produces a less transformed phenotype, as supported by modulation of anchorage-independent growth in vitro. At the molecular level, SEN461 treatment enhanced the stability of the scaffold protein Axin1, a key negative regulator of the Wnt signaling with tumor suppressor function, resulting in downstream effects coherent with inhibition of canonical Wnt signaling. Genetic phenocopy of small molecule Axin stabilization, through Axin1 over-expression, coherently resulted in strong impairment of soft-agar growth. Importantly, sarcoma growth inhibition through pharmacological Axin stabilization was also observed in a xenograft model in vivo in female CD-1 nude mice. Our findings suggest the usefulness of Wnt inhibitors with Axin stabilization activity as a potentialyl clinical relevant strategy for certain types of sarcomas.

  19. [Comparison between J-hook and micro-implant anchorage in the treatment of patients with bimaxillary protrusion].

    Science.gov (United States)

    Chen, Wen-Jing; Li, Qing-Yi; Gong, Ai-Xiu; Hu, Fang; Gu, Yong-Jia

    2008-02-01

    To compare the difference between J-hook and micro-implant anchorage in the treatment of patient with bimaxillary protrusion. Thirty patients with bimaxillary protrusion were divided into two groups (J-hook and micro-implant groups) and treated with MBT appliance. Four first premolars were extracted in all patients. Cephalometric analyses were carried out before and after treatment. In J-hook group and micro-implant group,computerized cephalometric analysis revealed that before treatment U6C-PP was (12.4 +/- 0.2) mm and (12.5 +/- 0.1) mm, respectively,and after treatment U6C-PP was (12.6 +/- 0.1) mm and (12.8 +/- 0.1) mm,respectively. The difference between J-hook group and microimplant group was significant (P micro-implant group was not significant. Both J-hook and micro-implant could provide adequate anchorage in the treatment of patients with bimaxillary protrusion.

  20. The Neurofibromatosis 2 Tumor Suppressor Gene Product, Merlin, Regulates Human Meningioma Cell Growth by Signaling through YAP

    Directory of Open Access Journals (Sweden)

    Katherine Striedinger

    2008-11-01

    Full Text Available Neurofibromatosis type 2 (NF2 is an autosomal dominant disorder characterized by the occurrence of schwannomas and meningiomas. Several studies have examined the ability of the NF2 gene product, merlin, to function as a tumor suppressor in diverse cell types; however, little is known about merlin growth regulation in meningiomas. In Drosophila, merlin controls cell proliferation and apoptosis by signaling through the Hippo pathway to inhibit the function of the transcriptional coactivator Yorkie. The Hippo pathway is conserved in mammals. On the basis of these observations, we developed human meningioma cell lines matched for merlin expression to evaluate merlin growth regulation and investigate the relationship between NF2 status and Yes-associated protein (YAP, the mammalian homolog of Yorkie. NF2 loss in meningioma cells was associated with loss of contact-dependent growth inhibition, enhanced anchorage-independent growth and increased cell proliferation due to increased S-phase entry. In addition, merlin loss in both meningioma cell lines and primary tumors resulted in increased YAP expression and nuclear localization. Finally, siRNA-mediated reduction of YAP in NF2-deficient meningioma cells rescued the effects of merlin loss on cell proliferation and S-phase entry. Collectively, these results represent the first demonstration that merlin regulates cell growth in human cancer cells by suppressing YAP.

  1. Anchorage onto deciduous teeth: effectiveness of early rapid maxillary expansion in increasing dental arch dimension and improving anterior crowding.

    Science.gov (United States)

    Mutinelli, Sabrina; Manfredi, Mario; Guiducci, Antonio; Denotti, Gloria; Cozzani, Mauro

    2015-01-01

    Anchorage onto permanent dentition is a common procedure in rapid maxillary expansion. However, replacing first permanent molars with the second deciduous molars seems to be an option to reduce some negative side effects during orthodontic treatment. The purpose of this study was to evaluate the dental effect of rapid maxillary expansion with anchorage exclusively onto deciduous teeth performed in the first period of transition. Twenty patients with a lateral cross-bite treated exclusively by a Haas expander in early mixed dentition were retrospectively analyzed before treatment, at appliance removal, and at 21 months out of retention. The sagittal and transverse dimensions, together with the inter-canine arch and irregularity index, were digitally measured on scanned images of dental casts. The patients were compared with three balanced control groups (in total, 60 individuals) matched for gender. Two control groups had the same canine dental class as the treated group at T1, were in the inter-transitional period, and either had or lacked a lateral cross-bite. The last control group was comprised of adolescents in permanent dentition with a dental class I. The statistical analysis was performed by means of repeated-measures ANOVA for paired data and one-way ANOVA, the Kruskal-Wallis test, and the Mann-Whitney test for independent measures (α-level p dentition), the dental arch dimensions of treated patients were similar to those of adolescents with a dental class I and significantly wider than those of patients with a lateral cross-bite. Also, the anterior irregularity index was lower among patients who had undergone expansion treatments than in all untreated study participants. The Haas expander anchored to the deciduous teeth is effective in increasing the dental arch width in patients with a lateral cross-bite. The dimensions of the dental arch were modified earlier toward the values of the permanent dentition.

  2. A material-independent cell–environment niche based on microreciprocating motion for cell growth enhancement

    International Nuclear Information System (INIS)

    Li, Ching-Wen; Wang, Gou-Jen

    2013-01-01

    In tissue engineering, cell–cell, cell–scaffold and cell–environment communication balances regulate how cell populations participate in tissue generation, maintenance and repair. These communication balances are called niches. In this study, an easily implemented and material-independent cell–environment niche based on microreciprocating motions is developed to enhance cell growth. A micropositioning piezoelectric lead zirconate titanate stage is used to provide precise microreciprocating shear stress motions. Various shear stresses were applied to bovine endothelial cells (BECs) that were cultured on the artificially synthesized materials to obtain the suitable shear stress for growth enhancement. It was found that the suitable shear stress for apparent enhancement of BEC growth ranges from 1.8 to 2.2 N m −2 . Biopolymers were further used to verify the feasibility of the proposed approach using the optimized shear stress obtained from the culture on artificially synthesized polymers. The results further confirmed that the growth of BECs was enhanced as expected under the calculated reciprocating frequencies based on the suitable shear stress. It is hoped that the proposed microshear-stress-based niche could be a more cost- and time-effective solution for the enhancement of cell growth in tissue engineering applications. (paper)

  3. A novel role for drebrin in regulating progranulin bioactivity in bladder cancer.

    Science.gov (United States)

    Xu, Shi-Qiong; Buraschi, Simone; Morcavallo, Alaide; Genua, Marco; Shirao, Tomoaki; Peiper, Stephen C; Gomella, Leonard G; Birbe, Ruth; Belfiore, Antonino; Iozzo, Renato V; Morrione, Andrea

    2015-05-10

    We recently established a critical role for the growth factor progranulin in bladder cancer insofar as progranulin promotes urothelial cancer cell motility and contributes, as an autocrine growth factor, to the transformed phenotype by modulating invasion and anchorage-independent growth. In addition, progranulin expression is upregulated in invasive bladder cancer tissues compared to normal controls. However, the molecular mechanisms of progranulin action in bladder cancer have not been fully elucidated. In this study, we searched for novel progranulin-interacting proteins using pull-down assays with recombinant progranulin and proteomics. We discovered that drebrin, an F-actin binding protein, bound progranulin in urothelial cancer cells. We characterized drebrin function in urothelial cancer cell lines and showed that drebrin is critical for progranulin-dependent activation of the Akt and MAPK pathways and modulates motility, invasion and anchorage-independent growth. In addition, drebrin regulates tumor formation in vivo and its expression is upregulated in bladder cancer tissues compared to normal tissue controls. Our data are translationally relevant as indicate that drebrin exerts an essential functional role in the regulation of progranulin action and may constitute a novel target for therapeutic intervention in bladder tumors. In addition, drebrin may serve as novel biomarker for bladder cancer.

  4. Management of post midface distraction occlusal discrepancy using temporary anchorage devices in a cleft patient

    Science.gov (United States)

    Koteswara Prasad, N. K.; Hussain, Syed Altaf; Chitharanjan, Arun B.; Murthy, Jyotsna

    2015-01-01

    Open bite deformity following a successful midface advancement by distraction osteogenesis is a common complication. Temporary anchorage devices can be deployed during the distraction and post-distraction settling phases for restoring the occlusion even in severe cases. The following report describes the management of severe anterior open bite following maxillary distraction. PMID:25991895

  5. Sublethal concentrations of the platinum(II) complex [Pt(O,O'-acac)(gamma-acac)(DMS)] alter the motility and induce anoikis in MCF-7 cells.

    Science.gov (United States)

    Muscella, Antonella; Calabriso, Nadia; Vetrugno, Carla; Urso, Loredana; Fanizzi, Francesco Paolo; De Pascali, Sandra Angelica; Marsigliante, Santo

    2010-07-01

    We showed previously that a new Pt(II) complex ([Pt(O,O'-acac)(gamma-acac)(DMS)]) exerted high and fast apoptotic processes in MCF-7 cells. The objective of this study was to investigate the hypothesis that [Pt(O,O'-acac)(gamma-acac)(DMS)] is also able to exert anoikis and alter the migration ability of MCF-7 cells, and to show some of the signalling events leading to these alterations. Cells were treated with sublethal doses of [Pt(O,O'-acac)(gamma-acac)(DMS)], and the efficiency of colony initiation and anchorage-independent growth was assayed; cell migration was examined by in vitro culture wounding assay. Gelatin zymography for MMP-2 and -9 activities, Western blottings of MMPs, MAPKs, Src, PKC-epsilon and FAK, after [Pt(O,O'-acac)(gamma-acac)(DMS)] treatment, were also performed. Sub-cytotoxic drug concentrations decreased the: (i) anchorage-dependent and -independent growth; (ii) migration ability; and (iii) expression and activity of MMP-2 and MMP-9. [Pt(O,O'-acac)(gamma-acac)(DMS)] provoked the generation of reactive oxygen species (ROS), and the activation of p38MAPK, Src and PKC-epsilon. p38MAPK phosphorylation, cell anoikis and migration due to [Pt(O,O'-acac)(gamma-acac)(DMS)] were blocked by PKC-epsilon inhibition. Furthermore, Src inhibition blocked the [Pt(O,O'-acac)(gamma-acac)(DMS)]-provoked activation of PKC-epsilon, while ROS generation blockage inhibited the activation of Src, and also the decrement of phosphorylated FAK observed in detached [Pt(O,O'-acac)(gamma-acac)(DMS)]-treated cells. Sublethal concentrations of [Pt(O,O'-acac)(gamma-acac)(DMS)] induced anoikis and prevented events leading to metastasis via alterations in cell migration, anchorage independency, stromal interactions and MMP activity. Hence, [Pt(O,O'-acac)(gamma-acac)(DMS)] may be a promising therapeutic agent for preventing growth and metastasis of breast cancer.

  6. Modified Miniplates for Temporary Skeletal Anchorage in Orthodontics: Placement and Removal Surgeries

    Science.gov (United States)

    Cornelis, Marie A.; Scheffler, Nicole R.; Mahy, Pierre; Siciliano, Sergio; De Clerck, Hugo J.; Tulloch, J.F. Camilla

    2009-01-01

    Purpose Skeletal anchorage systems are increasingly used in orthodontics. This article describes the techniques of placement and removal of modified surgical miniplates used for temporary orthodontic anchorage and reports surgeons’ perceptions of their use. Patients and Methods We enrolled 97 consecutive orthodontic patients having miniplates placed as an adjunct to treatment. A total of 200 miniplates were placed by 9 oral surgeons. Patients and surgeons completed questionnaires after placement and removal surgeries. Results Fifteen miniplates needed to be removed prematurely. Antibiotics and anti-inflammatories were generally prescribed after placement but not after removal surgery. Most surgeries were performed with the patient under local anesthesia. Placement surgery lasted on average between 15 and 30 minutes per plate and was considered by the surgeons to be very easy to moderately easy. The surgery to remove the miniplates was considered easier and took less time. The patients’ chief complaint was swelling, lasting on average 5.3 ± 2.8 days after placement and 4.5 ± 2.6 days after removal. Conclusions Although miniplate placement/removal surgery requires the elevation of a flap, this was considered an easy and relatively short surgical procedure that can typically be performed with the patient under local anesthesia without complications, and it may be considered a safe and effective adjunct for orthodontic treatment. PMID:18571028

  7. A Manual for the Anchorage School District Bilingual Education Program Revised Scope and Sequence, K-3.

    Science.gov (United States)

    Heinrich, Maria Nieves Bumanlag Lilagan

    The manual offers a systematic set of procedures and relevant information to facilitate effective use of the Anchorage school district (ASD) bilingual education program (BEP). The historical background of the program's development is presented, available manuals for teaching English to limited English proficiency (LEP) students and related…

  8. Exposure time independent summary statistics for assessment of drug dependent cell line growth inhibition.

    Science.gov (United States)

    Falgreen, Steffen; Laursen, Maria Bach; Bødker, Julie Støve; Kjeldsen, Malene Krag; Schmitz, Alexander; Nyegaard, Mette; Johnsen, Hans Erik; Dybkær, Karen; Bøgsted, Martin

    2014-06-05

    In vitro generated dose-response curves of human cancer cell lines are widely used to develop new therapeutics. The curves are summarised by simplified statistics that ignore the conventionally used dose-response curves' dependency on drug exposure time and growth kinetics. This may lead to suboptimal exploitation of data and biased conclusions on the potential of the drug in question. Therefore we set out to improve the dose-response assessments by eliminating the impact of time dependency. First, a mathematical model for drug induced cell growth inhibition was formulated and used to derive novel dose-response curves and improved summary statistics that are independent of time under the proposed model. Next, a statistical analysis workflow for estimating the improved statistics was suggested consisting of 1) nonlinear regression models for estimation of cell counts and doubling times, 2) isotonic regression for modelling the suggested dose-response curves, and 3) resampling based method for assessing variation of the novel summary statistics. We document that conventionally used summary statistics for dose-response experiments depend on time so that fast growing cell lines compared to slowly growing ones are considered overly sensitive. The adequacy of the mathematical model is tested for doxorubicin and found to fit real data to an acceptable degree. Dose-response data from the NCI60 drug screen were used to illustrate the time dependency and demonstrate an adjustment correcting for it. The applicability of the workflow was illustrated by simulation and application on a doxorubicin growth inhibition screen. The simulations show that under the proposed mathematical model the suggested statistical workflow results in unbiased estimates of the time independent summary statistics. Variance estimates of the novel summary statistics are used to conclude that the doxorubicin screen covers a significant diverse range of responses ensuring it is useful for biological

  9. Menadione (Vitamin K3) induces apoptosis of human oral cancer cells and reduces their metastatic potential by modulating the expression of epithelial to mesenchymal transition markers and inhibiting migration.

    Science.gov (United States)

    Suresh, Shruthy; Raghu, Dinesh; Karunagaran, Devarajan

    2013-01-01

    Oral cancer is one of the most commonly occurring cancers worldwide, decreasing the patient's survival rate due to tumor recurrence and metastasis. Menadione (Vitamin K3) is known to exhibit cytotoxicity in various cancer cells but the present study focused on its effects on viability, apoptosis, epithelial to mesenchymal transition (EMT), anchorage independent growth and migration of oral cancer cells. The results show that menadione is more cytotoxic to SAS (oral squamous carcinoma) cells but not to non-tumorigenic HEK293 and HaCaT cells. Menadione treatment increased the expression of pro-apoptotic proteins, Bax and p53, with a concurrent decrease in anti-apoptotic proteins, Bcl-2 and p65. Menadione induced the expression of E-cadherin but reduced the expression of EMT markers, vimentin and fibronectin. Menadione also inhibited anchorage independent growth and migration in SAS cells. These findings reveal and confirm that menadione is a potential candidate in oral cancer therapy as it exhibits cytotoxic, antineoplastic and antimigratory effects besides effectively blocking EMT in oral cancer cells.

  10. Management of post midface distraction occlusal discrepancy using temporary anchorage devices in a cleft patient

    Directory of Open Access Journals (Sweden)

    N K Koteswara Prasad

    2015-01-01

    Full Text Available Open bite deformity following a successful midface advancement by distraction osteogenesis is a common complication. Temporary anchorage devices can be deployed during the distraction and post-distraction settling phases for restoring the occlusion even in severe cases. The following report describes the management of severe anterior open bite following maxillary distraction.

  11. Down-regulation of Survivin by Antisense Oligonucleotides Increases Apoptosis, Inhibits Cytokinesis and Anchorage-Independent Growth

    Directory of Open Access Journals (Sweden)

    Jun Chen

    2000-05-01

    Full Text Available Survivin, a member of the inhibitor of apoptosis protein (IAP family, is detected in most common human cancers but not in adjacent normal cells. Previous studies suggest that survivin associates with the mitotic spindle and directly inhibits caspase activity. To further investigate the function of survivin, we used a survivin antisense (AS oligonucleotide to downregulate survivin expression in normal and cancer cells. We found that inhibition of survivin expression increased apoptosis and polyploidy while decreasing colony formation in soft agar. Immunohistochemistry showed that cells without survivin can initiate the cleavage furrow and contractile ring, but cannot complete cytokinesis, thus resulting in multinucleated cells. These findings indicate that survivin plays important roles in a late stage of cytokinesis, as well as in apoptosis.

  12. A novel, substrate independent three-step process for the growth of uniform ZnO nanorod arrays

    International Nuclear Information System (INIS)

    Byrne, D.; McGlynn, E.; Henry, M.O.; Kumar, K.; Hughes, G.

    2010-01-01

    We report a three-step deposition process for uniform arrays of ZnO nanorods, involving chemical bath deposition of aligned seed layers followed by nanorod nucleation sites and subsequent vapour phase transport growth of nanorods. This combines chemical bath deposition techniques, which enable substrate independent seeding and nucleation site generation with vapour phase transport growth of high crystalline and optical quality ZnO nanorod arrays. Our data indicate that the three-step process produces uniform nanorod arrays with narrow and rather monodisperse rod diameters (∼ 70 nm) across substrates of centimetre dimensions. X-ray photoelectron spectroscopy, scanning electron microscopy and X-ray diffraction were used to study the growth mechanism and characterise the nanostructures.

  13. Mini-screw implant or transpalatal arch-mediated anchorage reinforcement during canine retraction: a randomized clinical trial.

    Science.gov (United States)

    Sharma, Mohit; Sharma, Vineet; Khanna, Bharat

    2012-06-01

    To compare mesial movement of upper first molars during maxillary canine retraction using a pre-adjusted edgewise appliance provided by anchorage reinforcement and a transpalatal arch or mini-screw implant. Randomized clinical trial. Department of Orthodontics and Dentofacial Orthopedics, Armed Forces Medical College, Pune, India. From a cohort of subjects requiring the extraction of both upper first premolars and pre-adjusted edgewise appliances to correct their malocclusion, a total of 30 were randomly allocated to receive two different forms of anchorage reinforcement: group A--receiving mini-screw implant and group B--receiving a transpalatal arch Group A subjects received titanium mini-screw implants placed at the start of treatment between the maxillary second premolar and maxillary first molar. Maxillary second premolars were secured to the mini-screw implants using of 0.010-inch stainless steel ligature wire. Group B subjects received a custom-made transpalatal arch which was soldered to maxillary first molar bands. Active canine retraction was initiated in both groups on placement of a 0.019×0.025-inch stainless steel archwire using nickel titanium closed coil springs. Mesial movement of the upper first molars as measured on pre- (T1) and post-treatment (T2) lateral skull radiographs. The results showed that in group A the mean mesial movement of the first molars between T1 and T2 was 0.0 mm (SD 0.02; P = 0.90), whereas in Group B there was a mean forward movement of the first maolars of 2.48 mm (SD 0.71; Pimplants placed prior to levelling and aligning were able to provide absolute anchorage during maxillary canine retraction, in contrast to a transpalatal arch.

  14. Orthodontic retreatment using anchorage with miniplate to camouflage a Class III skeletal pattern

    OpenAIRE

    Farret,Marcel Marchiori

    2016-01-01

    ABSTRACT This manuscript describes the treatment of a 27-year-old patient who was previously treated with two maxillary first premolar extractions. The patient had skeletal Class III malocclusion, Class III canine relationship, anterior crossbite, and a concave profile. As the patient refused orthognathic surgery, a miniplate was used on the right side of the lower arch as an anchorage unit after the extraction of mandibular first premolars, aiding the retraction of anterior teeth. At the end...

  15. Dental Extrusion with Orthodontic Miniscrew Anchorage: A Case Report Describing a Modified Method

    OpenAIRE

    Horliana, Ricardo Fidos; Horliana, Anna Carolina Ratto Tempestini; Wuo, Alexandre do Vale; Perez, Fl?vio Eduardo Guillin; Abr?o, Jorge

    2015-01-01

    In recent years, the skeletal anchorage through miniscrews has expanded the treatment options in orthodontics (Yamaguchi et al., 2012). We hereby present a modified method for tooth extrusion for cases where crown-lengthening surgery is contraindicated for aesthetic reasons. This modified method uses three orthodontic appliances: a mini-implant, an orthodontic wire, and a bracket. The aim of this case report was to increase the length of the clinical crown of a fractured tooth (tooth 23) by m...

  16. 77 FR 35104 - Notice of Request To Release Airport Property at Merrill Field Airport, Anchorage, AK

    Science.gov (United States)

    2012-06-12

    ... delivered to: Michelle Colby, Real Estate Services Manager, DOWL HKM, 4041 B Street, Anchorage, AK 99503...- 271-3665, email [email protected] or Michelle Colby, Real Estate Services Manager, DOWL HKM, 4041... Section 6.13 of the State of Alaska Right of Way Manual. This purchase offer was predicated on DOT&PF's...

  17. Efficacy of the Frame and Hu mathematical model for the quantitative analysis of agents influencing growth of chick embryo fibroblasts

    International Nuclear Information System (INIS)

    Korohoda, K.; Czyz, J.

    1994-01-01

    The experiments on the effect of various sera and substratum surface area upon growth of chick embryo fibroblasts-like in secondary cultures are described and discussed on the grounds of a mathematical model for growth of anchorage-dependent cells proposed by Frame and Hu. The model and presented results demonstrate the mutual independence of the effects of agent influencing of rate of cell proliferation (i.e. accelerating or retarding growth) and the agents that modify the limitation of cell proliferation (i.e. maximum cell density at confluence). The model proposed by Frame and Hu due to its relative simplicity offers and easy mode of description and quantitative evaluation of experiments concerning cell growth regulation. It is shown that various sera added at constant concentration significantly modify the rate of cell proliferation with little effect upon the maximum cell density attainable. The cells grew much more slowly in the presence of calf serum than in the presence of chick serum and the addition of iron and zinc complexes to calf serum significantly accelerated cell growth. An increase in the substratum surface area by the addition of glass wool to culture vessels significantly increased cell density per constant volume of medium even when retardation of growth was observed. The results presented point to the need of direct cell counting for estimation of cell growth curves and discussion of effects of agents influencing parameters characterizing cell proliferation. (author). 34 refs, 5 figs, 2 tabs

  18. Transfer and anchorage bond behaviour in self-compacting concrete

    Directory of Open Access Journals (Sweden)

    Rigueira-Víctor, J. W.

    2006-12-01

    Full Text Available Self-compacting concretes (SCC provide solutions to the problems facing precast concrete construction, enhancing competitiveness, reducing turnaround times and improving final product quality. SCC is fast becoming a key product for the future development of the precast pre-stressed concrete industry.The present paper compares the bond performance of SCC and traditional concrete (TC. The bond performance results confirm the viability of SCC in precast pre-stressed concrete manufacture, despite a slightly higher loss of pre-stressing force and slightly greater anchorage lengths in SCC with a low water/cement ratio. No differences in transfer or anchorage length were detected,however, when high strength TC and SCC were compared. The ECADA test method proved to be well suited to detecting the differences between the concretes analyzed.El desarrollo de los hormigones autocompactantes (SCCofrece muchas posibilidades a las construcciones con hormigón prefabricado, aumentando su competitividad, reduciéndolos plazos de fabricación y ofreciendo mejoras en la calidad del producto final. El SCC se está convirtiendo en un producto clave para el futuro desarrollo de la industria de prefabricados de hormigón pretensado.En este estudio se compara el comportamiento adherente de los SCC con el de los hormigones tradicionales (TC actuales. Los resultados obtenidos confirman la viabilidad del uso de los SCC para la fabricación de elementos prefabricados con hormigón pretensado, en lo relativo a su comportamiento adherente, aunque con la necesidad de considerar unas pérdidas de pretensado ligeramente mayores. Asimismo,debe esperarse un ligero aumento de las longitudes de anclaje cuando se trabaje con SCC de baja relación agua/cemento. Sin embargo, no se han detectado diferencias de comportamiento entre ambos tipos de hormigón cuando la resistencia a compresión es alta en lo relativo a las longitudes de transmisión y anclaje. El método de ensayo ECADA

  19. Digital lingual orthodontics and temporary anchorage devices for efficient biomechanics

    Directory of Open Access Journals (Sweden)

    Pravin Shetty

    2016-01-01

    Full Text Available Adult patients seeking orthodontic treatment at all times present with an esthetic demand even during treatment. The lingual orthodontics, apart from its esthetic values, also presents several other advantages. Currently, it has become a complete system in itself, starting from an accurate diagnosis, treatment protocol, and laboratory procedure to placement of the appliance in the patient′s mouth. With the advent of computer-aided design/computer-aided manufacturing system, the lingual orthodontics is more evolved and made ease operators in respect to more efficient mechanics and reduced archwire adjustments. The present article presents two cases to show the efficiency of lingual orthodontics with temporary anchorage devices and anterior retraction hook.

  20. Verification of the local structural response of building structures in the anchorage areas of heavy components

    International Nuclear Information System (INIS)

    Krutzik, N.J.; Tropp, R.

    1989-01-01

    In conventional dynamic structural analyses for determining dynamic system response for various locations at which components are installed inside the structures it is common practice (in order to simplify analytical effort) to assume that the anchorage (anchor plate, anchor bolts or throughbolts, concrete and reinforcement in the area of bound) has rigid body characteristics and that the building structure itself does not display any local response of its own. The influence of the stiffness of the anchor plate as well anchor bolts and its stress level on the dynamic response is also neglected. For a large number of anchoring systems, especially for all those components and systems having only a small mass, this assumption is certainly appropriate. At some locations, particularly at points where heavy components are anchored or when loading input has been increased, this can lead to local loading of the anchor system as well as of the building structure well into the nonlinear range. Often, verification of capability to accommodate these loads is not possible without changing the wall thicknesses or increasing the percentage of reinforcement. Since the presence of linear or nonlinear effects can be expected to result in energy dissipation (increase in damping capacity and also a change in the stiffness of the coupled system) it must be assumed that the dynamic response between the theoretical coupling point A and the real connection point B of the component on the anchor plate can be considerably altered. Some changes of the dynamic response in the connection point B have to be expected generally even in cases of linear-elastic loading of the anchorage. Using typical anchoring systems as an example, the influence of consideration of nonlinear effects in the anchorage area of a typical anchor plate on the dynamic response as well as the conservatism of conventional analytical approaches are investigated

  1. Probing non-standard gravity with the growth index: a background independent analysis

    International Nuclear Information System (INIS)

    Steigerwald, Heinrich; Marinoni, Christian; Bel, Julien

    2014-01-01

    Measurements of the growth index of linear matter density fluctuations γ(z) provide a clue as to whether Einstein's field equations encompass gravity also on large cosmic scales, those where the expansion of the universe accelerates. We show that the information encoded in this function can be satisfactorily parameterized using a small set of coefficients γ i , in such a way that the true scaling of the growth index is recovered to better than 1% in most dark energy and dark gravity models. We find that the likelihood of current data, given this formalism and the Λ Cold Dark Matter (ΛCDM) expansion model of Planck, is maximal for γ 0 = 0.74 +0.44 −0.41 and γ 1 = 0.01 +0.46 −0.46 , a measurement compatible with the ΛCDM predictions (γ 0 = 0.545, γ 1 = −0.007). In addition, data tend to favor models predicting slightly less growth of structures than the Planck ΛCDM scenario. The main aim of the paper is to provide a prescription for routinely calculating, in an analytic way, the amplitude of the growth indices γ i in relevant cosmological scenarios, and to show that these parameters naturally define a space where predictions of alternative theories of gravity can be compared against growth data in a manner which is independent from the expansion history of the cosmological background. As the standard Ω-plane provides a tool to identify different expansion histories H(t) and their relation to various cosmological models, the γ-plane can thus be used to locate different growth rate histories f(t) and their relation to alternatives model of gravity. As a result, we find that the Dvali-Gabadadze-Porrati gravity model is rejected with a 95% confidence level. By simulating future data sets, such as those that a Euclid-like mission will provide, we also show how to tell apart ΛCDM predictions from those of more extreme possibilities, such as smooth dark energy models, clustering quintessence or parameterized post-Friedmann cosmological models

  2. 78 FR 11745 - Anchorages; Lower Mississippi River, Above Head of Passes, Convent, LA and Point Pleasant, LA

    Science.gov (United States)

    2013-02-20

    ... able to maneuver in, around, and through the anchorage. Operators who choose to maneuver their vessels... respects the First Amendment rights of protesters. Protesters are asked to contact the person listed in the FOR FURTHER INTFORMATION CONTACT section to coordinate protest activities so that your message can be...

  3. Protein Kinase C alpha (PKCα) dependent signaling mediates endometrial cancer cell growth and tumorigenesis

    Science.gov (United States)

    Haughian, James M.; Reno, Elaine M.; Thorne, Alicia M.; Bradford, Andrew P.

    2009-01-01

    Endometrial cancer is the most common invasive gynecologic malignancy, yet molecular mechanisms and signaling pathways underlying its etiology and pathophysiology remain poorly characterized. We sought to define a functional role for the protein kinase C (PKC) isoform, PKCα, in an established cell model of endometrial adenocarcinoma. Ishikawa cells depleted of PKCα protein grew slower, formed fewer colonies in anchorage-independent growth assays and exhibited impaired xenograft tumor formation in nude mice. Consistent with impaired growth, PKCα knockdown increased levels of the cyclin dependent kinase (CDK) inhibitors p21Cip1/WAF1 (p21) and p27Kip1 (p27). Despite the absence of functional phosphatase and tensin homologue (PTEN) protein in Ishikawa cells, PKCα knockdown reduced Akt phosphorylation at serine 473 and concomitantly inhibited phosphorylation of the Akt target, glycogen synthase kinase-3β (GSK-3β). PKCα knockdown also resulted in decreased basal ERK phosphorylation and attenuated ERK activation following EGF stimulation. p21 and p27 expression was not increased by treatment of Ishikawa cells with ERK and Akt inhibitors, suggesting PKCα regulates CDK expression independently of Akt and ERK. Immunohistochemical analysis of grade 1 endometrioid adenocarcinoma revealed aberrant PKCα expression, with foci of elevated PKCα staining, not observed in normal endometrium. These studies demonstrate a critical role for PKCα signaling in endometrial tumorigenesis by regulating expression of CDK inhibitors p21 and p27 and activation of Akt and ERK dependent proliferative pathways. Thus, targeting PKCα may provide novel therapeutic options in endometrial tumors. PMID:19672862

  4. Kalimantan energy resource management to support energy independence and industry growth

    International Nuclear Information System (INIS)

    Rizki Firmansyah Setya Budi; Wiku Lulus Widodo; Djati Hoesen Salimy

    2014-01-01

    There are a large number of energy resource in Kalimantan such as coal, oil, CBM, gas and nuclear. While the electricity consumption still low. That condition caused by the bad energy planning. The aim of the study are to know the number and the ability of energy resource to supply the energy demand that support the growth of Kalimantan industry. The methodology are collecting and processing data through calculation using MESSAGE Program. The result is energy resource in Kalimantan can support Kalimantan energy independence and industry growth in Kalimantan. The coal resource is 34,814 million ton consumption 835 million ton, gas resource is 31,814 BSCF consumption 3,281 BSCF, Oil resource is 920 MMSTB consumption 4406 MMSTB, CBM resource is 210 TCF consumption 2.1 TCF, U 3 O 8 resource is 12,409 ton consumption zero. Whereas for hydro and biomass, the resource are 256 and 138 MWyr, the maximum consumption 185 and 126 MWyr every year. Oil consumption will exceed the resource so need import from other island or replaced by others energy that have large resource such as gas, CBM, or coal. Potency to make cleaner environment can be done by used nuclear energy. (author)

  5. Mechanical anchorage of FRP tendons – A literature review

    DEFF Research Database (Denmark)

    Schmidt, Jacob W.; Bennitz, Anders; Täljsten, Björn

    2012-01-01

    High tensile strength, good resistance to degradation and creep, low weight and, to some extent, the ability to change the modulus of elasticity are some of the advantages of using prestressed, unidirectional FRP (Fibre Reinforced Polymer) tendon systems. Bonded and non-bonded versions of these s......High tensile strength, good resistance to degradation and creep, low weight and, to some extent, the ability to change the modulus of elasticity are some of the advantages of using prestressed, unidirectional FRP (Fibre Reinforced Polymer) tendon systems. Bonded and non-bonded versions...... with such systems. This is especially important in external post-tensioned tendon systems, where the anchorage points are exposed to the full load throughout the life span of the structure. Consequently, there are large requirements related to the long-term capacity and fatigue resistance of such systems. Several...

  6. 33 CFR 110.236 - Pacific Ocean off Barbers Point, Island of Oahu, Hawaii: Offshore pipeline terminal anchorages.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Pacific Ocean off Barbers Point... Grounds § 110.236 Pacific Ocean off Barbers Point, Island of Oahu, Hawaii: Offshore pipeline terminal... regulations. (1) No vessels may anchor, moor, or navigate in anchorages A, B, C, or D except: (i) Vessels...

  7. Asymmetrical distalization of maxillary molars with zygomatic anchorage, improved superelastic nickel-titanium alloy wires, and open-coil springs.

    Science.gov (United States)

    Ishida, Takayoshi; Yoon, Hyung Sik; Ono, Takashi

    2013-10-01

    In nongrowing patients with skeletal Class II malocclusion, premolar extraction or maxillary distalization can be used as camouflage treatment. Zygomatic anchorage enables distalization in uncooperative or noncompliant patients. We describe 1 such procedure in a 24-year-old woman. We used novel improved superelastic nickel-titanium archwires combined with nickel-titanium open-coil springs to provide a constant and continuous low force to the dentition. We were able to successfully eliminate the protrusive profile and correct the Class II molar relationship using this system of zygomatic anchorage. The posterior occlusal relationships were improved to achieve Class I canine and molar relationships on both sides, and ideal overbite and overjet relationships were established. Facial esthetics was improved with decreased protrusion of the upper and lower lips. The method used here is a promising alternative to traditional distalization techniques and might offer an effective and simple means of distalizing maxillary molars in uncooperative patients. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  8. Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain.

    Directory of Open Access Journals (Sweden)

    Jeffrey C Lee

    2006-12-01

    Full Text Available Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant transformation, and appear to be a major determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy.Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR coding sequence in glioma tumor samples and cell lines. We identified novel missense mutations in the extracellular domain of EGFR in 13.6% (18/132 of glioblastomas and 12.5% (1/8 of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR kinase inhibitors.Our results suggest extracellular missense mutations as a novel mechanism for oncogenic EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for treatment of glioblastoma.

  9. Expression of activated PIK3CA in ovarian surface epithelium results in hyperplasia but not tumor formation.

    Directory of Open Access Journals (Sweden)

    Shun Liang

    Full Text Available The Phosphatidylinositol 3'-kinase is a key regulator in various cancer-associated signal transduction pathways. Genetic alterations of its catalytic subunit alpha, PIK3CA, have been identified in ovarian cancer. Our in vivo data suggests that PIK3CA activation is one of the early genetic events in ovarian cancer. However, its role in malignant transformation of ovarian surface epithelium (OSE is largely unclear.Using the Müllerian inhibiting substance type II receptor (MISIIR promoter, we generated transgenic mice that expressed activated PIK3CA in the Müllerian epithelium. Overexpression of PIK3CA in OSE induced remarkable hyperplasia, but was not able to malignantly transform OSE in vivo. The consistent result was also observed in primary cultured OSEs. Although enforced expression of PIK3CA could not induce OSE anchorage-independent growth, it significantly increased anchorage-independent growth of OSE transformed by mutant K-ras.While PIK3CA activation may not be able to initiate OSE transformation, we conclude that activation of PIK3CA may be an important molecular event contributing to the maintenance of OSE transformation initiated by oncogenes such as K-ras.

  10. Dental extrusion with orthodontic miniscrew anchorage: a case report describing a modified method.

    Science.gov (United States)

    Horliana, Ricardo Fidos; Horliana, Anna Carolina Ratto Tempestini; Wuo, Alexandre do Vale; Perez, Flávio Eduardo Guillin; Abrão, Jorge

    2015-01-01

    In recent years, the skeletal anchorage through miniscrews has expanded the treatment options in orthodontics (Yamaguchi et al., 2012). We hereby present a modified method for tooth extrusion for cases where crown-lengthening surgery is contraindicated for aesthetic reasons. This modified method uses three orthodontic appliances: a mini-implant, an orthodontic wire, and a bracket. The aim of this case report was to increase the length of the clinical crown of a fractured tooth (tooth 23) by means of an orthodontic extrusion with the modified method of Roth and Diedrich.

  11. Expression and functional role of orphan receptor GPR158 in prostate cancer growth and progression.

    Directory of Open Access Journals (Sweden)

    Nitin Patel

    Full Text Available Prostate cancer (PCa is the second-leading cause of cancer-related mortality, after lung cancer, in men from developed countries. In its early stages, primary tumor growth is dependent on androgens, thus generally can be controlled by androgen deprivation therapy (ADT. Eventually however, the disease progresses to castration-resistant prostate cancer (CRPC, a lethal form in need of more effective treatments. G-protein coupled receptors (GPCRs comprise a large clan of cell surface proteins that have been implicated as therapeutic targets in PCa growth and progression. The findings reported here provide intriguing evidence of a role for the newly characterized glutamate family member GPR158 in PCa growth and progression. We found that GPR158 promotes PCa cell proliferation independent of androgen receptor (AR functionality and that this requires its localization in the nucleus of the cell. This suggests that GPR158 acts by mechanisms different from other GPCRs. GPR158 expression is stimulated by androgens and GPR158 stimulates AR expression, implying a potential to sensitize tumors to low androgen conditions during ADT via a positive feedback loop. Further, we found GPR158 expression correlates with a neuroendocrine (NE differentiation phenotype and promotes anchorage-independent colony formation implying a role for GPR158 in therapeutic progression and tumor formation. GPR158 expression was increased at the invading front of prostate tumors that formed in the genetically defined conditional Pten knockout mouse model, and co-localized with elevated AR expression in the cell nucleus. Kaplan-Meier analysis on a dataset from the Memorial Sloan Kettering cancer genome portal showed that increased GPR158 expression in tumors is associated with lower disease-free survival. Our findings strongly suggest that pharmaceuticals targeting GPR158 activities could represent a novel and innovative approach to the prevention and management of CRPC.

  12. HOXB13 promotes androgen independent growth of LNCaP prostate cancer cells by the activation of E2F signaling

    Directory of Open Access Journals (Sweden)

    Choi Chan

    2010-05-01

    Full Text Available Abstract Background Androgen signaling plays a critical role in the development of prostate cancer and its progression. However, androgen-independent prostate cancer cells emerge after hormone ablation therapy, resulting in significant clinical problems. We have previously demonstrated that the HOXB13 homeodomain protein functions as a prostate cancer cell growth suppressor by inhibiting androgen-mediated signals. However, the role of the HOXB13 in androgen-independent growth of prostate cancer cells remains unexplained. Results In this report, we first demonstrated that HOXB13 was highly overexpressed in hormone-refractory tumors compared to tumors without prostate-specific antigen after initial treatment. Functionally, in an androgen-free environment minimal induction of HOXB13 in LNCaP prostate cancer cells, to the level of the normal prostate, markedly promoted cell proliferation while suppression inhibited cell proliferation. The HOXB13-mediated cell growth promotion in the absence of androgen, appears to be mainly accomplished through the activation of RB-E2F signaling by inhibiting the expression of the p21waf tumor suppressor. Indeed, forced expression of HOXB13 dramatically decreased expression of p21waf; this inhibition largely affected HOXB13-mediated promotion of E2F signaling. Conclusions Taken together, the results of this study demonstrated the presence of a novel pathway that helps understand androgen-independent survival of prostate cancer cells. These findings suggest that upregulation of HOXB13 is associated with an additive growth advantage of prostate cancer cells in the absence of or low androgen concentrations, by the regulation of p21-mediated E2F signaling.

  13. ING3 promotes prostate cancer growth by activating the androgen receptor.

    Science.gov (United States)

    Nabbi, Arash; McClurg, Urszula L; Thalappilly, Subhash; Almami, Amal; Mobahat, Mahsa; Bismar, Tarek A; Binda, Olivier; Riabowol, Karl T

    2017-05-16

    The androgen receptor (AR) is a major driver of prostate cancer, and increased AR levels and co-activators of the receptor promote the development of prostate cancer. INhibitor of Growth (ING) proteins target lysine acetyltransferase or lysine deacetylase complexes to the histone H3K4Me3 mark of active transcription, to affect chromatin structure and gene expression. ING3 is a stoichiometric member of the TIP60 lysine acetyltransferase complex implicated in prostate cancer development. Biopsies of 265 patients with prostate cancer were stained for ING3, pan-cytokeratin, and DNA. LNCaP and C4-2 androgen-responsive cells were used for in vitro assays including immunoprecipitation, western blotting, Luciferase reporter assay and quantitative polymerase chain reaction. Cell viability and migration assays were performed in prostate cancer cell lines using scrambled siRNA or siRNA targeting ING3. We find that ING3 levels and AR activity positively correlate in prostate cancer. ING3 potentiates androgen effects, increasing expression of androgen-regulated genes and androgen response element-driven reporters to promote growth and anchorage-independent growth. Conversely, ING3 knockdown inhibits prostate cancer cell growth and invasion. ING3 activates the AR by serving as a scaffold to increase interaction between TIP60 and the AR in the cytoplasm, enhancing receptor acetylation and translocation to the nucleus. Activation is independent of ING3's ability to target the TIP60 complex to H3K4Me3, identifying a previously unknown chromatin-independent cytoplasmic activity for ING3. In agreement with in vitro observations, analysis of The Cancer Genome Atlas (TCGA) data (n = 498) and a prostate cancer tissue microarray (n = 256) show that ING3 levels are higher in aggressive prostate cancers, with high levels of ING3 predicting shorter patient survival in a low AR subgroup. Including ING3 levels with currently used indicators such as the Gleason score provides more

  14. Differential effects of miR-34c-3p and miR-34c-5p on SiHa cells proliferation apoptosis, migration and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, Jesus Adrian [Laboratorio de Terapia Genica, Departamento de Genetica y Biologia Molecular, CINVESTAV, Av. IPN 2508, Mexico 07360 D.F. (Mexico); Alvarez-Salas, Luis Marat, E-mail: lalvarez@cinvestav.mx [Laboratorio de Terapia Genica, Departamento de Genetica y Biologia Molecular, CINVESTAV, Av. IPN 2508, Mexico 07360 D.F. (Mexico)

    2011-06-10

    Highlights: {yields} In this study we examine miR-34c-3p and miR-34c-5p functions in SiHa cells. {yields} We study miRNA effect on cell proliferation, anchorage independent growth, apoptosis, cell motility and invasion. {yields} We find that miR-34c-3p and miR-34c-5p inhibition of proliferation and anchorage independent growth are exclusive to SiHa cells. {yields} miR-34c-3p induces apoptosis and inhibits cell motility and invasion in SiHa cells. {yields} In this study we conclude that miR-34c-3p functions as a tumor suppressor differ from miR-34c-5p. -- Abstract: MicroRNAs (miRNA) regulate expression of several genes associated with human cancer. Here, we analyzed the function of miR-34c, an effector of p53, in cervical carcinoma cells. Expression of either miR-34c-3p or miR-34c-5p mimics caused inhibition of cell proliferation in the HPV-containing SiHa cells but not in other cervical cells irrespective of tumorigenicity and HPV content. These results suggest that SiHa cells may lack of regulatory mechanisms for miR-34c. Monolayer proliferation results showed that miR-34c-3p produced a more pronounced inhibitory effect although both miRNAs caused inhibition of anchorage independent growth at similar extent. However, ectopic expression of pre-miR-34c-3p, but not pre-miR-34c-5p, caused S-phase arrest in SiHa cells triggering a strong dose-dependent apoptosis. A significant inhibition was observed only for miR-34c-3p on SiHa cells migration and invasion, therefore implying alternative regulatory pathways and targets. These results suggest differential tumor suppressor roles for miR-34c-3p and miR-34c-5p and provide new insights in the understanding of miRNA biology.

  15. Differential effects of miR-34c-3p and miR-34c-5p on SiHa cells proliferation apoptosis, migration and invasion

    International Nuclear Information System (INIS)

    Lopez, Jesus Adrian; Alvarez-Salas, Luis Marat

    2011-01-01

    Highlights: → In this study we examine miR-34c-3p and miR-34c-5p functions in SiHa cells. → We study miRNA effect on cell proliferation, anchorage independent growth, apoptosis, cell motility and invasion. → We find that miR-34c-3p and miR-34c-5p inhibition of proliferation and anchorage independent growth are exclusive to SiHa cells. → miR-34c-3p induces apoptosis and inhibits cell motility and invasion in SiHa cells. → In this study we conclude that miR-34c-3p functions as a tumor suppressor differ from miR-34c-5p. -- Abstract: MicroRNAs (miRNA) regulate expression of several genes associated with human cancer. Here, we analyzed the function of miR-34c, an effector of p53, in cervical carcinoma cells. Expression of either miR-34c-3p or miR-34c-5p mimics caused inhibition of cell proliferation in the HPV-containing SiHa cells but not in other cervical cells irrespective of tumorigenicity and HPV content. These results suggest that SiHa cells may lack of regulatory mechanisms for miR-34c. Monolayer proliferation results showed that miR-34c-3p produced a more pronounced inhibitory effect although both miRNAs caused inhibition of anchorage independent growth at similar extent. However, ectopic expression of pre-miR-34c-3p, but not pre-miR-34c-5p, caused S-phase arrest in SiHa cells triggering a strong dose-dependent apoptosis. A significant inhibition was observed only for miR-34c-3p on SiHa cells migration and invasion, therefore implying alternative regulatory pathways and targets. These results suggest differential tumor suppressor roles for miR-34c-3p and miR-34c-5p and provide new insights in the understanding of miRNA biology.

  16. Advances in cell culture: anchorage dependence

    Science.gov (United States)

    Merten, Otto-Wilhelm

    2015-01-01

    Anchorage-dependent cells are of great interest for various biotechnological applications. (i) They represent a formidable production means of viruses for vaccination purposes at very large scales (in 1000–6000 l reactors) using microcarriers, and in the last decade many more novel viral vaccines have been developed using this production technology. (ii) With the advent of stem cells and their use/potential use in clinics for cell therapy and regenerative medicine purposes, the development of novel culture devices and technologies for adherent cells has accelerated greatly with a view to the large-scale expansion of these cells. Presently, the really scalable systems—microcarrier/microcarrier-clump cultures using stirred-tank reactors—for the expansion of stem cells are still in their infancy. Only laboratory scale reactors of maximally 2.5 l working volume have been evaluated because thorough knowledge and basic understanding of critical issues with respect to cell expansion while retaining pluripotency and differentiation potential, and the impact of the culture environment on stem cell fate, etc., are still lacking and require further studies. This article gives an overview on critical issues common to all cell culture systems for adherent cells as well as specifics for different types of stem cells in view of small- and large-scale cell expansion and production processes. PMID:25533097

  17. Teacher Certification and Academic Growth among English Learner Students in the Houston Independent School District. REL 2018-284

    Science.gov (United States)

    Ruiz de Castilla, Verónica

    2018-01-01

    Aware of the challenges set before the Houston Independent school District by rapid growth in the numbers of English learner students, and a critical shortage of teachers with bilingual certification for more than a decade, members of Regional Educational Laboratory Southwest's English Learners Research Alliance sought information that districts…

  18. Gamma-Klotho exhibits multiple roles in tumor growth of human bladder cancer.

    Science.gov (United States)

    Hori, Shunta; Miyake, Makito; Tatsumi, Yoshihiro; Morizawa, Yosuke; Nakai, Yasushi; Onishi, Sayuri; Onishi, Kenta; Iida, Kota; Gotoh, Daisuke; Tanaka, Nobumichi; Fujimoto, Kiyohide

    2018-04-13

    Alpha-Klotho (KLα) and beta-Klotho (KLβ) have recently been reported to correlate with cancer prognosis in some malignancies and we previously reported the association between KLα, KLβ, and urothelial carcinoma of the bladder (UCB), indicating that KLβ acts as a tumor promoter. However, the association between gamma-Klotho (KLγ) and cancer prognosis remains unclear. In the present study, we evaluated the association between KLγ and UCB. To evaluate the effect of KLγ on human bladder cancer cell lines in vitro assays were performed. Exogenous KLγ increased the ability of human bladder cancer cells to proliferate, migrate, invade, form colonies, and provide anchorage-independent growth potential. In in vivo assays, eighteen mice bearing xenografts inoculated using UM-UC-3, were randomly divided into three groups and treated with a small interfering RNA (siRNA) by intratumoral administration once a week for four weeks. Knockdown of KLγ with siRNA led to a dramatic change in tumor growth and suggested that KLγ had effects on tumor growth, including promotion of cell proliferation, inhibition of apoptosis, and enhancement of the epithelial-mesenchymal transition. To confirm the study, human tissue samples were used and patients were divided into two groups according to KLγ expression level. High expression of KLγ was significantly associated with higher stage and grade cancer and the presence of lymphovascular invasion compared to patients with lower expression of KLγ. Our results suggest that KLγ plays an important role in tumor invasion and progression and these results may lead to the development of new therapies and diagnostic methods for UCB.

  19. Increased linear bone growth by GH in the absence of SOCS2 is independent of IGF-1.

    Science.gov (United States)

    Dobie, Ross; Ahmed, Syed F; Staines, Katherine A; Pass, Chloe; Jasim, Seema; MacRae, Vicky E; Farquharson, Colin

    2015-11-01

    Growth hormone (GH) signaling is essential for postnatal linear bone growth, but the relative importance of GHs actions on the liver and/or growth plate cartilage remains unclear. The importance of liver derived insulin like-growth factor-1 (IGF-1) for endochondral growth has recently been challenged. Here, we investigate linear growth in Suppressor of Cytokine Signaling-2 (SOCS2) knockout mice, which have enhanced growth despite normal systemic GH/IGF-1 levels. Wild-type embryonic ex vivo metatarsals failed to exhibit increased linear growth in response to GH, but displayed increased Socs2 transcript levels (P growth over a 12 day period. Despite this increase, IGF-1 transcript and protein levels were not increased in response to GH. In accordance with these data, IGF-1 levels were unchanged in GH-challenged postnatal Socs2(-/-) conditioned medium despite metatarsals showing enhanced linear growth. Growth-plate Igf1 mRNA levels were not elevated in juvenile Socs2(-/-) mice. GH did however elevate IGF-binding protein 3 levels in conditioned medium from GH challenged metatarsals and this was more apparent in Socs2(-/-) metatarsals. GH did not enhance the growth of Socs2(-/-) metatarsals when the IGF receptor was inhibited, suggesting that IGF receptor mediated mechanisms are required. IGF-2 may be responsible as IGF-2 promoted metatarsal growth and Igf2 expression was elevated in Socs2(-/-) (but not WT) metatarsals in response to GH. These studies emphasise the critical importance of SOCS2 in regulating GHs ability to promote bone growth. Also, GH appears to act directly on the metatarsals of Socs2(-/-) mice, promoting growth via a mechanism that is independent of IGF-1. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  20. Bio-cultural anchorage of the prickly pear cactus in Tlalnepantla (Morelos, Mexico

    Directory of Open Access Journals (Sweden)

    Torres-Salcido, Gerardo

    2016-06-01

    Full Text Available The prickly pear cactus is a source of food with strong bio-cultural anchorage in Mexico. This is due to at least three factors: 1 the nature and heritage of cacti; 2 cultural heritage; and 3 the socio-cultural relationships with historical and symbolic roots that have facilitated knowledge of how to cultivate it and how to use it. The aim of this article is to put factors of territorial anchorage and its historical transformation in context by examining the case of the municipality of Tlalnepantla in the state of Morelos, Mexico. This community has experienced accelerated change due to the exchange of traditional crops for the prickly pear cactus and the integration of farming, commercialization and agro-transformation. Our hypothesis is that the market, internal conflicts and a lack of socio-institutional coordination have put social organization into crisis, favoring the territorial spread of the prickly pear cactus and making the Local Agro-Food Systems (LAFS of Tlalnepantla less competitive. The conclusions highlight important economic and social advances whose roots lie in the strengthening and anchorage of the territory-product. However, circumstances both internal and external to the community persist, such as intra-community conflicts, the international market and cultural paradigm shifts that affect the producers and put consolidation of the LAFS at risk.El nopal es un alimento con un fuerte anclaje bio-cultural en México, propiciado por al menos tres factores: 1 la naturaleza y el patrimonio de cactáceas; 2 el patrimonio cultural; y, 3 las relaciones socio-culturales que han permitido un “saber hacer” y un “saber utilizar” con raíces históricas y simbólicas. El objetivo es situar los factores de anclaje territorial y su transformación histórica tomando como caso el municipio de Tlalnepantla, en el estado de Morelos, México. Esta comunidad ha experimentado un acelerado cambio por la reconversión de los cultivos

  1. Neurotensin-induced Erk1/2 phosphorylation and growth of human colonic cancer cells are independent from growth factors receptors activation

    Energy Technology Data Exchange (ETDEWEB)

    Massa, Fabienne; Tormo, Aurelie; Beraud-Dufour, Sophie; Coppola, Thierry [Institut de Pharmacologie Moleculaire et Cellulaire, Universite de Nice-Sophia Antipolis, CNRS UMR 6097, 660 route des Lucioles, 06560 Valbonne (France); Mazella, Jean, E-mail: mazella@ipmc.cnrs.fr [Institut de Pharmacologie Moleculaire et Cellulaire, Universite de Nice-Sophia Antipolis, CNRS UMR 6097, 660 route des Lucioles, 06560 Valbonne (France)

    2011-10-14

    Highlights: {yields} We compare intracellular pathways of NT and EGF in HT29 cells. {yields} NT does not transactivate EGFR. {yields} Transactivation of EGFR is not a general rule in cancer cell growth. -- Abstract: Neurotensin (NT) promotes the proliferation of human colonic cancer cells by undefined mechanisms. We already demonstrated that, in the human colon adenocarcinoma cell line HT29, the effects of NT were mediated by a complex formed between the NT receptor-1 (NTSR1) and-3 (NTSR3). Here we examined cellular mechanisms that led to NT-induced MAP kinase phosphorylation and growth factors receptors transactivation in colonic cancer cells and proliferation in HT29 cells. With the aim to identify upstream signaling involved in NT-elicited MAP kinase activation, we found that the stimulatory effects of the peptide were totally independent from the activation of the epidermal growth factor receptor (EGFR) both in the HT29 and the HCT116 cells. NT was unable to promote phosphorylation of EGFR and to compete with EGF for its binding to the receptor. Pharmacological approaches allowed us to differentiate EGF and NT signaling in HT29 cells since only NT activation of Erk1/2 was shown to be sensitive to PKC inhibitors and since only NT increased the intracellular level of calcium. We also observed that NT was not able to transactivate Insulin-like growth factor receptor. Our findings indicate that, in the HT29 and HCT116 cell lines, NT stimulates MAP kinase phosphorylation and cell growth by a pathway which does not involve EGF system but rather NT receptors which transduce their own intracellular effectors. These results indicate that depending on the cell line used, blocking EGFR is not the general rule to inhibit NT-induced cancer cell proliferation.

  2. Prestressed CFRP Strips with Gradient Anchorage for Structural Concrete Retrofitting: Experiments and Numerical Modeling

    Directory of Open Access Journals (Sweden)

    Julien Michels

    2014-01-01

    Full Text Available This paper presents a study on the load carrying capacity of reinforced concrete (RC beams strengthened with externally bonded (EB carbon fiber reinforced polymer (CFRP strips prestressed up to 0.6% in strain. At the strip ends, the innovative gradient anchorage is used instead of conventional mechanical fasteners. This method, based on the epoxy resin’s ability to rapidly cure under high temperatures, foresees a sector-wise heating followed by a gradual decrease of the initial prestress force towards the strip ends. The experimental investigation shows a promising structural behavior, resulting in high strip tensile strains, eventually almost reaching tensile failure of the composite strip. Additionally, ductility when considering deflection at steel yielding and at ultimate load is satisfying, too. From a practical point of view, it is demonstrated that premature strip grinding in the anchorage zone is not beneficial. In addition, a non-commercial 1D finite element code has been enlarged to an EB reinforcement with prestressed composite strips. A bilinear bond stress-slip relation obtained in earlier investigations is introduced as an additional failure criterion to the code. The numerical code is able to almost perfectly predict the overall structural behavior. Furthermore, the calculations are used for comparison purposes between an initially unstressed and a prestressed externally bonded composite reinforcement. The increase in cracking and yielding load, as well as differences in structural stiffness are apparent.

  3. Verification of the local structural response of building structures in the anchorage areas of heavy components

    International Nuclear Information System (INIS)

    Krutzik, N.J.; Tropp, R.

    1993-01-01

    In both nuclear and non-nuclear areas of power plants, sections of structures, parts of systems and components are attached to walls and floors by means of anchor plates with bolts, anchor sleeves and bolts and through bolts arranged either in groups or individually. In order to simplify the determination of the transfered vibrations induced by external events (e.g. earthquake, aircraft crash), it is normally assumed that the nodal point between component and concrete possesses rigid body characteristics and the building structure (walls, floors) is also inflexible in the anchorage area. In the course of the parametric studies performed, the nonlinear effects on the anchorage area of a component (in this case an anchor plate and concrete slab) were calculated and the effect of these on the actual vibration behavior and the local structural responses of the building structure at the place of installation of heavy components were investigated. The investigations performed reveal that by taking into account the local behaviour in the anchoring point, it is possible to reduce the dynamic response considerably. More detailed examination of the influence of additional parameters (especially of the geometry of the anchor plates and anchor bolts and their material characteristics) will require further investigations aimed at establishing the characteristics of typical anchor plates. (orig.)

  4. Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity

    International Nuclear Information System (INIS)

    Powell, Ashley A; Akare, Sandeep; Qi, Wenqing; Herzer, Pascal; Jean-Louis, Samira; Feldman, Rebecca A; Martinez, Jesse D

    2006-01-01

    There is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA. To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis. We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth. We conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype

  5. Design of steel-liners and their anchorage with regard to non-linear behaviour of liner-material and anchorage

    International Nuclear Information System (INIS)

    Oberpichler, R.

    1979-01-01

    The thin steel liner attached by studs or rib-type anchors to the interior wall of a Prestressed Concrete Reactor Pressure Vessel (PCRV) or a Concrete Containment Vessel (PCCV) has to provide the leak-tightness of the vessel. The liner also may serve as internal shuttering for placing concrete as well as a support for the cooling system or thermal isolation. Mainly strained by self-limited loads imposed on the liner by deformations of the vessel-wall or by heatup inside the vessel the liner predominantly will function in a compressive biaxially strained state like a membrane. The vessel-wall is assumed to be a rigid boundary without reactions caused by the liner-anchor-restraints. Furthermore it is assumed that the liner supported in a close-spaced pattern to the concrete with respect to self-limited loads and all effects of non-linear behaviour of liner-material and non-linear anchor-characteristics will not fail by instability, especially not by an effect of snapthrough. Only one essential mode of failure, the shear connector failure is assumed to be basis for all liner investigations. Design of the liner and its anchorage therefore is based on the analysis of large deformations with regard to elastic-plastic behaviour of liner-material and non-linear anchor characteristics. By this method both economical and safe sizing and spacing of the anchors can be calculated. (orig.)

  6. Radiation leukemia virus and x-irradiation induce in C57BL/6 mice two distinct T-cell neoplasms: a growth factor-dependent lymphoma and a growth factor-independent lymphoma

    International Nuclear Information System (INIS)

    Haas, Martin; Rothenberg, Ellen; Bogart, M.H.; Jones, O.W.

    1987-01-01

    Two different classes of neoplastic T cells were isolated from radiation leukemia virus (RadLV)-inoculated and from X-ray-treated C57BL/6 mice. One consisted of growth factor-dependent T-cell lymphoma (FD-TCL) lines which were established from the spleens and thymuses of treated mice within a day of lymphoma detection. Non-thymic, factor-dependent TCL cells produced interleukin-2 upon lectin stimulation, and were autostimulatory because they secreted growth factor(s) constitutively. In vivo, FD-TCL cells that were injected intraperitoneally or intravenously homed to the spleen, proliferated in it and killed the injected mice. The isolation and study of FD-TCL cells was facilitated by their cultivation on stromal hematopoietic monolayers in supplemented ''lymphocyte medium'', until an autostimulating, self-sustaining concentration of FD-TCL cells was obtained. FD-TCL cells could not be grown from lymphoid tissue of normal, control mice. In contrast, T-cell lymphoma (TCL) lines, which were established from virus-induced thymomas which had been kept in situ for 4-6 weeks after detection, consisted of factor-independent cells that possessed an aneuploid karyotype. The phenotypic markers of TCL cells differed from those of FD-TCL cells, suggesting heterogeneity in the stages of differentiation at which cells can give rise to growth factor-independent (TCL) and to growth factor-dependent (FD-TCL) lines. (author)

  7. Growth platform-dependent and -independent phenotypic and metabolic responses of Arabidopsis and its halophytic relative, Eutrema salsugineum, to salt stress.

    Science.gov (United States)

    Kazachkova, Yana; Batushansky, Albert; Cisneros, Aroldo; Tel-Zur, Noemi; Fait, Aaron; Barak, Simon

    2013-07-01

    Comparative studies of the stress-tolerant Arabidopsis (Arabidopsis thaliana) halophytic relative, Eutrema salsugineum, have proven a fruitful approach to understanding natural stress tolerance. Here, we performed comparative phenotyping of Arabidopsis and E. salsugineum vegetative development under control and salt-stress conditions, and then compared the metabolic responses of the two species on different growth platforms in a defined leaf developmental stage. Our results reveal both growth platform-dependent and -independent phenotypes and metabolic responses. Leaf emergence was affected in a similar way in both species grown in vitro but the effects observed in Arabidopsis occurred at higher salt concentrations in E. salsugineum. No differences in leaf emergence were observed on soil. A new effect of a salt-mediated reduction in E. salsugineum leaf area was unmasked. On soil, leaf area reduction in E. salsugineum was mainly due to a fall in cell number, whereas both cell number and cell size contributed to the decrease in Arabidopsis leaf area. Common growth platform-independent leaf metabolic signatures such as high raffinose and malate, and low fumarate contents that could reflect core stress tolerance mechanisms, as well as growth platform-dependent metabolic responses were identified. In particular, the in vitro growth platform led to repression of accumulation of many metabolites including sugars, sugar phosphates, and amino acids in E. salsugineum compared with the soil system where these same metabolites accumulated to higher levels in E. salsugineum than in Arabidopsis. The observation that E. salsugineum maintains salt tolerance despite growth platform-specific phenotypes and metabolic responses suggests a considerable degree of phenotypic and metabolic adaptive plasticity in this extremophile.

  8. Maxillary protraction in adult cleft lip and palate by a rigid external distraction device with dentoskeletal anchorage

    Science.gov (United States)

    Akarsu, Bengisu; Taner, Tulin; Tuncbilek, Gokhan; Mavili, M. Emin

    2012-01-01

    Objective: The objective is to evaluate the effects of maxillary distraction osteogenesis (DO) in an adult patient with unilateral cleft lip and palate (UCLP) by using a rigid external distraction (RED) device with dentoskeletal anchorage. Method: 31-year-old male patient with UCLP with severe maxillary hypoplasia, dolichofacial growth pattern, negative overjet and 1.5 mm openbite. After pre-surgical orthodontic treatment, an intra-oral appliance was modified to prevent extrusion of the molars and clockwise rotation of the mandible. Stainless steel plates were soldered bilaterally to the intra oral appliance at the level of canines. During surgery, miniplates were inserted in the maxillary segment and fixed to the plates of the intra oral appliance with screws. Results: The mean distraction length was 12 mm immediately after DO. SNA increased from 73o to 82o after distraction. A significant advancement of the maxilla and correction of the sagittal Class III skeletal relationship was achieved. The vertical position of the mandible and the face was kept stable, and the soft tissue profile became more balanced. Conclusion: This intra oral appliance design achieved desired skeletal changes during maxillary protraction with RED device in dolichofacial CLP patient. Occlusion and facial profile changes was found to be stable in 1-year follow-up. PMID:22509125

  9. Maxillary protraction in adult cleft lip and palate by a rigid external distraction device with dentoskeletal anchorage.

    Science.gov (United States)

    Akarsu, Bengisu; Taner, Tulin; Tuncbilek, Gokhan; Mavili, M Emin

    2012-04-01

    The objective is to evaluate the effects of maxillary distraction osteogenesis (DO) in an adult patient with unilateral cleft lip and palate (UCLP) by using a rigid external distraction (RED) device with dentoskeletal anchorage. 31-year-old male patient with UCLP with severe maxillary hypoplasia, dolichofacial growth pattern, negative overjet and 1.5 mm openbite. After pre-surgical orthodontic treatment, an intra-oral appliance was modified to prevent extrusion of the molars and clockwise rotation of the mandible. Stainless steel plates were soldered bilaterally to the intra oral appliance at the level of canines. During surgery, miniplates were inserted in the maxillary segment and fixed to the plates of the intra oral appliance with screws. The mean distraction length was 12 mm immediately after DO. SNA increased from 73o to 82o after distraction. A significant advancement of the maxilla and correction of the sagittal Class III skeletal relationship was achieved. The vertical position of the mandible and the face was kept stable, and the soft tissue profile became more balanced. This intra oral appliance design achieved desired skeletal changes during maxillary protraction with RED device in dolichofacial CLP patient. Occlusion and facial profile changes was found to be stable in 1-year follow-up.

  10. Alterations in integrin expression modulates invasion of pancreatic cancer cells.

    LENUS (Irish Health Repository)

    Walsh, Naomi

    2009-01-01

    BACKGROUND: Factors mediating the invasion of pancreatic cancer cells through the extracellular matrix (ECM) are not fully understood. METHODS: In this study, sub-populations of the human pancreatic cancer cell line, MiaPaCa-2 were established which displayed differences in invasion, adhesion, anoikis, anchorage-independent growth and integrin expression. RESULTS: Clone #3 displayed higher invasion with less adhesion, while Clone #8 was less invasive with increased adhesion to ECM proteins compared to MiaPaCa-2. Clone #8 was more sensitive to anoikis than Clone #3 and MiaPaCa-2, and displayed low colony-forming efficiency in an anchorage-independent growth assay. Integrins beta 1, alpha 5 and alpha 6 were over-expressed in Clone #8. Using small interfering RNA (siRNA), integrin beta1 knockdown in Clone #8 cells increased invasion through matrigel and fibronectin, increased motility, decreased adhesion and anoikis. Integrin alpha 5 and alpha 6 knockdown also resulted in increased motility, invasion through matrigel and decreased adhesion. CONCLUSION: Our results suggest that altered expression of integrins interacting with different extracellular matrixes may play a significant role in suppressing the aggressive invasive phenotype. Analysis of these clonal populations of MiaPaCa-2 provides a model for investigations into the invasive properties of pancreatic carcinoma.

  11. Bone metabolism in adolescent girls with eating disorders and weight loss: independent effects of weight change, insulin-like growth factor-1 and oestradiol.

    Science.gov (United States)

    Swenne, Ingemar; Stridsberg, Mats

    2015-03-01

    Adolescents with eating disorders (ED) are at risk of developing osteoporosis if weight is not recovered. Previous investigations do not separate the effects of weight change per se from those of concomitant hormonal changes. In this investigation serum osteocalcin (OC), C-terminal telopeptide of collagen (CTX), insulin-like growth factor-1 (IGF-1) and oestradiol were measured at assessment of 498 girls with ED and during weight gain of 59 girls. At assessment, OC concentrations were associated independently with weight (change), IGF-1 and oestradiol. Low weight, a high rate of weight loss and the hormone concentrations were associated with low OC. Low weight and high rate of weight loss were associated with high CTX concentrations but there were no associations independent of weight (change) with the hormones. During weight recovery, OC and CTX were independently and positively associated with weight, weight gain, IGF-1 and oestradiol. Bone metabolism markers are related to weight change independently of IGF-1 and oestradiol during both weight loss and weight gain. During weight gain, when pubertal development and growth are resumed there is an additional independent positive association between the markers and IGF-1 and oestradiol. These relationships are strongest in premenarcheal girls.

  12. Morphologic and hemodynamic analysis of dental pulp in dogs after molar intrusion with the skeletal anchorage system.

    Science.gov (United States)

    Konno, Yuichi; Daimaruya, Takayoshi; Iikubo, Masahiro; Kanzaki, Reiko; Takahashi, Ichiro; Sugawara, Junji; Sasano, Takashi

    2007-08-01

    We have successfully treated skeletal open bite by intruding posterior teeth with the skeletal anchorage system. Our aim in this study was to morphologically and hemodynamically evaluate the changes in pulp tissues when molars are radically intruded. The mandibular fourth premolars of 9 adult beagle dogs were divided into 3 groups: a sham operated group (n = 6, 3 dogs), 4-month intrusion group (n = 6, 3 dogs), and a further 4-month retention group (n = 6, 3 dogs). We evaluated the morphological changes of the pulp and dentin-the amount of vacuolar degeneration in the odontoblast layer, the predentin width and nervous continuity in the pulp tissue, and the pulpal blood-flow response evoked by electrical stimulation in the dental pulp. Extreme molar intrusion with the skeletal anchorage system caused slight degenerative changes in the pulp tissue, followed by recovery after the orthodontic force was released. Circulatory system and nervous functions were basically maintained during the intrusion, although a certain level of downregulation was observed. These morphologic and functional regressive changes in the pulp tissue after molar intrusion improved during the retention period. Histologic changes and changes in pulpal blood flow and function are reversible, even during radical intrusion of molars.

  13. Analysing the mechanical performance and growth adaptation of Norway spruce using a non-linear finite-element model and experimental data.

    Science.gov (United States)

    Lundström, T; Jonas, T; Volkwein, A

    2008-01-01

    Thirteen Norway spruce [Picea abies (L.) Karst.] trees of different size, age, and social status, and grown under varying conditions, were investigated to see how they react to complex natural static loading under summer and winter conditions, and how they have adapted their growth to such combinations of load and tree state. For this purpose a non-linear finite-element model and an extensive experimental data set were used, as well as a new formulation describing the degree to which the exploitation of the bending stress capacity is uniform. The three main findings were: material and geometric non-linearities play important roles when analysing tree deflections and critical loads; the strengths of the stem and the anchorage mutually adapt to the local wind acting on the tree crown in the forest canopy; and the radial stem growth follows a mechanically high-performance path because it adapts to prevailing as well as acute seasonal combinations of the tree state (e.g. frozen or unfrozen stem and anchorage) and load (e.g. wind and vertical and lateral snow pressure). Young trees appeared to adapt to such combinations in a more differentiated way than older trees. In conclusion, the mechanical performance of the Norway spruce studied was mostly very high, indicating that their overall growth had been clearly influenced by the external site- and tree-specific mechanical stress.

  14. Wingless promotes proliferative growth in a gradient-independent manner.

    Science.gov (United States)

    Baena-Lopez, Luis Alberto; Franch-Marro, Xavier; Vincent, Jean-Paul

    2009-10-06

    Morphogens form concentration gradients that organize patterns of cells and control growth. It has been suggested that, rather than the intensity of morphogen signaling, it is its gradation that is the relevant modulator of cell proliferation. According to this view, the ability of morphogens to regulate growth during development depends on their graded distributions. Here, we describe an experimental test of this model for Wingless, one of the key organizers of wing development in Drosophila. Maximal Wingless signaling suppresses cellular proliferation. In contrast, we found that moderate and uniform amounts of exogenous Wingless, even in the absence of endogenous Wingless, stimulated proliferative growth. Beyond a few cell diameters from the source, Wingless was relatively constant in abundance and thus provided a homogeneous growth-promoting signal. Although morphogen signaling may act in combination with as yet uncharacterized graded growth-promoting pathways, we suggest that the graded nature of morphogen signaling is not required for proliferation, at least in the developing Drosophila wing, during the main period of growth.

  15. GP88 (PC-Cell Derived Growth Factor, progranulin stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells

    Directory of Open Access Journals (Sweden)

    Sabnis Gauri

    2011-06-01

    Full Text Available Abstract Background Aromatase inhibitors (AI that inhibit breast cancer cell growth by blocking estrogen synthesis have become the treatment of choice for post-menopausal women with estrogen receptor positive (ER+ breast cancer. However, some patients display de novo or acquired resistance to AI. Interactions between estrogen and growth factor signaling pathways have been identified in estrogen-responsive cells as one possible reason for acquisition of resistance. Our laboratory has characterized an autocrine growth factor overexpressed in invasive ductal carcinoma named PC-Cell Derived Growth Factor (GP88, also known as progranulin. In the present study, we investigated the role GP88 on the acquisition of resistance to letrozole in ER+ breast cancer cells Methods We used two aromatase overexpressing human breast cancer cell lines MCF-7-CA cells and AC1 cells and their letrozole resistant counterparts as study models. Effect of stimulating or inhibiting GP88 expression on proliferation, anchorage-independent growth, survival and letrozole responsiveness was examined. Results GP88 induced cell proliferation and conferred letrozole resistance in a time- and dose-dependent fashion. Conversely, naturally letrozole resistant breast cancer cells displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. GP88 overexpression, or exogenous addition blocked the inhibitory effect of letrozole on proliferation, and stimulated survival and soft agar colony formation. In letrozole resistant cells, silencing GP88 by siRNA inhibited cell proliferation and restored their sensitivity to letrozole. Conclusion Our findings provide information on the role of an alternate growth and survival factor on the acquisition of aromatase inhibitor resistance in ER+ breast cancer.

  16. FBXW7 Acts as an Independent Prognostic Marker and Inhibits Tumor Growth in Human Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Zhanchun Li

    2015-01-01

    Full Text Available F-box and WD repeat domain-containing 7 (FBXW7 is a potent tumor suppressor in human cancers including breast cancer, colorectal cancer, gastric cancer and hepatocellular carcinoma. In this study, we found that the expressions of FBXW7 protein and mRNA levels in osteosarcoma (OS cases were significantly lower than those in normal bone tissues. Clinical analysis indicated that FBXW7 was expressed at lower levels in OS patients with advanced clinical stage, high T classification and poor histological differentiation. Furthermore, we demonstrated that high expression of FBXW7 was correlated with a better 5-year survival of OS patients. Multivariate Cox regression analysis indicated that FBXW7 was an independent prognostic marker in OS. Our in vitro studies showed that FBXW7 overexpression inhibited cell cycle transition and cell proliferation, and promoted apoptosis in both U2OS and MG-63 cells. In a nude mouse xenograft model, FBXW7 overexpression slowed down tumor growth by inducing apoptosis and growth arrest. Mechanistically, FBXW7 inversely regulated oncoprotein c-Myc and cyclin E levels in both U2OS and MG-63 cells. Together these findings suggest that FBXW7 may serve as a prognostic biomarker and inhibit tumor progression by inducing apoptosis and growth arrest in OS.

  17. The LKB1 tumor suppressor differentially affects anchorage independent growth of HPV positive cervical cancer cell lines

    International Nuclear Information System (INIS)

    Mack, Hildegard I.D.; Munger, Karl

    2013-01-01

    Infection with high-risk human papillomaviruses is causally linked to cervical carcinogenesis. However, most lesions caused by high-risk HPV infections do not progress to cancer. Host cell mutations contribute to malignant progression but the molecular nature of such mutations is unknown. Based on a previous study that reported an association between liver kinase B1 (LKB1) tumor suppressor loss and poor outcome in cervical cancer, we sought to determine the molecular basis for this observation. LKB1-negative cervical and lung cancer cells were reconstituted with wild type or kinase defective LKB1 mutants and we examined the importance of LKB1 catalytic activity in known LKB1-regulated processes including inhibition of cell proliferation and elevated resistance to energy stress. Our studies revealed marked differences in the biological activities of two kinase defective LKB1 mutants in the various cell lines. Thus, our results suggest that LKB1 may be a cell-type specific tumor suppressor. - Highlights: • LKB1 is a tumor suppressor that is linked to Peutz-Jeghers syndrome. • Peutz-Jeghers syndrome patients have a high incidence of cervical cancer. • Cervical cancer is caused by HPV infections. • This study investigates LKB1 tumor suppressor activity in cervical cancer

  18. Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis.

    Science.gov (United States)

    Halder, Sunil K; Beauchamp, R Daniel; Datta, Pran K

    2005-07-01

    Smad proteins play a key role in the intracellular signaling of the transforming growth factor beta (TGF-beta) superfamily of extracellular polypeptides that initiate signaling to regulate a wide variety of biological processes. The inhibitory Smad, Smad7, has been shown to function as intracellular antagonists of TGF-beta family signaling and is upregulated in several cancers. To determine the effect of Smad7-mediated blockade of TGF-beta signaling, we have stably expressed Smad7 in a TGF-beta-sensitive, well-differentiated, and non-tumorigenic cell line, FET, that was derived from human colon adenocarcinoma. Smad7 inhibits TGF-beta-induced transcriptional responses by blocking complex formation between Smad 2/3 and Smad4. While Smad7 has no effect on TGF-beta-induced activation of p38 MAPK and ERK, it blocks the phosphorylation of Akt by TGF-beta and enhances TGF-beta-induced phosphorylation of c-Jun. FET cells expressing Smad7 show anchorage-independent growth and enhance tumorigenicity in athymic nude mice. Smad7 blocks TGF-beta-induced growth inhibition by preventing TGF-beta-induced G1 arrest. Smad7 inhibits TGF-beta-mediated downregulation of c-Myc, CDK4, and Cyclin D1, and suppresses the expression of p21(Cip1). As a result, Smad7 inhibits TGF-beta-mediated downregulation of Rb phosphorylation. Furthermore, Smad7 inhibits the apoptosis of these cells. Together, Smad7 may increase the tumorigenicity of FET cells by blocking TGF-beta-induced growth inhibition and by inhibiting apoptosis. Thus, this study provides a mechanism by which a portion of human colorectal tumors may become refractory to tumor-suppressive actions of TGF-beta that might result in increased tumorigenicity.

  19. Anthelmintic drug ivermectin inhibits angiogenesis, growth and survival of glioblastoma through inducing mitochondrial dysfunction and oxidative stress

    International Nuclear Information System (INIS)

    Liu, Yingying; Fang, Shanshan; Sun, Qiushi; Liu, Bo

    2016-01-01

    Glioblastoma is one of the most vascular brain tumour and highly resistant to current therapy. Targeting both glioblastoma cells and angiogenesis may present an effective therapeutic strategy for glioblastoma. In our work, we show that an anthelmintic drug, ivermectin, is active against glioblastoma cells in vitro and in vivo, and also targets angiogenesis. Ivermectin significantly inhibits growth and anchorage-independent colony formation in U87 and T98G glioblastoma cells. It induces apoptosis in these cells through a caspase-dependent manner. Ivermectin significantly suppresses the growth of two independent glioblastoma xenograft mouse models. In addition, ivermectin effectively targets angiogenesis through inhibiting capillary network formation, proliferation and survival in human brain microvascular endothelial cell (HBMEC). Mechanistically, ivermectin decreases mitochondrial respiration, membrane potential, ATP levels and increases mitochondrial superoxide in U87, T98G and HBMEC cells exposed to ivermectin. The inhibitory effects of ivermectin are significantly reversed in mitochondria-deficient cells or cells treated with antioxidants, further confirming that ivermectin acts through mitochondrial respiration inhibition and induction of oxidative stress. Importantly, we show that ivermectin suppresses phosphorylation of Akt, mTOR and ribosomal S6 in glioblastoma and HBMEC cells, suggesting its inhibitory role in deactivating Akt/mTOR pathway. Altogether, our work demonstrates that ivermectin is a useful addition to the treatment armamentarium for glioblastoma. Our work also highlights the therapeutic value of targeting mitochondrial metabolism in glioblastoma. - Highlights: • Ivermectin is effective in glioblastoma cells in vitro and in vivo. • Ivermectin inhibits angiogenesis. • Ivermectin induces mitochondrial dysfunction and oxidative stress. • Ivermectin deactivates Akt/mTOR signaling pathway.

  20. Bst1 is required for Candida albicans infecting host via facilitating cell wall anchorage of Glycosylphosphatidyl inositol anchored proteins

    Science.gov (United States)

    Liu, Wei; Zou, Zui; Huang, Xin; Shen, Hui; He, Li Juan; Chen, Si Min; Li, Li Ping; Yan, Lan; Zhang, Shi Qun; Zhang, Jun Dong; Xu, Zheng; Xu, Guo Tong; An, Mao Mao; Jiang, Yuan Ying

    2016-01-01

    Glycosylphosphatidyl inositol anchored proteins (GPI-APs) on fungal cell wall are essential for invasive infections. While the function of inositol deacylation of GPI-APs in mammalian cells has been previously characterized the impact of inositol deacylation in fungi and implications to host infection remains largely unexplored. Herein we describe our identification of BST1, an inositol deacylase of GPI-Aps in Candida albicans, was critical for GPI-APs cell wall attachment and host infection. BST1-deficient C. albicans (bst1Δ/Δ) was associated with severely impaired cell wall anchorage of GPI-APs and subsequen unmasked β-(1,3)-glucan. Consistent with the aberrant cell wall structures, bst1Δ/Δ strain did not display an invasive ability and could be recognized more efficiently by host immune systems. Moreover, BST1 null mutants or those expressing Bst1 variants did not display inositol deacylation activity and exhibited severely attenuated virulence and reduced organic colonization in a murine systemic candidiasis model. Thus, Bst1 can facilitate cell wall anchorage of GPI-APs in C. albicans by inositol deacylation, and is critical for host invasion and immune escape. PMID:27708385

  1. Pyrvinium targets the unfolded protein response to hypoglycemia and its anti-tumor activity is enhanced by combination therapy.

    Directory of Open Access Journals (Sweden)

    De-Hua Yu

    Full Text Available We identified pyrvinium pamoate, an old anthelminthic medicine, which preferentially inhibits anchorage-independent growth of cancer cells over anchorage-dependent growth (approximately 10 fold. It was also reported by others to have anti-tumor activity in vivo and selective toxicity against cancer cells under glucose starvation in vitro, but with unknown mechanism. Here, we provide evidence that pyrvinium suppresses the transcriptional activation of GRP78 and GRP94 induced by glucose deprivation or 2-deoxyglucose (2DG, a glycolysis inhibitor, but not by tunicamycin or A23187. Other UPR pathways induced by glucose starvation, e.g. XBP-1, ATF4, were also found suppressed by pyrvinium. Constitutive expression of GRP78 via transgene partially protected cells from pyrvinium induced cell death under glucose starvation, suggesting that suppression of the UPR is involved in pyrvinium mediated cytotoxicity under glucose starvation. Xenograft experiments showed rather marginal overall anti-tumor activity for pyrvinium as a monotherapy. However, the combination of pyrvinium and Doxorubicin demonstrated significantly enhanced efficacy in vivo, supporting a mechanistic treatment concept based on tumor hypoglycemia and UPR.

  2. A comparison of lower canine retraction and loss of anchorage between conventional and self-ligating brackets: a single-center randomized split-mouth controlled trial.

    Science.gov (United States)

    da Costa Monini, André; Júnior, Luiz Gonzaga Gandini; Vianna, Alexandre Protásio; Martins, Renato Parsekian

    2017-05-01

    To evaluate the rate of lower canine retraction, anchorage loss, and changes on lower canines and first molars axial inclination using self-ligating and conventional brackets. Twenty-five adult patients with a treatment plan involving extractions of four first premolars were selected for this split-mouth trial and had either conventional or self-ligating brackets bonded to lower canines in a block randomization. Retraction was accomplished using 100-g nickel titanium closed-coil springs, which were reactivated each 4 weeks. Oblique radiographs were taken before and after total canine retraction and the cephalograms were superimposed on stable structures of the mandible. Cephalometric points were digitized twice by a single-blinded operator for error control and the average of the points were used to determine the following variables: canine cusp horizontal changes, molar cusp horizontal changes, and angulation changes in canines and molars. Paired t tests were used to analyze the blinded data for group differences. All patients reached final phase without bracket debonds. No differences were found between the two groups for all variables tested. No serious harm was observed. Both brackets showed the same rate of canine retraction and loss of anteroposterior anchorage of the molars. No changes were found between brackets regarding the inclination of canines and first molars. Using self-ligating brackets to retract lower canines will not increase the velocity of tooth movement, does not increase anchorage, and does not decrease tipping.

  3. Osseointegration by bone morphogenetic protein-2 and transforming growth factor beta2 coated titanium implants in femora of New Zealand white rabbits

    Directory of Open Access Journals (Sweden)

    Fritz Thorey

    2011-01-01

    Conclusions: No differences between BMP-2 alone and a combination of BMP-2+TGF-β2 could be seen in the present study. However, the results of this study confirm the results of other studies that a coating with growth factors is able to enhance bone implant ingrowth. This may be of importance in defect situations during revision surgery to support the implant ingrowth and implant anchorage.

  4. Independent regulation of skeletal growth by Ihh and IGF signaling.

    Science.gov (United States)

    Long, Fanxin; Joeng, Kyu-Sang; Xuan, Shouhong; Efstratiadis, Argiris; McMahon, Andrew P

    2006-10-01

    The insulin-like growth factors (IGFs) play a major role in regulating the systemic growth of mammals. However, it is unclear to what extent their systemic and/or local functions act in concert with other local growth factors controlling the sizes of individual organs. We have specifically addressed whether growth control of the skeleton by IGFs interacts genetically with that by Indian hedgehog (Ihh), a locally produced growth signal for the endochondral skeleton. Here, we report that disruption of both IGF and Ihh signaling resulted in additive reduction in the size of the embryonic skeleton. Thus, IGF and Ihh signaling appear to control the growth of the skeleton in parallel pathways.

  5. Transverse maxillary distraction in patients with periodontal pathology or insufficient tooth anchorage using custom-made devices.

    Science.gov (United States)

    Fernández-Sanromán, Jacinto; Donascimento, Montserrat González; López, Alberto Costas; Ferro, Martín Fernández; Berrondo, Ibon Almandoz

    2010-07-01

    We present our experience using modified Hyrax devices for treating transverse deficiencies of the maxilla in adult patients with periodontal pathology or insufficient tooth anchorage. The surgical technique, clinical indications, and results are discussed. Eight adult patients (6 females, 2 males) requiring maxillary expansion were studied prospectively between July 2002 and July 2007. All the patients had periodontal pathology or insufficient tooth anchorage preventing the use of conventional Hyrax devices. Patients underwent surgically assisted rapid maxillary expansion with the use of custom-made modified Hyrax devices (bone-borne or tooth-bone-borne devices). Patients received preoperatively (T1), at the end of distraction (T2), at removal of the expansion device (T3), and 12 months after surgery (T4) lateral and posterior anterior cephalograms and study models to measure the width of the anterior and posterior dental arches with a digital sliding calliper. Mean age was 28.5 years (range, 18-45 years). A significant widening of the anterior (6.3 +/- 1.6 mm) and posterior (7.1 +/- 1.2 mm) dental arches was demonstrated. No significant differences were found when comparing T3 with T4 measures. No significant complications were found. The results indicated that maxillary expansion with custom-made devices in adults was an easy, affordable, predictable and stable technique without significant complications in patients who suffer periodontal pathology or patients without enough dental support. Copyright 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  6. British Orthodontic Society national audit of temporary anchorage devices (TADs): report of the first thousand TADs placed.

    Science.gov (United States)

    Bearn, David R; Alharbi, Fahad

    2015-09-01

    To provide data from the British Orthodontic Society (BOS) national clinical audit on temporary anchorage device (TAD) use following the recommendations of the National Institute for Health and Clinical Excellence (NIHCE) Design and setting: The Audit commenced on 1 January 2008 and is still ongoing. This article reports the data for TADs placed from 1 January 2008 to 1 November 2013. Audit data was collected from participants using a system of both on-line data entry and hard copy forms. The criteria and standards for the audit were set following the NIHCE report in conjunction with the Development and Standards Committee of the BOS. Virtually all participants used the on-line data entry available on the BOS website. The data submitted was checked and entered manually into an Excel spreadsheet, and transferred to SPSS for analysis. Written information and documented discussion of risks were provided in over 90% of TADs placed, but 17.4% were placed without a specific signed consent form. Temporary anchorage device failure rate was 24.2% overall. Among failed TADs, 93.1% were lost or removed due to excess mobility. Infection or inflammation resulting in loss or removal was reported in 6% of TADs. The only audit standard that was met was failures due to infection of inflammation. The rest of the audit standards were not met. Recommendations are made to address these issues.

  7. Autocrine growth induced by the insulin-related factor in the insulin-independent teratoma cell line 1246-3A

    International Nuclear Information System (INIS)

    Yamada, Yukio; Serrero, G.

    1988-01-01

    An insulin-independent teratoma-derived cell line, called 1246-3A, has been isolated from the adipogenic cell line 1246, which stringently requires insulin for proliferation. The 1246-3A cell line, which can proliferate in the absence of exogenous insulin, produces in its conditioned medium a growth factor similar to pancreatic insulin by its biological and immunological properties. This factor, called insulin-related factor (IRF), was purified and iodinated to study its binding to cell surface receptors. 125 I-labeled IRF binding to intact 1246-3A cells is lower than to 1246 cells. Cell surface binding can be restored by culturing the 1246-3A cells in the presence of an anti-porcine insulin monoclonal antibody of by acid prewash of the cells prior to performing the binding. Scatchard analysis of binding indicates that IRF secreted by the 1246-3A cells partially occupies high-affinity binding sites on the producer cells. Moreover, insulin monoclonal antibody inhibits the proliferation of the IRF-producing 1246-3A cells, suggesting that these cells are dependent on the secreted IRF for growth in culture. The authors conclude that the insulin-related factor secreted by the insulin-independent 1246-3A cells stimulates their proliferation in an autocrine fashion

  8. Enhancer of Zeste Homolog 2 Overexpression in Nasopharyngeal Carcinoma: An Independent Poor Prognosticator That Enhances Cell Growth

    International Nuclear Information System (INIS)

    Hwang, Chung-Feng; Huang, Hsuan-Ying; Chen, Chang-Han; Chien, Chih-Yen; Hsu, Yao-Chung; Li, Chien-Feng

    2012-01-01

    Purpose: As a key component of polycomb-repressive complex 2, enhancer of zeste homolog 2 (EZH2) represses target genes through histone methylation and is frequently overexpressed and associated with poor prognosis in common carcinomas. For the first time, we reported EZH2 expression and its biological and clinical significance in nasopharyngeal carcinoma (NPC). Methods and Materials: In NPC cell lines and specimens, endogenous expression of EZH2 mRNA and protein was determined by semiquantitative reverse transcription–polymerase chain reaction and immunoblotting, respectively. To analyze the effect on cell growth, stable silencing of EZH2 was established in EZH2-expressing TW02 NPC cells with RNA interference. EZH2 immunolabeling was assessable for 89 primary NPC biopsy samples and correlated with clinicopathological variables, disease-specific survival (DSS), and overall survival (OS). Results: Growth activity of TW02 cells was significantly suppressed (p < 0.001) with stable EZH2 silencing. Compared with normal nasopharyngeal tissue, expression levels of EZH2 transcript and protein were apparently upregulated in NPC specimens. As a continuous variable, higher EZH2 expression preferentially occurred in NPCs of T3 to T4 stages (p = 0.03) and significantly predicted inferior DSS (p = 0.0010) and OS (p = 0.004). The prognostic implications for DSS (p = 0.010) and OS (p = 0.006) still remained valid when using the median (≥60%) of EZH2 immunolabeling index to dichotomize the cohort. In the multivariate model, higher EZH2 expression was an independent adverse factor of both DSS (p = 0.012) and OS (p = 0.011), along with American Joint Committee on Cancer Stages III to IV (p = 0.024 for DSS, p = 0.017 for OS). Conclusion: At least partly through promoting cell growth, EZH2 implicates disease progression, confers tumor aggressiveness, and represents an independent adverse prognosticator in patients with NPC.

  9. Remains of the ancient ports and anchorage points at Miyani and Visawada, on the west coast of India: A study based on underwater investigations

    Digital Repository Service at National Institute of Oceanography (India)

    Gaur, A.S.; Sundaresh; Tripati, S.

    as an excellent natural harbour. The important antiquities include varieties of stone anchors, which are very similar to those reported from Dwarka and Bet Dwarka. The identification of ancient anchorage points between water depth of 5 and 15 m is another...

  10. Matrix-Dependent Regulation of AKT in Hepsin-Overexpressing PC3 Prostate Cancer Cells12

    Science.gov (United States)

    Wittig-Blaich, Stephanie M; Kacprzyk, Lukasz A; Eismann, Thorsten; Bewerunge-Hudler, Melanie; Kruse, Petra; Winkler, Eva; Strauss, Wolfgang S L; Hibst, Raimund; Steiner, Rudolf; Schrader, Mark; Mertens, Daniel; Sültmann, Holger; Wittig, Rainer

    2011-01-01

    The serine-protease hepsin is one of the most prominently overexpressed genes in human prostate carcinoma. Forced expression of the enzyme in mice prostates is associated with matrix degradation, invasive growth, and prostate cancer progression. Conversely, hepsin overexpression in metastatic prostate cancer cell lines was reported to induce cell cycle arrest and reduction of invasive growth in vitro. We used a system for doxycycline (dox)-inducible target gene expression in metastasis-derived PC3 cells to analyze the effects of hepsin in a quantitative manner. Loss of viability and adhesion correlated with hepsin expression levels during anchorage-dependent but not anchorage-independent growth. Full expression of hepsin led to cell death and detachment and was specifically associated with reduced phosphorylation of AKT at Ser473, which was restored by growth on matrix derived from RWPE1 normal prostatic epithelial cells. In the chorioallantoic membrane xenograft model, hepsin overexpression in PC3 cells reduced the viability of tumors but did not suppress invasive growth. The data presented here provide evidence that elevated levels of hepsin interfere with cell adhesion and viability in the background of prostate cancer as well as other tissue types, the details of which depend on the microenvironment provided. Our findings suggest that overexpression of the enzyme in prostate carcinogenesis must be spatially and temporally restricted for the efficient development of tumors and metastases. PMID:21750652

  11. Matrix-Dependent Regulation of AKT in Hepsin-Overexpressing PC3 Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Stephanie M Wittig-Blaich

    2011-07-01

    Full Text Available The serine-protease hepsin is one of the most prominently overexpressed genes in human prostate carcinoma. Forced expression of the enzyme in mice prostates is associated with matrix degradation, invasive growth, and prostate cancer progression. Conversely, hepsin overexpression in metastatic prostate cancer cell lines was reported to induce cell cycle arrest and reduction of invasive growth in vitro. We used a system for doxycycline (dox-inducible target gene expression in metastasis-derived PC3 cells to analyze the effects of hepsin in a quantitative manner. Loss of viability and adhesion correlated with hepsin expression levels during anchorage-dependent but not anchorage-independent growth. Full expression of hepsin led to cell death and detachment and was specifically associated with reduced phosphorylation of AKT at Ser473, which was restored by growth on matrix derived from RWPE1 normal prostatic epithelial cells. In the chorioallantoic membrane xenograft model, hepsin overexpression in PC3 cells reduced the viability of tumors but did not suppress invasive growth. The data presented here provide evidence that elevated levels of hepsin interfere with cell adhesion and viability in the background of prostate cancer as well as other tissue types, the details of which depend on the microenvironment provided. Our findings suggest that overexpression of the enzyme in prostate carcinogenesis must be spatially and temporally restricted for the efficient development of tumors and metastases.

  12. Pumpkin seed extract: Cell growth inhibition of hyperplastic and cancer cells, independent of steroid hormone receptors.

    Science.gov (United States)

    Medjakovic, Svjetlana; Hobiger, Stefanie; Ardjomand-Woelkart, Karin; Bucar, Franz; Jungbauer, Alois

    2016-04-01

    Pumpkin seeds have been known in folk medicine as remedy for kidney, bladder and prostate disorders since centuries. Nevertheless, pumpkin research provides insufficient data to back up traditional beliefs of ethnomedical practice. The bioactivity of a hydro-ethanolic extract of pumpkin seeds from the Styrian pumpkin, Cucurbita pepo L. subsp. pepo var. styriaca, was investigated. As pumpkin seed extracts are standardized to cucurbitin, this compound was also tested. Transactivational activity was evaluated for human androgen receptor, estrogen receptor and progesterone receptor with in vitro yeast assays. Cell viability tests with prostate cancer cells, breast cancer cells, colorectal adenocarcinoma cells and a hyperplastic cell line from benign prostate hyperplasia tissue were performed. As model for non-hyperplastic cells, effects on cell viability were tested with a human dermal fibroblast cell line (HDF-5). No transactivational activity was found for human androgen receptor, estrogen receptor and progesterone receptor, for both, extract and cucurbitin. A cell growth inhibition of ~40-50% was observed for all cell lines, with the exception of HDF-5, which showed with ~20% much lower cell growth inhibition. Given the receptor status of some cell lines, a steroid-hormone receptor independent growth inhibiting effect can be assumed. The cell growth inhibition for fast growing cells together with the cell growth inhibition of prostate-, breast- and colon cancer cells corroborates the ethnomedical use of pumpkin seeds for a treatment of benign prostate hyperplasia. Moreover, due to the lack of androgenic activity, pumpkin seed applications can be regarded as safe for the prostate. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  13. A comparitive clinical study between self tapping and drill free screws as a source of rigid orthodontic anchorage.

    Science.gov (United States)

    Gupta, Nishant; Kotrashetti, S M; Naik, Vijay

    2012-03-01

    Self-tapping miniscrews are commonly being used as a temporary anchorage device for orthodontic purpose. A prerequisite for the insertion of these screws is the preparation of a pilot hole, which is time consuming and may result in damage to nerves, tooth root, drill bit breakage and thermal necrosis of bone. On the other hand the design of drill-free screws enables them to be inserted without drilling. The aim of this prospective study was to compare the stability and clinical response of the soft tissue around the self tapping and drill free screws when used for orthodontic anchorage for en mass retraction of maxillary anterior teeth. The study sample consisted of 20 patients requiring retraction of maxillary anterior teeth. The screws were placed in the alveolar bone between maxillary 2nd premolar and 1st molar bilaterally at the junction of attached gingiva and moveable mucosa. Pilot hole was drilled on the side which was selected for insertion of the self tapping screw under copious irrigation, after which it was inserted. Drill free screw was inserted on the contralateral side without predrilling. All screws were immediately loaded with 150-200 gm of retraction force. Patients were recalled for regular follow up for a period of 6 months. If the screws became mobile or showed any signs of inflammation during the course of the study, they were considered to be a failure. After a period of 6 months an overall success rate of 77.5% was noted. Four self tapping and five drill-free screws failed during the study. There was no statistically significant difference between the two types of screws with respect to success/failure. Mobility was found to be the major cause for the failure. Both self-tapping and the drill-free screws are effective anchorage units. But the latter have an edge over the conventional self-tapping screws because of decrease in operative time, little bone debris, less thermal damage, lower morbidity, and minimal patient discomfort as

  14. Resveratrol, a Red Wine Polyphenol, Suppresses Pancreatic Cancer by Inhibiting Leukotriene A4 Hydrolase

    Science.gov (United States)

    Oi, Naomi; Jeong, Chul-Ho; Nadas, Janos; Cho, Yong-Yeon; Pugliese, Angelo; Bode, Ann M.; Dong, Zigang

    2016-01-01

    The anticancer effects of red wine have attracted considerable attention. Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a well-known polyphenolic compound of red wine with cancer chemopreventive activity. However, the basis for this activity is unclear. We studied leukotriene A4 hydrolase (LTA4H) as a relevant target in pancreatic cancer. LTA4H knockdown limited the formation of leukotriene B4 (LTB4), the enzymatic product of LTA4H, and suppressed anchorage-independent growth of pancreatic cancer cells. An in silico shape similarity algorithm predicted that LTA4H might be a potential target of resveratrol. In support of this idea, we found that resveratrol directly bound to LTA4H in vitro and in cells and suppressed proliferation and anchorage-independent growth of pancreatic cancer by inhibiting LTB4 production and expression of the LTB4 receptor 1 (BLT1). Notably, resveratrol exerted relatively stronger inhibitory effects than bestatin, an established inhibitor of LTA4H activity, and the inhibitory effects of resveratrol were reduced in cells where LTA4H was suppressed by shRNA-mediated knockdown. Importantly, resveratrol inhibited tumor formation in a xenograft mouse model of human pancreatic cancer by inhibiting LTA4H activity. Our findings identify LTA4H as a functionally important target for mediating the anticancer properties of resveratrol. PMID:20952510

  15. Inhibition and reversal of nickel-induced transformation by the histone deacetylase inhibitor trichostatin A

    International Nuclear Information System (INIS)

    Zhang Qunwei; Salnikow, Konstantin; Kluz, Thomas; Chen, L.C.; Su, W.C.; Costa, Max

    2003-01-01

    The carcinogenic process initiated by nongenotoxic carcinogens involves modulation of gene expression. Nickel compounds have low mutagenic activity, but are highly carcinogenic. In vitro both mouse and human cells can be efficiently transformed by soluble and insoluble nickel compounds to anchorage-independent growth. Because previous studies have shown that carcinogenic nickel compounds silence genes by inhibiting histone acetylation and enhancing DNA methylation, we investigated the effect of enhancing histone acetylation on cell transformation. The exposure of nickel-transformed cells to the histone deacetylase inhibitor trichostatin A (TSA) resulted in the appearance of significant number of revertants measured by their inability to grow in soft agar. Using the Affymetrix GeneChip we found that the level of expression of a significant number of genes was changed (suppressed or upregulated) in nickel-transformed clones but returned to a normal level in revertants obtained following TSA treatment. Moreover, we found that treatment of cells with TSA inhibited the ability of nickel to transform mouse PW cells to anchorage-independent growth. Treatment with TSA also inhibited the ability of nickel to transform human HOS cells, although to a lesser extent. In contrast, treatment with TSA was not able to revert established cancer cell lines as readily as the nickel-transformed cells. These data indicated that modulation of gene expression is important for nickel-induced transformation

  16. Downregulation of Cyclophilin A by siRNA diminishes non-small cell lung cancer cell growth and metastasis via the regulation of matrix metallopeptidase 9

    Directory of Open Access Journals (Sweden)

    Qian Zhe

    2012-10-01

    Full Text Available Abstract Background Cyclophilin A (CypA is a cytosolic protein possessing peptidyl-prolyl isomerase activity that was recently reported to be overexpressed in several cancers. Here, we explored the biology and molecular mechanism of CypA in non-small cell lung cancer (NSCLC. Methods The expression of CypA in human NSCLC cell lines was detected by real-time reverse transcription PCR. The RNA interference-mediated knockdown of CypA was established in two NSCLC cell lines (95C and A549. 239836 CypA inhibitor was also used to suppress CypA activity. Tumorigenesis was assessed based on cellular proliferation, colony formation assays, and anchorage-independent growth assays; metastasis was assessed based on wound healing and transwell assays. Results Suppression of CypA expression inhibited the cell growth and colony formation of A549 and 95C cells. CypA knockdown resulted in the inhibition of cell motility and invasion. Significantly, we show for the first time that CypA increased NSCLC cell invasion by regulating the activity of secreted matrix metallopeptidase 9 (MMP9. Likewise, suppression of CypA with 239836 CypA inhibitor decreased cell proliferation and MMP9 activity. Conclusions The suppression of CypA expression was correlated with decreased NSCLC cell tumorigenesis and metastasis.

  17. Peptide array-based interaction assay of solid-bound peptides and anchorage-dependant cells and its effectiveness in cell-adhesive peptide design.

    Science.gov (United States)

    Kato, Ryuji; Kaga, Chiaki; Kunimatsu, Mitoshi; Kobayashi, Takeshi; Honda, Hiroyuki

    2006-06-01

    Peptide array, the designable peptide library covalently synthesized on cellulose support, was applied to assay peptide-cell interaction, between solid-bound peptides and anchorage-dependant cells, to study objective peptide design. As a model case, cell-adhesive peptides that could enhance cell growth as tissue engineering scaffold material, was studied. On the peptide array, the relative cell-adhesion ratio of NIH/3T3 cells was 2.5-fold higher on the RGDS (Arg-Gly-Asp-Ser) peptide spot as compared to the spot with no peptide, thus indicating integrin-mediated peptide-cell interaction. Such strong cell adhesion mediated by the RGDS peptide was easily disrupted by single residue substitution on the peptide array, thus indicating that the sequence recognition accuracy of cells was strictly conserved in our optimized scheme. The observed cellular morphological extension with active actin stress-fiber on the RGD motif-containing peptide supported our strategy that peptide array-based interaction assay of solid-bound peptide and anchorage-dependant cells (PIASPAC) could provide quantitative data on biological peptide-cell interaction. The analysis of 180 peptides obtained from fibronectin type III domain (no. 1447-1629) yielded 18 novel cell-adhesive peptides without the RGD motif. Taken together with the novel candidates, representative rules of ineffective amino acid usage were obtained from non-effective candidate sequences for the effective designing of cell-adhesive peptides. On comparing the amino acid usage of the top 20 and last 20 peptides from the 180 peptides, the following four brief design rules were indicated: (i) Arg or Lys of positively charged amino acids (except His) could enhance cell adhesion, (ii) small hydrophilic amino acids are favored in cell-adhesion peptides, (iii) negatively charged amino acids and small amino acids (except Gly) could reduce cell adhesion, and (iv) Cys and Met could be excluded from the sequence combination since they have

  18. Decreased expression of insulin-like growth factor binding protein-related protein-1 (IGFBP-rP1) in radiation-induced mouse hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Teishima, Jun [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine

    2002-04-01

    Insulin-like growth factor binding protein-related protein-1 (IGFBP-rP1) is a member of the IGFBP family, which was called IGFBP-7 or mac25 previously. Decreased expression of IGFBP-rP1 has been shown in breast cancer and prostatic cancer, and tumor suppressive effects of IGFBP-rP1 have been reported in prostatic cancer and osteosarcoma cell lines. In the present study, we investigated whether expression levels of IGFBP-rP1 were related to the development and the growth of radiation-induced hepatomas of B6C3F1 mice. In northern blot analysis, decreased expressions of IGFBP-rP1 gene were shown in radiation-induced mouse hepatomas compared to normal livers. In hepatoma cell lines established from these hepatomas, decreased expressions of IGFBP-rP1 were strongly related to the grade of anchorage-independent growth. In cell lines which were transfected with IGFBP-rP1cDNA, the doubling time of cell growth was increased, and the number and the size of colony formation in soft agar culture were decreased. In tumor formation assay by injecting these cells to B6C3F1 mice subcutaneously, the volume of tumors were decreased. Furthermore, the decreased expression of IGFBP-rP1 gene was observed in human hepatomas by northern blot analysis. These results may suggest that the suppression of IGFBP-rP1 is related to development and progression of mouse and human hepatomas. (author)

  19. IGF-IR promotes prostate cancer growth by stabilizing α5β1 integrin protein levels.

    Directory of Open Access Journals (Sweden)

    Aejaz Sayeed

    Full Text Available Dynamic crosstalk between growth factor receptors, cell adhesion molecules and extracellular matrix is essential for cancer cell migration and invasion. Integrins are transmembrane receptors that bind extracellular matrix proteins and enable cell adhesion and cytoskeletal organization. They also mediate signal transduction to regulate cell proliferation and survival. The type 1 insulin-like growth factor receptor (IGF-IR mediates tumor cell growth, adhesion and inhibition of apoptosis in several types of cancer. We have previously demonstrated that β1 integrins regulate anchorage-independent growth of prostate cancer (PrCa cells by regulating IGF-IR expression and androgen receptor-mediated transcriptional functions. Furthermore, we have recently reported that IGF-IR regulates the expression of β1 integrins in PrCa cells. We have dissected the mechanism through which IGF-IR regulates β1 integrin expression in PrCa. Here we report that IGF-IR is crucial for PrCa cell growth and that β1 integrins contribute to the regulation of proliferation by IGF-IR. We demonstrate that β1 integrin regulation by IGF-IR does not occur at the mRNA level. Exogenous expression of a CD4 - β1 integrin cytoplasmic domain chimera does not interfere with such regulation and fails to stabilize β1 integrin expression in the absence of IGF-IR. This appears to be due to the lack of interaction between the β1 cytoplasmic domain and IGF-IR. We demonstrate that IGF-IR stabilizes the β1 subunit by protecting it from proteasomal degradation. The α5 subunit, one of the binding partners of β1, is also downregulated along with β1 upon IGF-IR knockdown while no change is observed in the expression of the α2, α3, α4, α6 and α7 subunits. Our results reveal a crucial mechanistic role for the α5β1 integrin, downstream of IGF-IR, in regulating cancer growth.

  20. Success rates and factors associated with failure of temporary anchorage devices: A prospective clinical trial.

    Science.gov (United States)

    Aly, Shehab A; Alyan, Doha; Fayed, Mona S; Alhammadi, Maged S; Mostafa, Yehya A

    2018-03-06

    The objective of the present study was to investigate success rates and associated factors affecting temporary anchorage device (TAD) failure in different biomechanical applications. A total of 180 TADs were used as a part of 82 patients' treatment plan (24 males and 58 females); their mean age was 21.41 years. Three types of TADs were used: 50 (3M ESPE, Neuss, Germany), 56 (Bone screw; Jeil Medical, Seoul, Korea), and 74 (Morelli, Sorocaba, Brazil). Eight maxillary and four mandibular sites were selected for insertion. Three different lengths (6, 8, and 10 mm) and three different diameters (1.5, 1.6, and 1.8 mm) were used. The force levels were set at 50, 100, 150, 200, and 250 g. Patient-, implant-, and operator-dependent factors were evaluated throughout the 266 days of function. Qualitative variables were described by proportions and percentages and analyzed using χ 2 test. The overall success rate was 82.2%. The higher age group showed a significantly higher success rate. Oral hygiene showed a statistically-significant (P ˂ .05) difference between both success and failure groups. All other patient-related factors showed no significant differences. Regarding force levels used, the highest success rate was in 250 g and the lowest was in 100 g. There were no significant differences between both groups regarding other implant- and operator-related factors. Temporary anchorage devices have a good success rate and are beneficial to be integrated in orthodontic treatment planning. Patient age, oral hygiene, and force level are the most significant factors affecting TAD success. © 2018 John Wiley & Sons Australia, Ltd.

  1. RhoG regulates anoikis through a phosphatidylinositol 3-kinase-dependent mechanism

    International Nuclear Information System (INIS)

    Yamaki, Nao; Negishi, Manabu; Katoh, Hironori

    2007-01-01

    In normal epithelial cells, cell-matrix interaction is required for cell survival and proliferation, whereas disruption of this interaction causes epithelial cells to undergo apoptosis called anoikis. Here we show that the small GTPase RhoG plays an important role in the regulation of anoikis. HeLa cells are capable of anchorage-independent cell growth and acquire resistance to anoikis. We found that RNA interference-mediated knockdown of RhoG promoted anoikis in HeLa cells. Previous studies have shown that RhoG activates Rac1 and induces several cellular functions including promotion of cell migration through its effector ELMO and the ELMO-binding protein Dock180 that function as a Rac-specific guanine nucleotide exchange factor. However, RhoG-induced suppression of anoikis was independent of the ELMO- and Dock180-mediated activation of Rac1. On the other hand, the regulation of anoikis by RhoG required phosphatidylinositol 3-kinase (PI3K) activity, and constitutively active RhoG bound to the PI3K regulatory subunit p85α and induced the PI3K-dependent phosphorylation of Akt. Taken together, these results suggest that RhoG protects cells from apoptosis caused by the loss of anchorage through a PI3K-dependent mechanism, independent of its activation of Rac1

  2. ABI3 ectopic expression reduces in vitro and in vivo cell growth properties while inducing senescence

    Directory of Open Access Journals (Sweden)

    Riggins Gregory J

    2011-01-01

    Full Text Available Abstract Background Mounting evidence has indicated that ABI3 (ABI family member 3 function as a tumor suppressor gene, although the molecular mechanism by which ABI3 acts remains largely unknown. Methods The present study investigated ABI3 expression in a large panel of benign and malignant thyroid tumors and explored a correlation between the expression of ABI3 and its potential partner ABI3-binding protein (ABI3BP. We next explored the biological effects of ABI3 ectopic expression in thyroid and colon carcinoma cell lines, in which its expression was reduced or absent. Results We not only observed that ABI3 expression is reduced or lost in most carcinomas but also that there is a positive correlation between ABI3 and ABI3BP expression. Ectopic expression of ABI3 was sufficient to lead to a lower transforming activity, reduced tumor in vitro growth properties, suppressed in vitro anchorage-independent growth and in vivo tumor formation while, cellular senescence increased. These responses were accompanied by the up-regulation of the cell cycle inhibitor p21 WAF1 and reduced ERK phosphorylation and E2F1 expression. Conclusions Our result links ABI3 to the pathogenesis and progression of some cancers and suggests that ABI3 or its pathway might have interest as therapeutic target. These results also suggest that the pathways through which ABI3 works should be further characterized.

  3. The addition of calcitriol or its synthetic analog EB1089 to lapatinib and neratinib treatment inhibits cell growth and promotes apoptosis in breast cancer cells.

    Science.gov (United States)

    Segovia-Mendoza, Mariana; Díaz, Lorenza; Prado-Garcia, Heriberto; Reginato, Mauricio J; Larrea, Fernando; García-Becerra, Rocío

    2017-01-01

    In breast cancer the use of small molecule inhibitors of tyrosine kinase activity of the ERBB family members improves survival thus represents a valuable therapeutic strategy. The addition of calcitriol, the most active metabolite of vitamin D, or some of its analogs, to conventional anticancer drugs, including tyrosine kinase inhibitors (TKIs), has shown an increased effect on the inhibition of cancer cell growth. In this work, we have evaluated the effects and the mechanism of action of the combination of calcitriol or its analog EB1089 with lapatinib or neratinib on EGFR and/or HER2 positive breast cancer cell lines. Lapatinib, neratinib, calcitriol and EB1089 inhibited breast cancer cell proliferation in a concentration-dependent manner. Addition of calcitriol or EB1089 to TKIs treatment induced more effective inhibiting effect on cell growth and AKT and MAPK phosphorylation than all compounds alone. The combined treatments incremented also the expression of active caspase 3 and induced cell death in two and three-dimensional cell culture and significantly inhibited anchorage-independent colony formation. Our results suggest that the addition of calcitriol or its analog EB1089 to conventional targeted therapies, including lapatinib or neratinib might be of benefit to patients with breast cancer, particularly those with an EGFR and/or HER2 positive phenotype.

  4. [The application of Edgewise technique auxillary with extra oral anchorage and class III elastic in the treatment of bimaxillary protrusion.].

    Science.gov (United States)

    Liu, H H; Weng, S E; Chen, R J

    1995-12-01

    In the treatment of growing bimaxillary protrusion patients,Edgewise technique auxillary with extra oral anchorage and class III elastic help to improve the patient's chin shape,recover his beauty of lower facial part and get a good occlusion along with the growing of mandible.The purpose of this study is:analysis the force system in the treatment and evaluate the result of the treatment with some typical cases.

  5. Regulation of proliferation of embryonic heart mesenchyme: Role of transforming growth factor-beta 1 and the interstitial matrix

    International Nuclear Information System (INIS)

    Choy, M.; Armstrong, M.T.; Armstrong, P.B.

    1990-01-01

    Proliferation of atrioventricular cushion mesenchyme of the embryonic avian heart maintained in three-dimensional aggregate culture is stimulated by interaction with the interstitial matrix. Chicken serum or transforming growth factor-beta 1, which stimulates proliferation, induces matrix deposition in regions of the aggregate showing high labeling indices with tritiated thymidine. Dispersed heart mesenchyme interstitial matrix introduced into serum-free culture is incorporated into the aggregate and stimulates cellular proliferation similar to serum or transforming growth factor-beta 1. Proliferation is reversibly inhibited by the peptide Gly-Arg-Gly-Asp-Ser-Pro. It is suggested that transforming growth factor-beta 1 stimulates the production of interstitial matrix and that a sufficient stimulus for proliferation in this system is the presence of the matrix, which acts as the adhesive support for cellular anchorage

  6. DNA binding-independent transcriptional activation of the vascular endothelial growth factor gene (VEGF) by the Myb oncoprotein

    International Nuclear Information System (INIS)

    Lutwyche, Jodi K.; Keough, Rebecca A.; Hunter, Julie; Coles, Leeanne S.; Gonda, Thomas J.

    2006-01-01

    Myb is a key transcription factor that can regulate proliferation, differentiation, and apoptosis, predominantly in the haemopoietic system. Abnormal expression of Myb is associated with a number of cancers, both haemopoietic and non-haemopoietic. In order to better understand the role of Myb in normal and tumorigenic processes, we undertook a cDNA array screen to identify genes that are regulated by this factor. In this way, we identified the gene encoding vascular endothelial growth factor (VEGF) as being potentially regulated by the Myb oncoprotein in myeloid cells. To determine whether this was a direct effect on VEGF gene transcription, we examined the activity of the murine VEGF promoter in the presence of either wild-type (WT) or mutant forms of Myb. It was found that WT Myb was able to activate the VEGF promoter and that a minimal promoter region of 120 bp was sufficient to confer Myb responsiveness. Surprisingly, activation of the VEGF promoter was independent of DNA binding by Myb. This was shown by the use of DNA binding-defective Myb mutants and by mutagenesis of a potential Myb-binding site in the minimal promoter. Mutation of Sp1 sites within this region abolished Myb-mediated regulation of a reporter construct, suggesting that Myb DNA binding-independent activation of VEGF expression occurs via these Sp1 binding elements. Regulation of VEGF production by Myb has implications for the potential role of Myb in myeloid leukaemias and in solid tumours where VEGF may be functioning as an autocrine growth factor

  7. Progressive transfusion and growth factor independence with adjuvant sertraline in low risk myelodysplastic syndrome treated with an erythropoiesis stimulating agent and granulocyte-colony stimulating factor

    Directory of Open Access Journals (Sweden)

    Kirtan Nautiyal

    2015-01-01

    Full Text Available Refractoriness to growth factor therapy is commonly associated with inferior outcome in patients with low-risk myelodysplastic syndrome (LR-MDS who require treatment for cytopenias. However, the mechanisms leading to refractoriness are unknown. Here we describe a clinically depressed 74-year-old male with refractory cytopenia with multilineage dysplasia (RCMD and documented growth factor refractory anemia after erythropoeisis stimulating agent (ESA therapy, who attained transfusion and growth factor independence after the addition of sertraline to his medication regimen. Our case demonstrates hematological improvement-erythroid (HI-E in growth factor refractory, low risk MDS and highlights a potential mechanistic link between common inflammatory diseases and LR-MDS.

  8. Mammary tumors that become independent of the type I insulin-like growth factor receptor express elevated levels of platelet-derived growth factor receptors

    Directory of Open Access Journals (Sweden)

    Campbell Craig I

    2011-11-01

    Full Text Available Abstract Background Targeted therapies are becoming an essential part of breast cancer treatment and agents targeting the type I insulin-like growth factor receptor (IGF-IR are currently being investigated in clinical trials. One of the limitations of targeted therapies is the development of resistant variants and these variants typically present with unique gene expression patterns and characteristics compared to the original tumor. Results MTB-IGFIR transgenic mice, with inducible overexpression of the IGF-IR were used to model mammary tumors that develop resistance to IGF-IR targeting agents. IGF-IR independent mammary tumors, previously shown to possess characteristics associated with EMT, were found to express elevated levels of PDGFRα and PDGFRβ. Furthermore, these receptors were shown to be inversely expressed with the IGF-IR in this model. Using cell lines derived from IGF-IR-independent mammary tumors (from MTB-IGFIR mice, it was demonstrated that PDGFRα and to a lesser extent PDGFRβ was important for cell migration and invasion as RNAi knockdown of PDGFRα alone or PDGFRα and PDGFRβ in combination, significantly decreased tumor cell migration in Boyden chamber assays and suppressed cell migration in scratch wound assays. Somewhat surprisingly, concomitant knockdown of PDGFRα and PDGFRβ resulted in a modest increase in cell proliferation and a decrease in apoptosis. Conclusion During IGF-IR independence, PDGFRs are upregulated and function to enhance tumor cell motility. These results demonstrate a novel interaction between the IGF-IR and PDGFRs and highlight an important, therapeutically relevant pathway, for tumor cell migration and invasion.

  9. Platelet-rich plasma-an 'Elixir' for treatment of alopecia: personal experience on 117 patients with review of literature.

    Science.gov (United States)

    Garg, Suruchi; Manchanda, Shweta

    2017-01-01

    Platelet-rich plasma (PRP) has emerged as a new treatment modality in regenerative plastic surgery and dermatology. PRP is a simple, cost-effective and feasible treatment option with high patient satisfaction for hair loss and can be regarded as a valuable adjuvant treatment modality for androgenic alopecia and other types of non-scarring alopecias. Authors have proposed a hair model termed "Golden anchorage with 'molecular locking' of ectodermal and mesenchymal components for survival and integrity of hair follicle (HF)" in this article. Golden anchorage comprises of bulge stem cells, ectodermal basement membrane and bulge portion of APM. PRP with its autologous supply of millions of growth factors works on 'Golden anchorage' along with keratinocytes (PDGF), dermal papilla (IGF and fibroblast growth factor), vasculature (VEGF and PDGF) and neural cells (Nerve Growth Factor) in a multipronged manner serving as an 'elixir' for hair growth and improving overall environment.

  10. Anchorage of TiO2-blasted, HA-coated, and machined implants: an experimental study with rabbits

    DEFF Research Database (Denmark)

    Gotfredsen, K; Wennerberg, A; Johansson, C

    1995-01-01

    The purpose of this study was to evaluate the histometrical and biomechanical anchorage of TiO2-blasted implants and TiO2-blasted implants coated with hydroxyapatite. The control implants were machined. Twenty-six rabbits had a total of 156 implants placed in the proximal part of the tibia. Each...... rabbit had a machined, a TiO2-blasted, and a TiO2-blasted, HA-coated implant placed in each tibia. After a healing period of 3 and 12 weeks, respectively, the implants placed in the right tibia were used for removal torque test, and the implants placed in the left tibia were used for histomorphometrical...

  11. Reversible adaptive plasticity: A mechanism for neuroblastoma cell heterogeneity and chemo-resistance

    Directory of Open Access Journals (Sweden)

    Lina eChakrabarti

    2012-08-01

    Full Text Available We describe a novel form of tumor cell plasticity characterized by reversible adaptive plasticity in murine and human neuroblastoma. Two cellular phenotypes were defined by their ability to exhibit adhered, anchorage dependent (AD or sphere forming, anchorage independent (AI growth. The tumor cells could transition back and forth between the two phenotypes and the transition was dependent on the culture conditions. Both cell phenotypes exhibited stem-like features such as expression of nestin, self-renewal capacity and mesenchymal differentiation potential. The AI tumorspheres were found to be more resistant to chemotherapy and proliferated slower in vitro compared to the AD cells. Identification of specific molecular markers like MAP2, β-catenin and PDGFRβ enabled us to characterize and observe both phenotypes in established mouse tumors. Irrespective of the phenotype originally implanted in mice, tumors grown in vivo show phenotypic heterogeneity in molecular marker signatures and are indistinguishable in growth or histologic appearance. Similar molecular marker heterogeneity was demonstrated in primary human tumor specimens. Chemotherapy or growth factor receptor inhibition slowed tumor growth in mice and promoted initial loss of AD or AI heterogeneity, respectively. Simultaneous targeting of both phenotypes led to further tumor growth delay with emergence of new unique phenotypes. Our results demonstrate that neuroblastoma cells are plastic, dynamic and may optimize their ability to survive by changing their phenotype. Phenotypic switching appears to be an adaptive mechanism to unfavorable selection pressure and could explain the phenotypic and functional heterogeneity of neuroblastoma.

  12. Reversible Adaptive Plasticity: A Mechanism for Neuroblastoma Cell Heterogeneity and Chemo-Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Chakrabarti, Lina; Abou-Antoun, Thamara; Vukmanovic, Stanislav; Sandler, Anthony D., E-mail: asandler@childrensnational.org [The Joseph E. Robert Center for Surgical Care, Children’s National Medical Center, Washington, DC (United States); The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Medical Center, Washington, DC (United States)

    2012-08-02

    We describe a novel form of tumor cell plasticity characterized by reversible adaptive plasticity in murine and human neuroblastoma. Two cellular phenotypes were defined by their ability to exhibit adhered, anchorage dependent (AD) or sphere forming, anchorage independent (AI) growth. The tumor cells could transition back and forth between the two phenotypes and the transition was dependent on the culture conditions. Both cell phenotypes exhibited stem-like features such as expression of nestin, self-renewal capacity, and mesenchymal differentiation potential. The AI tumorspheres were found to be more resistant to chemotherapy and proliferated slower in vitro compared to the AD cells. Identification of specific molecular markers like MAP2, β-catenin, and PDGFRβ enabled us to characterize and observe both phenotypes in established mouse tumors. Irrespective of the phenotype originally implanted in mice, tumors grown in vivo show phenotypic heterogeneity in molecular marker signatures and are indistinguishable in growth or histologic appearance. Similar molecular marker heterogeneity was demonstrated in primary human tumor specimens. Chemotherapy or growth factor receptor inhibition slowed tumor growth in mice and promoted initial loss of AD or AI heterogeneity, respectively. Simultaneous targeting of both phenotypes led to further tumor growth delay with emergence of new unique phenotypes. Our results demonstrate that neuroblastoma cells are plastic, dynamic, and may optimize their ability to survive by changing their phenotype. Phenotypic switching appears to be an adaptive mechanism to unfavorable selection pressure and could explain the phenotypic and functional heterogeneity of neuroblastoma.

  13. Treatment of hyperdivergent growth pattern and anterior open bite with posterior metallic bite planes.

    Science.gov (United States)

    Ciavarella, Domenico; Lo Russo, Lucio; Nichelini, Jeffrey; Mastrovincenzo, Mario; Barbato, Ersilia; Laurenziello, Michele; Montaruli, Graziano; Lo Muzio, Lorenzo

    2017-12-01

    In the present paper, the authors analyze the effect of the "Swallowing Occlusal Contact Intercept Appliance" (SOCIA) in treatment of children with hyperdivergent Class II malocclusion. This functional appliance has no intra-oral anchorage, but induces a continuous periodontal, muscular, and articular stimulation. Twenty-six patients with hyperdivergent growth and class II malocclusion were selected and treated with SOCIA appliance. Cephalometric analysis was performed before treatment (T1) and immediately after the treatment (T2). After 24 months treatment authors observed a modification of maxillary growth with a reduction of the divergence with an increase of the posterior facial height, a modification of condylar inclination and forward position of the a hyoid. No modifications was observed about the ANB angle. After treatment the open bite was resolved with a reduction of the inclination of the upper incisors. SOCIA is a reliable functional appliance in growing age patients with a hyperdivergent pattern growth, anterior open bite and class II molar malocclusion.

  14. Multistep carcinogenesis of normal human fibroblasts. Human fibroblasts immortalized by repeated treatment with Co-60 gamma rays were transformed into tumorigenic cells with Ha-ras oncogenes.

    Science.gov (United States)

    Namba, M; Nishitani, K; Fukushima, F; Kimoto, T

    1988-01-01

    Two normal mortal human fibroblast cell strains were transformed into immortal cell lines, SUSM-1 and KMST-6, by treatment with 4-nitroquinoline 1-oxide (4NQO) and Co-60 gamma rays, respectively. These immortalized cell lines showed morphological changes of cells and remarkable chromosome aberrations, but neither of them grew in soft agar or formed tumors in nude mice. The immortal cell line, KMST-6, was then converted into neoplastic cells by treatment with Harvey murine sarcoma virus (Ha-MSV) or the c-Ha-ras oncogene derived from a human lung carcinoma. These neoplastically transformed cells acquired anchorage-independent growth potential and developed tumors when transplanted into nude mice. All the tumors grew progressively without regression until the animals died of tumors. In addition, the tumors were transplantable into other nude mice. Normal human fibroblasts, on the other hand, were not transformed into either immortal or tumorigenic cells by treatment with Ha-MSV or c-Ha-ras alone. Our present data indicate that (1) the chemical carcinogen, 4NQO, or gamma rays worked as an initiator of carcinogenesis in normal human cells, giving rise to immortality, and (2) the ras gene played a role in the progression of the immortally transformed cells to more malignant cells showing anchorage-independent growth and tumorigenicity. In other words, the immortalization process of human cells seems to be a pivotal or rate-limiting step in the carcinogenesis of human cells.

  15. Orthodontic retreatment using anchorage with miniplate to camouflage a Class III skeletal pattern.

    Science.gov (United States)

    Farret, Marcel Marchiori

    2016-06-01

    This manuscript describes the treatment of a 27-year-old patient who was previously treated with two maxillary first premolar extractions. The patient had skeletal Class III malocclusion, Class III canine relationship, anterior crossbite, and a concave profile. As the patient refused orthognathic surgery, a miniplate was used on the right side of the lower arch as an anchorage unit after the extraction of mandibular first premolars, aiding the retraction of anterior teeth. At the end of treatment, anterior crossbite was corrected, in which first molars and canines were in a Class I relationship, and an excellent intercuspation was reached. Furthermore, patient's profile remarkably improved as a result of mandibular incisor retraction. A 30-month follow-up showed good stability of the results obtained. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO) as one of the requirements to become diplomate by the BBO.

  16. Cellular shear stiffness reflects progression of arsenic-induced transformation during G1

    DEFF Research Database (Denmark)

    Muñoz, Alexandra; Eldridge, Will J; Jakobsen, Nina Munkholt

    2017-01-01

    epithelial cells were exposed to sodium arsenite to initiate early stages of transformation. Exposed cells were cultured in soft agar to further transformation and select for clonal populations exhibiting anchorage independent growth. Shear stiffness of various cell populations in G1 was assessed using...... reduced stiffness relative to control clonal lines, which were cultured in soft agar but did not receive arsenic treatment. The relative standard deviation of the stiffness of Arsenic clones was reduced compared to control clones, as well as to the arsenic exposed cell population. Cell stiffness...

  17. Characterization of the aspects of osteoprogenitor cell interactions with physical tetracalcium phosphate anchorage on titanium implant surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Chia-Ling [Advanced Medical Devices and Composites Laboratory, Department of Fiber and Composite Materials, Feng Chia University, Taichung 40724, Taiwan (China); Dental Medical Devices and Materials Research Center, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chang, Ya-Yuan; Liou, Cian-Hua [Alliance Global Technology Co., Ltd., Kaohsiung Medical Device Special Zone in Southern Taiwan Science Park, Kaohsiung 82151, Taiwan (China); Chen, Wen-Cheng, E-mail: wencchen@fcu.edu.tw [Advanced Medical Devices and Composites Laboratory, Department of Fiber and Composite Materials, Feng Chia University, Taichung 40724, Taiwan (China)

    2015-04-01

    Well-designed implants are used not only to modify the geometry of the implant but also to change the chemical properties of its surfaces. The present study aims to assess the biofunctional effects of tetracalcium phosphate (TTCP) particles as a physical anchor on the implant surface derived through sandblasting. The characteristics of the surface, cell viability, and alkaline phosphatase (ALP) activity toward osteoprogenitor cells (D1) were obtained. D1 cells were cultured on a plain surface that underwent sandblasting and acid etching (SLA) (control SLA group) and on different SLA surfaces with different anchoring TTCP rates (new test groups, M and H). The mean anchoring rates were 57% (M) and 74% (H), and the anchored thickness was estimated to range from 12.6 μm to 18.3 μm. Compared with the control SLA surface on Ti substrate, the new test groups with different TTCP anchoring rates (M and H) failed to improve cell proliferation significantly but had a well-differentiated D1 cell phenotype that enhanced ALP expression in the early stage of cell cultures, specifically, at day 7. Results suggest that the SLA surface with anchored TTCP can accelerate progenitor bone cell mineralization. This study shows the potential clinical application of the constructed geometry in TTCP anchorage on Ti for dental implant surface modification. - Highlights: • TTCP (tetracalcium phosphate) as a physical anchorage on implant is characterized. • Theoretical values of anchored thickness and capping areas were estimated. • TTCP anchored by sandblasting can accelerate progenitor bone cell mineralization. • TTCP anchored on SLA (sandblasting and acid etching) surface is a promising method.

  18. Characterization of the aspects of osteoprogenitor cell interactions with physical tetracalcium phosphate anchorage on titanium implant surfaces

    International Nuclear Information System (INIS)

    Ko, Chia-Ling; Chang, Ya-Yuan; Liou, Cian-Hua; Chen, Wen-Cheng

    2015-01-01

    Well-designed implants are used not only to modify the geometry of the implant but also to change the chemical properties of its surfaces. The present study aims to assess the biofunctional effects of tetracalcium phosphate (TTCP) particles as a physical anchor on the implant surface derived through sandblasting. The characteristics of the surface, cell viability, and alkaline phosphatase (ALP) activity toward osteoprogenitor cells (D1) were obtained. D1 cells were cultured on a plain surface that underwent sandblasting and acid etching (SLA) (control SLA group) and on different SLA surfaces with different anchoring TTCP rates (new test groups, M and H). The mean anchoring rates were 57% (M) and 74% (H), and the anchored thickness was estimated to range from 12.6 μm to 18.3 μm. Compared with the control SLA surface on Ti substrate, the new test groups with different TTCP anchoring rates (M and H) failed to improve cell proliferation significantly but had a well-differentiated D1 cell phenotype that enhanced ALP expression in the early stage of cell cultures, specifically, at day 7. Results suggest that the SLA surface with anchored TTCP can accelerate progenitor bone cell mineralization. This study shows the potential clinical application of the constructed geometry in TTCP anchorage on Ti for dental implant surface modification. - Highlights: • TTCP (tetracalcium phosphate) as a physical anchorage on implant is characterized. • Theoretical values of anchored thickness and capping areas were estimated. • TTCP anchored by sandblasting can accelerate progenitor bone cell mineralization. • TTCP anchored on SLA (sandblasting and acid etching) surface is a promising method

  19. Assessing the Frequency and Material Consequences of Collisions with Vessels Lying at an Anchorage in Line with IALA iWrap MkII

    Directory of Open Access Journals (Sweden)

    Hans-Christoph Burmeister

    2014-03-01

    Full Text Available This paper proposes a collision model for ships underway and temporary objects as an extension to state-of-the-art maritime risk assessment like IALA iWrap MkII. It gives a brief review of frequency modeling's and consequence calculation theory as well as its applications, before it analogously derives a model to assess the risk of anchorage areas. Subsequently, its benefit is demonstrated by an example scenario.

  20. Isolated scaphotrapeziotrapezoid osteoarthritis treatment using resurfacing arthroplasty with scaphoid anchorage.

    Science.gov (United States)

    Humada Álvarez, G; Simón Pérez, C; García Medrano, B; Faour Martín, O; Marcos Rodríguez, J J; Vega Castrillo, A; Martín Ferrero, M A

    The aim of this study is to show the results of scaphotrapeziotrapezoid (STT) joint osteoarthritis treatment performing resurfacing arthroplasty with scaphoid anchorage. An observational, descriptive and retrospective study was performed. Ten patients with isolated STT joint osteoarthritis were studied between 2013 and 2015. The mean follow-up time was 26months. Clinical results, functional and subjective scores were reviewed. The patients were satisfied, achieving an average of 2.1 (0-3) on the VAS score and 16 (2 to 28) in the DASH questionnaire, and returning to work in the first three months post-surgery. Recovery of range of motion compared to the contralateral wrist was 96% in extension, 95% in flexion, 87% in ulnar deviation and 91% in radial deviation. The average handgrip strength of the wrist was 95% and pinch strength was 95% compared to the contralateral side. There were no intraoperative complications or alterations in postoperative carpal alignment. Resurfacing arthroplasty is proposed as a good and novel alternative in treating isolated SST joint arthritis. Achieving the correct balance between the strength and mobility of the wrist, without causing carpal destabilisation, is important to obtain satisfactory clinical and functional results. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  1. Radiation Response of Cancer Stem-Like Cells From Established Human Cell Lines After Sorting for Surface Markers

    International Nuclear Information System (INIS)

    Al-Assar, Osama; Muschel, Ruth J.; Mantoni, Tine S.; McKenna, W. Gillies; Brunner, Thomas B.

    2009-01-01

    Purpose: A subpopulation of cancer stem-like cells (CSLC) is hypothesized to exist in different cancer cell lines and to mediate radioresistance in solid tumors. Methods and Materials: Cells were stained for CSLC markers and sorted (fluorescence-activated cell sorter/magnetic beads) to compare foci and radiosensitivity of phosphorylated histone H2AX at Ser 139 (γ-H2AX) in sorted vs. unsorted populations in eight cell lines from different organs. CSLC properties were examined using anchorage-independent growth and levels of activated Notch1. Validation consisted of testing tumorigenicity and postirradiation enrichment of CSLC in xenograft tumors. Results: The quantity of CSLC was generally in good agreement with primary tumors. CSLC from MDA-MB-231 (breast) and Panc-1 and PSN-1 (both pancreatic) cells had fewer residual γ-H2AX foci than unsorted cells, pointing to radioresistance of CSLC. However, only MDA-MB-231 CSLC were more radioresistant than unsorted cells. Furthermore, MDA-MB-231 CSLC showed enhanced anchorage-independent growth and overexpression of activated Notch1 protein. The expression of cancer stem cell surface markers in the MDA-MB-231 xenograft model was increased after exposure to fractionated radiation. In contrast to PSN-1 cells, a growth advantage for MDA-MB-231 CSLC xenograft tumors was found compared to tumors arising from unsorted cells. Conclusions: CSLC subpopulations showed no general radioresistant phenotype, despite the quantities of CSLC subpopulations shown to correspond relatively well in other reports. Likewise, CSLC characteristics were found in some but not all of the tested cell lines. The reported problems in testing for CSLC in cell lines may be overcome by additional techniques, beyond sorting for markers.

  2. Specific intracellular signal transduction pathways downstream of CSF-1 receptors: their relationship to breast cancer local recurrence and distant relapse in vivo. Potential targets for the development of new, specific anti-breast cancer therapies to improve local control and block metastatic spread?

    International Nuclear Information System (INIS)

    Kacinski, Barry M.; Sapi, Eva; Flick, Maryann B.; Turner, Bruce; Perrotta, Peter; Maher, M. Grey; Carter, Darryl; Haffy, Bruce

    1997-01-01

    Purpose/Objective: Several earlier studies have implicated CSF-1 and its receptor (CSF-1R) in the biology of mammary neoplasms and those of the female reproductive tract. CSF-1Rs are expressed by the majority (<80%) of invasive breast carcinomas and their activation as evidenced by co-expression of CSF-1 has been correlated with adverse prognosis both in breast and ovarian carcinomas. In the studies, summarized below, we attempt to further correlate expression of CSF-1R with prognosis in breast cancer. We have also attempted to better define the intracellular signal transduction pathways controlled by CSF-1R which are responsible for such clinically relevant phenotypes as protease production, invasiveness, and tumorigenicity and have designed immunological reagents capable of discriminating the activated tyrosine phosphorylated form of CSF-1R from its inactive, unphosphorylated precursor in fixed tissue. Materials and Methods and Results: To study the role of specific tyrosine phosphorylations on downstream signal transduction pathways, we transfected the murine mammary epithelial cell line HC11 with a wild-type murine CSF-1R and two mutant CSF-1Rs in which two of the earliest and most prominent sites of tyrosine autophosphorylation TYR-721 (which couples the receptor to PI-3' kinase and indirectly to pp70-S6kinase and PKC) and TYR-809 (which couples the receptor to RAS-GAP) were mutated to PHE. Transfection of HC11 cells with an unmutated, wild-type CSF-1R increased cellular synthesis of active urokinase and increased their ability to invade basement membrane analogues. It also rendered them competent for anchorage- independent growth in soft agar and able to form pulmonary metastases in isogenic C57 mice after intravenous injection. A TYR-721→PHE mutation completely abolished anchorage- independent growth in vitro and pulmonary metastatic tumorigenicity in vivo without any effects on urokinase production or on cellular ability to invade basement membrane

  3. Study on reinforced concrete high-rise building using prefabricated beam-column joints. Part 3. ; Basic anchorage behaviors of longitudinal bars of beams. Hahsirater dot hari setsugobu PC ka koho (PG connection koho) wo mochiita RC koso tatemono no kaihatsu. 3. ; Hari shukin no kisoteki teichaku seijo

    Energy Technology Data Exchange (ETDEWEB)

    SEkine, M.; Yoshioka, K.; Eto, H. (Obayashi Corp., Tokyo (Japan))

    1991-08-10

    Pull-out tests were carried out to examine basic anchorage behaviors of through holes for beam re-bars by using a PG connection method, in which columns and beam-column joints with through holes for beam re-bars in the reinforced concrete framed construction are precast simultaneously. Specimens made by the PG connection method showed better anchorage behaviors than specimens made by the conventional anchorage method. In case of anchorage width of 80cm and concrete strength of about 350kgf/cm{sup 2}, it was recognized that large slipping of re-bars did not occur under allowable bond stress when the interval between re-bars was not less than 15cm and covering depth to the core of re-bars was not less than 8cm. Concerning a specimen which did not show splitting bond failure because of lateral compressive stress, bond stress of re-bars when large slipping occurred was 1.5 times or more in comparison with the allowable bond stress. Since this specimen held high slipping rigidity even after increase of slipping, its anchoring stress increased by 32-57% compared with a specimen without lateral compressive stress. 4 refs., 7 figs., 3 tabs.

  4. Orthodontic retreatment using anchorage with miniplate to camouflage a Class III skeletal pattern

    Directory of Open Access Journals (Sweden)

    Marcel Marchiori Farret

    Full Text Available ABSTRACT This manuscript describes the treatment of a 27-year-old patient who was previously treated with two maxillary first premolar extractions. The patient had skeletal Class III malocclusion, Class III canine relationship, anterior crossbite, and a concave profile. As the patient refused orthognathic surgery, a miniplate was used on the right side of the lower arch as an anchorage unit after the extraction of mandibular first premolars, aiding the retraction of anterior teeth. At the end of treatment, anterior crossbite was corrected, in which first molars and canines were in a Class I relationship, and an excellent intercuspation was reached. Furthermore, patient's profile remarkably improved as a result of mandibular incisor retraction. A 30-month follow-up showed good stability of the results obtained. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO as one of the requirements to become diplomate by the BBO.

  5. E-cadherin homophilic ligation inhibits cell growth and epidermal growth factor receptor signaling independently of other cell interactions

    DEFF Research Database (Denmark)

    Perrais, Michaël; Chen, Xiao; Perez-Moreno, Mirna

    2007-01-01

    growth inhibitory signals. To address this question, we have selectively formed E-cadherin homophilic bonds at the cell surface of isolated epithelial cells by using functionally active recombinant E-cadherin protein attached to microspheres. We find that E-cadherin ligation alone reduces the frequency...... of cells entering the S phase, demonstrating that E-cadherin ligation directly transduces growth inhibitory signals. E-cadherin binding to beta-catenin is required for cell growth inhibition, but beta-catenin/T-cell factor transcriptional activity is not involved in growth inhibition resulting from...... homophilic binding. Neither E-cadherin binding to p120-catenin nor beta-catenin binding to alpha-catenin, and thereby the actin cytoskeleton, is required for growth inhibition. E-cadherin ligation also inhibits epidermal growth factor (EGF) receptor-mediated growth signaling by a beta...

  6. 77 FR 50914 - Anchorage; Change to Cottonwood Island Anchorage, Columbia River, Oregon and Washington

    Science.gov (United States)

    2012-08-23

    ... under Executive Order 13211. 13. Technical Standards The National Technology Transfer and Advancement... of Proposed Rulemaking A. Regulatory History and Information On June 13, 2011, the Coast Guard...'' comprises small businesses, not-for-profit organizations that are independently owned and operated and are...

  7. Human cell transformation in the study of sunlight-induced cancers in the skin of man

    International Nuclear Information System (INIS)

    Sutherland, B.M.; Bennett, P.V.

    1988-01-01

    Human cell transformation provides a powerful approach to understanding - at the cellular and molecular levels - induction of cancers in the skin of man. A principal approach to this problem is the direct transformation of human skin cells by exposure to ultraviolet and/or near-UV radiation. The frequency of human cells transformed to anchorage independence increases with radiation exposure; the relative transforming efficiencies of different wavelengths implies that direct absorption by nucleic acids is a primary initial event. Partial reversal of potential transforming lesions by photoreactivation suggests that pyrimidine dimers, as well as other lesions, are important in UV transformation of human cells. Human cells can also be transformed by transfection with cloned oncogenes, or with DNAs from tumors or tumor cell lines. Cells treated by the transfection procedure (but without DNA) or cells transfected with DNAs from normal mammalian cells or tissues show only background levels of transformation. Human cells can be transformed to anchorage-independent growth by DNAs ineffective in transformation of NIH 3T3 cells (including most human skin cancers), permitting the analysis of oncogenic molecular changes even in tumor DNAs difficult or impossible to analyze in rodent cell systems. 29 refs.; 4 figs.; 1 table

  8. CUB-domain-containing protein 1 overexpression in solid cancers promotes cancer cell growth by activating Src family kinases.

    Science.gov (United States)

    Leroy, C; Shen, Q; Strande, V; Meyer, R; McLaughlin, M E; Lezan, E; Bentires-Alj, M; Voshol, H; Bonenfant, D; Alex Gaither, L

    2015-10-29

    The transmembrane glycoprotein, CUB (complement C1r/C1s, Uegf, Bmp1) domain-containing protein 1 (CDCP1) is overexpressed in several cancer types and is a predictor of poor prognosis for patients on standard of care therapies. Phosphorylation of CDCP1 tyrosine sites is induced upon loss of cell adhesion and is thought to be linked to metastatic potential of tumor cells. Using a tyrosine-phosphoproteomics screening approach, we characterized the phosphorylation state of CDCP1 across a panel of breast cancer cell lines. We focused on two phospho-tyrosine pTyr peptides of CDCP1, containing Tyr707 and Tyr806, which were identified in all six lines, with the human epidermal growth factor 2-positive HCC1954 cells showing a particularly high phosphorylation level. Pharmacological modulation of tyrosine phosphorylation indicated that, the Src family kinases (SFKs) were found to phosphorylate CDCP1 at Tyr707 and Tyr806 and play a critical role in CDCP1 activity. We demonstrated that CDCP1 overexpression in HEK293 cells increases global phosphotyrosine content, promotes anchorage-independent cell growth and activates several SFK members. Conversely, CDCP1 downregulation in multiple solid cancer cell lines decreased both cell growth and SFK activation. Analysis of primary human tumor samples demonstrated a correlation between CDCP1 expression, SFK and protein kinase C (PKC) activity. Taken together, our results suggest that CDCP1 overexpression could be an interesting therapeutic target in multiple solid cancers and a good biomarker to stratify patients who could benefit from an anti-SFK-targeted therapy. Our data also show that multiple tyrosine phosphorylation sites of CDCP1 are important for the functional regulation of SFKs in several tumor types.

  9. Role of Pin1 in UVA-induced cell proliferation and malignant transformation in epidermal cells

    International Nuclear Information System (INIS)

    Han, Chang Yeob; Hien, Tran Thi; Lim, Sung Chul; Kang, Keon Wook

    2011-01-01

    Highlights: → Pin1 expression is enhanced by low energy UVA irradiation in both skin tissues of hairless mice and JB6 C141 epidermal cells. → UVA irradiation increases activator protein-1 activity and cyclin D1 in a Pin1-dependent manner. → UVA potentiates EGF-inducible, anchorage-independent growth of epidermal cells, and this is suppressed by Pin1 inhibition or by anti-oxidant. -- Abstract: Ultraviolet A (UVA) radiation (λ = 320-400 nm) is considered a major cause of human skin cancer. Pin1, a peptidyl prolyl isomerase, is overexpressed in most types of cancer tissues and plays an important role in cell proliferation and transformation. Here, we demonstrated that Pin1 expression was enhanced by low energy UVA (300-900 mJ/cm 2 ) irradiation in both skin tissues of hairless mice and JB6 C141 epidermal cells. Exposure of epidermal cells to UVA radiation increased cell proliferation and cyclin D1 expression, and these changes were blocked by Pin1 inhibition. UVA irradiation also increased activator protein-1 (AP-1) minimal reporter activity and nuclear levels of c-Jun, but not c-Fos, in a Pin1-dependent manner. The increases in Pin1 expression and in AP-1 reporter activity in response to UVA were abolished by N-acetylcysteine (NAC) treatment. Finally, we found that pre-exposure of JB6 C141 cells to UVA potentiated EGF-inducible, anchorage-independent growth, and this effect was significantly suppressed by Pin1inhibition or by NAC.

  10. Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

    International Nuclear Information System (INIS)

    Wright, K.T.; Seabright, R.; Logan, A.; Lilly, A.J.; Khanim, F.; Bunce, C.M.; Johnson, W.E.B.

    2010-01-01

    Research highlights: → Extracellular Nm23H1 stimulates nerve growth. → Extracellular Nm23H1 provides pathfinding cues to growth cones. → The neurotrophic activity of Nm23H1 is independent of NDP kinase activity. → The neurotrophic activity of Nm23H1 is independent of NGF. -- Abstract: The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems.

  11. Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

    Energy Technology Data Exchange (ETDEWEB)

    Wright, K.T. [Keele University at the RJAH Orthopaedic Hospital, Oswestry, Shropshire (United Kingdom); Seabright, R.; Logan, A. [Neuropharmacology and Neurobiology, School of Clinical and Experimental Medicine, Birmingham University, Birmingham (United Kingdom); Lilly, A.J.; Khanim, F.; Bunce, C.M. [Biosciences, Birmingham University, Birmingham (United Kingdom); Johnson, W.E.B., E-mail: w.e.johnson@aston.ac.uk [Life and Health Sciences, Aston University, Birmingham (United Kingdom)

    2010-07-16

    Research highlights: {yields} Extracellular Nm23H1 stimulates nerve growth. {yields} Extracellular Nm23H1 provides pathfinding cues to growth cones. {yields} The neurotrophic activity of Nm23H1 is independent of NDP kinase activity. {yields} The neurotrophic activity of Nm23H1 is independent of NGF. -- Abstract: The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems.

  12. Long chain fatty Acyl-CoA synthetase 4 is a biomarker for and mediator of hormone resistance in human breast cancer.

    Directory of Open Access Journals (Sweden)

    Xinyu Wu

    Full Text Available The purpose of this study was to determine the role of long-chain fatty acyl-CoA synthetase 4 (ACSL4 in breast cancer. Public databases were utilized to analyze the relationship between ACSL4 mRNA expression and the presence of steroid hormone and human epidermal growth factor receptor 2 (HER2 in both breast cancer cell lines and tissue samples. In addition, cell lines were utilized to assess the consequences of either increased or decreased levels of ACSL4 expression. Proliferation, migration, anchorage-independent growth and apoptosis were used as biological end points. Effects on mRNA expression and signal transduction pathways were also monitored. A meta-analysis of public gene expression databases indicated that ACSL4 expression is positively correlated with a unique subtype of triple negative breast cancer (TNBC, characterized by the absence of androgen receptor (AR and therefore referred to as quadruple negative breast cancer (QNBC. Results of experiments in breast cancer cell lines suggest that simultaneous expression of ACSL4 and a receptor is associated with hormone resistance. Forced expression of ACSL4 in ACSL4-negative, estrogen receptor α (ER-positive MCF-7 cells resulted in increased growth, invasion and anchorage independent growth, as well as a loss of dependence on estrogen that was accompanied by a reduction in the levels of steroid hormone receptors. Sensitivity to tamoxifen, triacsin C and etoposide was also attenuated. Similarly, when HER2-positive, ACSL4-negative, SKBr3 breast cancer cells were induced to express ACSL4, the proliferation rate increased and the apoptotic effect of lapatinib was reduced. The growth stimulatory effect of ACSL4 expression was also observed in vivo in nude mice when MCF-7 control and ACSL4-expressing cells were utilized to induce tumors. Our data strongly suggest that ACSL4 can serve as both a biomarker for, and mediator of, an aggressive breast cancer phenotype.

  13. Resistance to experimental tumorigenesis in cells of a long-lived mammal, the naked mole-rat (Heterocephalus glaber).

    Science.gov (United States)

    Liang, Sitai; Mele, James; Wu, Yuehong; Buffenstein, Rochelle; Hornsby, Peter J

    2010-08-01

    The naked mole-rat (NMR, Heterocephalus glaber) is a long-lived mammal in which spontaneous cancer has not been observed. To investigate possible mechanisms for cancer resistance in this species, we studied the properties of skin fibroblasts from the NMR following transduction with oncogenes that cause cells of other mammalian species to form malignant tumors. Naked mole-rat fibroblasts were transduced with a retrovirus encoding SV40 large T antigen and oncogenic Ras(G12V). Following transplantation of transduced cells into immunodeficient mice, cells rapidly entered crisis, as evidenced by the presence of anaphase bridges, giant cells with enlarged nuclei, multinucleated cells, and cells with large number of chromosomes or abnormal chromatin material. In contrast, similarly transduced mouse and rat fibroblasts formed tumors that grew rapidly without crisis. Crisis was also observed after > 40 population doublings in SV40 TAg/Ras-expressing NMR cells in culture. Crisis in culture was prevented by additional infection of the cells with a retrovirus encoding hTERT (telomerase reverse transcriptase). SV40 TAg/Ras/hTERT-expressing NMR cells formed tumors that grew rapidly in immunodeficient mice without evidence of crisis. Crisis could also be induced in SV40 TAg/Ras-expressing NMR cells by loss of anchorage, but after hTERT transduction, cells were able to proliferate normally following loss of anchorage. Thus, rapid crisis is a response of oncogene-expressing NMR cells to growth in an in vivo environment, which requires anchorage independence, and hTERT permits cells to avoid crisis and to achieve malignant tumor growth. The unique reaction of NMR cells to oncogene expression may form part of the cancer resistance of this species.

  14. Maternal factors associated with fetal growth and birthweight are independent determinants of placental weight and exhibit differential effects by fetal sex.

    Directory of Open Access Journals (Sweden)

    Marie Cecilie Paasche Roland

    Full Text Available INTRODUCTION: Maternal nutritional and metabolic factors influence the developmental environment of the fetus. Virtually any nutritional factor in the maternal blood has to pass the placental membranes to reach the fetal blood. Placental weight is a commonly used measure to summarize placental growth and function. Placental weight is an independent determinant of fetal growth and birthweight and modifies the associations between maternal metabolic factors and fetal growth. We hypothesized that maternal factors known to be related to fetal growth, newborn size and body composition are determinants of placental weight and that effects of maternal metabolic factors on placental weight differ between the genders. METHODS: The STORK study is a prospective longitudinal study including 1031 healthy pregnant women of Scandinavian heritage with singleton pregnancies. Maternal determinants (parity, body mass index, gestational weight gain and fasting plasma glucose of placental weight were explored by linear regression models, stratified by fetal sex. RESULTS: Parity, maternal BMI, gestational weight gain and fasting glucose had positive effects on placental weight. There was a sex specific effect in these associations. Fasting glucose was significantly associated with placental weight in females but not in males. CONCLUSION: Maternal factors known to influence fetal growth, birthweight and neonatal body composition are determinants of placental weight. The effect of maternal factors on placental weight is influenced by sex as illustrated in the relation between maternal glucose and placental weight.

  15. A phosphatase-independent gain-of-function mutation in PTEN triggers aberrant cell growth in astrocytes through an autocrine IGF-1 loop.

    Science.gov (United States)

    Fernández, S; Genis, L; Torres-Alemán, I

    2014-08-07

    Loss-of-function mutations in the phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome10) contribute to aberrant cell growth in part through upregulation of the mitogenic IGF-1/PI3K/Akt pathway. In turn, this pathway exerts a homeostatic feedback over PTEN. Using mutagenesis analysis to explore a possible impact of this mutual control on astrocyte growth, we found that truncation of the C-terminal region of PTEN (Δ51) associates with a marked increase in NFκB activity, a transcription factor overactivated in astrocyte tumors. Whereas mutations of PTEN are considered to lead to a loss-of-function, PTENΔ51, a truncation that comprises a region frequently mutated in human gliomas, displayed a neomorphic (gain-of-function) activity that was independent of its phosphatase activity. This gain-of-function of PTENΔ51 includes stimulation of IGF-1 synthesis through protein kinase A activation of the IGF-1 promoter. Increased IGF-1 originates an autocrine loop that activates Akt and NFκB. Constitutive activation of NFκB in PTENΔ51-expressing astrocytes leads to aberrant cell growth; astrocytes expressing this mutant PTEN generate colonies in vitro and tumors in vivo. Mutations converting a tumor suppressor such as PTEN into a tumor promoter through a gain-of-function involving IGF-1 production may further our understanding of the role played by this growth factor in glioma growth and help us define druggable targets for personalized therapy.

  16. Independent signaling by Drosophila insulin receptor for axon guidance and growth

    Directory of Open Access Journals (Sweden)

    Caroline Rita Li

    2014-01-01

    Full Text Available The Drosophila insulin receptor (DInR regulates a diverse array of biological processes including growth, axon guidance, and sugar homeostasis. Growth regulation by DInR is mediated by Chico, the Drosophila homolog of vertebrate insulin-receptor-substrate proteins IRS1-4. In contrast, DInR regulation of photoreceptor axon guidance in the developing visual system is mediated by the SH2-SH3 domain adaptor protein Dreadlocks (Dock. In vitro studies by others identified five NPXY motifs, one in the juxtamembrane region and four in the signaling C-terminal tail (C-tail, important for interaction with Chico. Here we used yeast two-hybrid assays to identify regions in the DInR C-tail that interact with Dock. These Dock-binding sites were in separate portions of the C-tail from the previously identified Chico-binding sites. To test whether these sites are required for growth or axon guidance in whole animals, a panel of DInR proteins, in which the putative Chico and Dock interaction sites had been mutated individually or in combination, were tested for their ability to rescue viability, growth, and axon guidance defects of dinr mutant flies. Sites required for viability were identified. Unexpectedly, mutation of both putative Dock binding sites, either individually or in combination, did not lead to defects in photoreceptor axon guidance. Thus, either sites also required for viability are necessary for DInR function in axon guidance and/or there is redundancy built into the DInR/Dock interaction such that Dock is able to interact with multiple regions of DInR. We also found that simultaneous mutation of all 5 NPXY motifs implicated in Chico interaction drastically decreased growth in both male and female adult flies. Mutation of these 5 NPXY motifs did not affect photoreceptor axon guidance, showing that different sites within DInR control growth and axon guidance.

  17. International exploration by independents

    International Nuclear Information System (INIS)

    Bertagne, R.G.

    1992-01-01

    Recent industry trends indicate that the smaller U.S. independents are looking at foreign exploration opportunities as one of the alternatives for growth in the new age of exploration. The problems of communications and logistics caused by different cultures and by geographic distances must be carefully evaluated. A mid-term to long-term strategy tailored to the goals and the financial capabilities of the company should be prepared and followed by a careful planning of the operations. This paper addresses some aspects of foreign exploration that should be considered before an independent venture into the foreign field. It also provides some guidelines for conducting successful overseas operations. When properly assessed, foreign exploration is well within the reach of smaller U.S. independents and presents no greater risk than domestic exploration; the rewards, however, can be much larger. Furthermore, the Oil and Gas Journal surveys of the 300 largest U.S. petroleum companies show that companies with a consistent foreign exploration policy have fared better financially during difficult times

  18. The PDZ protein tax-interacting protein-1 inhibits beta-catenin transcriptional activity and growth of colorectal cancer cells.

    Science.gov (United States)

    Kanamori, Mutsumi; Sandy, Peter; Marzinotto, Stefania; Benetti, Roberta; Kai, Chikatoshi; Hayashizaki, Yoshihide; Schneider, Claudio; Suzuki, Harukazu

    2003-10-03

    Wnt signaling is essential during development while deregulation of this pathway frequently leads to the formation of various tumors including colorectal carcinomas. A key component of the pathway is beta-catenin that, in association with TCF-4, directly regulates the expression of Wnt-responsive genes. To identify novel binding partners of beta-catenin that may control its transcriptional activity, we performed a mammalian two-hybrid screen and isolated the Tax-interacting protein (TIP-1). The in vivo complex formation between beta-catenin and TIP-1 was verified by coimmunoprecipitation, and a direct physical association was revealed by glutathione S-transferase pull-down experiments in vitro. By using a panel of deletion mutants of both proteins, we demonstrate that the interaction is mediated by the PDZ (PSD-95/DLG/ZO-1 homology) domain of TIP-1 and requires primarily the last four amino acids of beta-catenin. TIP-1 overexpression resulted in a dose-dependent decrease in the transcriptional activity of beta-catenin when tested on the TOP/FOPFLASH reporter system. Conversely, siRNA-mediated knock-down of endogenous TIP-1 slightly increased endogenous beta-catenin transactivation function. Moreover, we show that overexpression of TIP-1 reduced the proliferation and anchorage-independent growth of colorectal cancer cells. These data suggest that TIP-1 may represent a novel regulatory element in the Wnt/beta-catenin signaling pathway.

  19. Independent signaling by Drosophila insulin receptor for axon guidance and growth.

    Science.gov (United States)

    Li, Caroline R; Guo, Dongyu; Pick, Leslie

    2013-01-01

    The Drosophila insulin receptor (DInR) regulates a diverse array of biological processes including growth, axon guidance, and sugar homeostasis. Growth regulation by DInR is mediated by Chico, the Drosophila homolog of vertebrate insulin receptor substrate proteins IRS1-4. In contrast, DInR regulation of photoreceptor axon guidance in the developing visual system is mediated by the SH2-SH3 domain adaptor protein Dreadlocks (Dock). In vitro studies by others identified five NPXY motifs, one in the juxtamembrane region and four in the signaling C-terminal tail (C-tail), important for interaction with Chico. Here we used yeast two-hybrid assays to identify regions in the DInR C-tail that interact with Dock. These Dock binding sites were in separate portions of the C-tail from the previously identified Chico binding sites. To test whether these sites are required for growth or axon guidance in whole animals, a panel of DInR proteins, in which the putative Chico and Dock interaction sites had been mutated individually or in combination, were tested for their ability to rescue viability, growth and axon guidance defects of dinr mutant flies. Sites required for viability were identified. Unexpectedly, mutation of both putative Dock binding sites, either individually or in combination, did not lead to defects in photoreceptor axon guidance. Thus, either sites also required for viability are necessary for DInR function in axon guidance and/or there is redundancy built into the DInR/Dock interaction such that Dock is able to interact with multiple regions of DInR. We also found that simultaneous mutation of all five NPXY motifs implicated in Chico interaction drastically decreased growth in both male and female adult flies. These animals resembled chico mutants, supporting the notion that DInR interacts directly with Chico in vivo to control body size. Mutation of these five NPXY motifs did not affect photoreceptor axon guidance, segregating the roles of DInR in the

  20. Extracellular matrix organization modulates fibroblast growth and growth factor responsiveness.

    Science.gov (United States)

    Nakagawa, S; Pawelek, P; Grinnell, F

    1989-06-01

    To learn more about the relationship between extracellular matrix organization, cell shape, and cell growth control, we studied DNA synthesis by fibroblasts in collagen gels that were either attached to culture dishes or floating in culture medium during gel contraction. After 4 days of contraction, the collagen density (initially 1.5 mg/ml) reached 22 mg/ml in attached gels and 55 mg/ml in floating gels. After contraction, attached collagen gels were well organized; collagen fibrils were aligned in the plane of cell spreading; and fibroblasts had an elongated, bipolar morphology. Floating collagen gels, however, were unorganized; collagen fibrils were arranged randomly; and fibroblasts had a stellate morphology. DNA synthesis by fibroblasts in contracted collagen gels was suppressed if the gels were floating in medium but not if the gels were attached, and inhibition was independent of the extent of gel contraction. Therefore, growth of fibroblasts in contracted collagen gels could be regulated by differences in extracellular matrix organization and cell shape independently of extracellular matrix density. We also compared the responses of fibroblasts in contracted collagen gels and monolayer culture to peptide growth factors including fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, and interleukin 1. Cells in floating collagen gels were generally unresponsive to any of the growth factors. Cells in attached collagen gels and monolayer culture were affected similarly by fibroblast growth factor but not by the others. Our results indicate that extracellular matrix organization influenced not only cell growth, but also fibroblast responsiveness to peptide growth factors.

  1. Targeting tumor multicellular aggregation through IGPR-1 inhibits colon cancer growth and improves chemotherapy.

    Science.gov (United States)

    Woolf, N; Pearson, B E; Bondzie, P A; Meyer, R D; Lavaei, M; Belkina, A C; Chitalia, V; Rahimi, N

    2017-09-18

    Adhesion to extracellular matrix (ECM) is crucially important for survival of normal epithelial cells as detachment from ECM triggers specific apoptosis known as anoikis. As tumor cells lose the requirement for anchorage to ECM, they rely on cell-cell adhesion 'multicellular aggregation' for survival. Multicellular aggregation of tumor cells also significantly determines the sensitivity of tumor cells to the cytotoxic effects of chemotherapeutics. In this report, we demonstrate that expression of immunoglobulin containing and proline-rich receptor-1 (IGPR-1) is upregulated in human primary colon cancer. Our study demonstrates that IGPR-1 promotes tumor multicellular aggregation, and interfering with its adhesive function inhibits multicellular aggregation and, increases cell death. IGPR-1 supports colon carcinoma tumor xenograft growth in mouse, and inhibiting its activity by shRNA or blocking antibody inhibits tumor growth. More importantly, IGPR-1 regulates sensitivity of tumor cells to the chemotherapeutic agent, doxorubicin/adriamycin by a mechanism that involves doxorubicin-induced AKT activation and phosphorylation of IGPR-1 at Ser220. Our findings offer novel insight into IGPR-1's role in colorectal tumor growth, tumor chemosensitivity, and as a possible novel anti-cancer target.

  2. En-masse retraction with a preformed nickel-titanium and stainless steel archwire assembly and temporary skeletal anchorage devices without posterior bonding.

    Science.gov (United States)

    Jee, Jeong-Hyun; Ahn, Hyo-Won; Seo, Kyung-Won; Kim, Seong-Hun; Kook, Yoon-Ah; Chung, Kyu-Rhim; Nelson, Gerald

    2014-09-01

    To evaluate the therapeutic effects of a preformed assembly of nickel-titanium (NiTi) and stainless steel (SS) archwires (preformed C-wire) combined with temporary skeletal anchorage devices (TSADs) as the sole source of anchorage and to compare these effects with those of a SS version of C-wire (conventional C-wire) for en-masse retraction. Thirty-one adult female patients with skeletal Class I or II dentoalveolar protrusion, mild-to-moderate anterior crowding (3.0-6.0 mm), and stable Class I posterior occlusion were divided into conventional (n = 15) and preformed (n = 16) C-wire groups. All subjects underwent first premolar extractions and en-masse retraction with pre-adjusted edgewise anterior brackets, the assigned C-wire, and maxillary C-tubes or C-implants; bonded mesh-tube appliances were used in the mandibular dentition. Differences in pretreatment and post-retraction measurements of skeletal, dental, and soft-tissue cephalometric variables were statistically analyzed. Both groups showed full retraction of the maxillary anterior teeth by controlled tipping and space closure without altered posterior occlusion. However, the preformed C-wire group had a shorter retraction period (by 3.2 months). Furthermore, the maxillary molars in this group showed no significant mesialization, mesial tipping, or extrusion; some mesialization and mesial tipping occurred in the conventional C-wire group. Preformed C-wires combined with maxillary TSADs enable simultaneous leveling and space closure from the beginning of the treatment without maxillary posterior bonding. This allows for faster treatment of dentoalveolar protrusion without unwanted side effects, when compared with conventional C-wire, evidencing its clinical expediency.

  3. The contribution of heavy metals in cigarette smoke condensate to malignant transformation of breast epithelial cells and in vivo initiation of neoplasia through induction of a PI3K–AKT–NFκB cascade

    Energy Technology Data Exchange (ETDEWEB)

    Mohapatra, Purusottam; Preet, Ranjan; Das, Dipon; Satapathy, Shakti Ranjan [Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Orissa 751024 (India); Siddharth, Sumit [Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Orissa 751024 (India); Department of Infection Biology, Institute of Life Science, Nalco Square, Bhubaneswar, Orissa 751021 (India); Choudhuri, Tathagata [Department of Infection Biology, Institute of Life Science, Nalco Square, Bhubaneswar, Orissa 751021 (India); Wyatt, Michael D. [Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC (United States); Kundu, Chanakya Nath, E-mail: cnkundu@gmail.com [Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Orissa 751024 (India)

    2014-01-01

    Cigarette smoking is a crucial factor in the development and progression of multiple cancers including breast. Here, we report that repeated exposure to a fixed, low dose of cigarette smoke condensate (CSC) prepared from Indian cigarettes is capable of transforming normal breast epithelial cells, MCF-10A, and delineate the biochemical basis for cellular transformation. CSC transformed cells (MCF-10A-Tr) were capable of anchorage-independent growth, and their anchorage dependent growth and colony forming ability were higher compared to the non-transformed MCF-10A cells. Increased expression of biomarkers representative of oncogenic transformation (NRP-1, Nectin-4), and anti-apoptotic markers (PI3K, AKT, NFκB) were also noted in the MCF-10A-Tr cells. Short tandem repeat (STR) profiling of MCF-10A and MCF-10A-Tr cells revealed that transformed cells acquired allelic variation during transformation, and had become genetically distinct. MCF-10A-Tr cells formed solid tumors when implanted into the mammary fat pads of Balb/c mice. Data revealed that CSC contained approximately 1.011 μg Cd per cigarette equivalent, and Cd (0.0003 μg Cd/1 × 10{sup 7} cells) was also detected in the lysates from MCF-10A cells treated with 25 μg/mL CSC. In similar manner to CSC, CdCl{sub 2} treatment in MCF-10A cells caused anchorage independent colony growth, higher expression of oncogenic proteins and increased PI3K–AKT–NFκB protein expression. An increase in the expression of PI3K–AKT–NFκB was also noted in the mice xenografts. Interestingly, it was noted that CSC and CdCl{sub 2} treatment in MCF-10A cells increased ROS. Collectively, results suggest that heavy metals present in cigarettes of Indian origin may substantially contribute to tumorigenesis by inducing intercellular ROS accumulation and increased expression of PI3K, AKT and NFκB proteins. - Highlights: • Repeated exposure of CSC causes malignant transformation in MCF-10A. • MCF-10A-Tr cells showed a distinct

  4. The contribution of heavy metals in cigarette smoke condensate to malignant transformation of breast epithelial cells and in vivo initiation of neoplasia through induction of a PI3K–AKT–NFκB cascade

    International Nuclear Information System (INIS)

    Mohapatra, Purusottam; Preet, Ranjan; Das, Dipon; Satapathy, Shakti Ranjan; Siddharth, Sumit; Choudhuri, Tathagata; Wyatt, Michael D.; Kundu, Chanakya Nath

    2014-01-01

    Cigarette smoking is a crucial factor in the development and progression of multiple cancers including breast. Here, we report that repeated exposure to a fixed, low dose of cigarette smoke condensate (CSC) prepared from Indian cigarettes is capable of transforming normal breast epithelial cells, MCF-10A, and delineate the biochemical basis for cellular transformation. CSC transformed cells (MCF-10A-Tr) were capable of anchorage-independent growth, and their anchorage dependent growth and colony forming ability were higher compared to the non-transformed MCF-10A cells. Increased expression of biomarkers representative of oncogenic transformation (NRP-1, Nectin-4), and anti-apoptotic markers (PI3K, AKT, NFκB) were also noted in the MCF-10A-Tr cells. Short tandem repeat (STR) profiling of MCF-10A and MCF-10A-Tr cells revealed that transformed cells acquired allelic variation during transformation, and had become genetically distinct. MCF-10A-Tr cells formed solid tumors when implanted into the mammary fat pads of Balb/c mice. Data revealed that CSC contained approximately 1.011 μg Cd per cigarette equivalent, and Cd (0.0003 μg Cd/1 × 10 7 cells) was also detected in the lysates from MCF-10A cells treated with 25 μg/mL CSC. In similar manner to CSC, CdCl 2 treatment in MCF-10A cells caused anchorage independent colony growth, higher expression of oncogenic proteins and increased PI3K–AKT–NFκB protein expression. An increase in the expression of PI3K–AKT–NFκB was also noted in the mice xenografts. Interestingly, it was noted that CSC and CdCl 2 treatment in MCF-10A cells increased ROS. Collectively, results suggest that heavy metals present in cigarettes of Indian origin may substantially contribute to tumorigenesis by inducing intercellular ROS accumulation and increased expression of PI3K, AKT and NFκB proteins. - Highlights: • Repeated exposure of CSC causes malignant transformation in MCF-10A. • MCF-10A-Tr cells showed a distinct STR profile and

  5. Insulin-like growth factor 1 (IGF-1): a growth hormone

    Science.gov (United States)

    Laron, Z

    2001-01-01

    Aim—To contribute to the debate about whether growth hormone (GH) and insulin-like growth factor 1 (IGF-1) act independently on the growth process. Methods—To describe growth in human and animal models of isolated IGF-1 deficiency (IGHD), such as in Laron syndrome (LS; primary IGF-1 deficiency and GH resistance) and IGF-1 gene or GH receptor gene knockout (KO) mice. Results—Since the description of LS in 1966, 51 patients were followed, many since infancy. Newborns with LS are shorter (42–47 cm) than healthy babies (49–52 cm), suggesting that IGF-1 has some influence on intrauterine growth. Newborn mice with IGF-1 gene KO are 30% smaller. The postnatal growth rate of patients with LS is very slow, the distance from the lowest normal centile increasing progressively. If untreated, the final height is 100–136 cm for female and 109–138 cm for male patients. They have acromicia, organomicria including the brain, heart, gonads, genitalia, and retardation of skeletal maturation. The availability of biosynthetic IGF-1 since 1988 has enabled it to be administered to children with LS. It accelerated linear growth rates to 8–9 cm in the first year of treatment, compared with 10–12 cm/year during GH treatment of IGHD. The growth rate in following years was 5–6.5 cm/year. Conclusion—IGF-1 is an important growth hormone, mediating the protein anabolic and linear growth promoting effect of pituitary GH. It has a GH independent growth stimulating effect, which with respect to cartilage cells is possibly optimised by the synergistic action with GH. PMID:11577173

  6. Future independent power generation and implications for instruments and controls

    International Nuclear Information System (INIS)

    Williams, J.H.

    1991-01-01

    This paper reports that the independent power producers market is comprised of cogeneration, small power generation, and independent power production (IPP) segments. Shortfalls in future electric supply are expected to lead to significant growth in this market. The opportunities for instruments and controls will shift from traditional electric utility applications to the independent power market with a more diverse set of needs. Importance will be placed on system reliability, quality of power and increased demand for clean kWh

  7. A New Concept for Androgen Receptor-Independent Growth of Prostate Cancer

    National Research Council Canada - National Science Library

    Hu, Guo-fu; Kishikawa, Hiroko; Yoshioka, Norie

    2006-01-01

    Angiogenin is an angiogenic ribonuclease that is upregulated in prostate cancer. The objective of this project is to explore the role angiogenin plays in the development of androgen-independent disease...

  8. Arsenite induces cell transformation by reactive oxygen species, AKT, ERK1/2, and p70S6K1

    International Nuclear Information System (INIS)

    Carpenter, Richard L.; Jiang, Yue; Jing, Yi; He, Jun; Rojanasakul, Yon; Liu, Ling-Zhi; Jiang, Bing-Hua

    2011-01-01

    Highlights: ► Chronic exposure to arsenite induces cell proliferation and transformation. ► Arsenite-induced transformation increases ROS production and downstream signalings. ► Inhibition of ROS levels via catalase reduces arsenite-induced cell transformation. ► Interruption of AKT, ERK, or p70S6K1 inhibits arsenite-induced cell transformation. -- Abstract: Arsenic is naturally occurring element that exists in both organic and inorganic formulations. The inorganic form arsenite has a positive association with development of multiple cancer types. There are significant populations throughout the world with high exposure to arsenite via drinking water. Thus, human exposure to arsenic has become a significant public health problem. Recent evidence suggests that reactive oxygen species (ROS) mediate multiple changes to cell behavior after acute arsenic exposure, including activation of proliferative signaling and angiogenesis. However, the role of ROS in mediating cell transformation by chronic arsenic exposure is unknown. We found that cells chronically exposed to sodium arsenite increased proliferation and gained anchorage-independent growth. This cell transformation phenotype required constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. We also observed these cells constitutively produce ROS, which was required for the constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. Suppression of ROS levels by forced expression of catalase also reduced cell proliferation and anchorage-independent growth. These results indicate cell transformation induced by chronic arsenic exposure is mediated by increased cellular levels of ROS, which mediates activation of AKT, ERK1/2, and p70S6K1.

  9. Dual expression of Epstein-Barr virus, latent membrane protein-1 and human papillomavirus-16 E6 transform primary mouse embryonic fibroblasts through NF-κB signaling.

    Science.gov (United States)

    Shimabuku, Tetsuya; Tamanaha, Ayumi; Kitamura, Bunta; Tanabe, Yasuka; Tawata, Natsumi; Ikehara, Fukino; Arakaki, Kazunari; Kinjo, Takao

    2014-01-01

    The prevalence of Epstein-Barr virus (EBV) and high-risk human papilloma virus (HPV) infections in patients with oral cancer in Okinawa, southwest islands of Japan, has led to the hypothesis that carcinogenesis is related to EBV and HPV co-infection. To explore the mechanisms of transformation induced by EBV and HPV co-infection, we analyzed the transformation of primary mouse embryonic fibroblasts (MEFs) expressing EBV and HPV-16 genes, alone or in combination. Expression of EBV latent membrane protein-1 (LMP-1) alone or in combination with HPV-16 E6 increased cell proliferation and decreased apoptosis, whereas single expression of EBV nuclear antigen-1 (EBNA-1), or HPV-16 E6 did not. Co-expression of LMP-1 and E6 induced anchorage-independent growth and tumor formation in nude mice, whereas expression of LMP-1 alone did not. Although the singular expression of these viral genes showed increased DNA damage and DNA damage response (DDR), co-expression of LMP-1 and E6 did not induce DDR, which is frequently seen in cancer cells. Furthermore, co-expression of LMP-1 with E6 increased NF-κB signaling, and the knockdown of LMP-1 or E6 in co-expressing cells decreased cell proliferation, anchorage independent growth, and NF-κB activation. These data suggested that expression of individual viral genes is insufficient for inducing transformation and that co-expression of LMP-1 and E6, which is associated with suppression of DDR and increased NF-κB activity, lead to transformation. Our findings demonstrate the synergistic effect by the interaction of oncogenes from different viruses on the transformation of primary MEFs.

  10. Biologic consequences of Stat1-independent IFN signaling

    OpenAIRE

    Gil, M. Pilar; Bohn, Erwin; O'Guin, Andrew K.; Ramana, Chilakamarti V.; Levine, Beth; Stark, George R.; Virgin, Herbert W.; Schreiber, Robert D.

    2001-01-01

    Although Stat1 is required for many IFN-dependent responses, recent work has shown that IFNγ functions independently of Stat1 to affect the growth of tumor cells or immortalized fibroblasts. We now demonstrate that both IFNγ and IFNα/β regulate proliferative responses in cells of the mononuclear phagocyte lineage derived from Stat1-null mice. Using both representational difference analysis and gene arrays, we show that IFNγ exerts its Stat1-independent actions on m...

  11. Hsa-mir-182 suppresses lung tumorigenesis through down regulation of RGS17 expression in vitro

    International Nuclear Information System (INIS)

    Sun, Yihua; Fang, Rong; Li, Chenguang; Li, Li; Li, Fei; Ye, Xiaolei; Chen, Haiquan

    2010-01-01

    Lung cancer is one of the most devastating diseases worldwide. RGS17 is previously shown to be over-expressed in human lung adenocarcinomas and plays an important role in lung tumor growth. Here we have identified a miRNA, has-mir-182, involved in the regulation of RGS17 expression through two conserved sites located in its 3' UTR region. Consistently, endogenous RGS17 expression level is regulated by hsa-mir-182 in human lung cancer cell lines. Similar to the knockdown of RGS17, ectopic expression of hsa-mir-182 significantly inhibits lung cancer cell proliferation and anchorage-independent cell growth, which can be rescued by re-expression of RGS17. Taken together, these data have provided the first evidence of miRNA regulation of RGS17 expression in lung cancer.

  12. Connection between the growth rate distribution and the size dependent crystal growth

    Science.gov (United States)

    Mitrović, M. M.; Žekić, A. A.; IIić, Z. Z.

    2002-07-01

    The results of investigations of the connection between the growth rate dispersions and the size dependent crystal growth of potassium dihydrogen phosphate (KDP), Rochelle salt (RS) and sodium chlorate (SC) are presented. A possible way out of the existing confusion in the size dependent crystal growth investigations is suggested. It is shown that the size independent growth exists if the crystals belonging to one growth rate distribution maximum are considered separately. The investigations suggest possible reason for the observed distribution maxima widths, and the high data scattering on the growth rate versus the crystal size dependence.

  13. Pedicle screw anchorage of carbon fiber-reinforced PEEK screws under cyclic loading.

    Science.gov (United States)

    Lindtner, Richard A; Schmid, Rene; Nydegger, Thomas; Konschake, Marko; Schmoelz, Werner

    2018-03-01

    Pedicle screw loosening is a common and significant complication after posterior spinal instrumentation, particularly in osteoporosis. Radiolucent carbon fiber-reinforced polyetheretherketone (CF/PEEK) pedicle screws have been developed recently to overcome drawbacks of conventional metallic screws, such as metal-induced imaging artifacts and interference with postoperative radiotherapy. Beyond radiolucency, CF/PEEK may also be advantageous over standard titanium in terms of pedicle screw loosening due to its unique material properties. However, screw anchorage and loosening of CF/PEEK pedicle screws have not been evaluated yet. The aim of this biomechanical study therefore was to evaluate whether the use of this alternative nonmetallic pedicle screw material affects screw loosening. The hypotheses tested were that (1) nonmetallic CF/PEEK pedicle screws resist an equal or higher number of load cycles until loosening than standard titanium screws and that (2) PMMA cement augmentation further increases the number of load cycles until loosening of CF/PEEK screws. In the first part of the study, left and right pedicles of ten cadaveric lumbar vertebrae (BMD 70.8 mg/cm 3  ± 14.5) were randomly instrumented with either CF/PEEK or standard titanium pedicle screws. In the second part, left and right pedicles of ten vertebrae (BMD 56.3 mg/cm 3  ± 15.8) were randomly instrumented with either PMMA-augmented or nonaugmented CF/PEEK pedicle screws. Each pedicle screw was subjected to cyclic cranio-caudal loading (initial load ranging from - 50 N to + 50 N) with stepwise increasing compressive loads (5 N every 100 cycles) until loosening or a maximum of 10,000 cycles. Angular screw motion ("screw toggling") within the vertebra was measured with a 3D motion analysis system every 100 cycles and by stress fluoroscopy every 500 cycles. The nonmetallic CF/PEEK pedicle screws resisted a similar number of load cycles until loosening as the contralateral standard

  14. En-masse retraction with a preformed nickel-titanium and stainless steel archwire assembly and temporary skeletal anchorage devices without posterior bonding

    Science.gov (United States)

    Jee, Jeong-Hyun; Ahn, Hyo-Won; Seo, Kyung-Won; Kook, Yoon-Ah; Chung, Kyu-Rhim; Nelson, Gerald

    2014-01-01

    Objective To evaluate the therapeutic effects of a preformed assembly of nickel-titanium (NiTi) and stainless steel (SS) archwires (preformed C-wire) combined with temporary skeletal anchorage devices (TSADs) as the sole source of anchorage and to compare these effects with those of a SS version of C-wire (conventional C-wire) for en-masse retraction. Methods Thirty-one adult female patients with skeletal Class I or II dentoalveolar protrusion, mild-to-moderate anterior crowding (3.0-6.0 mm), and stable Class I posterior occlusion were divided into conventional (n = 15) and preformed (n = 16) C-wire groups. All subjects underwent first premolar extractions and en-masse retraction with pre-adjusted edgewise anterior brackets, the assigned C-wire, and maxillary C-tubes or C-implants; bonded mesh-tube appliances were used in the mandibular dentition. Differences in pretreatment and post-retraction measurements of skeletal, dental, and soft-tissue cephalometric variables were statistically analyzed. Results Both groups showed full retraction of the maxillary anterior teeth by controlled tipping and space closure without altered posterior occlusion. However, the preformed C-wire group had a shorter retraction period (by 3.2 months). Furthermore, the maxillary molars in this group showed no significant mesialization, mesial tipping, or extrusion; some mesialization and mesial tipping occurred in the conventional C-wire group. Conclusions Preformed C-wires combined with maxillary TSADs enable simultaneous leveling and space closure from the beginning of the treatment without maxillary posterior bonding. This allows for faster treatment of dentoalveolar protrusion without unwanted side effects, when compared with conventional C-wire, evidencing its clinical expediency. PMID:25309863

  15. Abnormal sex chromosome constitution and longitudinal growth

    DEFF Research Database (Denmark)

    Aksglaede, Lise; Skakkebaek, Niels E; Juul, Anders

    2008-01-01

    Growth is a highly complex process regulated by the interaction between sex steroids and the GH IGF-axis. However, other factors such as sex chromosome-related genes play independent roles.......Growth is a highly complex process regulated by the interaction between sex steroids and the GH IGF-axis. However, other factors such as sex chromosome-related genes play independent roles....

  16. Growth of Verticillium longisporum in Xylem Sap of Brassica napus is Independent from Cultivar Resistance but Promoted by Plant Aging.

    Science.gov (United States)

    Lopisso, Daniel Teshome; Knüfer, Jessica; Koopmann, Birger; von Tiedemann, Andreas

    2017-09-01

    As Verticillium stem striping of oilseed rape (OSR), a vascular disease caused by Verticillium longisporum, is extending into new geographic regions and no control with fungicides exists, the demand for understanding mechanisms of quantitative resistance increases. Because V. longisporum is strictly limited to the xylem and resistance is expressed in the systemic stage post root invasion, we investigated a potential antifungal role of soluble constituents and nutritional conditions in xylem sap as determinants of cultivar resistance of OSR to V. longisporum. Assessment of biometric and molecular genetic parameters applied to describe V. longisporum resistance (net area under disease progress curve, stunting, stem thickness, plant biomass, and V. longisporum DNA content) showed consistent susceptibility of cultivar 'Falcon' in contrast to two resistant genotypes, 'SEM' and 'Aviso'. Spectrophotometric analysis revealed a consistently stronger in vitro growth of V. longisporum in xylem sap extracted from OSR compared with the water control. Further comparisons of fungal growth in xylem sap of different cultivars revealed the absence of constitutive or V. longisporum induced antifungal activity in the xylem sap of resistant versus susceptible genotypes. The similar growth of V. longisporum in xylem sap, irrespective of cultivar, infection with V. longisporum and xylem sap filtration, was correlated with about equal amounts of total soluble proteins in xylem sap from these treatments. Interestingly, compared with younger plants, xylem sap from older plants induced significantly stronger fungal growth. Growth enhancement of V. longisporum in xylem sap of aging plants was reflected by increased contents of carbohydrates, which was consistent in mock or V. longisporum-infected plants and independent from cultivar resistance. The improved nutritional conditions in the xylem of more mature plants may explain the late appearance of disease symptoms, which are observed only in

  17. Making Judges Independent – Some Proposals Regarding the Judiciary

    OpenAIRE

    Lars P. Feld; Stefan Voigt

    2004-01-01

    It is argued that an independent judiciary is a necessary condition for both individual liberty and economic prosperity. After having surveyed the literature dealing with how to arrange for an independent judiciary, the authors derive some additional policy implications by drawing on two indicators of judicial independence (JI) recently introduced by them. De facto JI has a robust and highly significant impact on economic growth. Individual components of both de jure and de facto JI on econom...

  18. The non-small cell lung cancer EGFR extracellular domain mutation, M277E, is oncogenic and drug-sensitive

    Directory of Open Access Journals (Sweden)

    Yu S

    2017-09-01

    Full Text Available Su Yu,1,2 Yang Zhang,1 Yunjian Pan,1 Chao Cheng,1,3 Yihua Sun,1,3 Haiquan Chen1–4 1Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; 2Cancer Research Center, Fudan University Shanghai Cancer Center, Shanghai, China; 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; 4Institutes of Biomedical Sciences, Fudan University, Shanghai, China Purpose: To identify novel oncogenic mutations in non-small cell lung cancer patient specimens that lack mutations in known targetable genes (“pan-negative” patients.Methods: Comprehensive mutational analyses were performed on 1,356 lung adenocarcinoma specimens. In this cohort of patients, common lung cancer oncogenic driver mutations were detected in the epidermal growth factor receptor (EGFR kinase domain, the human epidermal growth factor receptor 2 kinase domain, as well as the KRAS, BRAF, ALK, ROS1 and RET genes. A sub-cohort of pan-negative patient specimens was assayed for mutations in the EGFR extracellular domain (ECD. Additionally, EGFR mutant NIH-3T3 stable cell lines were constructed and assessed for protein content, anchorage-independent growth, and tumor formation in xenograft models to identify oncogenic mutations. BaF3 lymphocytes were also used to test sensitivities of the mutations to tyrosine kinase inhibitors.Results: In pan-negative lung adenocarcinoma cases, a novel oncogenic EGFR ECD mutation was identified (M277E. EGFR M277E mutations encoded oncoproteins that transformed NIH-3T3 cells to grow in the absence of exogenous epidermal growth factor. Transformation was further evidenced by anchorage-independent growth and tumor formation in immunocompromised xenograft mouse models. Finally, as seen in the canonical EGFR L858R mutation, the M277E mutation conferred sensitivity to both erlotinib and cetuximab in BaF3 cell lines and to erlotinib in xenograft models.Conclusion: Here, a new EGFR driver mutation, M277E

  19. Role for chondroitin sulfate glycosaminoglycan in NEDD9-mediated breast cancer cell growth.

    Science.gov (United States)

    Iida, Joji; Dorchak, Jesse; Clancy, Rebecca; Slavik, Juliana; Ellsworth, Rachel; Katagiri, Yasuhiro; Pugacheva, Elena N; van Kuppevelt, Toin H; Mural, Richard J; Cutler, Mary Lou; Shriver, Craig D

    2015-01-15

    There are lines of evidence demonstrating that NEDD9 (Cas-L, HEF-1) plays a key role in the development, progression, and metastasis of breast cancer cells. We previously reported that NEDD9 plays a critical role for promoting migration and growth of MDA-MB-231. In order to further characterize the mechanisms of NEDD9-mediated cancer migration and growth, stable cells overexpressing NEDD9 were generated using HCC38 as a parental cell line which expresses low level of endogenous NEDD9. Microarray studies demonstrated that core proteins of CD44 and Serglycin were markedly upregulated in HCC38(NEDD9) cells compared to HCC38(Vector) cells, while those of Syndecan-1, Syndecan-2, and Versican were downregulated in HCC38(NEDD9). Importantly, enzymes generating chondroitin sulfate glycosaminoglycans (CS) such as CHST11, CHST15, and CSGALNACT1 were upregulated in HCC38(NEDD9) compared to HCC38(Vector). Immunofluorescence studies using specific antibody, GD3G7, confirmed the enhanced expression of CS-E subunit in HCC38(NEDD9). Immunoprecipitation and western blotting analysis demonstrated that CS-E was attached to CD44 core protein. We demonstrated that removing CS by chondroitinase ABC significantly inhibited anchorage-independent colony formation of HCC38(NEDD9) in methylcellulose. Importantly, the fact that GD3G7 significantly inhibited colony formation of HCC38(NEDD9) cells suggests that CS-E subunit plays a key role in this process. Furthermore, treatment of HCC38(NEDD9) cells with chondroitinase ABC or GD3G7 significantly inhibited mammosphere formation. Exogenous addition of CS-E enhanced colony formation and mammosphere formation of HCC38 parental and HCC38(Vector) cells. These results suggest that NEDD9 regulates the synthesis and expression of tumor associated glycocalyx structures including CS-E, which plays a key role in promoting and regulating breast cancer progression and metastasis and possibly stem cell phenotypes. Copyright © 2014 Elsevier Inc. All rights

  20. Africa's Growth and Development Strategies: A Critical Review ...

    African Journals Online (AJOL)

    At independence in the late 1950s and early 1960s, there were high hopes about the growth prospects of the new politically independent. African states. Economic conditions, such as per capita real income, were comparable to other developing countries like South Korea and. Taiwan. By the mid-1970s, the growth profile ...

  1. An epithelial marker promoter induction screen identifies histone deacetylase inhibitors to restore epithelial differentiation and abolishes anchorage independence growth in cancers.

    Science.gov (United States)

    Tang, H M; Kuay, K T; Koh, P F; Asad, M; Tan, T Z; Chung, V Y; Lee, S C; Thiery, J P; Huang, Ry-J

    2016-01-01

    Epithelial-mesenchymal transition (EMT), a crucial mechanism in development, mediates aggressiveness during carcinoma progression and therapeutic refractoriness. The reversibility of EMT makes it an attractive strategy in designing novel therapeutic approaches. Therefore, drug discovery pipelines for EMT reversal are in need to discover emerging classes of compounds. Here, we outline a pre-clinical drug screening platform for EMT reversal that consists of three phases of drug discovery and validation. From the Phase 1 epithelial marker promoter induction (EpI) screen on a library consisting of compounds being approved by Food and Drug Administration (FDA), Vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), is identified to exert EMT reversal effects by restoring the expression of an epithelial marker, E-cadherin. An expanded screen on 41 HDACi further identifies 28 compounds, such as class I-specific HDACi Mocetinosat, Entinostat and CI994, to restore E-cadherin and ErbB3 expressions in ovarian, pancreatic and bladder carcinoma cells. Mocetinostat is the most potent HDACi to restore epithelial differentiation with the lowest concentration required for 50% induction of epithelial promoter activity (EpIC-50).The HDACi exerts paradoxical effects on EMT transcriptional factors such as SNAI and ZEB family and the effects are context-dependent in epithelial- and mesenchymal-like cells. In vitro functional studies further show that HDACi induced significant increase in anoikis and decrease in spheroid formation in ovarian and bladder carcinoma cells with mesenchymal features. This study demonstrates a robust drug screening pipeline for the discovery of compounds capable of restoring epithelial differentiation that lead to significant functional lethality.

  2. Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer

    International Nuclear Information System (INIS)

    Yu, Wei; Chai, Hongyan; Li, Ying; Zhao, Haixia; Xie, Xianfei; Zheng, Hao; Wang, Chenlong; Wang, Xue; Yang, Guifang; Cai, Xiaojun; Falck, John R.; Yang, Jing

    2012-01-01

    Cytochrome P450 (CYP) 4Z1, a novel CYP4 family member, is over-expressed in human mammary carcinoma and associated with high-grade tumors and poor prognosis. However, the precise role of CYP4Z1 in tumor progression is unknown. Here, we demonstrate that CYP4Z1 overexpression promotes tumor angiogenesis and growth in breast cancer. Stable expression of CYP4Z1 in T47D and BT-474 human breast cancer cells significantly increased mRNA expression and production of vascular endothelial growth factor (VEGF)-A, and decreased mRNA levels and secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2), without affecting cell proliferation and anchorage-independent cell growth in vitro. Notably, the conditioned medium from CYP4Z1-expressing cells enhanced proliferation, migration and tube formation of human umbilical vein endothelial cells, and promoted angiogenesis in the zebrafish embryo and chorioallantoic membrane of the chick embryo. In addition, there were lower levels of myristic acid and lauric acid, and higher contents of 20-hydroxyeicosatetraenoic acid (20-HETE) in CYP4Z1-expressing T47D cells compared with vector control. CYP4Z1 overexpression significantly increased tumor weight and microvessel density by 2.6-fold and 1.9-fold in human tumor xenograft models, respectively. Moreover, CYP4Z1 transfection increased the phosphorylation of ERK1/2 and PI3K/Akt, while PI3K or ERK inhibitors and siRNA silencing reversed CYP4Z1-mediated changes in VEGF-A and TIMP-2 expression. Conversely, HET0016, an inhibitor of the CYP4 family, potently inhibited the tumor-induced angiogenesis with associated changes in the intracellular levels of myristic acid, lauric acid and 20-HETE. Collectively, these data suggest that increased CYP4Z1 expression promotes tumor angiogenesis and growth in breast cancer partly via PI3K/Akt and ERK1/2 activation. -- Highlights: ► CYP4Z1 overexpression promotes human breast cancer growth and angiogenesis. ► The pro-angiogenic effects of CYP4Z1 have

  3. Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Wei [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Li, Ying; Zhao, Haixia; Xie, Xianfei; Zheng, Hao; Wang, Chenlong; Wang, Xue [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yang, Guifang [Department of Pathology, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Cai, Xiaojun [Department of Ophthalmology, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Falck, John R. [Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 (United States); Yang, Jing, E-mail: yangjingliu@yahoo.com.cn [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2012-10-01

    Cytochrome P450 (CYP) 4Z1, a novel CYP4 family member, is over-expressed in human mammary carcinoma and associated with high-grade tumors and poor prognosis. However, the precise role of CYP4Z1 in tumor progression is unknown. Here, we demonstrate that CYP4Z1 overexpression promotes tumor angiogenesis and growth in breast cancer. Stable expression of CYP4Z1 in T47D and BT-474 human breast cancer cells significantly increased mRNA expression and production of vascular endothelial growth factor (VEGF)-A, and decreased mRNA levels and secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2), without affecting cell proliferation and anchorage-independent cell growth in vitro. Notably, the conditioned medium from CYP4Z1-expressing cells enhanced proliferation, migration and tube formation of human umbilical vein endothelial cells, and promoted angiogenesis in the zebrafish embryo and chorioallantoic membrane of the chick embryo. In addition, there were lower levels of myristic acid and lauric acid, and higher contents of 20-hydroxyeicosatetraenoic acid (20-HETE) in CYP4Z1-expressing T47D cells compared with vector control. CYP4Z1 overexpression significantly increased tumor weight and microvessel density by 2.6-fold and 1.9-fold in human tumor xenograft models, respectively. Moreover, CYP4Z1 transfection increased the phosphorylation of ERK1/2 and PI3K/Akt, while PI3K or ERK inhibitors and siRNA silencing reversed CYP4Z1-mediated changes in VEGF-A and TIMP-2 expression. Conversely, HET0016, an inhibitor of the CYP4 family, potently inhibited the tumor-induced angiogenesis with associated changes in the intracellular levels of myristic acid, lauric acid and 20-HETE. Collectively, these data suggest that increased CYP4Z1 expression promotes tumor angiogenesis and growth in breast cancer partly via PI3K/Akt and ERK1/2 activation. -- Highlights: ► CYP4Z1 overexpression promotes human breast cancer growth and angiogenesis. ► The pro-angiogenic effects of CYP4Z1 have

  4. Inhibition of furin results in increased growth, invasiveness and cytokine production of synoviocytes from patients with rheumatoid arthritis.

    Science.gov (United States)

    Wu, Changshun; Song, Zezhong; Liu, Huiling; Pan, Jihong; Jiang, Huiyu; Liu, Chao; Yan, Zexing; Feng, Hong; Sun, Shui

    2017-07-01

    Fibroblast-like synoviocytes derived from patients with rheumatoid arthritis play a key role by local production of cytokines and proteolytic enzymes that degrade the extracellular matrix and cartilage. These synoviocytes acquire phenotypic characteristics commonly observed in transformed cells, like anchorage-independent growth, increased proliferation and invasiveness, and insensitivity to apoptosis. Furin is a ubiquitous proprotein convertase that is capable of cleaving precursors of a wide variety of proteins. In patients with rheumatoid arthritis, furin is reported to be highly expressed in the synovial pannus compared with healthy persons. However, the mechanisms are poorly understood. This study is to explore the effect of furin overexpression in rheumatoid synoviocytes. In this study, RNA interference was used to knock down furin expression and to assess the resultant effects on biological behaviors of synoviocytes, such as cell proliferation, invasion, migration, cell cycle and cell apoptosis. In addition, the production of inflammatory cytokines was evaluated. The results showed that the inhibition of furin enhanced proliferation, invasion, and migration of synoviocytes in vitro. Cell cycle was accelerated and cell death was affected by furin knockdown. Also, the inhibition of furin increased interleukin-1β and tumor necrosis factor-α secretion of synoviocytes. Inhibition of furin enhances invasive phenotype of synoviocytes from patients with rheumatoid arthritis, implying a protective role of furin. Agents targeting upregulation of furin may have therapeutic potential for rheumatoid arthritis. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  5. DIRECT USAGE OF MINISCREW ANCHORAGE TO INTRUDE OVERERUPTED MAXILLARY POSTERIOR TEETH BEFORE PROSTHODONTIC PREPARATION:A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Yasemin Bahar Acar

    2016-01-01

    Full Text Available Overeruption of maxillary molars due loss of opposing teeth creates occlusal and functional interferences. Before reconstruction can be initiated, intrusion of overerupted molars becomes essential. This report illustrates treatment of overerupted maxillary premolar and molar via direct use of miniscrew anchorage. A 24-year old female had lost first and second left mandibular molars due to pulpal necrotizing agents, resulting with a large alveolar bone defect and overerupted maxillary premolar and molar. She had a history of unsuccessful alveolar distraction of mandibular left premolars to increase the alveolar bone height prior to implant placement. Patient was satisfied with her smile and refused comprehensive orthodontic treatment. Maxillary premolar and molar were intruded segmentally for 4mm in 8 months, using a combination of a mini-implant and partialfixed edgewise appliances. Biological responses of teeth and surrounding bony structures to intrusion appeared normal and acceptable in radiographic and clinical examination.

  6. Central bank independence and its effect on money market stability

    Directory of Open Access Journals (Sweden)

    MSc. Anera Alishani

    2012-06-01

    Full Text Available Since 1990s many countries have moved toward greater central bank independence (CBI by either amending their Central Bank’s laws or writing them de novo. Also countries of Western Balkans and many other transition countries have moved toward greater CBI. There are many potential benefits associated with greater CBI, and one of them is stable growth of money and liquidity. For a given level of money market development the hypothesis is that a more independent CB is likely to promote more stable growth of money supply (Dželetović et al., 2008. As a result the main research task of this work is to estimate the effects of CBI on money market growth for five Western Balkans countries and five other European transition countries. Because the empirical studies were very limited for the relationship between CBI and money market growth, there were no clear conclusions. In addition, there were different measuring methodologies that attempt to quantify the extent of legal and actual CBI. Related to the main research task, this dissertation has examined the effects of CBI on money market stability (proxied by bank deposit growth for a sample of 10 countries for a period from 1999-2009 by using fixed effect model. Through this methodology different regressions have been estimated, but the results were not robust and there are no clear finding on the relationship between CBI and money market growth.

  7. HOXA1 is overexpressed in oral squamous cell carcinomas and its expression is correlated with poor prognosis

    Directory of Open Access Journals (Sweden)

    Bitu Carolina

    2012-04-01

    Full Text Available Abstract Background HOX genes encode homeodomain-containing transcription factors involved in the regulation of cellular proliferation and differentiation during embryogenesis. However, members of this family demonstrated oncogenic properties in some malignancies. The present study investigated whether genes of the HOXA cluster play a role in oral cancer. Methods In order to identify differentially expressed HOXA genes, duplex RT-PCR in oral samples from healthy mucosa and squamous cell carcinoma was used. The effects of HOXA1 on proliferation, apoptosis, adhesion, invasion, epithelial-mesenchymal transition (EMT and anchorage-independent growth were assessed in cells with up- and down-regulation of HOXA1. Immunohistochemical analysis using a tissue microarray (TMA containing 127 oral squamous cell carcinomas (OSCC was performed to determine the prognostic role of HOXA1 expression. Results We showed that transcripts of HOXA genes are more abundant in OSCC than in healthy oral mucosa. In particular, HOXA1, which has been described as one of the HOX members that plays an important role in tumorigenesis, was significantly more expressed in OSCCs compared to healthy oral mucosas. Further analysis demonstrated that overexpression of HOXA1 in HaCAT human epithelial cells promotes proliferation, whereas downregulation of HOXA1 in human OSCC cells (SCC9 cells decreases it. Enforced HOXA1 expression in HaCAT cells was not capable of modulating other events related to tumorigenesis, including apoptosis, adhesion, invasion, EMT and anchorage-independent growth. A high number of HOXA1-positive cells was significantly associated with T stage, N stage, tumor differentiation and proliferative potential of the tumors, and was predictive of poor survival. In multivariate analysis, HOXA1 was an independent prognostic factor for OSCC patients (HR: 2.68; 95% CI: 1.59-2.97; p = 0.026. Conclusion Our findings indicate that HOXA1 may contribute to oral carcinogenesis

  8. HOXA1 is overexpressed in oral squamous cell carcinomas and its expression is correlated with poor prognosis

    International Nuclear Information System (INIS)

    Bitu, Carolina Cavalcante; Destro, Maria Fernanda de Souza Setúbal; Carrera, Manoela; Silva, Sabrina Daniela da; Graner, Edgard; Kowalski, Luiz Paulo; Soares, Fernando Augusto; Coletta, Ricardo D

    2012-01-01

    HOX genes encode homeodomain-containing transcription factors involved in the regulation of cellular proliferation and differentiation during embryogenesis. However, members of this family demonstrated oncogenic properties in some malignancies. The present study investigated whether genes of the HOXA cluster play a role in oral cancer. In order to identify differentially expressed HOXA genes, duplex RT-PCR in oral samples from healthy mucosa and squamous cell carcinoma was used. The effects of HOXA1 on proliferation, apoptosis, adhesion, invasion, epithelial-mesenchymal transition (EMT) and anchorage-independent growth were assessed in cells with up- and down-regulation of HOXA1. Immunohistochemical analysis using a tissue microarray (TMA) containing 127 oral squamous cell carcinomas (OSCC) was performed to determine the prognostic role of HOXA1 expression. We showed that transcripts of HOXA genes are more abundant in OSCC than in healthy oral mucosa. In particular, HOXA1, which has been described as one of the HOX members that plays an important role in tumorigenesis, was significantly more expressed in OSCCs compared to healthy oral mucosas. Further analysis demonstrated that overexpression of HOXA1 in HaCAT human epithelial cells promotes proliferation, whereas downregulation of HOXA1 in human OSCC cells (SCC9 cells) decreases it. Enforced HOXA1 expression in HaCAT cells was not capable of modulating other events related to tumorigenesis, including apoptosis, adhesion, invasion, EMT and anchorage-independent growth. A high number of HOXA1-positive cells was significantly associated with T stage, N stage, tumor differentiation and proliferative potential of the tumors, and was predictive of poor survival. In multivariate analysis, HOXA1 was an independent prognostic factor for OSCC patients (HR: 2.68; 95% CI: 1.59-2.97; p = 0.026). Our findings indicate that HOXA1 may contribute to oral carcinogenesis by increasing tumor cell proliferation, and suggest that HOXA1

  9. The Effect of Different Competition Indices on Diameter Growth of Individual Tree Growth in Mixed Stands of Caucasion fir and Oriental spruce

    Directory of Open Access Journals (Sweden)

    Aydın Kahriman

    2012-11-01

    Full Text Available The aim of this study is to investigate statistical relations between each of 12 competition indices (both distance-dependent and distance-independent and diameter growth of trees. Also we investigated the relations between each of 12 competition indices together with diameter at breast height and diameter growth. For that reason, six sampling plots (ranging from 1000 to 2000 m2 in size were taken from in mixed stands of Caucasion fir and Oriental spruce located within the Forest Management Districts of Torul and Artvin. Our results from those sampling plots were in agreement with general growth models. Regression analysis between each of competition indexes and diameter growth resulted in coefficients of determination (R2 values ranging from 30 to 64%. The distance-dependent competition indices gave stronger correlations with diameter growth than the distance-independent competition indexes. Coefficients of determination were even higher when competition indexes and dbh were used together as independent variables (R2 = 0.31 - 0.82.

  10. Fetal growth disorders in twin gestations.

    LENUS (Irish Health Repository)

    Breathnach, Fionnuala M

    2012-06-01

    Twin growth is frequently mismatched. This review serves to explore the pathophysiologic mechanisms that underlie growth aberrations in twin gestations, the prenatal recognition of abnormal twin growth, and the critical importance of stratifying management of abnormal twin growth by chorionicity. Although poor in utero growth of both twins may reflect maternal factors resulting in global uteroplacental dysfunction, discordant twin growth may be attributed to differences in genetic potential between co-twins, placental dysfunction confined to one placenta only, or one placental territory within a shared placenta. In addition, twin-twin transfusion syndrome represents a distinct entity of which discordant growth is a common feature. Discordant growth is recognized as an independent risk factor for adverse perinatal outcome. Intertwin birth weight disparity of 18% or more should be considered to represent a discordance threshold, which serves as an independent risk factor for adverse perinatal outcome. At this cutoff, perinatal morbidity is found to increase both for the larger and the smaller twin within a discordant pair. There remains uncertainty surrounding the sonographic parameters that are most predictive of discordance. Although heightening of fetal surveillance in the face of discordant twin growth follows the principles applied to singleton gestations complicated by fetal growth restriction, the timing of intervention is largely influenced by chorionicity.

  11. Insulin-like growth factor II messenger RNA-binding protein-3 is an independent prognostic factor in uterine leiomyosarcoma.

    Science.gov (United States)

    Yasutake, Nobuko; Ohishi, Yoshihiro; Taguchi, Kenichi; Hiraki, Yuka; Oya, Masafumi; Oshiro, Yumi; Mine, Mari; Iwasaki, Takeshi; Yamamoto, Hidetaka; Kohashi, Kenichi; Sonoda, Kenzo; Kato, Kiyoko; Oda, Yoshinao

    2018-04-01

    The aim of this study was to identify the prognostic factors of uterine leiomyosarcoma (ULMS). We reviewed 60 cases of surgically resected ULMSs and investigated conventional clinicopathological factors, together with the expression of insulin-like growth factor II messenger RNA-binding protein-3 (IMP3), hormone receptors and cell cycle regulatory markers by immunohistochemistry. Mediator complex subunit 12 (MED12) mutation analysis was also performed. Univariate analyses revealed that advanced stage (P < 0.0001), older age (P = 0.0244) and IMP3 expression (P = 0.0011) were significant predictors of a poor outcome. Multivariate analysis revealed advanced stage (P < 0.0001) and IMP3 (P = 0.0373) as independent predictors of a poor prognosis. Expressions of cell cycle markers and hormone receptors, and MED12 mutations (12% in ULMSs) were not identified as prognostic markers in this study. IMP3 expression in ULMS could be a marker of a poor prognosis. © 2017 John Wiley & Sons Ltd.

  12. MicroRNA-195 inhibits the proliferation of human glioma cells by directly targeting cyclin D1 and cyclin E1.

    Directory of Open Access Journals (Sweden)

    Wang Hui

    Full Text Available Glioma proliferation is a multistep process during which a sequence of genetic and epigenetic alterations randomly occur to affect the genes controlling cell proliferation, cell death and genetic stability. microRNAs are emerging as important epigenetic modulators of multiple target genes, leading to abnormal cellular signaling involving cellular proliferation in cancers.In the present study, we found that expression of miR-195 was markedly downregulated in glioma cell lines and human primary glioma tissues, compared to normal human astrocytes and matched non-tumor associated tissues. Upregulation of miR-195 dramatically reduced the proliferation of glioma cells. Flow cytometry analysis showed that ectopic expression of miR-195 significantly decreased the percentage of S phase cells and increased the percentage of G1/G0 phase cells. Overexpression of miR-195 dramatically reduced the anchorage-independent growth ability of glioma cells. Furthermore, overexpression of miR-195 downregulated the levels of phosphorylated retinoblastoma (pRb and proliferating cell nuclear antigen (PCNA in glioma cells. Conversely, inhibition of miR-195 promoted cell proliferation, increased the percentage of S phase cells, reduced the percentage of G1/G0 phase cells, enhanced anchorage-independent growth ability, upregulated the phosphorylation of pRb and PCNA in glioma cells. Moreover, we show that miR-195 inhibited glioma cell proliferation by downregulating expression of cyclin D1 and cyclin E1, via directly targeting the 3'-untranslated regions (3'-UTR of cyclin D1 and cyclin E1 mRNA. Taken together, our results suggest that miR-195 plays an important role to inhibit the proliferation of glioma cells, and present a novel mechanism for direct miRNA-mediated suppression of cyclin D1 and cyclin E1 in glioma.

  13. The oncogenic properties of EWS/WT1 of desmoplastic small round cell tumors are unmasked by loss of p53 in murine embryonic fibroblasts

    International Nuclear Information System (INIS)

    Bandopadhayay, Pratiti; Thomas, David M; Algar, Elizabeth; Ekert, Paul G; Jabbour, Anissa M; Riffkin, Christopher; Salmanidis, Marika; Gordon, Lavinia; Popovski, Dean; Rigby, Lin; Ashley, David M; Watkins, David N

    2013-01-01

    Desmoplastic small round cell tumor (DSRCT) is characterized by the presence of a fusion protein EWS/WT1, arising from the t (11;22) (p13;q12) translocation. Here we examine the oncogenic properties of two splice variants of EWS/WT1, EWS/WT1-KTS and EWS/WT1 + KTS. We over-expressed both EWS/WT1 variants in murine embryonic fibroblasts (MEFs) of wild-type, p53 +/- and p53 -/- backgrounds and measured effects on cell-proliferation, anchorage-independent growth, clonogenicity after serum withdrawal, and sensitivity to cytotoxic drugs and gamma irradiation in comparison to control cells. We examined gene expression profiles in cells expressing EWS/WT1. Finally we validated our key findings in a small series of DSRCT. Neither isoform of EWS/WT1 was sufficient to transform wild-type MEFs however the oncogenic potential of both was unmasked by p53 loss. Expression of EWS/WT1 in MEFs lacking at least one allele of p53 enhanced cell-proliferation, clonogenic survival and anchorage-independent growth. EWS/WT1 expression in wild-type MEFs conferred resistance to cell-cycle arrest after irradiation and daunorubicin induced apoptosis. We show DSRCT commonly have nuclear localization of p53, and copy-number amplification of MDM2/MDMX. Expression of either isoform of EWS/WT1 induced characteristic mRNA expression profiles. Gene-set enrichment analysis demonstrated enrichment of WNT pathway signatures in MEFs expressing EWS/WT1 + KTS. Wnt-activation was validated in cell lines with over-expression of EWS/WT1 and in DSRCT. In conclusion, we show both isoforms of EWS/WT1 have oncogenic potential in MEFs with loss of p53. In addition we provide the first link between EWS/WT1 and Wnt-pathway signaling. These data provide novel insights into the function of the EWS/WT1 fusion protein which characterize DSRCT

  14. Novel Growth Factor as Prognostic Marker for Estrogen-Independence in Breast Cancer

    National Research Council Canada - National Science Library

    Serrero, Ginette

    2002-01-01

    ...-independence and tamoxifen resistance. Here, wave conducted a study with 206 paraffin embedded human breast cancer biopsies and measured PCDGF expression by immunohistochemistry using an anti-PCDGF developed in our laboratory...

  15. Novel Growth Factor as Prognostic Marker for Estrogen-Independence in Breast Cancer

    National Research Council Canada - National Science Library

    Serrero, Ginette

    2003-01-01

    The Concept Award focused on investigating the expression on the biomarker PCDGF/GP88 in breast cancer and its effect on the acquisition of estrogen independence and tamoxifen resistance, a hallmark...

  16. Annexin A6 contributes to the invasiveness of breast carcinoma cells by influencing the organization and localization of functional focal adhesions

    Energy Technology Data Exchange (ETDEWEB)

    Sakwe, Amos M., E-mail: asakwe@mmc.edu [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Koumangoye, Rainelli; Guillory, Bobby [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Ochieng, Josiah [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Center for Aids Health Disparity Research, Meharry Medical College, Nashville, TN 37208 (United States); Department of Cancer Biology, Vanderbilt University, Nashville, TN (United States)

    2011-04-01

    The interaction of annexin A6 (AnxA6) with membrane phospholipids and either specific extracellular matrix (ECM) components or F-actin suggests that it may influence cellular processes associated with rapid plasma membrane reorganization such as cell adhesion and motility. Here, we examined the putative roles of AnxA6 in adhesion-related cellular processes that contribute to breast cancer progression. We show that breast cancer cells secrete annexins via the exosomal pathway and that the secreted annexins are predominantly cell surface-associated. Depletion of AnxA6 in the invasive BT-549 breast cancer cells is accompanied by enhanced anchorage-independent cell growth but cell-cell cohesion, cell adhesion/spreading onto collagen type IV or fetuin-A, cell motility and invasiveness were strongly inhibited. To explain the loss in adhesion/motility, we show that vinculin-based focal adhesions in the AnxA6-depleted BT-549 cells are elongated and randomly distributed. These focal contacts are also functionally defective because the activation of focal adhesion kinase and the phosphoinositide-3 kinase/Akt pathway were strongly inhibited while the MAP kinase pathway remained constitutively active. Compared with normal human breast tissues, reduced AnxA6 expression in breast carcinoma tissues correlates with enhanced cell proliferation. Together this suggests that reduced AnxA6 expression contributes to breast cancer progression by promoting the loss of functional cell-cell and/or cell-ECM contacts and anchorage-independent cell proliferation.

  17. Annexin A6 contributes to the invasiveness of breast carcinoma cells by influencing the organization and localization of functional focal adhesions

    International Nuclear Information System (INIS)

    Sakwe, Amos M.; Koumangoye, Rainelli; Guillory, Bobby; Ochieng, Josiah

    2011-01-01

    The interaction of annexin A6 (AnxA6) with membrane phospholipids and either specific extracellular matrix (ECM) components or F-actin suggests that it may influence cellular processes associated with rapid plasma membrane reorganization such as cell adhesion and motility. Here, we examined the putative roles of AnxA6 in adhesion-related cellular processes that contribute to breast cancer progression. We show that breast cancer cells secrete annexins via the exosomal pathway and that the secreted annexins are predominantly cell surface-associated. Depletion of AnxA6 in the invasive BT-549 breast cancer cells is accompanied by enhanced anchorage-independent cell growth but cell-cell cohesion, cell adhesion/spreading onto collagen type IV or fetuin-A, cell motility and invasiveness were strongly inhibited. To explain the loss in adhesion/motility, we show that vinculin-based focal adhesions in the AnxA6-depleted BT-549 cells are elongated and randomly distributed. These focal contacts are also functionally defective because the activation of focal adhesion kinase and the phosphoinositide-3 kinase/Akt pathway were strongly inhibited while the MAP kinase pathway remained constitutively active. Compared with normal human breast tissues, reduced AnxA6 expression in breast carcinoma tissues correlates with enhanced cell proliferation. Together this suggests that reduced AnxA6 expression contributes to breast cancer progression by promoting the loss of functional cell-cell and/or cell-ECM contacts and anchorage-independent cell proliferation.

  18. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp transcription factors

    Directory of Open Access Journals (Sweden)

    Pathi Satya

    2011-08-01

    Full Text Available Abstract Background Betulinic acid (BA inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. Methods The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a and ZBTB10 mRNA expression. Results BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS, ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. Conclusions These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent.

  19. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors

    International Nuclear Information System (INIS)

    Chintharlapalli, Sudhakar; Papineni, Sabitha; Lei, Ping; Pathi, Satya; Safe, Stephen

    2011-01-01

    Betulinic acid (BA) inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression. BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent

  20. [Three dimensional finite element analysis of maxillary anterior teeth retraction with micro-implant anchorage and sliding mechanics].

    Science.gov (United States)

    Zhang, Yi; Zhang, Lei; Fan, Yu-bo; Song, Jin-lin; Deng, Feng

    2009-10-01

    To investigate the biomechanical effects of micro-implant anchorage technique with sliding mechanics on maxillary anterior teeth retraction under different implant insertion heights and different retraction hook heights. The three dimensional finite element model of maxillary anterior teeth retraction force system was constructed with CT scanning and MIMICS software and the relationships between brackets, teeth, wire and micro-implant were simulating the clinical factions. Then the initial tooth displacement was calculated when the insertion heights were 4 mm and 8 mm and the retraction hook heights were 1, 4, 7, 10 mm respectively. With retraction hook height added, the anterior teeth movement changed from lingual crown tipping to labial crown tipping and the intrusion movement was more apparent when the micro-implant was inserted in a higher location. The ideal teeth movement control could be achieved by different insertion heights of micro-implant and different retraction hook heights in straight wire retraction force system.

  1. Biologic consequences of Stat1-independent IFN signaling

    Science.gov (United States)

    Gil, M. Pilar; Bohn, Erwin; O'Guin, Andrew K.; Ramana, Chilakamarti V.; Levine, Beth; Stark, George R.; Virgin, Herbert W.; Schreiber, Robert D.

    2001-01-01

    Although Stat1 is required for many IFN-dependent responses, recent work has shown that IFNγ functions independently of Stat1 to affect the growth of tumor cells or immortalized fibroblasts. We now demonstrate that both IFNγ and IFNα/β regulate proliferative responses in cells of the mononuclear phagocyte lineage derived from Stat1-null mice. Using both representational difference analysis and gene arrays, we show that IFNγ exerts its Stat1-independent actions on mononuclear phagocytes by regulating the expression of many genes. This result was confirmed by monitoring changes in expression and function of the corresponding gene products. Regulation of the expression of these genes requires the IFNγ receptor and Jak1. The physiologic relevance of IFN-dependent, Stat1-independent signaling was demonstrated by monitoring antiviral responses in Stat1-null mice. Thus, the IFN receptors engage alternative Stat1-independent signaling pathways that have important physiological consequences. PMID:11390995

  2. Characterization of a novel oncogenic K-ras mutation in colon cancer

    International Nuclear Information System (INIS)

    Akagi, Kiwamu; Uchibori, Ryosuke; Yamaguchi, Kensei; Kurosawa, Keiko; Tanaka, Yoichiro; Kozu, Tomoko

    2007-01-01

    Activating mutations of RAS are frequently observed in subsets of human cancers, indicating that RAS activation is involved in tumorigenesis. Here, we identified and characterized a novel G to T transversion mutation of the K-ras gene at the third position of codon 19 (TTG) which substituted phenylalanine for leucine in 3 primary colon carcinomas. Biological and biochemical activity was examined using transformed NIH3T3 cells expressing mutant or wild-type K-ras. Transformants harboring the K-ras mutation at codon 19 showed proliferative capacity under serum-starved conditions, less contact inhibition, anchorage-independent growth, tumorigenicity in nude mice and elevation of active Ras-GTP levels. These results indicated that this novel mutation possesses high oncogenic activity

  3. Are Independent Probes Truly Independent?

    Science.gov (United States)

    Camp, Gino; Pecher, Diane; Schmidt, Henk G.; Zeelenberg, Rene

    2009-01-01

    The independent cue technique has been developed to test traditional interference theories against inhibition theories of forgetting. In the present study, the authors tested the critical criterion for the independence of independent cues: Studied cues not presented during test (and unrelated to test cues) should not contribute to the retrieval…

  4. Independent colimitation for carbon dioxide and inorganic phosphorus.

    Directory of Open Access Journals (Sweden)

    Elly Spijkerman

    Full Text Available Simultaneous limitation of plant growth by two or more nutrients is increasingly acknowledged as a common phenomenon in nature, but its cellular mechanisms are far from understood. We investigated the uptake kinetics of CO(2 and phosphorus of the algae Chlamydomonas acidophila in response to growth at limiting conditions of CO(2 and phosphorus. In addition, we fitted the data to four different Monod-type models: one assuming Liebigs Law of the minimum, one assuming that the affinity for the uptake of one nutrient is not influenced by the supply of the other (independent colimitation and two where the uptake affinity for one nutrient depends on the supply of the other (dependent colimitation. In addition we asked whether the physiological response under colimitation differs from that under single nutrient limitation.We found no negative correlation between the affinities for uptake of the two nutrients, thereby rejecting a dependent colimitation. Kinetic data were supported by a better model fit assuming independent uptake of colimiting nutrients than when assuming Liebigs Law of the minimum or a dependent colimitation. Results show that cell nutrient homeostasis regulated nutrient acquisition which resulted in a trade-off in the maximum uptake rates of CO(2 and phosphorus, possibly driven by space limitation on the cell membrane for porters for the different nutrients. Hence, the response to colimitation deviated from that to a single nutrient limitation. In conclusion, responses to single nutrient limitation cannot be extrapolated to situations where multiple nutrients are limiting, which calls for colimitation experiments and models to properly predict growth responses to a changing natural environment. These deviations from single nutrient limitation response under colimiting conditions and independent colimitation may also hold for other nutrients in algae and in higher plants.

  5. Independent Colimitation for Carbon Dioxide and Inorganic Phosphorus

    Science.gov (United States)

    Spijkerman, Elly; de Castro, Francisco; Gaedke, Ursula

    2011-01-01

    Simultaneous limitation of plant growth by two or more nutrients is increasingly acknowledged as a common phenomenon in nature, but its cellular mechanisms are far from understood. We investigated the uptake kinetics of CO2 and phosphorus of the algae Chlamydomonas acidophila in response to growth at limiting conditions of CO2 and phosphorus. In addition, we fitted the data to four different Monod-type models: one assuming Liebigs Law of the minimum, one assuming that the affinity for the uptake of one nutrient is not influenced by the supply of the other (independent colimitation) and two where the uptake affinity for one nutrient depends on the supply of the other (dependent colimitation). In addition we asked whether the physiological response under colimitation differs from that under single nutrient limitation. We found no negative correlation between the affinities for uptake of the two nutrients, thereby rejecting a dependent colimitation. Kinetic data were supported by a better model fit assuming independent uptake of colimiting nutrients than when assuming Liebigs Law of the minimum or a dependent colimitation. Results show that cell nutrient homeostasis regulated nutrient acquisition which resulted in a trade-off in the maximum uptake rates of CO2 and phosphorus, possibly driven by space limitation on the cell membrane for porters for the different nutrients. Hence, the response to colimitation deviated from that to a single nutrient limitation. In conclusion, responses to single nutrient limitation cannot be extrapolated to situations where multiple nutrients are limiting, which calls for colimitation experiments and models to properly predict growth responses to a changing natural environment. These deviations from single nutrient limitation response under colimiting conditions and independent colimitation may also hold for other nutrients in algae and in higher plants. PMID:22145031

  6. Independent colimitation for carbon dioxide and inorganic phosphorus.

    Science.gov (United States)

    Spijkerman, Elly; de Castro, Francisco; Gaedke, Ursula

    2011-01-01

    Simultaneous limitation of plant growth by two or more nutrients is increasingly acknowledged as a common phenomenon in nature, but its cellular mechanisms are far from understood. We investigated the uptake kinetics of CO(2) and phosphorus of the algae Chlamydomonas acidophila in response to growth at limiting conditions of CO(2) and phosphorus. In addition, we fitted the data to four different Monod-type models: one assuming Liebigs Law of the minimum, one assuming that the affinity for the uptake of one nutrient is not influenced by the supply of the other (independent colimitation) and two where the uptake affinity for one nutrient depends on the supply of the other (dependent colimitation). In addition we asked whether the physiological response under colimitation differs from that under single nutrient limitation.We found no negative correlation between the affinities for uptake of the two nutrients, thereby rejecting a dependent colimitation. Kinetic data were supported by a better model fit assuming independent uptake of colimiting nutrients than when assuming Liebigs Law of the minimum or a dependent colimitation. Results show that cell nutrient homeostasis regulated nutrient acquisition which resulted in a trade-off in the maximum uptake rates of CO(2) and phosphorus, possibly driven by space limitation on the cell membrane for porters for the different nutrients. Hence, the response to colimitation deviated from that to a single nutrient limitation. In conclusion, responses to single nutrient limitation cannot be extrapolated to situations where multiple nutrients are limiting, which calls for colimitation experiments and models to properly predict growth responses to a changing natural environment. These deviations from single nutrient limitation response under colimiting conditions and independent colimitation may also hold for other nutrients in algae and in higher plants.

  7. 76 FR 11961 - Safety Zone, Dredging Operations; Delaware River, Marcus Hook, PA

    Science.gov (United States)

    2011-03-04

    ... term ``small entities'' comprises small businesses, not-for-profit organizations that are independently... effect for only a limited period. Vessel traffic will be diverted through the lower end of Anchorage 7 to...

  8. Targeting non-small cell lung cancer cells by dual inhibition of the insulin receptor and the insulin-like growth factor-1 receptor.

    Directory of Open Access Journals (Sweden)

    Emma E Vincent

    Full Text Available Phase III trials of the anti-insulin-like growth factor-1 receptor (IGF1R antibody figitumumab in non-small cell lung cancer (NSCLC patients have been discontinued owing to lack of survival benefit. We investigated whether inhibition of the highly homologous insulin receptor (IR in addition to the IGF1R would be more effective than inhibition of the IGF1R alone at preventing the proliferation of NSCLC cells. Signalling through IGF1R and IR in the NSCLC cell lines A549 and Hcc193 was stimulated by a combination of IGF1, IGF2 and insulin. It was inhibited by antibodies that block ligand binding, αIR3 (IGF1R and IR47-9 (IR, and by the ATP-competitive small molecule tyrosine kinase inhibitors AZ12253801 and NVPAWD742 which inhibit both IGF1R and IR tyrosine kinases. The effect of inhibitors was determined by an anchorage-independent proliferation assay and by analysis of Akt phosphorylation. In Hcc193 cells the reduction in cell proliferation and Akt phosphorylation due to anti-IGF1R antibody was enhanced by antibody-mediated inhibition of the IR whereas in A549 cells, with a relatively low IR:IGF1R expression ratio, it was not. In each cell line proliferation and Akt phosphorylation were more effectively inhibited by AZ12253801 and NVPAWD742 than by combined αIR3 and IR47-9. When the IGF1R alone is inhibited, unencumbered signalling through the IR can contribute to continued NSCLC cell proliferation. We conclude that small molecule inhibitors targeting both the IR and IGF1R more effectively reduce NSCLC cell proliferation in a manner independent of the IR:IGF1R expression ratio, providing a therapeutic rationale for the treatment of this disease.

  9. Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young H. [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Apolo, Andrea B. [Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Agarwal, Piyush K.; Bottaro, Donald P., E-mail: dbottaro@helix.nih.gov [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2014-11-25

    There is mounting evidence of oncogenic hepatocyte growth factor (HGF)/Met signaling in urothelial carcinoma (UC) of the bladder. The effects of three kinase inhibitors, cabozantinib, crizotinib and EMD1214063, on HGF-driven signaling and cell growth, invasion and tumorigenicity were analyzed in cultured UC cell lines. SW780 xenograft growth in SCID and human HGF knock-in SCID (hHGF/SCID) mice treated with cabozantinib or vehicle, as well as tumor levels of Met and pMet, were also determined. Met content was robust in most UC-derived cell lines. Basal pMet content and effector activation state in quiescent cells were low, but significantly enhanced by added HGF, as were cell invasion, proliferation and anchorage independent growth. These HGF-driven effects were reversed by Met inhibitor treatment. Tumor xenograft growth was significantly higher in hHGF/SCID mice vs. SCID mice and significantly inhibited by cabozantinib, as was tumor phospho-Met content. These studies indicate the prevalence and functionality of the HGF/Met signaling pathway in UC cells, suggest that paracrine HGF may contribute to UC tumor growth and progression, and that support further preclinical investigation of Met inhibitors for the treatment of UC is warranted.

  10. Functional inhibition of Ubiquitin conjugating Enzyme (UBE2C) reduces proliferation and sensitizes cervical and breast cancer cells to radiation, doxorubicin, tamoxifen and letrozole

    International Nuclear Information System (INIS)

    Bose, Mayil Vahanan; Rawat, Akhilesh; Gopisetty, Gopal; Thangarajan, Rajkumar; Ganesharaja, Selvaluxmy

    2014-01-01

    Cervical cancer is the second most common cancer in women, worldwide. About 80% of cervical cancer cases occur in developing countries. Breast cancer has overtaken cervical cancer in most of the urban centers in India. In recent years, interest in the role of Ubiquitin conjugating Enzyme E2C (UBE2C) in cancer has shown a dramatic increase. Several studies have reported UBE2C as a potential oncogene and therapeutic target. The objective of the study was to elucidate radiation and chemo-sensitivity in response to functional inhibition of UBE2C in cervical and breast cancer cell lines. Taqman Real time PCR was performed to measure UBE2C levels in cervical and breast cancer cell lines. A dominant negative form of UBE2C (DN-UBE2C) was used to functionally inhibit wild type UBE2C. Cell proliferation and anchorage independent growth were measured by colorimetric assay and soft agar assay respectively. Radiation and chemo response of cell lines were assessed by colorimetric assay and clonogenic assay. Difference in sensitivity to radiation was observed among the cervical cancer cell lines studied. The growth rate of SiHa and HeLa transfected with DN- UBE2C was significantly reduced compared to vector control. Further, DN-UBE2C mediated radio-sensitivity was correlated with a significant decrease in resistance to radiation by SiHa and HeLa cells after transfection when compared to control cultures. Similarly, both the growth rate and the anchorage independent growth of MCF7 and MDAMB231 cells transfected with DN-UBE2C were significantly reduced compared to cells transfected with vector alone. MCF7 and MDAMB231 cells expressing DN-UBE2C were significantly more sensitive to different doses of radiation and doxorubicin compared to controls. In addition, DN-UBE2C transfected MCF7 cells were more sensitive to inhibition by tamoxifen and letrozole compared to vector controls. These results suggest that UBE2C can be used as a potential therapeutic target for cervical and breast

  11. Technical Education in Pre and Post Independent India

    Science.gov (United States)

    Janardhana, G.; Rajasekhar, M.

    2012-01-01

    This paper deals with technical education growth, policies in pre and post independent India. The world is moving forward rapidly and positively, into an era where societies and economies are incrementally based on knowledge. The importance of nations in the 21st Century shall be judged not by their economic strength alone, but also by their power…

  12. Cyclophilin B as a co-regulator of prolactin-induced gene expression and function in breast cancer cells.

    Science.gov (United States)

    Fang, Feng; Zheng, Jiamao; Galbaugh, Traci L; Fiorillo, Alyson A; Hjort, Elizabeth E; Zeng, Xianke; Clevenger, Charles V

    2010-06-01

    The effects of prolactin (PRL) during the pathogenesis of breast cancer are mediated in part though Stat5 activity enhanced by its interaction with its transcriptional inducer, the prolyl isomerase cyclophilin B (CypB). We have demonstrated that knockdown of CypB decreases cell growth, proliferation, and migration, and CypB expression is associated with malignant progression of breast cancer. In this study, we examined the effect of CypB knockdown on PRL signaling in breast cancer cells. CypB knockdown with two independent siRNAs was shown to impair PRL-induced reporter expression in breast cancer cell line. cDNA microarray analysis was performed on these cells to assess the effect of CypB reduction, and revealed a significant decrease in PRL-induced endogenous gene expression in two breast cancer cell lines. Parallel functional assays revealed corresponding alterations of both anchorage-independent cell growth and cell motility of breast cancer cells. Our results demonstrate that CypB expression levels significantly modulate PRL-induced function in breast cancer cells ultimately resulting in enhanced levels of PRL-responsive gene expression, cell growth, and migration. Given the increasingly appreciated role of PRL in the pathogenesis of breast cancer, the actions of CypB detailed here are of biological significance.

  13. Central bank independence and its effect on money market stability

    OpenAIRE

    MSc. Anera Alishani

    2012-01-01

    Since 1990s many countries have moved toward greater central bank independence (CBI) by either amending their Central Bank’s laws or writing them de novo. Also countries of Western Balkans and many other transition countries have moved toward greater CBI. There are many potential benefits associated with greater CBI, and one of them is stable growth of money and liquidity. For a given level of money market development the hypothesis is that a more independent CB is likely to promote more stab...

  14. Movimentação de molares inferiores ancorados em mini-parafusos Mandibular molar uprighting, using mini-screw as anchorage

    Directory of Open Access Journals (Sweden)

    Rosana Canteras Di Matteo

    2005-08-01

    Full Text Available Freqüentemente a movimentação ortodôntica exige recursos adicionais de ancoragem. Os mini-parafusos têm-se apresentado como uma possível solução. O propósito deste trabalho foi estabelecer um método para a verticalização de molares inferiores inclinados para mesial, utilizando ancoragem em mini-parafusos colocados na região de linha oblíqüa externa da mandíbula. Foram selecionados três pacientes entre 40 a 48 anos (dois do gênero feminino, um do gênero masculino, com molares inferiores inclinados para mesial e distalmente posicionados às áreas edêntulas. Os pacientes foram tratados ortodonticamente durante um período de 6 a 12 meses, com técnica ortodôntica MD3. Mini-parafusos de titânio foram colocados bilateralmente com anestesia local. Uma incisão sobre a linha oblíqüa externa da mandíbula, medindo aproximadamente 1 cm foi realizada em cada lado, distalmente aos molares inclinados. Após descolamento muco-periosteal, mini-parafusos foram implantados e foram realizadas suturas deixando suas cabeças exteriorizadas. Uma semana após a remoção das suturas, cargas ortodônticas (entre 150 a 200 gramas/força foram aplicadas através de forças elásticas. Verificamos que alguma inflamação foi observada ao redor dos mini-parafusos, mas foi controlada com procedimentos de higienização. O procedimento cirúrgico é simples, podendo ser realizado pelo ortodontista; as formas dimensionais dos mini-parafusos são adequadas e estes são de fácil remoção após uso. Concluímos que o uso de mini-parafusos representa uma alternativa efetiva de ancoragem ortodôntica na verticalização de molares inferiores.Tooth movement frequently requires additional anchorage resources. Mini-screws have been used as a possible solution to this matter. The purpose of this study was to establish a method of mandibular molar uprighting, using mini-screw as anchorage, positioned on the mandibular external oblique line, behind and

  15. Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Davis Rodney

    2006-07-01

    Full Text Available Abstract Background Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF, was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. Methods We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. Results We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM or nucleolin (on the cell surfaces eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of

  16. Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells

    International Nuclear Information System (INIS)

    Tate, Amanda; Isotani, Shuji; Bradley, Michael J; Sikes, Robert A; Davis, Rodney; Chung, Leland WK; Edlund, Magnus

    2006-01-01

    Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF), was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF) were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM) and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM) or nucleolin (on the cell surfaces) eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of laminin-binding integrins, nor can they be linked to

  17. Growth rate of late passage sarcoma cells is independent of epigenetic events but dependent on the amount of chromosomal aberrations

    International Nuclear Information System (INIS)

    Becerikli, Mustafa; Jacobsen, Frank; Rittig, Andrea; Köhne, Wiebke; Nambiar, Sandeep; Mirmohammadsadegh, Alireza; Stricker, Ingo; Tannapfel, Andrea; Wieczorek, Stefan; Epplen, Joerg Thomas; Tilkorn, Daniel; Steinstraesser, Lars

    2013-01-01

    Soft tissue sarcomas (STS) are characterized by co-participation of several epigenetic and genetic events during tumorigenesis. Having bypassed cellular senescence barriers during oncogenic transformation, the factors further affecting growth rate of STS cells remain poorly understood. Therefore, we investigated the role of gene silencing (DNA promoter methylation of LINE-1, PTEN), genetic aberrations (karyotype, KRAS and BRAF mutations) as well as their contribution to the proliferation rate and migratory potential that underlies “initial” and “final” passage sarcoma cells. Three different cell lines were used, SW982 (synovial sarcoma), U2197 (malignant fibrous histiocytoma (MFH)) and HT1080 (fibrosarcoma). Increased proliferative potential of final passage STS cells was not associated with significant differences in methylation (LINE-1, PTEN) and mutation status (KRAS, BRAF), but it was dependent on the amount of chromosomal aberrations. Collectively, our data demonstrate that these fairly differentiated/advanced cancer cell lines have still the potential to gain an additional spontaneous growth benefit without external influences and that maintenance of increased proliferative potential towards longevity of STS cells (having crossed senescence barriers) may be independent of overt epigenetic alterations. -- Highlights: Increased proliferative potential of late passage STS cells was: • Not associated with epigenetic changes (methylation changes at LINE-1, PTEN). • Not associated with mutation status of KRAS, BRAF. • Dependent on presence/absence of chromosomal aberrations

  18. Mutations that promote furin-independent growth of Semliki Forest virus affect p62-E1 interactions and membrane fusion

    International Nuclear Information System (INIS)

    Zhang Xinyong; Kielian, Margaret

    2004-01-01

    The enveloped alphavirus Semliki Forest virus (SFV) infects cells via a low pH-triggered membrane fusion reaction mediated by the E1 protein. E1's fusion activity is regulated by its heterodimeric interaction with a companion membrane protein E2. Mature E2 protein is generated by furin processing of the precursor p62. Processing destabilizes the heterodimer, allowing dissociation at acidic pH, E1 conformational changes, and membrane fusion. We used a furin-deficient cell line, FD11, to select for SFV mutants that show increased growth in the absence of p62 processing. We isolated and characterized 7 such pci mutants (p62 cleavage independent), which retained the parental furin cleavage site but showed significant increases in their ability to carry out membrane fusion in the p62 form. Sequence analysis of the pci mutants identified mutations primarily on the E2 protein, and suggested sites important in the interaction of p62 with E1 and the regulation of fusion

  19. Flash Foods' Job Creation and Petroleum Independence with E85

    Energy Technology Data Exchange (ETDEWEB)

    Walk, Steve [Protec Fuel Management LLC, Boca Raton, FL (United States)

    2016-11-21

    Protec Fuel Management project objectives are to help design, build, provide, promote and supply biofuels for the greater energy independence, national security and domestic economic growth through job creations, infrastructure projects and supply chain business stimulants.

  20. The eukaryotic translation elongation factor eEF1A2 induces neoplastic properties and mediates tumorigenic effects of ZNF217 in precursor cells of human ovarian carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yu; Wong, Nicholas; Guan, Yinghui; Salamanca, Clara M.; Cheng, Jung Chien; Lee, Jonathan M.; Gray, Joe W.; Auersperg, Nelly

    2008-04-25

    Ovarian epithelial carcinomas (OEC) frequently exhibit amplifications at the 20q13 locus which is the site of several oncogenes, including the eukaryotic elongation factor EEF1A2 and the transcription factor ZNF217. We reported previously that overexpressed ZNF217 induces neoplastic characteristics in precursor cells of OEC. Unexpectedly, ZNF217, which is a transcriptional repressor, enhanced expression of eEF1A2. In this study, array comparative genomic hybridization, single nucleotide polymorphism and Affymetrix analysis of ZNF217-overexpressing cell lines confirmed consistently increased expression of eEF1A2 but not of other oncogenes, and revealed early changes in EEF1A2 gene copy numbers and increased expression at crisis during immortalization. We defined the influence of eEF1A2 overexpression on immortalized ovarian surface epithelial cells, and investigated interrelationships between effects of ZNF217 and eEF1A2 on cellular phenotypes. Lentivirally induced eEF1A2 overexpression caused delayed crisis, apoptosis resistance and increases in serum-independence, saturation densities, and anchorage independence. siRNA to eEF1A2 reversed apoptosis resistance and reduced anchorage independence in eEF1A2-overexpressing lines. Remarkably, siRNA to eEF1A2 was equally efficient in inhibiting both anchorage independence and resistance to apoptosis conferred by ZNF217 overexpression. Our data define neoplastic properties that are caused by eEF1A2 in nontumorigenic ovarian cancer precursor cells, and suggest that eEF1A2 plays a role in mediating ZNF217-induced neoplastic progression.

  1. HER-2 as a Progression Factor and Therapeutic Target in Breast Cancer

    National Research Council Canada - National Science Library

    1999-01-01

    ...). We had observed previously that upon reduction of llER-2 in MCF-7 cells by ribozyme-targeting estradiol lost its ability to induce anchorage- independent colony formation in soft agar of the tumor cell...

  2. Platelet-rich plasma—an ‘Elixir’ for treatment of alopecia: personal experience on 117 patients with review of literature

    Science.gov (United States)

    Manchanda, Shweta

    2017-01-01

    Platelet-rich plasma (PRP) has emerged as a new treatment modality in regenerative plastic surgery and dermatology. PRP is a simple, cost-effective and feasible treatment option with high patient satisfaction for hair loss and can be regarded as a valuable adjuvant treatment modality for androgenic alopecia and other types of non-scarring alopecias. Authors have proposed a hair model termed “Golden anchorage with ‘molecular locking’ of ectodermal and mesenchymal components for survival and integrity of hair follicle (HF)” in this article. Golden anchorage comprises of bulge stem cells, ectodermal basement membrane and bulge portion of APM. PRP with its autologous supply of millions of growth factors works on ‘Golden anchorage’ along with keratinocytes (PDGF), dermal papilla (IGF and fibroblast growth factor), vasculature (VEGF and PDGF) and neural cells (Nerve Growth Factor) in a multipronged manner serving as an ‘elixir’ for hair growth and improving overall environment. PMID:28815175

  3. MK-2206, an AKT Inhibitor, Promotes Caspase-Independent Cell Death and Inhibits Leiomyoma Growth

    Science.gov (United States)

    Sefton, Elizabeth C.; Qiang, Wenan; Serna, Vanida; Kurita, Takeshi; Wei, Jian-Jun; Chakravarti, Debabrata

    2013-01-01

    Uterine leiomyomas (ULs), benign tumors of the myometrium, are the number one indication for hysterectomies in the United States due to a lack of an effective alternative therapy. ULs show activation of the pro-survival AKT pathway compared with normal myometrium; however, substantial data directly linking AKT to UL cell survival are lacking. We hypothesized that AKT promotes UL cell survival and that it is a viable target for inhibiting UL growth. We used the investigational AKT inhibitor MK-2206, currently in phase II trials, on cultured primary human UL and myometrial cells, immortalized leiomyoma cells, and in leiomyoma grafts grown under the kidney capsule in mice. MK-2206 inhibited AKT and PRAS40 phosphorylation but did not regulate serum- and glucocorticoid-induced kinase and ERK1/2, demonstrating its specificity for AKT. MK-2206 reduced UL cell viability and decreased UL tumor volumes. UL cells exhibited disruption of mitochondrial structures and underwent cell death that was independent of caspases. Additionally, mammalian target of rapamycin and p70S6K phosphorylation were reduced, indicating that mammalian target of rapamycin complex 1 signaling was compromised by AKT inhibition in UL cells. MK-2206 also induced autophagy in UL cells. Pretreatment of primary UL cells with 3-methyladenine enhanced MK-2206-mediated UL cell death, whereas knockdown of ATG5 and/or ATG7 did not significantly influence UL cell viability in the presence of MK-2206. Our data provide molecular evidence for the involvement of AKT in UL cell survival and suggest that AKT inhibition by MK-2206 may be a viable option to consider for the treatment of ULs. PMID:24002033

  4. Panel estimation for renewable and non-renewable energy consumption, economic growth, CO2 emissions, the composite trade intensity, and financial openness of the commonwealth of independent states.

    Science.gov (United States)

    Rasoulinezhad, Ehsan; Saboori, Behnaz

    2018-04-13

    This article investigates the long-run and causal linkages between economic growth, CO 2 emissions, renewable and non-renewable (fossil fuels) energy consumption, the Composite Trade Intensity (CTI) as a proxy for trade openness, and the Chinn-Ito index as a proxy for financial openness for a panel of the Commonwealth of Independent States (CIS) region including Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Turkmenistan, Ukraine, and Uzbekistan over the period of 1992-2015. It is the first time that CTI and the Chinn-Ito indexes are used in an economic-pollution model. Employing three panel unit root tests, panel cointegration estimation methods (DOLS and FMOLS), and two panel causality tests, the main empirical results provided evidence for the bidirectional long-run relationship between all the variables in all 12 sampled countries except for economic growth-renewable energy use linkage. The findings of causality tests indicated that there is a unidirectional short-run panel causality running from economic growth, financial openness, and trade openness to CO 2 emissions and from fossil fuel energy consumption to renewable energy use.

  5. Sociological explanations of economic growth.

    Science.gov (United States)

    Marsh, R M

    1988-01-01

    Even if questions of how resources are distributed within and between societies are the main concern, it is necessary to continue to grapple with the issue of the causes of economic growth since economic growth and level of development continue to be among the most important causes of inequality, poverty, unemployment, and the quality of life. This paper's dependent variable is the economic growth rate of 55 less developed countries (LDCs) over 2 time periods. 1970-78 and 1965-84. The causal model consists of control variables--level of development and domestic investment in 1965--and a variety of independent variables drawn from major sociological theories of economic growth published during the last 3 decades. Multiple regression analysis shows that, net of the effects of the 2 control variables, the variables which have the strongest effect on economic growth are: 1) direct foreign investment, which has a negative effect, 2) the proportion of the population in military service, and 3) the primary school enrollment ratio, both of which have positive effects on economic growth. On the other hand, variables drawn from some theories receive no empirical support. The mass media of communications, ethnolinguistic heterogeneity, democracy and human rights, income inequality, and state-centric theory's key variable, state strength, all fail to show any significant impact on economic growth rates when the control variables and the significant independent variables are held constant. The theoretical implications of these findings are discussed.

  6. Assessing Effects and interactions among key variables affecting the growth of mixotrophic microalgae: pH, inoculum volume, and growth medium composition

    DEFF Research Database (Denmark)

    Ale, Marcel Tutor; Pinelo, Manuel; Meyer, Anne S.

    2014-01-01

    of growth medium (MWC) and wastewater at different proportions (from 20 to 50% of MWC) and at different pH (from 7 to 9). Multilinear regression analysis of the biomass productivity data showed that for SA and CD the biomass productivity was independent of the proportion of medium (MWC), while the growth...... of CV and CR slowed down in mixtures with high proportions of wastewater. However, the biomass productivity of SA was dependent on pH, while the growth of the other microalgae was independent of pH (7-9). When evaluating the influence of pH and proportion of medium, CD appeared most robust among...

  7. Growth hormone mediates pubertal skeletal development independent of hepatic IGF-1 production.

    Science.gov (United States)

    Courtland, Hayden-William; Sun, Hui; Beth-On, Mordechay; Wu, Yingjie; Elis, Sebastien; Rosen, Clifford J; Yakar, Shoshana

    2011-04-01

    Deficiencies in either growth hormone (GH) or insulin-like growth factor 1 (IGF-1) are associated with reductions in bone size during growth in humans and animal models. Liver-specific IGF-1-deficient (LID) mice, which have 75% reductions in serum IGF-1, were created previously to separate the effects of endocrine (serum) IGF-1 from autocrine/paracrine IGF-1. However, LID mice also have two- to threefold increases in GH, and this may contribute to the observed pubertal skeletal phenotype. To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age. Treatment of LID mice with pegvisomant resulted in significant reductions in body weight, femur length (Le), and femur total area (Tt.Ar), as well as further reductions in serum IGF-1 levels by 8 weeks of age, compared with the mean values of vehicle-treated LID mice. Reductions in both Tt.Ar and Le were proportional after treatment with pegvisomant. On the other hand, the relative amount of cortical tissue formed (RCA) in LID mice treated with pegvisomant was significantly less than that in both vehicle-treated LID and control mice, indicating that antagonizing GH action, either directly (through GH receptor signaling inhibition) or indirectly (through further reductions in serum/tissue IGF-1 levels), results in disproportionate reductions in the amount of cortical bone formed. This resulted in bones with significantly reduced mechanical properties (femoral whole-bone stiffness and work to failure were markedly decreased), suggesting that compensatory increases of GH in states of IGF-1 deficiency (LID mice) act to protect against a severe inhibition of bone modeling during growth, which otherwise would result in bones that are too weak for normal and/or extreme loading conditions. Copyright © 2011 American Society for

  8. Poverty in Independent India : a History and Family Memoirs | CRDI ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Poverty in Independent India : a History and Family Memoirs. India's Dalits have historically been subjected to devastating social and economic discrimination. The economic growth experienced by the country since 1990 has seen Dalit incomes more than double. Nevertheless, 300 million Indians still live below the poverty ...

  9. Wolbachia wStri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication.

    Science.gov (United States)

    Schultz, M J; Tan, A L; Gray, C N; Isern, S; Michael, S F; Frydman, H M; Connor, J H

    2018-05-22

    Mosquito-transmitted viruses are spread globally and present a great risk to human health. Among the many approaches investigated to limit the diseases caused by these viruses are attempts to make mosquitos resistant to virus infection. Coinfection of mosquitos with the bacterium Wolbachia pipientis from supergroup A is a recent strategy employed to reduce the capacity for major vectors in the Aedes mosquito genus to transmit viruses, including dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV). Recently, a supergroup B Wolbachia w Stri, isolated from Laodelphax striatellus , was shown to inhibit multiple lineages of ZIKV in Aedes albopictus cells. Here, we show that w Stri blocks the growth of positive-sense RNA viruses DENV, CHIKV, ZIKV, and yellow fever virus by greater than 99.9%. w Stri presence did not affect the growth of the negative-sense RNA viruses LaCrosse virus or vesicular stomatitis virus. Investigation of the stages of the ZIKV life cycle inhibited by w Stri identified two distinct blocks in viral replication. We found a reduction of ZIKV entry into w Stri-infected cells. This was partially rescued by the addition of a cholesterol-lipid supplement. Independent of entry, transfected viral genome was unable to replicate in Wolbachia -infected cells. RNA transfection and metabolic labeling studies suggested that this replication defect is at the level of RNA translation, where we saw a 66% reduction in mosquito protein synthesis in w Stri-infected cells. This study's findings increase the potential for application of w Stri to block additional arboviruses and also identify specific blocks in viral infection caused by Wolbachia coinfection. IMPORTANCE Dengue, Zika, and yellow fever viruses are mosquito-transmitted diseases that have spread throughout the world, causing millions of infections and thousands of deaths each year. Existing programs that seek to contain these diseases through elimination of the mosquito population have so

  10. Epigenetic mediated transcriptional activation of WNT5A participates in arsenical-associated malignant transformation

    International Nuclear Information System (INIS)

    Jensen, Taylor J.; Wozniak, Ryan J.; Eblin, Kylee E.; Wnek, Sean M.; Gandolfi, A. Jay; Futscher, Bernard W.

    2009-01-01

    Arsenic is a human carcinogen with exposure associated with cancer of the lung, skin, and bladder. Many potential mechanisms have been implicated as playing a role in the process of arsenical-induced malignancy including the perturbation of signaling pathways and aberrant epigenetic regulation. We initiated studies to examine the role of a member of the non-canonical WNT signaling pathway, WNT5A, in UROtsa cells and arsenite [URO-ASSC] and monomethylarsonous acid [URO-MSC] malignantly transformed variants. We present data herein that suggest that WNT5A is transcriptionally activated during arsenical-induced malignant transformation. This WNT5A transcriptional activation is correlated with the enrichment of permissive histone modifications and the reduction of repressive modifications in the WNT5A promoter region. The epigenetic activation of WNT5A expression and acetylation of its promoter remain after the removal of the arsenical, consistent with the maintenance of an anchorage independent growth phenotype in these cells. Additionally, treatment with epigenetic modifying drugs supports a functional role for these epigenetic marks in controlling gene expression. Reduction of WNT5A using lentiviral shRNA greatly attenuated the ability of these cells to grow in an anchorage independent fashion. Extension of our model into human bladder cancer cell lines indicates that each of the cell lines examined also express WNT5A. Taken together, these data suggest that the epigenetic remodeling of the WNT5A promoter is correlated with its transcriptional activation and this upregulation likely participates in arsenical-induced malignant transformation

  11. Bilateral en-masse distalization of maxillary posterior teeth with skeletal anchorage: a case report

    Directory of Open Access Journals (Sweden)

    Saeed Noorollahian

    Full Text Available ABSTRACT Objective: The aim of this study was to introduce a new method for bilateral distal movement of the entire maxillary posterior segment. Case report: A 17-year-old girl with Class I skeletal malocclusion (end-to-end molar relationships, deviated midline and space deficiency for left maxillary canine was referred for orthodontic treatment. She did not accept maxillary first premolars extraction. A modified Hyrax appliance (Dentaurum Ispringen, Germany was used for bilateral distalization of maxillary posterior teeth simultaneously. Expansion vector was set anteroposteriorly. Posterior legs of Hyrax were welded to first maxillary molar bands. All posterior teeth on each side consolidated with a segment of 0.017 × 0.025-in stainless steel wire from the buccal side. Anterior legs of Hyrax were bent into eyelet form and attached to the anterior palate with two mini-screws (2 × 10 mm (Jeil Medical Corporation Seoul, South Korea. Hyrax opening rate was 0.8 mm per month. Lateral cephalometric radiographs were used to evaluate the extent of distal movement. 3.5-mm distalization of posterior maxillary teeth was achieved in five months. Results: A nearly bodily distal movement without anchorage loss was obtained. Conclusion: The mini-screw-supported modified Hyrax appliance was found to be helpful for achieving en-masse distal movement of maxillary posterior teeth.

  12. Anchorage strength models for end-debonding predictions in RC beams strengthened with FRP composites

    Science.gov (United States)

    Nardini, V.; Guadagnini, M.; Valluzzi, M. R.

    2008-05-01

    The increase in the flexural capacity of RC beams obtained by externally bonding FRP composites to their tension side is often limited by the premature and brittle debonding of the external reinforcement. An in-depth understanding of this complex failure mechanism, however, has not yet been achieved. With specific regard to end-debonding failure modes, extensive experimental observations reported in the literature highlight the important distinction, often neglected in strength models proposed by researchers, between the peel-off and rip-off end-debonding types of failure. The peel-off failure is generally characterized by a failure plane located within the first few millimetres of the concrete cover, whilst the rip-off failure penetrates deeper into the concrete cover and propagates along the tensile steel reinforcement. A new rip-off strength model is described in this paper. The model proposed is based on the Chen and Teng peel-off model and relies upon additional theoretical considerations. The influence of the amount of the internal tensile steel reinforcement and the effective anchorage length of FRP are considered and discussed. The validity of the new model is analyzed further through comparisons with test results, findings of a numerical investigation, and a parametric study. The new rip-off strength model is assessed against a database comprising results from 62 beams tested by various researchers and is shown to yield less conservative results.

  13. International exploration by independents

    International Nuclear Information System (INIS)

    Bertagne, R.G.

    1991-01-01

    Recent industry trends indicate that the smaller US independents are looking at foreign exploration opportunities as one of the alternatives for growth in the new age of exploration. It is usually accepted that foreign finding costs per barrel are substantially lower than domestic because of the large reserve potential of international plays. To get involved overseas requires, however, an adaptation to different cultural, financial, legal, operational, and political conditions. Generally foreign exploration proceeds at a slower pace than domestic because concessions are granted by the government, or are explored in partnership with the national oil company. First, a mid- to long-term strategy, tailored to the goals and the financial capabilities of the company, must be prepared; it must be followed by an ongoing evaluation of quality prospects in various sedimentary basins, and a careful planning and conduct of the operations. To successfully explore overseas also requires the presence on the team of a minimum number of explorationists and engineers thoroughly familiar with the various exploratory and operational aspects of foreign work, having had a considerable amount of onsite experience in various geographical and climatic environments. Independents that are best suited for foreign expansion are those that have been financially successful domestically, and have a good discovery track record. When properly approached foreign exploration is well within the reach of smaller US independents and presents essentially no greater risk than domestic exploration; the reward, however, can be much larger and can catapult the company into the big leagues

  14. International exploration by independent

    International Nuclear Information System (INIS)

    Bertragne, R.G.

    1992-01-01

    Recent industry trends indicate that the smaller U.S. independents are looking at foreign exploration opportunities as one of the alternatives for growth in the new age of exploration. Foreign finding costs per barrel usually are accepted to be substantially lower than domestic costs because of the large reserve potential of international plays. To get involved in overseas exploration, however, requires the explorationist to adapt to different cultural, financial, legal, operational, and political conditions. Generally, foreign exploration proceeds at a slower pace than domestic exploration because concessions are granted by a country's government, or are explored in partnership with a national oil company. First, the explorationist must prepare a mid- to long-term strategy, tailored to the goals and the financial capabilities of the company; next, is an ongoing evaluation of quality prospects in various sedimentary basins, and careful planning and conduct of the operations. To successfully explore overseas also requires the presence of a minimum number of explorationists and engineers thoroughly familiar with the various exploratory and operational aspects of foreign work. Ideally, these team members will have had a considerable amount of on-site experience in various countries and climates. Independents best suited for foreign expansion are those who have been financially successful in domestic exploration. When properly approached, foreign exploration is well within the reach of smaller U.S. independents, and presents essentially no greater risk than domestic exploration; however, the reward can be much larger and can catapult the company into the 'big leagues.'

  15. Distance-independent individual tree diameter-increment model for Thuya [Tetraclinis articulata (VAHL. MAST.] stands in Tunisia

    Directory of Open Access Journals (Sweden)

    T. Sghaier

    2013-12-01

    Full Text Available Aim of study: The aim of the work was to develop an individual tree diameter-increment model for Thuya (Tetraclinis articulata in Tunisia.Area of study: The natural Tetraclinis articulata stands at Jbel Lattrech in north-eastern of Tunisia.Material and methods:  Data came from 200 trees located in 50 sample plots. The diameter at age t and the diameter increment for the last five years obtained from cores taken at breast height were measured for each tree. Four difference equations derived from the base functions of Richards, Lundqvist, Hossfeld IV and Weibull were tested using the age-independent formulations of the growth functions. Both numerical and graphical analyses were used to evaluate the performance of the candidate models.Main results: Based on the analysis, the age-independent difference equation derived from the base function Richards model was selected. Two of the three parameters (growth rate and shape parameter of the retained model were related to site quality, represented by a Growth Index, stand density and the basal area in larger trees divided by diameter of the subject tree expressing the inter-tree competition.Research highlights: The proposed model can be useful for predicting the diameter growth of Tetraclinis articulata in Tunisia when age is not available or for trees growing in uneven-aged stands.Keywords: Age-independent growth model; difference equations; Tetraclinis articulata; Tunisia.

  16. BAG-1 enhances cell-cell adhesion, reduces proliferation and induces chaperone-independent suppression of hepatocyte growth factor-induced epidermal keratinocyte migration

    International Nuclear Information System (INIS)

    Hinitt, C.A.M.; Wood, J.; Lee, S.S.; Williams, A.C.; Howarth, J.L.; Glover, C.P.; Uney, J.B.; Hague, A.

    2010-01-01

    Cell motility is important in maintaining tissue homeostasis, facilitating epithelial wound repair and in tumour formation and progression. The aim of this study was to determine whether BAG-1 isoforms regulate epidermal cell migration in in vitro models of wound healing. In the human epidermal cell line HaCaT, endogenous BAG-1 is primarily nuclear and increases with confluence. Both transient and stable p36-Bag-1 overexpression resulted in increased cellular cohesion. Stable transfection of either of the three human BAG-1 isoforms p36-Bag-1 (BAG-1S), p46-Bag-1 (BAG-1M) and p50-Bag-1 (BAG-1L) inhibited growth and wound closure in serum-containing medium. However, in response to hepatocyte growth factor (HGF) in serum-free medium, BAG-1S/M reduced communal motility and colony scattering, but BAG-1L did not. In the presence of HGF, p36-Bag-1 transfectants retained proliferative response to HGF with no change in ERK1/2 activation. However, the cells retained E-cadherin localisation at cell-cell junctions and exhibited pronounced cortical actin. Point mutations in the BAG domain showed that BAG-1 inhibition of motility is independent of its function as a chaperone regulator. These findings are the first to suggest that BAG-1 plays a role in regulating cell-cell adhesion and suggest an important function in epidermal cohesion.

  17. Comparison of in-vivo failure of single-thread and dual-thread temporary anchorage devices over 18 months: A split-mouth randomized controlled trial.

    Science.gov (United States)

    Durrani, Owais Khalid; Shaheed, Sohrab; Khan, Arsalan; Bashir, Ulfat

    2017-10-01

    The purpose of this study was to compare the in-vivo failure rates of single-thread and dual-thread temporary anchorage device (TAD) designs over 18 months. Thirty patients with skeletal Class II Division 1 malocclusion requiring anchorage from TADs for retraction of maxillary incisors into the extracted premolar space were recruited in this parallel group, split-mouth, randomized controlled trial. A block randomization sequence was generated with Random Allocation Software (version 2.0; Isfahan, Iran) with the allocations concealed in sequentially numbered, opaque, sealed envelopes. A total of 60 TADs (diameter, 2 mm; length, 10 mm) were placed in the maxillary arches of these patients with random allocation of the 2 types to the left and the right sides in a 1:1 ratio. All TADs were placed between the roots of the second premolar and the first molar and were immediately loaded. Patients were followed for a minimum of 12 months and a maximum of 18 months for the failure of the TADs. Data were analyzed blindly on an intention-to-treat basis. Four TADs (13.3%) failed in the single-thread group, and 6 TADs (20%) failed in the dual-thread group. The McNemar test showed an insignificant difference (P = 0.72) between the 2 groups. An odds ratio of 1.6 (95% confidence interval, 0.39-6.97) showed no significant associations among the variables. Most TADs failed in the first month after insertion (50%). The failure rate of dual-thread TADs compared with single-thread TADs is statistically insignificant when placed in the maxilla for retraction of the anterior segment. Registration: The trial was not registered before commencement. The protocol was not published before the trial. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  18. Are Independent Fiscal Institutions Really Independent?

    Directory of Open Access Journals (Sweden)

    Slawomir Franek

    2015-08-01

    Full Text Available In the last decade the number of independent fiscal institutions (known also as fiscal councils has tripled. They play an important oversight role over fiscal policy-making in democratic societies, especially as they seek to restore public finance stability in the wake of the recent financial crisis. Although common functions of such institutions include a role in analysis of fiscal policy, forecasting, monitoring compliance with fiscal rules or costing of spending proposals, their roles, resources and structures vary considerably across countries. The aim of the article is to determine the degree of independence of such institutions based on the analysis of the independence index of independent fiscal institutions. The analysis of this index values may be useful to determine the relations between the degree of independence of fiscal councils and fiscal performance of particular countries. The data used to calculate the index values will be derived from European Commission and IMF, which collect sets of information about characteristics of activity of fiscal councils.

  19. CYB5D2 requires heme-binding to regulate HeLa cell growth and confer survival from chemotherapeutic agents.

    Directory of Open Access Journals (Sweden)

    Anthony Bruce

    Full Text Available The cytochrome b5 domain containing 2 (CYB5D2; Neuferricin protein has been reported to bind heme, however, the critical residues responsible for heme-binding are undefined. Furthermore, the relationship between heme-binding and CYB5D2-mediated intracellular functions remains unknown. Previous studies examining heme-binding in two cytochrome b5 heme-binding domain-containing proteins, damage-associated protein 1 (Dap1; Saccharomyces cerevisiae and human progesterone receptor membrane component 1 (PGRMC1, have revealed that conserved tyrosine (Y 73, Y79, aspartic acid (D 86, and Y127 residues present in human CYB5D2 may be involved in heme-binding. CYB5D2 binds to type b heme, however, only the substitution of glycine (G at D86 (D86G within its cytochrome b5 heme-binding (cyt-b5 domain abolished its heme-binding ability. Both CYB5D2 and CYB5D2(D86G localize to the endoplasmic reticulum. Ectopic CYB5D2 expression inhibited cell proliferation and anchorage-independent colony growth of HeLa cells. Conversely, CYB5D2 knockdown and ectopic CYB5D2(D86G expression increased cell proliferation and colony growth. As PGRMC1 has been reported to regulate the expression and activities of cytochrome P450 proteins (CYPs, we examined the role of CYB5D2 in regulating the activities of CYPs involved in sterol synthesis (CYP51A1 and drug metabolism (CYP3A4. CYB5D2 co-localizes with cytochrome P450 reductase (CYPOR, while CYB5D2 knockdown reduced lanosterol demethylase (CYP51A1 levels and rendered HeLa cells sensitive to mevalonate. Additionally, knockdown of CYB5D2 reduced CYP3A4 activity. Lastly, CYB5D2 expression conferred HeLa cell survival from chemotherapeutic agents (paclitaxel, cisplatin and doxorubicin, with its ability to promote survival being dependent on its heme-binding ability. Taken together, this study provides evidence that heme-binding is critical for CYB5D2 in regulating HeLa cell growth and survival, with endogenous CYB5D2 being required to

  20. The Adoption of Internet Technologies by Independent Hotels in the UK

    OpenAIRE

    LIM, WAI MUN

    2007-01-01

    Merged with duplicate record 10026.1/670 on 27.02.2017 by CS (TIS) The growth of the technology and its range of possible uses have made it a necessity for independent hoteliers to examine their use of the internet, specifically its effectiveness for marketing and distribution purposes. It is widely recognised that the independent hotel sector makes up the bulk of the hotel industry in the UK and often do not have the resources or desire to keep up with new technologies. This s...

  1. Efficacy of Social Media Adoption on Client Growth for Independent Management Consultants

    Science.gov (United States)

    2017-02-01

    word -of- mouth promotion techniques. Social media also 22 created new opportunities for cultural influences and synthesis of activities and...approach as justification. According to Peters et al. (2013), users of the social media accelerate the potential for viral marketing through word -of- mouth ...denoted how word of mouth (WoM) and social media can benefit independent practices to expand their customer base (Peters, Chen, Kaplan,

  2. Chemoprevention of Colorectal Cancer by Artocarpin, a Dietary Phytochemical from Artocarpus heterophyllus.

    Science.gov (United States)

    Sun, Guochuan; Zheng, Zongping; Lee, Mee-Hyun; Xu, Yijuan; Kang, Soouk; Dong, Zigang; Wang, Mingfu; Gu, Zhennan; Li, Haitao; Chen, Wei

    2017-05-03

    Artocarpus heterophyllus is an evergreen tree distributed in tropical regions, and its fruit (jackfruit) is well-known as the world's largest tree-borne fruit. Although A. heterophyllus has been widely used in folk medicines against inflammation, its potential in cancer chemoprevention remains unclear. Herein we identified artocarpin from A. heterophyllus as a promising colorectal cancer chemopreventive agent by targeting Akt kinase. Phenotypically, artocarpin exhibited selective cytotoxicity against human colon cancer cells. Artocarpin impaired the anchorage-independent growth capability, suppressed colon cancer cell growth, and induced a G1 phase cell cycle arrest which was followed by apoptotic as well as autophagic cell death. Mechanistic studies revealed that artocarpin directly targeted Akt 1 and 2 kinase activity evidenced by in vitro kinase assay, ex vivo binding assay as well as Akt downstream cellular signal transduction. Importantly, oral administration of artocarpin attenuated colitis-associated colorectal tumorigenesis in mice. Taken together, artocarpin, a bioactive component of A. heterophyllus, might merit investigation as a potential colorectal cancer chemopreventive agent.

  3. Orthodontic treatment for a mandibular prognathic girl of short stature under growth hormone therapy

    Directory of Open Access Journals (Sweden)

    Chin-Yun Pan

    2013-12-01

    Full Text Available This report presents a case of a 12-year-old girl with maxillary deficiency, mandibular prognathism, and facial asymmetry, undergoing growth hormone (GH therapy due to idiopathic short stature. Children of short stature with or without GH deficiency have a deviating craniofacial morphology with overall smaller dimensions; facial retrognathism, especially mandibular retrognathism; and increased facial convexity. However, a complete opposite craniofacial pattern was presented in our case of a skeletal Class III girl with idiopathic short stature. The orthodontic treatment goal was to inhibit or change the direction of mandibular growth and stimulate the maxillary growth of the girl during a course of GH therapy. Maxillary protraction and mandibular retraction were achieved using occipitomental anchorage (OMA orthopedic appliance in the first stage of treatment. In the second stage, the patient was treated with a fixed orthodontic appliance using a modified multiple-loop edgewise archwire technique of asymmetric mechanics and an active retainer of vertical chin-cup. The treatment led to an acceptable facial profile and obvious facial asymmetry improvement. Class I dental occlusion and coincident dental midline were also achieved. A 3½-year follow-up of the girl at age 18 showed a stable result of the orthodontic and dentofacial orthopedic treatment. Our case shows that the OMA orthopedic appliance of maxillary protraction combined with mandibular retraction is effective for correcting skeletal Class III malocclusion with midface deficiency and mandibular prognathism in growing children with idiopathic short stature undergoing GH therapy.

  4. Use of reconstructed CT images for evaluation of the position of screw-type temporary anchorage devices implanted in the maxillary molar region

    International Nuclear Information System (INIS)

    Hashimoto, Kazuya

    2007-01-01

    Temporary anchorage devices (TAD) have recently been employed for orthodontic treatment. I attempted to find the safest position for placing the screw-type TAD in the maxillary molar region. Using reconstructed CT images, I investigated the buccolingual and mesiodistal lengths of the interalveolar septums between the maxillary first premolar, second premolar, first molar, and the second molar. For the first and second molars, I measured the distance from the alveolar crest to the maxillary sinus. The results indicated that the safest position for placing a screw-type TAD was the interalveolar septum between the maxillary first molar and the second premolar at about a depth of 4-6 mm from the alveolar crest on the buccal side, and at about a depth of 2-6 mm from the alveolar crest on the palatal side. (author)

  5. S6K1 and 4E-BP1 are independent regulated and control cellular growth in bladder cancer.

    Directory of Open Access Journals (Sweden)

    Roman Nawroth

    Full Text Available Aberrant activation and mutation status of proteins in the phosphatidylinositol-3-kinase (PI3K/Akt/mammalian target of rapamycin (mTOR and the mitogen activated protein kinase (MAPK signaling pathways have been linked to tumorigenesis in various tumors including urothelial carcinoma (UC. However, anti-tumor therapy with small molecule inhibitors against mTOR turned out to be less successful than expected. We characterized the molecular mechanism of this pathway in urothelial carcinoma by interfering with different molecular components using small chemical inhibitors and siRNA technology and analyzed effects on the molecular activation status, cell growth, proliferation and apoptosis. In a majority of tested cell lines constitutive activation of the PI3K was observed. Manipulation of mTOR or Akt expression or activity only regulated phosphorylation of S6K1 but not 4E-BP1. Instead, we provide evidence for an alternative mTOR independent but PI3K dependent regulation of 4E-BP1. Only the simultaneous inhibition of both S6K1 and 4E-BP1 suppressed cell growth efficiently. Crosstalk between PI3K and the MAPK signaling pathway is mediated via PI3K and indirect by S6K1 activity. Inhibition of MEK1/2 results in activation of Akt but not mTOR/S6K1 or 4E-BP1. Our data suggest that 4E-BP1 is a potential new target molecule and stratification marker for anti cancer therapy in UC and support the consideration of a multi-targeting approach against PI3K, mTORC1/2 and MAPK.

  6. Effects of the Trilemma Policies on Inflation, Growth and Volatility in Bulgaria

    Directory of Open Access Journals (Sweden)

    Yu HSING

    2012-04-01

    Full Text Available This paper finds evidence of the trilemma for Bulgaria, suggesting that exchange rate stability, monetary independence and free capital mobility are binding and constrained. The policy combination of exchange rate stability and monetary independence has been prevalent. More exchange rate stability increases the growth rate of real GDP whereas more monetary independence or free capital mobility reduces the growth rate. The inflation rate, inflation volatility and output volatility are not affected by either one of the three trilemma policies.

  7. A new model for simulating growth in fish

    Directory of Open Access Journals (Sweden)

    Johannes Hamre

    2014-01-01

    Full Text Available A real dynamic population model calculates change in population sizes independent of time. The Beverton & Holt (B&H model commonly used in fish assessment includes the von Bertalanffy growth function which has age or accumulated time as an independent variable. As a result the B&H model has to assume constant fish growth. However, growth in fish is highly variable depending on food availability and environmental conditions. We propose a new growth model where the length increment of fish living under constant conditions and unlimited food supply, decreases linearly with increasing fish length until it reaches zero at a maximal fish length. The model is independent of time and includes a term which accounts for the environmental variation. In the present study, the model was validated in zebrafish held at constant conditions. There was a good fit of the model to data on observed growth in Norwegian spring spawning herring, capelin from the Barents Sea, North Sea herring and in farmed coastal cod. Growth data from Walleye Pollock from the Eastern Bering Sea and blue whiting from the Norwegian Sea also fitted reasonably well to the model, whereas data from cod from the North Sea showed a good fit to the model only above a length of 70 cm. Cod from the Barents Sea did not grow according to the model. The last results can be explained by environmental factors and variable food availability in the time under study. The model implicates that the efficiency of energy conversion from food decreases as the individual animal approaches its maximal length and is postulated to represent a natural law of fish growth.

  8. Growth kinetics and initial stage growth during plasma-enhanced Ti atomic layer deposition

    CERN Document Server

    Kim, H

    2002-01-01

    We have investigated the growth kinetics of plasma-enhanced Ti atomic layer deposition (ALD) using a quartz crystal microbalance. Ti ALD films were grown at temperatures from 20 to 200 deg. C using TiCl sub 4 as a source gas and rf plasma-produced atomic H as the reducing agent. Postdeposition ex situ chemical analyses of thin films showed that the main impurity is oxygen, mostly incorporated during the air exposure prior to analysis. The thickness per cycle, corresponding to the growth rate, was measured by quartz crystal microbalance as a function of various key growth parameters, including TiCl sub 4 and H exposure time, rf plasma power, and sample temperature. The growth rates were independent of TiCl sub 4 exposure above 1x10 sup 3 L, indicating typical ALD mode growth. The key kinetic parameters for Cl extraction reaction and TiCl sub 4 adsorption kinetics were obtained and the growth kinetics were modeled to predict the growth rates based upon these results. Also, the dependency of growth kinetics on d...

  9. Mesialização de molares com ancoragem em mini-implantes Mesial movement of molars with mini-implants anchorage

    Directory of Open Access Journals (Sweden)

    Marcos Janson

    2008-10-01

    Full Text Available INTRODUÇÃO: é muito comum, na rotina do consultório odontológico, especialmente em Ortodontia, o paciente, após avaliar o plano de tratamento proposto, questionar sobre a possibilidade de fechamento de espaços presentes, ocasionados pela perda de dentes permanentes. O ortodontista, frente a essa questão, tem que avaliar diversos fatores, tais como a má oclusão presente, a integridade do osso e das raízes, o tempo de tratamento e a geometria do posicionamento dentário, que é o que permite avaliar se, com o fechamento dos espaços e, conseqüentemente, a perda de ancoragem dos segmentos anteriores, a finalização estará de acordo com os ideais que regem a especialidade. Com o advento dos mini-implantes, as possibilidades desta abordagem terapêutica aumentaram, pois o efeito adverso da perda de ancoragem pode ser eliminado e, com isso, o paciente pode ser beneficiado. No entanto, os outros fatores envolvidos, assim como a mecânica do movimento, requerem especial atenção. OBJETIVOS: no presente artigo serão abordados os fatores envolvidos neste tipo de tratamento, o raciocínio na tomada de decisões e os detalhes importantes que devem ser observados durante a condução da mecânica, ilustrados com casos clínicos.INTRODUCTION: It's routine, especially at the orthodontic office, the patient, after the assessment of the proposed treatment plan, answer about the possibility of closing their edentulous spaces caused by missed permanent teeth. In these situations, several factors must be evaluated, like the present malocclusion, the bone and roots integrity, the treatment time and the geometry of teeth positioning, that is what permits to assess if the loss of anchorage from the anterior segments, during the space closure, would permit the occlusion to end within the orthodontic ideals. With the mini-implants, the possibilities of this therapeutic approach have been improved, since the adverse effects are eliminated with the

  10. Creep-recovery constitutive equation and its time-independent limit

    International Nuclear Information System (INIS)

    Chang, S.J.

    1978-01-01

    The effect of strain recovery is taken into consideration in establishing a constitutive equation for metals at elevated temperatures. Internal state variables and Rice's flow potential are used in the representation. Growth law for the state variables is discussed and interpreted to be a more general form of the kinematic hardening condition. Yield condition is obtained from the flow law. Accordingly, the flow rule is established with the effect of the recovery mechanism, as a slightly general version of the time-independent theory with the kinematic hardening rule. In the discussion of the time-independent limit, the duration of time required for the inelastic strain to reach its saturated value is defined

  11. The nutrient transceptor/PKA pathway functions independently of TOR and responds to leucine and Gcn2 in a TOR-independent manner.

    Science.gov (United States)

    Conrad, Michaela; Kankipati, Harish Nag; Kimpe, Marlies; Van Zeebroeck, Griet; Zhang, Zhiqiang; Thevelein, Johan M

    2017-08-01

    Two nutrient-controlled signalling pathways, the PKA and TOR pathway, play a major role in nutrient regulation of growth as well as growth-correlated properties in yeast. The relationship between the two pathways is not well understood. We have used Gap1 and Pho84 transceptor-mediated activation of trehalase and phosphorylation of fragmented Sch9 as a read-out for rapid nutrient activation of PKA or TORC1, respectively. We have identified conditions in which L-citrulline-induced activation of Sch9 phosphorylation is compromised, but not activation of trehalase: addition of the TORC1 inhibitor, rapamycin and low levels of L-citrulline. The same disconnection was observed for phosphate activation in phosphate-starved cells. The leu2 auxotrophic mutation reduces amino acid activation of trehalase, which is counteracted by deletion of GCN2. Both effects were also independent of TORC1. Our results show that rapid activation of the TOR pathway by amino acids is not involved in rapid activation of the PKA pathway and that effects of Gcn2 inactivation as well as leu2 auxotrophy all act independently of the TOR pathway. Hence, rapid nutrient signalling to PKA and TOR in cells arrested by nutrient starvation acts through parallel pathways. © FEMS 2017.

  12. Posttraumatic Growth and Depreciation as Independent Experiences and Predictors of Well-Being

    Science.gov (United States)

    Cann, Arnie; Calhoun, Lawrence G.; Tedeschi, Richard G.; Solomon, David T.

    2010-01-01

    Positive changes (posttraumatic growth [PTG]) and negative changes (posttraumatic depreciation [PTD]) were assessed using the PTGI-42 with persons reporting changes from a stressful event. PTG and PTD were uncorrelated, and PTG was much greater than PTD. PTG was positively related to disruption of core beliefs and recent deliberate rumination and…

  13. Blockade of Aquaporin 1 Inhibits Proliferation, Motility, and Metastatic Potential of Mesothelioma In Vitro but not in an In Vivo Model

    Directory of Open Access Journals (Sweden)

    Sonja Klebe

    2015-01-01

    Full Text Available Background. Malignant mesothelioma (MM is an aggressive tumor of the serosal membranes, mostly the pleura. It is related to asbestos exposure and has a poor prognosis. MM has a long latency period, and incidence is predicted to remain stable or increase until 2020. Currently, no biomarkers for a specific targeted therapy are available. Previously, we observed that expression of aquaporin 1 (AQP1 was an indicator of prognosis in two independent cohorts. Here we determine whether AQP1 inhibition has therapeutic potential in the treatment of MM. Methods. Functional studies were performed with H226 cells and primary MM cells harvested from pleural effusions. AQP1 expression and mesothelial phenotype was determined by immunohistochemistry. AQP1 function was inhibited by a pharmacological blocker (AqB050 or AQP1-specific siRNA. Cell proliferation, migration, and anchorage-independent cell growth were assessed. A nude mouse heterotopic xenograft model of MM was utilised for the in vivo studies. Results. Inhibition of AQP1 significantly decreases cell proliferation, metastatic potential, and motility without inducing nonspecific cytotoxicity or increasing apoptosis. In vivo blockade of AQP1 had no biologically significant effect on growth of established tumours. Conclusions. Targeted blockade of AQP1 restricts MM growth and migration in vitro. Further work is warranted to fully evaluate treatment potential in vivo.

  14. Inhibition of Y-box binding protein-1 slows the growth of glioblastoma multiforme and sensitizes to temozolomide independent O6-methylguanine-DNA methyltransferase.

    Science.gov (United States)

    Gao, Yuanyuan; Fotovati, Abbas; Lee, Cathy; Wang, Michelle; Cote, Gilbert; Guns, Emma; Toyota, Brian; Faury, Damien; Jabado, Nada; Dunn, Sandra E

    2009-12-01

    Glioblastoma multiforme (GBM) is an aggressive type of brain tumor where 5 years. In adults, GBM is the most common type of brain tumor. It is rarer in children, where it constitutes approximately 15% of all brain tumors diagnosed. These tumors are often invasive, making surgical resection difficult. Further, they can be refractory to current therapies such as temozolomide. The current dogma is that temozolomide resistance rests on the expression of O6-methylguanine-DNA methyltransferase (MGMT) because it cleaves methylated DNA adducts formed by the drug. Our laboratory recently reported that another drug resistance gene known as the Y-box binding protein-1 (YB-1) is highly expressed in primary GBM but not in normal brain tissues based on the evaluation of primary tumors. We therefore questioned whether GBM depend on YB-1 for growth and/or response to temozolomide. Herein, we report that YB-1 inhibition reduced tumor cell invasion and growth in monolayer as well as in soft agar. Moreover, blocking this protein ultimately delayed tumor onset in mice. Importantly, inhibiting YB-1 enhanced temozolomide sensitivity in a manner that was independent of MGMT in models of adult and pediatric GBM. In conclusion, inhibiting YB-1 may be a novel way to improve the treatment of GBM.

  15. Resolving nanoparticle growth mechanisms from size- and time-dependent growth rate analysis

    Science.gov (United States)

    Pichelstorfer, Lukas; Stolzenburg, Dominik; Ortega, John; Karl, Thomas; Kokkola, Harri; Laakso, Anton; Lehtinen, Kari E. J.; Smith, James N.; McMurry, Peter H.; Winkler, Paul M.

    2018-01-01

    Atmospheric new particle formation occurs frequently in the global atmosphere and may play a crucial role in climate by affecting cloud properties. The relevance of newly formed nanoparticles depends largely on the dynamics governing their initial formation and growth to sizes where they become important for cloud microphysics. One key to the proper understanding of nanoparticle effects on climate is therefore hidden in the growth mechanisms. In this study we have developed and successfully tested two independent methods based on the aerosol general dynamics equation, allowing detailed retrieval of time- and size-dependent nanoparticle growth rates. Both methods were used to analyze particle formation from two different biogenic precursor vapors in controlled chamber experiments. Our results suggest that growth rates below 10 nm show much more variation than is currently thought and pin down the decisive size range of growth at around 5 nm where in-depth studies of physical and chemical particle properties are needed.

  16. Islam and Economic Growth in Malaysia

    National Research Council Canada - National Science Library

    bin

    2003-01-01

    .... This thesis discusses nation building by fusing Islam, pluralism, democracy, and modernity. It argues that Malaysia's religious tolerance and adherence to western development models fostered economic growth since its independence...

  17. Scleroderma keratinocytes promote fibroblast activation independent of transforming growth factor beta.

    Science.gov (United States)

    McCoy, Sara S; Reed, Tamra J; Berthier, Celine C; Tsou, Pei-Suen; Liu, Jianhua; Gudjonsson, Johann E; Khanna, Dinesh; Kahlenberg, J Michelle

    2017-11-01

    SSc is a devastating disease that results in fibrosis of the skin and other organs. Fibroblasts are a key driver of the fibrotic process through deposition of extracellular matrix. The mechanisms by which fibroblasts are induced to become pro-fibrotic remain unclear. Thus, we examined the ability of SSc keratinocytes to promote fibroblast activation and the source of this effect. Keratinocytes were isolated from skin biopsies of 9 lcSSc, 10 dcSSc and 13 control patients. Conditioned media was saved from the cultures. Normal fresh primary fibroblasts were exposed to healthy control and SSc keratinocyte conditioned media in the presence or absence of neutralizing antibodies for TGF-β. Gene expression was assessed by microarrays and real-time PCR. Immunocytochemistry was performed for α-smooth muscle actin (α-SMA), collagen type 1 (COL1A1) and CCL5 expression. SSc keratinocyte conditioned media promoted fibroblast activation, characterized by increased α-SMA and COL1A1 mRNA and protein expression. This effect was independent of TGF-β. Microarray analysis identified upregulation of nuclear factor κB (NF-κB) and downregulation of peroxisome proliferator-activated receptor γ (PPAR-γ) pathways in both SSc subtypes. Scleroderma keratinocytes exhibited increased expression of NF-κB-regulated cytokines and chemokines and lesional skin staining confirmed upregulation of CCL5 in basal keratinocytes. Scleroderma keratinocytes promote the activation of fibroblasts in a TGF-β-independent manner and demonstrate an imbalance in NF-κB1 and PPAR-γ expression leading to increased cytokine and CCL5 production. Further study of keratinocyte mediators of fibrosis, including CCL5, may provide novel targets for skin fibrosis therapy. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  18. Maternal di-(2-ethylhexyl) phthalate exposure during pregnancy causes fetal growth restriction in a stage-specific but gender-independent manner.

    Science.gov (United States)

    Shen, Ru; Zhao, Ling-Li; Yu, Zhen; Zhang, Cheng; Chen, Yuan-Hua; Wang, Hua; Zhang, Zhi-Hui; Xu, De-Xiang

    2017-01-01

    Di (2-ethylhexyl) phthalate (DEHP) is male developmental toxicant that impairs testis development with reduced anogenital distance. The present study aimed to investigate whether maternal DEHP exposure during pregnancy causes intrauterine growth restriction (IUGR) in a gender-specific manner and to identify the critical window of DEHP-induced fetal IUGR. Pregnant mice were administered with DEHP (0, 50 or 200mg/kg) by gavage. Fetal IUGR was observed not only in males but also in females when litters were exposed to DEHP on gestational day (GD)0-GD17. Interestingly, fetal weight and crown-rump length were reduced, markedly in dams with DEHP on GD13-GD17, slightly in dams with on GD7-GD12, but not in dams with on GD0-GD6. Further analysis showed that maternal DEHP exposure on GD7-GD12 inhibited cell proliferation, lowered placental weight, and reduced blood sinusoid area in placental labyrinth layer. These results suggest that maternal DEHP exposure induces IUGR in a stage-specific but gender-independent manner. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Gastric cancer: the role of insulin-like growth factor 2 (IGF 2) and its receptors (IGF 1R and M6-P/IGF 2R).

    Science.gov (United States)

    Pavelić, Kresimir; Kolak, Toni; Kapitanović, Sanja; Radosević, Senka; Spaventi, Sime; Kruslin, Bozo; Pavelić, Jasminka

    2003-11-01

    Insulin-like growth factor 2 (IGF 2) appears to be involved in the progression of many tumours. It binds to at least two different types of receptor: IGF type 1 (IGF 1R) and mannose 6-phosphate/IGF type 2 (M6-P/IGF 2R). Ligand binding to IGF 1R provokes mitogenic and anti-apoptotic effects. M6-P/IGF 2R has a tumour suppressor function--it mediates IGF 2 degradation. Mutation of M6-P/IGF 2R causes both diminished growth suppression and augmented growth stimulation. The aim of this study was to investigate the role of IGF 2 and its receptors (IGF 1R and IGF 2R) in human gastric cancer. The expression of IGF 2 and its receptors was measured in order to analyse the possible correlation between the activity of these genes and cell proliferation in two different gastric tumour types: diffuse and intestinal. The effect of IGF 1 receptor blockage on cell proliferation and anchorage-independent cell growth was also examined. Increased expression of IGF 2 and IGF 1R genes (at the mRNA and protein level) was found in gastric cancer when compared with non-tumour tissue. Furthermore, there was a significant difference between IGF 2 expression in the more aggressive diffuse type and that in the intestinal type of gastric cancer. Moreover, the IGF 2 peptide level in the culture media obtained from the diffuse type of cancer cells was significantly higher when compared with the intestinal type. The level of IGF 2 peptide in the conditioned media strongly correlated with [3H]thymidine incorporation and cell proliferation. On the contrary, IGF 2R mRNA expression was much higher in the intestinal type of cancer than in the diffuse type. In addition, IGF 2R protein expression was substantially lower with progression of the diffuse cancer type to a higher stage. The alphaIR3 monoclonal antibody strongly inhibited [3H]thymidine incorporation and decreased the number of colonies in soft agar of cells overexpressing IGF 2. These findings suggest that members of the IGF family are involved

  20. Adjusting the Stems Regional Forest Growth Model to Improve Local Predictions

    Science.gov (United States)

    W. Brad Smith

    1983-01-01

    A simple procedure using double sampling is described for adjusting growth in the STEMS regional forest growth model to compensate for subregional variations. Predictive accuracy of the STEMS model (a distance-independent, individual tree growth model for Lake States forests) was improved by using this procedure

  1. Bacterial growth on surfaces: Automated image analysis for quantification of growth rate-related parameters

    DEFF Research Database (Denmark)

    Møller, S.; Sternberg, Claus; Poulsen, L. K.

    1995-01-01

    species-specific hybridizations with fluorescence-labelled ribosomal probes to estimate the single-cell concentration of RNA. By automated analysis of digitized images of stained cells, we determined four independent growth rate-related parameters: cellular RNA and DNA contents, cell volume......, and the frequency of dividing cells in a cell population. These parameters were used to compare physiological states of liquid-suspended and surfacegrowing Pseudomonas putida KT2442 in chemostat cultures. The major finding is that the correlation between substrate availability and cellular growth rate found...

  2. Automation of the Design of the Anchorage System Taking into Account the Geomechanical State of the Massif and Mining Development Schemes

    Directory of Open Access Journals (Sweden)

    Demin Vladimir

    2018-01-01

    Full Text Available The article presents the system for the automation of the design of the anchorage, which regulates the calculation of the required parameters of the fasteners for the fastening of the fastening system. The main factors affecting the operation of the anchor support are grouped in the following way: mining and geological conditions, technical characteristics of the anchor support, geomechanical conditions for conducting and operating the mine workings. Mining and geological conditions for carrying out excavations include: physical and mechanical properties of rocks, the category of roof stability, fracturing, etc. Technical characteristics of the anchor support: material of the rod, filler, filling completeness, etc. Conditions (geomechanical of carrying out and exploitation of the mine workings: the depth of the conduct, the location relative to the zone of influence of the cleaning works, the location relative to the waste zone, etc. As a result of calculations the program gives out the basic parameters of the anchor support, which coincide with the parameters adopted by the passport.

  3. Effectiveness of en masse versus two-step retraction: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Mumen Z. Rizk

    2018-01-01

    Full Text Available Abstract Background This review aims to compare the effectiveness of en masse and two-step retraction methods during orthodontic space closure regarding anchorage preservation and anterior segment retraction and to assess their effect on the duration of treatment and root resorption. Methods An electronic search for potentially eligible randomized controlled trials and prospective controlled trials was performed in five electronic databases up to July 2017. The process of study selection, data extraction, and quality assessment was performed by two reviewers independently. A narrative review is presented in addition to a quantitative synthesis of the pooled results where possible. The Cochrane risk of bias tool and the Newcastle-Ottawa Scale were used for the methodological quality assessment of the included studies. Results Eight studies were included in the qualitative synthesis in this review. Four studies were included in the quantitative synthesis. En masse/miniscrew combination showed a statistically significant standard mean difference regarding anchorage preservation − 2.55 mm (95% CI − 2.99 to − 2.11 and the amount of upper incisor retraction − 0.38 mm (95% CI − 0.70 to − 0.06 when compared to a two-step/conventional anchorage combination. Qualitative synthesis suggested that en masse retraction requires less time than two-step retraction with no difference in the amount of root resorption. Conclusions Both en masse and two-step retraction methods are effective during the space closure phase. The en masse/miniscrew combination is superior to the two-step/conventional anchorage combination with regard to anchorage preservation and amount of retraction. Limited evidence suggests that anchorage reinforcement with a headgear produces similar results with both retraction methods. Limited evidence also suggests that en masse retraction may require less time and that no significant differences exist in the amount of root

  4. Declines in Birth weight and Fetal Growth Independent of Gestational Length

    Science.gov (United States)

    Morisaki, Naho; Esplin, M. Sean; Varner, Michael W.; Henry, Erick; Oken, Emily

    2014-01-01

    Objective Birth weight is decreasing in the US and elsewhere, even among term singletons, although trends in most maternal characteristics should contribute to increased birth weight. Some studies have attributed this decline to the simultaneous decrease in gestational length. Methods Using data from Intermountain Healthcare, where a successful initiative reduced the number of early term (37–38 week) elective deliveries, we examined trends in birth weight, small-for-gestational-age (SGA), and large-for-gestational-age (LGA) among 219,694 singleton infants born July 2000 to December 2008 at 37–41 weeks gestation. Results Over the 8.5 years, births through scheduled deliveries at 37–38 weeks decreased (9.4% to 4.4%), but overall scheduled deliveries increased (29% to 34%) and mean gestational age at birth (39.1 weeks) did not change. Mean birth weight (3410g to 3383g) and LGA (9.0% to 7.4%) both decreased, whereas SGA increased (7.5% to 8.2%). In multivariable analyses adjusting for maternal and infant characteristics, birth weight decreased (36g; 95% CI: 31, 42), especially among infants born at 37–38 weeks (40g; 30, 49) or that had medical indications for urgent deliveries (48g; 34, 63). Odds of LGA decreased (0.84; 0.80, 0.88) and odds of SGA increased (1.14; 1.08, 1.20). Conclusion Even in a population where gestation length did not change, birth weight and fetal growth declined. Decrease in not only gestational length but in fetal growth as well is likely to be contributing to the widely observed recent decrease in birth weight. PMID:23262927

  5. The effect of propagation methods on some growth and physiological characteristics of seed- and vegetatively propagated Eucalyptus varieties

    CSIR Research Space (South Africa)

    Mokotedi, O

    2011-11-01

    Full Text Available between root characteristics (hydraulics, anchorage efficiency) and above-ground parameters (survival, leaf gas exchange). Cold-tolerant GN clones are planted across low-productivity, high altitude sites in South Africa....

  6. View Point: Economic growth and child health in Sub Saharan Africa ...

    African Journals Online (AJOL)

    View Point: Economic growth and child health in Sub Saharan Africa. BA O'Hare, N Bar-Zeev, L Chiwaula. Abstract. After independence most African countries witnessed growth in their economies and decreases in child mortality. However both economic growth and the gains in under 5 mortality slowed dramatically in the ...

  7. Historical Evidence on the Finance-Trade-Growth Nexus

    OpenAIRE

    Michael D. Bordo; Peter L. Rousseau

    2011-01-01

    We study linkages between financial development, international trade, and long-run growth using data since 1880 for seventeen now-developed "Atlantic" economies and a set of cross-country and dynamic panel data models. We find that finance and trade reinforced each other before 1930, but that these effects did not persist after the Second World War. Financial development has positive effects on growth throughout the sample period, while trade affects growth strongly and independently after 19...

  8. Evaluation of stress patterns on maxillary posterior segment when intruded with mini implant anchorage: A three-dimensional finite element study

    Directory of Open Access Journals (Sweden)

    Nikhita Pekhale

    2016-01-01

    Full Text Available Introduction: The aim of this study is to evaluate stress and displacement effects of maxillary posterior intrusion mechanics with mini-implant anchorage by using finite element method. Materials and Methods: A computer stimulation of three-dimensional model maxilla with all teeth, PDL, bone, mini-implants, brackets, arch wire, force element, and transpalatal arch was constructed on the basis of average anatomic morphology. Finite element analysis was done to evaluate the amount of stress and its distribution during orthodontic intrusive force. Results: Increased Von Mises stress values were observed in mesio-cervical region of first molar. The middle third of second premolar and second molar and regions adjacent to force application sites also showed relatively high stress values. Minimum stress values were observed in apical region of first premolar as it is away from force application. Conclusion: Using three mini-implant and transpalatal arches, this study demonstrates that significant amount of true intrusion of maxillary molars could be obtained with lesser concentration of stresses in the apical area recorded.

  9. Every Day We're Shufflin': Empowering Students during In-School Independent Reading

    Science.gov (United States)

    Hall, Katrina W.; Hedrick, Wanda B.; Williams, Lunetta M.

    2014-01-01

    Research in the field of literacy has identified choice as a key component affecting students' reading habits and their resulting literacy growth. This article discusses an in-school independent reading project in which students are provided the freedom to choose books, use ambient music, and engage in book talks. The children showed increased…

  10. Focus formation and neoplastic transformation by herpes simplex virus type 2 inactivated intracellularly by 5-bromo-2'-deoxyuridine and near UV light

    International Nuclear Information System (INIS)

    Manak, M.M.; Aurelian, L.; Ts'o, P.O.

    1981-01-01

    The induction of focus formation in low serum and of neoplastic transformation of Syrian hamster embryo cells was examined after the expression of herpes simplex virus type 2 functions. Syrian hamster embryo cells infected at a high multiplicity (5 PFU/cell) with 5-bromo-2'-deoxyuridine-labeled herpes simplex virus type 2 (11% substitution of thymidine residues) were exposed to near UV light irradiation at various times postinfection. This procedure specifically inactivated the viral genome, while having little, if any, effect on the unlabeled cellular DNA. Focus formation in 1% serum and neoplastic transformation were observed in cells exposed to virus inactivated before infection, but the frequency was enhanced (15- to 27-fold) in cells in which the virus was inactivated at 4 to 8 h postinfection. Only 2 to 45 independently isolated foci were capable of establishing tumorigenic lines. The established lines exhibited phenotypic alterations characteristic of a transformed state, including reduced serum requirement, anchorage-independent growth, and tumorigenicity. They retained viral DNA sequences and, even at relatively late passage, expressed viral antigens, including ICP 10

  11. Human milk adiponectin is associated with infant growth in two independent cohorts.

    Science.gov (United States)

    Woo, Jessica G; Guerrero, M Lourdes; Altaye, Mekibib; Ruiz-Palacios, Guillermo M; Martin, Lisa J; Dubert-Ferrandon, Alix; Newburg, David S; Morrow, Ardythe L

    2009-06-01

    Adiponectin, a circulating adipocyte protein, is associated with lower obesity. We have previously shown that adiponectin is present in human milk. This study determined whether higher milk adiponectin is associated with infant growth and investigated milk adiponectin's oligomeric form. This is a study of two parallel longitudinal cohorts of breastfed infants born between 1998 and 2005. Forty-five mother-infant pairs from Cincinnati, OH and 277 mother-infant pairs from Mexico City, Mexico were analyzed. All participants were healthy, term infants breastfed at least 1 month who completed 6 months of follow-up. Monthly milk samples (n = 1,379) up to 6 months were assayed for adiponectin by radioimmunoassay. Infant weight-for-age, length-for-age, and weight-for-length Z-scores up to 6 months of age were calculated using World Health Organization standards. Repeated-measures analysis was conducted. The structural form of human milk adiponectin was assessed by western blot. In the population studies, initial milk adiponectin was 24.0 +/- 8.6 microg/L and did not differ by cohort. Over the first 6 months, higher milk adiponectin was associated with lower infant weight-for-age Z-score (-0.20 +/- 0.04, p milk adiponectin was predominantly in the biologically active high-molecular-weight form. Our data suggest milk adiponectin may play a role in the early growth and development of breastfed infants.

  12. Silencing of reversion-inducing cysteine-rich protein with Kazal motifs stimulates hyperplastic phenotypes through activation of epidermal growth factor receptor and hypoxia-inducible factor-2α.

    Directory of Open Access Journals (Sweden)

    You Mie Lee

    Full Text Available Reversion-inducing cysteine-rich protein with Kazal motifs (RECK, a tumor suppressor is down-regulated by the oncogenic signals and hypoxia, but the biological function of RECK in early tumorigenic hyperplastic phenotypes is largely unknown. Knockdown of RECK by small interfering RNA (siRECK or hypoxia significantly promoted cell proliferation in various normal epithelial cells. Hypoxia as well as knockdown of RECK by siRNA increased the cell cycle progression, the levels of cyclin D1 and c-Myc, and the phosphorylation of Rb protein (p-pRb, but decreased the expression of p21(cip1, p27(kip1, and p16(ink4A. HIF-2α was upregulated by knockdown of RECK, indicating HIF-2α is a downstream target of RECK. As knockdown of RECK induced the activation of epidermal growth factor receptor (EGFR and treatment of an EGFR kinase inhibitor, gefitinib, suppressed HIF-2α expression induced by the silencing of RECK, we can suggest that the RECK silenicng-EGFR-HIF-2α axis might be a key molecular mechanism to induce hyperplastic phenotype of epithelial cells. It was also found that shRNA of RECK induced larger and more numerous colonies than control cells in an anchorage-independent colony formation assay. Using a xenograft assay, epithelial cells with stably transfected with shRNA of RECK formed a solid mass earlier and larger than those with control cells in nude mice. In conclusion, the suppression of RECK may promote the development of early tumorigenic hyperplastic characteristics in hypoxic stress.

  13. Feedback amplification loop drives malignant growth in epithelial tissues.

    Science.gov (United States)

    Muzzopappa, Mariana; Murcia, Lada; Milán, Marco

    2017-08-29

    Interactions between cells bearing oncogenic mutations and the surrounding microenvironment, and cooperation between clonally distinct cell populations, can contribute to the growth and malignancy of epithelial tumors. The genetic techniques available in Drosophila have contributed to identify important roles of the TNF-α ligand Eiger and mitogenic molecules in mediating these interactions during the early steps of tumor formation. Here we unravel the existence of a tumor-intrinsic-and microenvironment-independent-self-reinforcement mechanism that drives tumor initiation and growth in an Eiger-independent manner. This mechanism relies on cell interactions between two functionally distinct cell populations, and we present evidence that these cell populations are not necessarily genetically different. Tumor-specific and cell-autonomous activation of the tumorigenic JNK stress-activated pathway drives the expression of secreted signaling molecules and growth factors to delaminating cells, which nonautonomously promote proliferative growth of the partially transformed epithelial tissue. We present evidence that cross-feeding interactions between delaminating and nondelaminating cells increase each other's sizes and that these interactions can explain the unlimited growth potential of these tumors. Our results will open avenues toward our molecular understanding of those social cell interactions with a relevant function in tumor initiation in humans.

  14. Gene trapping identifies a putative tumor suppressor and a new inducer of cell migration

    International Nuclear Information System (INIS)

    Guardiola-Serrano, Francisca; Haendeler, Judith; Lukosz, Margarete; Sturm, Karsten; Melchner, Harald von; Altschmied, Joachim

    2008-01-01

    Tumor necrosis factor alpha (TNFα) is a pleiotropic cytokine involved in apoptotic cell death, cellular proliferation, differentiation, inflammation, and tumorigenesis. In tumors it is secreted by tumor associated macrophages and can have both pro- and anti-tumorigenic effects. To identify genes regulated by TNFα, we performed a gene trap screen in the mammary carcinoma cell line MCF-7 and recovered 64 unique, TNFα-induced gene trap integration sites. Among these were the genes coding for the zinc finger protein ZC3H10 and for the transcription factor grainyhead-like 3 (GRHL3). In line with the dual effects of TNFα on tumorigenesis, we found that ZC3H10 inhibits anchorage independent growth in soft agar suggesting a tumor suppressor function, whereas GRHL3 strongly stimulated the migration of endothelial cells which is consistent with an angiogenic, pro-tumorigenic function

  15. TECHNOLOGY TRANSFER TO U.S. INDEPENDENT OIL AND NATURAL GAS PRODUCERS

    Energy Technology Data Exchange (ETDEWEB)

    Unknown

    2000-05-01

    During FY00, the Petroleum Technology Transfer Council (PTTC) continued pursuing its mission of helping U.S. independent oil and gas producers make timely, informed technology decisions. PTTC's national organization has active grassroots programs that connect with independents through its 10 Regional Lead Organizations (RLOs). These activities--including technology workshops, resource centers, websites, newsletters, and other outreach efforts--are guided by regional Producer Advisory Groups (PAGs). The role of the national headquarters (HQ) staff includes planning and managing the PTTC program, conducting nation-wide technology transfer activities, and implementing a comprehensive communications effort. This technical progress report summarizes PTTC's accomplishments during FY00, which lay the groundwork for further growth in the future.

  16. TECHNOLOGY TRANSFER TO U.S. INDEPENDENT OIL AND NATURAL GAS PRODUCERS

    Energy Technology Data Exchange (ETDEWEB)

    Donald Duttlinger

    1999-12-01

    During FY99, the Petroleum Technology Transfer Council (PTTC) continued pursuing its mission of helping U.S. independent oil and gas producers make timely, informed technology decisions. PTfC's national organization has active grassroots programs that connect with independents through its 10 Regional Lead Organizations (RLOs). These activities--including technology workshops, resource centers, websites, newsletters, and other outreach efforts--are guided by regional Producer Advisory Groups (PAGs). The role of the national headquarters (HQ) staff includes planning and managing the PTTC program, conducting nation-wide technology transfer activities, and implementing a comprehensive communications effort. This technical progress report summarizes PTTC's accomplishments during FY99, which lay the groundwork for further growth in the future.

  17. Gremlin-1 induces BMP-independent tumor cell proliferation, migration, and invasion.

    Directory of Open Access Journals (Sweden)

    Minsoo Kim

    Full Text Available Gremlin-1, a bone morphogenetic protein (BMP antagonist, is overexpressed in various cancerous tissues but its role in carcinogenesis has not been established. Here, we report that gremlin-1 binds various cancer cell lines and this interaction is inhibited by our newly developed gremlin-1 antibody, GRE1. Gremlin-1 binding to cancer cells was unaffected by the presence of BMP-2, BMP-4, and BMP-7. In addition, the binding was independent of vascular endothelial growth factor receptor-2 (VEGFR2 expression on the cell surface. Addition of gremlin-1 to A549 cells induced a fibroblast-like morphology and decreased E-cadherin expression. In a scratch wound healing assay, A549 cells incubated with gremlin-1 or transfected with gremlin-1 showed increased migration, which was inhibited in the presence of the GRE1 antibody. Gremlin-1 transfected A549 cells also exhibited increased invasiveness as well as an increased growth rate. These effects were also inhibited by the addition of the GRE1 antibody. In conclusion, this study demonstrates that gremlin-1 directly interacts with cancer cells in a BMP- and VEGFR2-independent manner and can induce cell migration, invasion, and proliferation.

  18. Emmprin (basigin/CD147): matrix metalloproteinase modulator and multifunctional cell recognition molecule that plays a critical role in cancer progression.

    Science.gov (United States)

    Nabeshima, Kazuki; Iwasaki, Hiroshi; Koga, Kaori; Hojo, Hironobu; Suzumiya, Junji; Kikuchi, Masahiro

    2006-07-01

    Emmprin (basigin, CD147) is a cell surface glycoprotein that belongs to the immunoglobulin superfamily. It is highly expressed on the surface of tumor cells and stimulates adjacent fibroblasts or tumor cells to produce matrix metalloproteinases. Moreover, it has recently been shown that emmprin also stimulates expression of vascular endothelial growth factor and hyaluronan, which leads to angiogenesis and anchorage-independent growth/multidrug resistance, respectively. These findings have made emmprin an important molecule in tumor progression and, thus, more attractive as a target for antitumor treatment. However, other functions of emmprin, including as an activator of T cells, a chaperone for monocarboxylate transporters, a receptor for cyclophilin A and a neural recognition molecule, are also being identified in physiological and pathological conditions. Therefore, it is essential to develop specific means to control particular functions of emmprin, for which elucidation of each mechanism is crucial. This review will discuss the role of emmprin in tumor progression and recent advances in the molecular mechanisms of diverse phenomena regulated by emmprin.

  19. Proteasomal degradation of sphingosine kinase 1 and inhibition of dihydroceramide desaturase by the sphingosine kinase inhibitors, SKi or ABC294640, induces growth arrest in androgen-independent LNCaP-AI prostate cancer cells.

    Science.gov (United States)

    McNaughton, Melissa; Pitman, Melissa; Pitson, Stuart M; Pyne, Nigel J; Pyne, Susan

    2016-03-29

    Sphingosine kinases (two isoforms termed SK1 and SK2) catalyse the formation of the bioactive lipid sphingosine 1-phosphate. We demonstrate here that the SK2 inhibitor, ABC294640 (3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide) or the SK1/SK2 inhibitor, SKi (2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole)) induce the proteasomal degradation of SK1a (Mr = 42 kDa) and inhibit DNA synthesis in androgen-independent LNCaP-AI prostate cancer cells. These effects are recapitulated by the dihydroceramide desaturase (Des1) inhibitor, fenretinide. Moreover, SKi or ABC294640 reduce Des1 activity in Jurkat cells and ABC294640 induces the proteasomal degradation of Des1 (Mr = 38 kDa) in LNCaP-AI prostate cancer cells. Furthermore, SKi or ABC294640 or fenretinide increase the expression of the senescence markers, p53 and p21 in LNCaP-AI prostate cancer cells. The siRNA knockdown of SK1 or SK2 failed to increase p53 and p21 expression, but the former did reduce DNA synthesis in LNCaP-AI prostate cancer cells. Moreover, N-acetylcysteine (reactive oxygen species scavenger) blocked the SK inhibitor-induced increase in p21 and p53 expression but had no effect on the proteasomal degradation of SK1a. In addition, siRNA knockdown of Des1 increased p53 expression while a combination of Des1/SK1 siRNA increased the expression of p21. Therefore, Des1 and SK1 participate in regulating LNCaP-AI prostate cancer cell growth and this involves p53/p21-dependent and -independent pathways. Therefore, we propose targeting androgen-independent prostate cancer cells with compounds that affect Des1/SK1 to modulate both de novo and sphingolipid rheostat pathways in order to induce growth arrest.

  20. Time-independent limit of a creep-recovery constitutive equation

    International Nuclear Information System (INIS)

    Chang, S.J.

    1984-01-01

    The effect of strain recovery is taken into consideration in ORNL efforts to establish unified constitutive equations for time-dependent plastic deformation for metals at elevated temperatures. Representation by internal state variables and Rice's flow potential are under consideration. Here the growth law for the internal state variables is discussed and interpreted in terms of a generalized form of the kinematic hardening condition of Prager. The yield condition is obtained from the flow potential representation of the inelastic strain rate. A consistency condition is derived from the yield condition and leads to a flow rule which assumes a slightly general form as compared with that of the classical plasticity due to the effect of strain recovery and the time-dependent property of the yield condition. Based on this representation, the time-independent limit is discussed. From a vanishing effect of recovery and a rate-independent limit for the yield condition at low temperature, this flow rule reduces to the well-known form of time-independent plasticity with a kinematic hardening condition. The duration of time (the characteristic time) required for the inelastic strain to reach its saturated value is defined for the inelastic loading condition. It provides the measure of a minimum duration of time which is required for a valid approximation made by the time-independent plasticity model

  1. Maternal depression and anxiety and fetal-neonatal growth

    Directory of Open Access Journals (Sweden)

    Tiago Miguel Pinto

    2017-09-01

    Conclusion: This study demonstrates the independent longitudinal effect of maternal anxiety on major markers of fetal-neonatal growth outcomes and trajectories, simultaneously considering the effect of maternal depression and anxiety.

  2. Dinosaur Metabolism and the Allometry of Maximum Growth Rate

    OpenAIRE

    Myhrvold, Nathan P.

    2016-01-01

    The allometry of maximum somatic growth rate has been used in prior studies to classify the metabolic state of both extant vertebrates and dinosaurs. The most recent such studies are reviewed, and their data is reanalyzed. The results of allometric regressions on growth rate are shown to depend on the choice of independent variable; the typical choice used in prior studies introduces a geometric shear transformation that exaggerates the statistical power of the regressions. The maximum growth...

  3. Causal independence between energy consumption and economic growth in Liberia: Evidence from a non-parametric bootstrapped causality test

    International Nuclear Information System (INIS)

    Wesseh, Presley K.; Zoumara, Babette

    2012-01-01

    This contribution investigates causal interdependence between energy consumption and economic growth in Liberia and proposes application of a bootstrap methodology. To better reflect causality, employment is incorporated as additional variable. The study demonstrates evidence of distinct bidirectional Granger causality between energy consumption and economic growth. Additionally, the results show that employment in Liberia Granger causes economic growth and apply irrespective of the short-run or long-run. Evidence from a Monte Carlo experiment reveals that the asymptotic Granger causality test suffers size distortion problem for Liberian data, suggesting that the bootstrap technique employed in this study is more appropriate. Given the empirical results, implications are that energy expansion policies like energy subsidy or low energy tariff for instance, would be necessary to cope with demand exerted as a result of economic growth in Liberia. Furthermore, Liberia might have the performance of its employment generation on the economy partly determined by adequate energy. Therefore, it seems fully justified that a quick shift towards energy production based on clean energy sources may significantly slow down economic growth in Liberia. Hence, the government’s target to implement a long-term strategy to make Liberia a carbon neutral country, and eventually less carbon dependent by 2050 is understandable. - Highlights: ► Causality between energy consumption and economic growth in Liberia investigated. ► There is bidirectional causality between energy consumption and economic growth. ► Energy expansion policies are necessary to cope with demand from economic growth. ► Asymptotic Granger causality test suffers size distortion problem for Liberian data. ► The bootstrap methodology employed in our study is more appropriate.

  4. Insulin-Like Growth Factor-I Induces Arginase Activity in Leishmania amazonensis Amastigote-Infected Macrophages through a Cytokine-Independent Mechanism

    Directory of Open Access Journals (Sweden)

    Celia Maria Vieira Vendrame

    2014-01-01

    Full Text Available Leishmania (Leishmania amazonensis exhibits peculiarities in its interactions with hosts. Because amastigotes are the primary form associated with the progression of infection, we studied the effect of insulin-like growth factor (IGF-I on interactions between L. (L. amazonensis amastigotes and macrophages. Upon stimulation of infected macrophages with IGF-I, we observed decreased nitric oxide production but increased arginase expression and activity, which lead to increased parasitism. However, stimulation of amastigote-infected macrophages with IGF-I did not result in altered cytokine levels compared to unstimulated controls. Because IGF-I is present in tissue fluids and also within macrophages, we examined the possible effect of this factor on phosphatidylserine (PS exposure on amastigotes, seen previously in tissue-derived amastigotes leading to increased parasitism. Stimulation with IGF-I induced PS exposure on amastigotes but not on promastigotes. Using a PS-liposome instead of amastigotes, we observed that the PS-liposome but not the control phosphatidylcholine-liposome led to increased arginase activity in macrophages, and this process was not blocked by anti-TGF-β antibodies. Our results suggest that in L. (L. amazonensis amastigote-infected macrophages, IGF-I induces arginase activity directly in amastigotes and in macrophages through the induction of PS exposure on amastigotes in the latter, which could lead to the alternative activation of macrophages through cytokine-independent mechanisms.

  5. Central Bank independence

    Directory of Open Access Journals (Sweden)

    Vasile DEDU

    2012-08-01

    Full Text Available In this paper we present the key aspects regarding central bank’s independence. Most economists consider that the factor which positively influences the efficiency of monetary policy measures is the high independence of the central bank. We determined that the National Bank of Romania (NBR has a high degree of independence. NBR has both goal and instrument independence. We also consider that the hike of NBR’s independence played an important role in the significant disinflation process, as headline inflation dropped inside the targeted band of 3% ± 1 percentage point recently.

  6. Product-Marketing Innovation, Skills, and Firm Productivity Growth

    DEFF Research Database (Denmark)

    Junge, Martin; Severgnini, Battista; Sørensen, Anders

    2016-01-01

    The role of product and marketing innovation for productivity growth is addressed using survey and register data for the Danish economy. It is hypothesized that product and marketing innovation are complementary inputs and that innovation activities are skill-intensive. It is established...... that product and marketing innovation in skill-intensive firms results in significantly faster productivity growth. Moreover, product and marketing innovation have independent roles in productivity growth, which cannot be attributed to organizational changes. Finally, we apply an instrument variable approach...... for firms, innovation choices to study endogeneity. The results strongly support the idea that product–marketing innovation leads to faster productivity growth in skill-intensive firms....

  7. Growth of Chlorella vulgaris and associated bacteria in photobioreactors

    Science.gov (United States)

    Lakaniemi, Aino‐Maija; Intihar, Veera M.; Tuovinen, Olli H.; Puhakka, Jaakko A.

    2012-01-01

    Summary The aim of this study was to test three flat plate photobioreactor configurations for growth of Chlorella vulgaris under non‐axenic conditions and to characterize and quantify associated bacterial communities. The photobioreactor cultivations were conducted using tap water‐based media to introduce background bacterial population. Growth of algae was monitored over time with three independent methods. Additionally, the quantity and quality of eukaryotes and bacteria were analysed using culture‐independent molecular tools based on denaturing gradient gel electrophoresis (PCR‐DGGE) and quantitative polymerase chain reaction (QPCR). Static mixers used in the flat plate photobioreactors did not generally enhance the growth at the low light intensities used. The maximum biomass concentration and maximum specific growth rate were 1.0 g l−1 and 2.0 day−1 respectively. Bacterial growth as determined by QPCR was associated with the growth of C. vulgaris. Based on PCR‐DGGE, bacteria in the cultures mainly originated from the tap water. Bacterial community profiles were diverse but reproducible in all flat plate cultures. Most prominent bacteria in the C. vulgaris cultures belonged to the class Alphaproteobacteria and especially to the genus Sphingomonas. Analysis of the diversity of non‐photosynthetic microorganisms in algal mass cultures can provide useful information on the public health aspects and unravel community interactions. PMID:21936882

  8. Lessons from independence

    International Nuclear Information System (INIS)

    Hauptfuhrer, R.R.

    1990-01-01

    The recent history of Oryx provides invaluable lessons for those who plan future energy strategies, relates the author of this paper. When Oryx became an independent oil and gas company, its reserves were declining, its stock was selling below asset values, and the price of oil seemed stuck below $15 per barrel. The message from Oryx management to Oryx employees was: We are in charge of our own destiny. We are about to create our own future. Oryx had developed a new, positive corporate culture and the corporate credit required for growth. This paper points to two basic principles that have guided the metamorphosis in Oryx's performance. The first objective was to improve operational efficiency and to identify the right performance indicators to measure this improvement. It states that the most critical performance indicator for an exploration and production company must be replacement and expansion of reserves at a competitive replacement cost. Oryx has cut its finding costs from $12 to $5 per barrel, while the BP acquisition provided proven reserves at a cost of only $4 per barrel. Another performance indicator measures Oryx's standing in the financial markets

  9. Coupling between p210bcr-abl and Shc and Grb2 adaptor proteins in hematopoietic cells permits growth factor receptor-independent link to ras activation pathway.

    Science.gov (United States)

    Tauchi, T; Boswell, H S; Leibowitz, D; Broxmeyer, H E

    1994-01-01

    Enforced expression of p210bcr-abl transforms interleukin 3 (IL-3)-dependent hematopoietic cell lines to growth factor-independent proliferation. It has been demonstrated that nonreceptor tyrosine kinase oncogenes may couple to the p21ras pathway to exert their transforming effect. In particular, p210bcr-abl was recently found to effect p21ras activation in hematopoietic cells. In this context, experiments were performed to evaluate a protein signaling pathway by which p210bcr-abl might regulate p21ras. It was asked whether Shc p46/p52, a protein containing a src-homology region 2 (SH2) domain, and known to function upstream from p21ras, might form specific complexes with p210bcr-abl and thus, possibly alter p21ras activity by coupling to the guanine nucleotide exchange factor (Sos/CDC25) through the Grb2 protein-Sos complex. This latter complex has been previously demonstrated to occur ubiquitously. We found that p210bcr-abl formed a specific complex with Shc and with Grb2 in three different murine cell lines transfected with a p210bcr-abl expression vector. There appeared to be a higher order complex containing Shc, Grb2, and bcr-abl proteins. In contrast to p210bcr-abl transformed cells, in which there was constitutive tight association between Grb2 and Shc, binding between Grb2 and Shc was Steel factor (SLF)-dependent in a SLF-responsive, nontransformed parental cell line. The SLF-dependent association between Grb2 and Shc in nontransformed cells involved formation of a complex of Grb2 with c-kit receptor after SLF treatment. Thus, p210bcr-abl appears to function in a hematopoietic p21ras activation pathway to allow growth factor-independent coupling between Grb2, which exists in a complex with the guanine nucleotide exchange factor (Sos), and p21ras. Shc may not be required for Grb2-c-kit interaction, because it fails to bind strongly to c-kit.

  10. Comparative study of the anchorage and the catalytic properties of nanoporous TiO2 films modified with ruthenium (II) and rhenium (I) carbonyl complexes

    Science.gov (United States)

    Oyarzún, Diego P.; Chardon-Noblat, Sylvie; Linarez Pérez, Omar E.; López Teijelo, Manuel; Zúñiga, César; Zarate, Ximena; Shott, Eduardo; Carreño, Alexander; Arratia-Perez, Ramiro

    2018-02-01

    In this article we study the anchoring of cis-[Ru(bpyC4pyr)(CO)2(CH3CN)2]2+, cis-[Ru(bpy)2(CO)2]2+ and cis-[Ru(bpyac)(CO)2Cl2], onto nanoporous TiO2 employing electropolymerization, electrostatic interaction and chemical bonding. Also, the [Re(bpyac)(CO)3Cl] rhenium(I) complex for chemical anchorage was analyzed. The characterization of TiO2/Ru(II) and TiO2/Re(I) nanocomposite films was performed by field emission scanning electron microscopy (FESEM), electron dispersive X-ray spectroscopy (EDS) and Raman spectroscopy. In addition, for the more stable nanocomposites obtained, the catalytic properties (solar energy conversion and CO2 reduction) were evaluated. The efficiency improvement in redox process derived from the (photo)electrochemical evidence indicates that modified nanoporous TiO2 structures enhance the rate of charge transfer reactions.

  11. Catch-up growth following fetal growth restriction promotes rapid restoration of fat mass but without metabolic consequences at one year of age.

    Directory of Open Access Journals (Sweden)

    Jacques Beltrand

    Full Text Available BACKGROUND: Fetal growth restriction (FGR followed by rapid weight gain during early life has been suggested to be the initial sequence promoting central adiposity and insulin resistance. However, the link between fetal and early postnatal growth and the associated anthropometric and metabolic changes have been poorly studied. METHODOLOGY/PRINCIPAL FINDINGS: Over the first year of post-natal life, changes in body mass index, skinfold thickness and hormonal concentrations were prospectively monitored in 94 infants in whom the fetal growth velocity had previously been measured using a repeated standardized procedure of ultrasound fetal measurements. 45 infants, thinner at birth, had experienced previous FGR (FGR+ regardless of birth weight. Growth pattern in the first four months of life was characterized by greater change in BMI z-score in FGR+ (+1.26+/-1.2 vs +0.58 +/-1.17 SD in FGR- resulting in the restoration of BMI and of fat mass to values similar to FGR-, independently of caloric intakes. Growth velocity after 4 months was similar and BMI z-score and fat mass remained similar at 12 months of age. At both time-points, fetal growth velocity was an independent predictor of fat mass in FGR+. At one year, fasting insulin levels were not different but leptin was significantly higher in the FGR+ (4.43+/-1.41 vs 2.63+/-1 ng/ml in FGR-. CONCLUSION: Early catch-up growth is related to the fetal growth pattern itself, irrespective of birth weight, and is associated with higher insulin sensitivity and lower leptin levels after birth. Catch-up growth promotes the restoration of body size and fat stores without detrimental consequences at one year of age on body composition or metabolic profile. The higher leptin concentration at one year may reflect a positive energy balance in children who previously faced fetal growth restriction.

  12. Response of Escherichia coli growth rate to osmotic shock.

    Science.gov (United States)

    Rojas, Enrique; Theriot, Julie A; Huang, Kerwyn Casey

    2014-05-27

    It has long been proposed that turgor pressure plays an essential role during bacterial growth by driving mechanical expansion of the cell wall. This hypothesis is based on analogy to plant cells, for which this mechanism has been established, and on experiments in which the growth rate of bacterial cultures was observed to decrease as the osmolarity of the growth medium was increased. To distinguish the effect of turgor pressure from pressure-independent effects that osmolarity might have on cell growth, we monitored the elongation of single Escherichia coli cells while rapidly changing the osmolarity of their media. By plasmolyzing cells, we found that cell-wall elastic strain did not scale with growth rate, suggesting that pressure does not drive cell-wall expansion. Furthermore, in response to hyper- and hypoosmotic shock, E. coli cells resumed their preshock growth rate and relaxed to their steady-state rate after several minutes, demonstrating that osmolarity modulates growth rate slowly, independently of pressure. Oscillatory hyperosmotic shock revealed that although plasmolysis slowed cell elongation, the cells nevertheless "stored" growth such that once turgor was reestablished the cells elongated to the length that they would have attained had they never been plasmolyzed. Finally, MreB dynamics were unaffected by osmotic shock. These results reveal the simple nature of E. coli cell-wall expansion: that the rate of expansion is determined by the rate of peptidoglycan insertion and insertion is not directly dependent on turgor pressure, but that pressure does play a basic role whereby it enables full extension of recently inserted peptidoglycan.

  13. Plant growth strategies are remodeled by spaceflight

    Directory of Open Access Journals (Sweden)

    Paul Anna-Lisa

    2012-12-01

    Full Text Available Abstract Background Arabidopsis plants were grown on the International Space Station within specialized hardware that combined a plant growth habitat with a camera system that can capture images at regular intervals of growth. The Imaging hardware delivers telemetric data from the ISS, specifically images received in real-time from experiments on orbit, providing science without sample return. Comparable Ground Controls were grown in a sister unit that is maintained in the Orbital Environment Simulator at Kennedy Space Center. One of many types of biological data that can be analyzed in this fashion is root morphology. Arabidopsis seeds were geminated on orbit on nutrient gel Petri plates in a configuration that encouraged growth along the surface of the gel. Photos were taken every six hours for the 15 days of the experiment. Results In the absence of gravity, but the presence of directional light, spaceflight roots remained strongly negatively phototropic and grew in the opposite direction of the shoot growth; however, cultivars WS and Col-0 displayed two distinct, marked differences in their growth patterns. First, cultivar WS skewed strongly to the right on orbit, while cultivar Col-0 grew with little deviation away from the light source. Second, the Spaceflight environment also impacted the rate of growth in Arabidopsis. The size of the Flight plants (as measured by primary root and hypocotyl length was uniformly smaller than comparably aged Ground Control plants in both cultivars. Conclusions Skewing and waving, thought to be gravity dependent phenomena, occur in spaceflight plants. In the presence of an orienting light source, phenotypic trends in skewing are gravity independent, and the general patterns of directional root growth typified by a given genotype in unit gravity are recapitulated on orbit, although overall growth patterns on orbit are less uniform. Skewing appears independent of axial orientation on the ISS – suggesting

  14. A local anesthetic, ropivacaine, suppresses activated microglia via a nerve growth factor-dependent mechanism and astrocytes via a nerve growth factor-independent mechanism in neuropathic pain

    Directory of Open Access Journals (Sweden)

    Sakamoto Atsuhiro

    2011-01-01

    Full Text Available Abstract Background Local anesthetics alleviate neuropathic pain in some cases in clinical practice, and exhibit longer durations of action than those predicted on the basis of the pharmacokinetics of their blocking effects on voltage-dependent sodium channels. Therefore, local anesthetics may contribute to additional mechanisms for reversal of the sensitization of nociceptive pathways that occurs in the neuropathic pain state. In recent years, spinal glial cells, microglia and astrocytes, have been shown to play critical roles in neuropathic pain, but their participation in the analgesic effects of local anesthetics remains largely unknown. Results Repetitive epidural administration of ropivacaine reduced the hyperalgesia induced by chronic constrictive injury of the sciatic nerve. Concomitantly with this analgesia, ropivacaine suppressed the increases in the immunoreactivities of CD11b and glial fibrillary acidic protein in the dorsal spinal cord, as markers of activated microglia and astrocytes, respectively. In addition, epidural administration of a TrkA-IgG fusion protein that blocks the action of nerve growth factor (NGF, which was upregulated by ropivacaine in the dorsal root ganglion, prevented the inhibitory effect of ropivacaine on microglia, but not astrocytes. The blockade of NGF action also abolished the analgesic effect of ropivacaine on neuropathic pain. Conclusions Ropivacaine provides prolonged analgesia possibly by suppressing microglial activation in an NGF-dependent manner and astrocyte activation in an NGF-independent manner in the dorsal spinal cord. Local anesthetics, including ropivacaine, may represent a new approach for glial cell inhibition and, therefore, therapeutic strategies for neuropathic pain.

  15. The role of psychological factors in the career of the independent dancer

    Directory of Open Access Journals (Sweden)

    Imogen eAujla

    2015-10-01

    Full Text Available Previous research indicates that psychological factors such as motivation and mental skills play an important role in relation to performance and to negotiating talent development stages. However, little is known about these factors in dance, particularly with regard to the independent dancer whose career may involve multiple roles, varied work patterns and periods of instability. The aim of this study was to explore dancers’ motivation to work in an independent capacity, and the extent to which dancers’ psychological characteristics and skills enabled them to navigate a career in this demanding sector. In-depth semi-structured interviews were conducted with 14 dancers at different stages of their careers. Interviews were transcribed verbatim and content analyzed. Analysis revealed that the dancers were intrinsically motivated and highly committed to the profession. Working in the independent sector offered dancers opportunities for growth and fulfillment; they appreciated the autonomy, flexibility and freedom that the independent career afforded, as well as working with new people across roles and disciplines. In order to overcome the various challenges associated with the independent role, optimism, self-belief, social support and career management skills were crucial. The mental skills reported by the participants had developed gradually in response to the demands that they faced. Therefore, mental skills training could be invaluable for dancers to help them successfully negotiate the independent sector.

  16. Re-Examining the Finance-Growth Nexus: Empirical Evidence from Indonesia

    Directory of Open Access Journals (Sweden)

    M. Shabri Abd. Majid

    2007-06-01

    Full Text Available This paper empirically examines the short- and long-run relationships between financial development and economic growth during the post-1997 financial crisis in Indonesia by employing a battery of times-series techniques, such as Autoregressive Dis-tributed Lag (ARDL model, vector error correction model (VECM, variance decompositions (VDCs, and impulse-response functions (IRFs. Based on the ARDL (2, 0, 1, 2 model, the study finds that there exists a long-run equilibrium between economic growth and financial depth, share of investment, and inflation. In the long run, inflation is found to be the only variable which significantly (negatively affects economic growth, implying a crucial role of maintaining a low rate of inflation in promoting the economic growth in the country. As for the dynamic causalities among the variables, the study finds the bidirectional causation between economic growth and investment, while the unidirectional causation is only found running from financial depth to investment. The finding of independence between economic growth and financial development supports the view of “the independent hypothesis” of Lucas (1988. Finally, based on VDCs and IRFs, the study documents that the variations in the economic growth respond more to shocks in the price stability (inflation, followed by investment and financial development. Our findings indicate that if policy makers want to promote growth, attention should be focused on long-run policies, i.e., maintaining the low rate of inflation.

  17. Arabidopsis CPR5 independently regulates seed germination and postgermination arrest of development through LOX pathway and ABA signaling.

    Directory of Open Access Journals (Sweden)

    Guilan Gao

    Full Text Available The phytohormone abscisic acid (ABA and the lipoxygenases (LOXs pathway play important roles in seed germination and seedling growth and development. Here, we reported on the functional characterization of Arabidopsis CPR5 in the ABA signaling and LOX pathways. The cpr5 mutant was hypersensitive to ABA in the seed germination, cotyledon greening and root growth, whereas transgenic plants overexpressing CPR5 were insensitive. Genetic analysis demonstrated that CPR5 gene may be located downstream of the ABI1 in the ABA signaling pathway. However, the cpr5 mutant showed an ABA independent drought-resistant phenotype. It was also found that the cpr5 mutant was hypersensitive to NDGA and NDGA treatment aggravated the ABA-induced delay in the seed germination and cotyledon greening. Taken together, these results suggest that the CPR5 plays a regulatory role in the regulation of seed germination and early seedling growth through ABA and LOX pathways independently.

  18. Effects of greywater irrigation on germination, growth and ...

    African Journals Online (AJOL)

    2016-04-02

    Apr 2, 2016 ... of greywater were largely independent of chlorine content. Applying greywater in excess ... The selection of seedling growth and physiological param- eters to be measured in ..... (Minolta SPAD-502, Minolta Camera Co. Ltd.).

  19. Relationship of Economic Growth with Tourism Sector

    Directory of Open Access Journals (Sweden)

    Abdul Holik

    2016-06-01

    Full Text Available This research aims to analyze the impact of  foreign tourists towards the economic growth. It was conducted from 1995 until 2012 on five ASEAN member countrie: Indonesia, Malaysia, Thailand, Philippines, and Singapore. It used the quantitative method; it is one-way random effect of panel regression. The data, which is functioned as dependent variables, were taken from WDI (World Development Indicator of the World Bank for the Gross Domestic Product (GDP. Meanwhile, the data of revenue from the foreign tourist visit (Rec, the number of foreign tourist arrival (Arr, and the exchange rate (Xrate are functioned as the independent variables. Based on the research result, there is evidence that international tourism can increase the economic growth in those countries. The three independent variables have a positive and  significant impact to the dependent variables. Based on the findings, the governments of five ASEAN member countries should be able to maintain the sustainability of tourism sector in order to be stronger and to have global market-orientation. In fact, tourism services can support the  economic growth because the potential of those ASEAN countries cannot be taken lightly.

  20. Relationship of Economic Growth with Tourism Sector

    Directory of Open Access Journals (Sweden)

    Abdul Holik

    2016-06-01

    Full Text Available This research aims to analyze the impact of foreign tourists towards the economic growth. It was conducted from 1995 until 2012 on five ASEAN member countrie: Indonesia, Malaysia, Thailand, Philippines, and Singapore. It used the quantitative method; it is one-way random effect of panel regression. The data, which is functioned as dependent variables, were taken from WDI (World Development Indicator of the World Bank for the Gross Domestic Product (GDP. Meanwhile, the data of revenue from the foreign tourist visit (Rec, the number of foreign tourist arrival (Arr, and the exchange rate (Xrate are functioned as the independent variables. Based on the research result, there is evidence that international tourism can increase the economic growth in those countries. The three independent variables have a positive and significant impact to the dependent variables. Based on the findings, the governments of five ASEAN member countries should be able to maintain the sustainability of tourism sector in order to be stronger and to have global market-orientation. In fact, tourism services can support the economic growth because the potential of those ASEAN countries cannot be taken lightly.

  1. Growth hormone (GH)-independent dimerization of GH receptor by a leucine zipper results in constitutive activation

    DEFF Research Database (Denmark)

    Behncken, S N; Billestrup, Nils; Brown, R

    2000-01-01

    Growth hormone initiates signaling by inducing homodimerization of two GH receptors. Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers of the gro......Growth hormone initiates signaling by inducing homodimerization of two GH receptors. Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers...

  2. Grain-growth law during Stage 1 sintering of materials

    International Nuclear Information System (INIS)

    He Zeming; Ma, J.

    2002-01-01

    This work investigates the grain-growth behaviour of powder compact during Stage 1 sintering (<90{%} theoretical density). It is widely accepted that grain size is an important state variable in the constitutive modelling in material sintering. However, it is noted that all the existing grain-growth laws proposed in the literature do not incorporate the effect of externally applied stress independently. In this work, a grain-growth law with externally applied stress as a variable was proposed. Alumina powders were forge-sintered at different applied stresses to examine the proposed grain-growth relationship. The proposed grain-growth law was then applied to model the grain-growth process on the sinter forging of tool steel. It is shown that the present proposed grain-growth law provides a good description on the experimental results. (author)

  3. Efficacy and mechanism of action of Proellex, an antiprogestin in aromatase overexpressing and Letrozole resistant T47D breast cancer cells.

    Science.gov (United States)

    Gupta, Akash; Mehta, Rajeshwari; Alimirah, Fatouma; Peng, Xinjian; Murillo, Genoveva; Wiehle, Ronald; Mehta, Rajendra G

    2013-01-01

    Aromatase inhibitors (AI) are considered as a first line therapy for ER+PR+ breast cancers. However, many patients acquire resistance to AI. In this study, we determined the response of antiprogestin CDB-4124 (Proellex) on the aromatase overexpressing and Letrozole resistant cell lines and also studies its mechanism of action in inhibition of breast cancer cell proliferation. For these studies we generated aromatase overexpressing T47D (T47Darom) and respective control (T47Dcon) breast cancer cell lines by stable transfection with plasmid containing CYP19A1 gene, or empty vector respectively. Letrozole resistant cell line (T47DaromLR) was generated by incubating T47Darom for 75 weeks in the presence of 10 μM Letrozole. Cell proliferation was determined by MTT or crystal violet assays. Gene expressions were quantified by QRT-PCR whereas proteins were identified by western blot analyses, flow cytometry and immunofluorescence staining. Aromatase activity was determined by estradiol ELISA. The effects of Proellex on the anchorage independent growth were measured by soft agar colony formation. Statistical differences between the various groups were determined by Student's 't' test or ANOVA followed by Bonferroni's post hoc test. Results showed that T47Darom and T47DaromLR cell lines had significantly higher aromatase expression (mRNA; 80-90 fold and protein) and as a result exhibited increased aromatization of testosterone to estradiol as compared to T47Dcon. Both these cell lines showed enhanced growth in the presence of Testosterone (50-60%). In T47DaromLR cells increased PR-B and EGFR expression as compared to T47Dcon cells was observed. Proellex and other known aromatase inhibitors (Letrozole, Anastrozole, and Exemestane) inhibited testosterone induced cell proliferation and anchorage independent growth of T47Darom cells. Cell growth inhibition was significantly greater when cells were treated with Proellex alone or in combination with other AIs as compared to AIs

  4. Recorded earthquake responses from the integrated seismic monitoring network of the Atwood Building, Anchorage, Alaska

    Science.gov (United States)

    Celebi, M.

    2006-01-01

    An integrated seismic monitoring system with a total of 53 channels of accelerometers is now operating in and at the nearby free-field site of the 20-story steel-framed Atwood Building in highly seismic Anchorage, Alaska. The building has a single-story basement and a reinforced concrete foundation without piles. The monitoring system comprises a 32-channel structural array and a 21-channel site array. Accelerometers are deployed on 10 levels of the building to assess translational, torsional, and rocking motions, interstory drift (displacement) between selected pairs of adjacent floors, and average drift between floors. The site array, located approximately a city block from the building, comprises seven triaxial accelerometers, one at the surface and six in boreholes ranging in depths from 15 to 200 feet (???5-60 meters). The arrays have already recorded low-amplitude shaking responses of the building and the site caused by numerous earthquakes at distances ranging from tens to a couple of hundred kilometers. Data from an earthquake that occurred 186 km away traces the propagation of waves from the deepest borehole to the roof of the building in approximately 0.5 seconds. Fundamental structural frequencies [0.58 Hz (NS) and 0.47 Hz (EW)], low damping percentages (2-4%), mode coupling, and beating effects are identified. The fundamental site frequency at approximately 1.5 Hz is close to the second modal frequencies (1.83 Hz NS and 1.43 EW) of the building, which may cause resonance of the building. Additional earthquakes prove repeatability of these characteristics; however, stronger shaking may alter these conclusions. ?? 2006, Earthquake Engineering Research Institute.

  5. Concrete Growth and Fatigue Analysis of Chickamauga Lock Miter Gate Anchorages

    Science.gov (United States)

    2017-09-19

    reaction that occurs between the cement and the aggregate used in the concrete. A gel forms during the chemical reaction, and the gel expands as it...for local highway construction, coal, oil, scrap steel , grain, chemicals for the Olin Chemical Plant, oversized components such as nuclear steam...future predicted structural conditions of the steel A-frames embedded in Monolith 47 (Figure 2), specifically (Figure 3 through Figure 5). Their

  6. Misexpression of AtTX12 encoding a Toll/interleukin-1 receptor domain induces growth defects and expression of defense-related genes partially independently of EDS1 in Arabidopsis.

    Science.gov (United States)

    Song, Sang-Kee

    2016-12-01

    In this study, a tissue-specific GAL4/UAS activation tagging system was used for the characterization of genes which could induce lethality when ubiquitously expressed. A dominant mutant exhibiting stunted growth was isolated and named defective root development 1-D (drd1-D). The T-DNA tag was located within the promoter region of AtTX12, which is predicted to encode a truncated nucleotide-binding leucinerich repeat (NLR) protein, containing a Toll/interleukin-1 receptor (TIR) domain. The transcript levels of AtTX12 and defense-related genes were elevated in drd1-D, and the misexpression of AtTX12 recapitulated the drd1-D phenotypes. In the presence of ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1), a key transducer of signals triggered by TIR-type NLRs, a low-level of AtTX12 misexpression induced strong defective phenotypes including seedling lethality whereas, in the absence of EDS1, a high-level of AtTX12 misexpression induced weak growth defects like dwarfism, suggesting that AtTX12 might function mainly in an EDS1-dependent and partially in an EDS1-independent manner. [BMB Reports 2016; 49(12): 693-698].

  7. Role of DNA lesions and repair in the transformation of human cells

    International Nuclear Information System (INIS)

    Maher, V.M.; McCormick, J.J.

    1987-01-01

    Results of studies on the transformation of diploid human fibroblasts in culture into tumor-forming cells by exposure to chemical carcinogens or radiation indicate that such transformation is multi-stepped process that at least one step, acquisition of anchorage independence, occurs as a mutagenic event. Studies comparing normal-repairing human cells with DNA repair-deficient cells, such as those derived from cancer-prone xeroderma pigmentosum patients, indicate that excision repair in human fibroblasts is essentially an error-free process that the ability to excise potentially cytotoxic, mutagenic, or transforming lesions induced DNA by carcinogens determines their ultimate biological consequences. Cells deficient in excision repair are abnormally sensitive to these agents. Studies with cells treated at various times in the cell cycle show that there is a certain limited amount of time available for DNA repair between the initial exposure and the onset of the cellular event responsible for mutation induction and transformation to anchorage independence. The data suggest that DNA replication on a template containing unexcised lesions (photoproducts, adducts) is the critical event

  8. Recent climatic drying leads to age-independent growth reductions of white spruce stands in western Canada.

    Science.gov (United States)

    Hogg, Edward H; Michaelian, Michael; Hook, Trisha I; Undershultz, Michael E

    2017-12-01

    Since 2001, climatic conditions have been notably drier than normal across large areas of the western Canadian interior, leading to widespread impacts on the forests of this region. This poses a major concern for the future, given climate change projections for continued warming and drying. We conducted tree-ring analysis in 75 pure stands of white spruce (Picea glauca) across Alberta and west-central Saskatchewan to examine the effects of recent climatic drying on the growth of this important boreal tree species. Allometric equations were used to calculate annual growth in aboveground tree biomass (G BM ) from ring width measurements. Results showed an increasing trend in G BM from the 1960s to the 1990s, followed by a sharp decline during the severe drought of 2001-2002. Of the 75 stands, only 18 recovered sufficiently to cause an increase in mean G BM from the predrought decade of 1991-2000 to the subsequent decade of 2001-2010. The remaining 57 stands exhibited a decline in mean G BM between these decades. Climatic drying was a major cause of the growth decline, as shown by the significant stand-level relationship between percentage change in decadal mean G BM and the change in decadal mean values of a climate moisture index from 1991-2000 to 2001-2010. Subsequent analyses of boreal stands sampled across Alberta during 2015 revealed that white spruce growth had declined even further as drought conditions intensified during 2014-2015. Overall, there was a 38% decrease in mean G BM between 1997 and 2015, but surprisingly, the percentage decrease was not significantly different for young, productive stands compared with older, less productive stands. Thus, stand ageing cannot explain the observed decline in white spruce growth during the past quarter century, suggesting that these forests are at risk if the trend towards more frequent, severe drought continues in the region. © 2017 Her Majesty the Queen in Right of Canada Global Change Biology ©2017 John Wiley

  9. Seasonal variations in ectotherm growth rates: Quantifying growth as an intermittent non steady state compensatory process

    Science.gov (United States)

    Guarini, J.-M.; Chauvaud, Laurent; Cloern, J.E.; Clavier, J.; Coston-Guarini, J.; Patry, Y.

    2011-01-01

    Generally, growth rates of living organisms are considered to be at steady state, varying only under environmental forcing factors. For example, these rates may be described as a function of light for plants or organic food resources for animals and these could be regulated (or not) by temperature or other conditions. But, what are the consequences for an individual's growth (and also for the population growth) if growth rate variations are themselves dynamic and not steady state? For organisms presenting phases of dormancy or long periods of stress, this is a crucial question. A dynamic perspective for quantifying short-term growth was explored using the daily growth record of the scallop Pecten maximus (L.). This species is a good biological model for ectotherm growth because the shell records growth striae daily. Independently, a generic mathematical function representing the dynamics of mean daily growth rate (MDGR) was implemented to simulate a diverse set of growth patterns. Once the function was calibrated with the striae patterns, the growth rate dynamics appeared as a forced damped oscillation during the growth period having a basic periodicity during two transitory phases (mean duration 43. days) and appearing at both growth start and growth end. This phase is most likely due to the internal dynamics of energy transfer within the organism rather than to external forcing factors. After growth restart, the transitory regime represents successive phases of over-growth and regulation. This pattern corresponds to a typical representation of compensatory growth, which from an evolutionary perspective can be interpreted as an adaptive strategy to coping with a fluctuating environment. ?? 2011 Elsevier B.V.

  10. Induction of anchorage-independent growth of human embryonic fibroblasts with a deletion in the short arm of chromosome 11 by human papillomavirus type 16 DNA

    International Nuclear Information System (INIS)

    Smits, H.L.; Raadsheer, E.; Rood, I.; Mehendale, S.; Slater, R.M.; van der Noordaa, J.; Ter Schegget, J.

    1988-01-01

    Human embryonic fibroblasts with a large deletion (11p11.11p15.1) in the short arm of one chromosome 11 (del-11 cells) appeared to be susceptible to transformation by early human papillomavirus type 16 (HPV-16) DNA, whereas diploid human embryonic fibroblasts were not. This difference in susceptibility might be explained by the absence of a tumor suppressor gene located within the deleted part on the short arm of chromosome 11. The presence of abundant viral early-gene transcripts in transformed cells suggests that transformation was induced by an elevated level of an HPV-16 early-gene product(s). The low transcriptional activity of HPV-16 in diploid cells may indicate that cellular genes affect viral transcription. Interruption of the HPV-16 E2 early open reading frame is probably required for high-level HPV-16 early-gene expression driven from the homologous enhancer-promoter region

  11. Economic Growth, Institutional Development and Personal Freedom: The Educational Needs of China.

    Science.gov (United States)

    Clarke, Thomas

    1999-01-01

    To sustain growth requires changes in the Chinese economy and society. The Asian financial crisis shows that independent institutions and individual freedoms are necessary to stimulate entrepreneurship and innovation. Conservative social values often promoted by the education and training system could hinder economic growth. (SK)

  12. Historical review of quartz crystal growth

    Science.gov (United States)

    Iwasaki, Fumiko; Iwasaki, Hideo

    2002-04-01

    The history of quartz crystal growth is reviewed from the origin to the industrialization. The developing process of growth techniques is divided into the following three stages: (1) The fundamental work based on the mineralogical genetic view point, which was performed in Italy during the end of the 19th to the beginning of the 20th centuries. (2) The works to attempt the industrial application made in Germany and in England during World War II. (3) The industrialization of quartz growth after World War II. These were initiated in England, in USA and independently in Russia. The highest mass production process was developed in Japan. The historical flow is traced by the interview of several persons based on the original references.

  13. Environmental vs Demographic Stochasticity in Population Growth

    OpenAIRE

    Braumann, C. A.

    2010-01-01

    Compares the effect on population growth of envinonmental stochasticity (random environmental variations described by stochastic differential equations) with demographic stochasticity (random variations in births and deaths described by branching processes and birth-and-death processes), in the density-independent and the density-dependent cases.

  14. Novel co-culture plate enables growth dynamic-based assessment of contact-independent microbial interactions.

    Directory of Open Access Journals (Sweden)

    Thomas J Moutinho

    Full Text Available Interactions between microbes are central to the dynamics of microbial communities. Understanding these interactions is essential for the characterization of communities, yet challenging to accomplish in practice. There are limited available tools for characterizing diffusion-mediated, contact-independent microbial interactions. A practical and widely implemented technique in such characterization involves the simultaneous co-culture of distinct bacterial species and subsequent analysis of relative abundance in the total population. However, distinguishing between species can be logistically challenging. In this paper, we present a low-cost, vertical membrane, co-culture plate to quantify contact-independent interactions between distinct bacterial populations in co-culture via real-time optical density measurements. These measurements can be used to facilitate the analysis of the interaction between microbes that are physically separated by a semipermeable membrane yet able to exchange diffusible molecules. We show that diffusion across the membrane occurs at a sufficient rate to enable effective interaction between physically separate cultures. Two bacterial species commonly found in the cystic fibrotic lung, Pseudomonas aeruginosa and Burkholderia cenocepacia, were co-cultured to demonstrate how this plate may be implemented to study microbial interactions. We have demonstrated that this novel co-culture device is able to reliably generate real-time measurements of optical density data that can be used to characterize interactions between microbial species.

  15. Mitochondrial ribosomal protein S18-2 evokes chromosomal instability and transforms primary rat skin fibroblasts

    KAUST Repository

    Kashuba, Elena

    2015-05-12

    We have shown earlier that overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2) led to immortalization of primary rat embryonic fibroblasts. The derived cells expressed the embryonic stem cell markers, and cellular pathways that control cell proliferation, oxidative phosphorylation, cellular respiration, and other redox reactions were activated in the immortalized cells. Here we report that, upon overexpression of S18-2 protein, primary rat skin fibroblasts underwent cell transformation. Cells passed more than 300 population doublings, and two out of three tested clones gave rise to tumors in experimental animals. Transformed cells showed anchorage-independent growth and loss of contact inhibition; they expressed epithelial markers, such as E-cadherin and β-catenin. Transformed cells showed increased telomerase activity, disturbance of the cell cycle, and chromosomal instability. Taken together, our data suggest that S18-2 is a newly identified oncoprotein that may be involved in cancerogenesis.

  16. Endothelial induced EMT in breast epithelial cells with stem cell properties

    DEFF Research Database (Denmark)

    Sigurdsson, Valgardur; Hilmarsdottir, Bylgja; Sigmundsdottir, Hekla

    2011-01-01

    endothelial cells might play a role in EMT. Using a 3D culture model we demonstrate that endothelial cells are potent inducers of EMT in D492 an immortalized breast epithelial cell line with stem cell properties. Endothelial induced mesenchymal-like cells (D492M) derived from D492, show reduced expression...... of keratins, a switch from E-Cadherin (E-Cad) to N-Cadherin (N-Cad) and enhanced migration. Acquisition of cancer stem cell associated characteristics like increased CD44(high)/CD24(low) ratio, resistance to apoptosis and anchorage independent growth was also seen in D492M cells. Endothelial induced EMT in D......492 was partially blocked by inhibition of HGF signaling. Basal-like breast cancer, a vascular rich cancer with stem cell properties and adverse prognosis has been linked with EMT. We immunostained several basal-like breast cancer samples for endothelial and EMT markers. Cancer cells close...

  17. MCF-10A-NeoST: A New Cell System for Studying Cell-ECM and Cell-Cell Interactions in Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zantek, Nicole Dodge; Walker-Daniels, Jennifer; Stewart, Jane; Hansen, Rhonda K.; Robinson, Daniel; Miao, Hui; Wang, Bingcheng; Kung, Hsing-Jien; Bissell, Mina J.; Kinch, Michael S.

    2001-08-22

    There is a continuing need for genetically matched cell systems to model cellular behaviors that are frequently observed in aggressive breast cancers. We report here the isolation and initial characterization of a spontaneously arising variant of MCF-10A cells, NeoST, which provides a new model to study cell adhesion and signal transduction in breast cancer. NeoST cells recapitulate important biological and biochemical features of metastatic breast cancer, including anchorage-independent growth, invasiveness in threedimensional reconstituted membranes, loss of E-cadherin expression, and increased tyrosine kinase activity. A comprehensive analysis of tyrosine kinase expression revealed overexpression or functional activation of the Axl, FAK, and EphA2 tyrosine kinases in transformed MCF-10A cells. MCF-10A and these new derivatives provide a genetically matched model to study defects in cell adhesion and signaling that are relevant to cellular behaviors that often typify aggressive breast cancer cells.

  18. Transformation and radiosensitivity of human diploid skin fibroblasts transfected with activated RAS oncogene and SV40 T-antigen

    Energy Technology Data Exchange (ETDEWEB)

    Su, L.-N.; Little, J.B. (Harvard School of Public Health, Boston, MA (United States))

    1992-08-01

    Three normal human diploid cell strains were transfected with an activated Ha-ras oncogene (EJ ras) or SV40 T-antigen. Multiple clones were examined for morphological alterations, growth requirements, ability to grow under anchorage independent conditions, immortality and tumorigenicity in nude mice. Clones expressing SV40 T-antigen alone or in combination with ras protein p21 were significantly radioresistant as compared with their parent cells or clones transfected with the neo gene only. This radioresistant phenotype persisted in post-crisis, immortalized cell lines. These data suggest that expression of the SV40 T-antigen but not activated Ha-ras plays an important role in the radiosensitivity of human diploid cells. The radioresistant phenotype in SV40 T transfected cells was not related to the enhanced level of genetic instability seen in pre-crisis and newly immortalized cells, nor to the process of immortalization itself. (author).

  19. Transformation and radiosensitivity of human diploid skin fibroblasts transfected with activated RAS oncogene and SV40 T-antigen

    International Nuclear Information System (INIS)

    Su, L.-N.; Little, J.B.

    1992-01-01

    Three normal human diploid cell strains were transfected with an activated Ha-ras oncogene (EJ ras) or SV40 T-antigen. Multiple clones were examined for morphological alterations, growth requirements, ability to grow under anchorage independent conditions, immortality and tumorigenicity in nude mice. Clones expressing SV40 T-antigen alone or in combination with ras protein p21 were significantly radioresistant as compared with their parent cells or clones transfected with the neo gene only. This radioresistant phenotype persisted in post-crisis, immortalized cell lines. These data suggest that expression of the SV40 T-antigen but not activated Ha-ras plays an important role in the radiosensitivity of human diploid cells. The radioresistant phenotype in SV40 T transfected cells was not related to the enhanced level of genetic instability seen in pre-crisis and newly immortalized cells, nor to the process of immortalization itself. (author)

  20. Effects of X-rays on seed setting and pollen tube growth in self-incompatible petunia

    International Nuclear Information System (INIS)

    Gilissen, L.J.W.

    1978-01-01

    The high sensitivity of seed setting and the relative insensitivity of pollen tube growth in the style to X-irradiation of pollen of Petunia hybrida L. indicated that pollen tube growth is independent of activities of the pollen genome. The S-specificity of the pollen grain in relation to incompatibility must, therefore, have built up during maturation of the pollen grain. X-irradiation of styles caused changes in some enzymes essential for basic metabolism, without affecting the pattern of compatible or incompatible pollen tube growth. Compatible and incompatible pollen tube growth in the style appeared to be independent of the metabolic state of the stylar cells and their simultaneous gene-activity. It is suggested that the S-specificity of the style, which is responsible for pollen tube growth regulation, is expressed at a very young stage of flower development. (Auth.)

  1. The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Spindler, Karen-Lise Garm; Andersen, Rikke Fredslund

    2010-01-01

    Abstract: New prognostic markers in patients with colorectal cancer (CRC) are a prerequisite for individualized treatment. Prognostic importance of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGF-A) gene has been proposed. The objective of the present study...... using the PHASE program. The prognostic influence was evaluated using Kaplan-Meir plots and log rank tests. Cox regression method was used to analyze the independent prognostic importance of different markers. All three SNPs were significantly related to survival. A haplotype combination, responsible...... findings in a second and independent cohort. Haplotype combinations call for further investigation. Keywords: colorectal neoplasm; single nucleotide polymorphisms; haplotypes; vascular endothelial growth factor A; survival...

  2. In utero glucocorticoid (GLC) exposure reduces fetal skeletal muscle growth in rats

    Science.gov (United States)

    Maternal undernutrition and stress expose the fetus to above normal levels of GLC and predispose to intrauterine growth restriction. The aim of this study was to determine if fetal GLC exposure impairs skeletal muscle growth independently of maternal undernutrition. Three groups (n=7/group) of timed...

  3. Co-Targeting Prostate Cancer Epithelium and Bone Stroma by Human Osteonectin-Promoter-Mediated Suicide Gene Therapy Effectively Inhibits Androgen-Independent Prostate Cancer Growth.

    Directory of Open Access Journals (Sweden)

    Shian-Ying Sung

    Full Text Available Stromal-epithelial interaction has been shown to promote local tumor growth and distant metastasis. We sought to create a promising gene therapy approach that co-targets cancer and its supporting stromal cells for combating castration-resistant prostate tumors. Herein, we demonstrated that human osteonectin is overexpressed in the prostate cancer epithelium and tumor stroma in comparison with their normal counterpart. We designed a novel human osteonectin promoter (hON-522E containing positive transcriptional regulatory elements identified in both the promoter and exon 1 region of the human osteonectin gene. In vitro reporter assays revealed that the hON-522E promoter is highly active in androgen receptor negative and metastatic prostate cancer and bone stromal cells compared to androgen receptor-positive prostate cancer cells. Moreover, in vivo prostate-tumor-promoting activity of the hON-522E promoter was confirmed by intravenous administration of an adenoviral vector containing the hON-522E promoter-driven luciferase gene (Ad-522E-Luc into mice bearing orthotopic human prostate tumor xenografts. In addition, an adenoviral vector with the hON-522E-promoter-driven herpes simplex virus thymidine kinase gene (Ad-522E-TK was highly effective against the growth of androgen-independent human prostate cancer PC3M and bone stromal cell line in vitro and in pre-established PC3M tumors in vivo upon addition of the prodrug ganciclovir. Because of the heterogeneity of human prostate tumors, hON-522E promoter-mediated gene therapy has the potential for the treatment of hormone refractory and bone metastatic prostate cancers.

  4. Advection-diffusion model for normal grain growth and the stagnation of normal grain growth in thin films

    International Nuclear Information System (INIS)

    Lou, C.

    2002-01-01

    An advection-diffusion model has been set up to describe normal grain growth. In this model grains are divided into different groups according to their topological classes (number of sides of a grain). Topological transformations are modelled by advective and diffusive flows governed by advective and diffusive coefficients respectively, which are assumed to be proportional to topological classes. The ordinary differential equations governing self-similar time-independent grain size distribution can be derived analytically from continuity equations. It is proved that the time-independent distributions obtained by solving the ordinary differential equations have the same form as the time-dependent distributions obtained by solving the continuity equations. The advection-diffusion model is extended to describe the stagnation of normal grain growth in thin films. Grain boundary grooving prevents grain boundaries from moving, and the correlation between neighbouring grains accelerates the stagnation of normal grain growth. After introducing grain boundary grooving and the correlation between neighbouring grains into the model, the grain size distribution is close to a lognormal distribution, which is usually found in experiments. A vertex computer simulation of normal grain growth has also been carried out to make a cross comparison with the advection-diffusion model. The result from the simulation did not verify the assumption that the advective and diffusive coefficients are proportional to topological classes. Instead, we have observed that topological transformations usually occur on certain topological classes. This suggests that the advection-diffusion model can be improved by making a more realistic assumption on topological transformations. (author)

  5. Growth rate in the dynamical dark energy models

    International Nuclear Information System (INIS)

    Avsajanishvili, Olga; Arkhipova, Natalia A.; Samushia, Lado; Kahniashvili, Tina

    2014-01-01

    Dark energy models with a slowly rolling cosmological scalar field provide a popular alternative to the standard, time-independent cosmological constant model. We study the simultaneous evolution of background expansion and growth in the scalar field model with the Ratra-Peebles self-interaction potential. We use recent measurements of the linear growth rate and the baryon acoustic oscillation peak positions to constrain the model parameter α that describes the steepness of the scalar field potential. (orig.)

  6. Growth rate in the dynamical dark energy models.

    Science.gov (United States)

    Avsajanishvili, Olga; Arkhipova, Natalia A; Samushia, Lado; Kahniashvili, Tina

    Dark energy models with a slowly rolling cosmological scalar field provide a popular alternative to the standard, time-independent cosmological constant model. We study the simultaneous evolution of background expansion and growth in the scalar field model with the Ratra-Peebles self-interaction potential. We use recent measurements of the linear growth rate and the baryon acoustic oscillation peak positions to constrain the model parameter [Formula: see text] that describes the steepness of the scalar field potential.

  7. The Adder Phenomenon Emerges from Independent Control of Pre- and Post-Start Phases of the Budding Yeast Cell Cycle.

    Science.gov (United States)

    Chandler-Brown, Devon; Schmoller, Kurt M; Winetraub, Yonatan; Skotheim, Jan M

    2017-09-25

    Although it has long been clear that cells actively regulate their size, the molecular mechanisms underlying this regulation have remained poorly understood. In budding yeast, cell size primarily modulates the duration of the cell-division cycle by controlling the G1/S transition known as Start. We have recently shown that the rate of progression through Start increases with cell size, because cell growth dilutes the cell-cycle inhibitor Whi5 in G1. Recent phenomenological studies in yeast and bacteria have shown that these cells add an approximately constant volume during each complete cell cycle, independent of their size at birth. These results seem to be in conflict, as the phenomenological studies suggest that cells measure the amount they grow, rather than their size, and that size control acts over the whole cell cycle, rather than specifically in G1. Here, we propose an integrated model that unifies the adder phenomenology with the molecular mechanism of G1/S cell-size control. We use single-cell microscopy to parameterize a full cell-cycle model based on independent control of pre- and post-Start cell-cycle periods. We find that our model predicts the size-independent amount of cell growth during the full cell cycle. This suggests that the adder phenomenon is an emergent property of the independent regulation of pre- and post-Start cell-cycle periods rather than the consequence of an underlying molecular mechanism measuring a fixed amount of growth. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Independence and Product Systems

    OpenAIRE

    Skeide, Michael

    2003-01-01

    Starting from elementary considerations about independence and Markov processes in classical probability we arrive at the new concept of conditional monotone independence (or operator-valued monotone independence). With the help of product systems of Hilbert modules we show that monotone conditional independence arises naturally in dilation theory.

  9. Finite element simulation for creep crack growth

    International Nuclear Information System (INIS)

    Miyazaki, Noriyuki; Sasaki, Toru; Nakagaki, Michihiko; Brust, F.W.

    1992-01-01

    A finite element method was applied to a generation phase simulation of creep crack growth. Experimental data on creep crack growth in a 1Cr-1Mo-1/4V steel compact tension specimen were numerically simulated using a node-release technique and the variations of various fracture mechanics parameters such as CTOA, J, C * and T * during creep crack growth were calculated. The path-dependencies of the integral parameters J, C * and T * were also obtained to examine whether or not they could characterize the stress field near the tip of a crack propagating under creep condition. The following conclusions were obtained from the present analysis. (1) The J integral shows strong path-dependency during creep crack growth, so that it is does not characterize creep crack growth. (2) The C * integral shows path-dependency to some extent during creep crack growth even in the case of Norton type steady state creep law. Strictly speaking, we cannot use it as a fracture mechanics parameter characterizing creep crack growth. It is, however, useful from the practical viewpoint because it correlates well the rate of creep crack growth. (3) The T * integral shows good path-independency during creep crack growth. Therefore, it is a candidate for a fracture mechanics parameter characterizing creep crack growth. (author)

  10. Residues in the alternative reading frame tumor suppressor that influence its stability and p53-independent activities

    International Nuclear Information System (INIS)

    Tommaso, Anne di; Hagen, Jussara; Tompkins, Van; Muniz, Viviane; Dudakovic, Amel; Kitzis, Alain; Ladeveze, Veronique; Quelle, Dawn E.

    2009-01-01

    The Alternative Reading Frame (ARF) protein suppresses tumorigenesis through p53-dependent and p53-independent pathways. Most of ARF's anti-proliferative activity is conferred by sequences in its first exon. Previous work showed specific amino acid changes occurred in that region during primate evolution, so we programmed those changes into human p14ARF to assay their functional impact. Two human p14ARF residues (Ala 14 and Thr 31 ) were found to destabilize the protein while two others (Val 24 and Ala 41 ) promoted more efficient p53 stabilization and activation. Despite those effects, all modified p14ARF forms displayed robust p53-dependent anti-proliferative activity demonstrating there are no significant biological differences in p53-mediated growth suppression associated with simian versus human p14ARF residues. In contrast, p53-independent p14ARF function was considerably altered by several residue changes. Val 24 was required for p53-independent growth suppression whereas multiple residues (Val 24 , Thr 31 , Ala 41 and His 60 ) enabled p14ARF to block or reverse the inherent chromosomal instability of p53-null MEFs. Together, these data pinpoint specific residues outside of established p14ARF functional domains that influence its expression and signaling activities. Most intriguingly, this work reveals a novel and direct role for p14ARF in the p53-independent maintenance of genomic stability.

  11. Disruption of NBS1 gene leads to early embryonic lethality in homozygous null mice and induces specific cancer in heterozygous mice

    Energy Technology Data Exchange (ETDEWEB)

    Kurimasa, Akihiro; Burma, Sandeep; Henrie, Melinda; Ouyang, Honghai; Osaki, Mitsuhiko; Ito, Hisao; Nagasawa, Hatsumi; Little, John B.; Oshimura, Mitsuo; Li, Gloria C.; Chen, David J.

    2002-04-15

    Nijmegen breakage syndrome (NBS) is a rare autosomal recessive chromosome instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition, with cellular features similar to that of ataxia telangiectasia (AT). NBS results from mutations in the mammalian gene Nbs1 that codes for a 95-kDa protein called nibrin, NBS1, or p95. To establish an animal model for NBS, we attempted to generate NBS1 knockout mice. However, NBS1 gene knockouts were lethal at an early embryonic stage. NBS1 homozygous(-/-) blastocyst cells cultured in vitro showed retarded growth and subsequently underwent growth arrest within 5 days of culture. Apoptosis, assayed by TUNEL staining, was observed in NBSI homozygous(-/-) blastocyst cells cultured for four days. NBSI heterozygous(+/-) mice were normal, and exhibited no specific phenotype for at least one year. However, fibroblast cells from NBSI heterozygous(+/-) mice displayed an enhanced frequency of spontaneous transformation to anchorage-independent growth as compared to NBS1 wild-type(+/+) cells. Furthermore, heterozygous(+/-) mice exhibited a high incidence of hepatocellular carcinoma after one year compared to wild-type mice, even though no significant differences in the incidence of other tumors such as lung adenocarcinoma and lymphoma were observed. Taken together, these results strongly suggest that NBS1 heterozygosity and reduced NBSI expression induces formation of specific tumors in mice.

  12. Contribution of polycomb homologues Bmi-1 and Mel-18 to medulloblastoma pathogenesis.

    Science.gov (United States)

    Wiederschain, Dmitri; Chen, Lin; Johnson, Brett; Bettano, Kimberly; Jackson, Dowdy; Taraszka, John; Wang, Y Karen; Jones, Michael D; Morrissey, Michael; Deeds, James; Mosher, Rebecca; Fordjour, Paul; Lengauer, Christoph; Benson, John D

    2007-07-01

    Bmi-1 and Mel-18 are structural homologues that belong to the Polycomb group of transcriptional regulators and are believed to stably maintain repression of gene expression by altering the state of chromatin at specific promoters. While a number of clinical and experimental observations have implicated Bmi-1 in human tumorigenesis, the role of Mel-18 in cancer cell growth has not been investigated. We report here that short hairpin RNA-mediated knockdown of either Bmi-1 or Mel-18 in human medulloblastoma DAOY cells results in the inhibition of proliferation, loss of clonogenic survival, anchorage-independent growth, and suppression of tumor formation in nude mice. Furthermore, overexpression of both Bmi-1 and Mel-18 significantly increases the clonogenic survival of Rat1 fibroblasts. In contrast, stable downregulation of Bmi-1 or Mel-18 alone does not affect the growth of normal human WI38 fibroblasts. Proteomics-based characterization of Bmi-1 and Mel-18 protein complexes isolated from cancer cells revealed substantial similarities in their respective compositions. Finally, gene expression analysis identified a number of cancer-relevant pathways that may be controlled by Bmi-1 and Mel-18 and also showed that these Polycomb proteins regulate a set of common gene targets. Taken together, these results suggest that Bmi-1 and Mel-18 may have overlapping functions in cancer cell growth.

  13. Target Therapy Using a Small Molecule Inhibitor against Angiogenic Receptors in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Peter Büchler

    2007-02-01

    Full Text Available PURPOSE: PD173074, a small molecule inhibitor of VEGF-RII and FGF-RI, targets neoangiogenesis and mitogenesis. This study aimed to analyze a singlecompound-driven inhibition of FGF and VEGF receptors in pancreatic cancer. EXPERIMENTAL DESIGN: RT-PCR and Western blots were performed to quantify protein expression and phosphorylation. Anchorage dependent and independent growth assays were used to study cell growth. With flow cytometry, cell cycle analysis and apoptosis were studied. In vivo HPAF-II and MIA PaCa-2 cells were xenografted. Animals were treated daily for 10 weeks. Immunohistochemistry was used to quantify microvessel density and apoptosis. RESULTS: Highest levels of FGF-RI were detectable in MIA PaCa-2 cells, lowest in HPAF-II cells. PD173074 inhibited cell growth most prominently in cells expressing high levels of FGF-RI. Cell cycle progression was inhibited by blocking transition in the G0/G1 phase, and consequently, apoptosis was increased. In vivo significant inhibition of orthotopic tumor growth was achieved by a combination effect of inhibition of mitogenesis, induction of apoptosis, and reduction of angiogenesis in PD173074-treated animals. CONCLUSIONS: These data highlight VEGF-RII and FGF-RI as therapeutic targets and suggest a potential role for the combined use of tyrosine kinase inhibitors in the management of inoperable pancreatic cancer patients.

  14. Organizing Independent Student Work

    Directory of Open Access Journals (Sweden)

    Zhadyra T. Zhumasheva

    2015-03-01

    Full Text Available This article addresses issues in organizing independent student work. The author defines the term “independence”, discusses the concepts of independent learner work and independent learner work under the guidance of an instructor, proposes a classification of assignments to be done independently, and provides methodological recommendations as to the organization of independent student work. The article discusses the need for turning the student from a passive consumer of knowledge into an active creator of it, capable of formulating a problem, analyzing the ways of solving it, coming up with an optimum outcome, and proving its correctness. The preparation of highly qualified human resources is the primary condition for boosting Kazakhstan’s competitiveness. Independent student work is a means of fostering the professional competence of future specialists. The primary form of self-education is independent work.

  15. Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

    Science.gov (United States)

    Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

  16. Comparison of short-term effects between face mask and skeletal anchorage therapy with intermaxillary elastics in patients with maxillary retrognathia.

    Science.gov (United States)

    Ağlarcı, Cahide; Esenlik, Elçin; Fındık, Yavuz

    2016-06-01

    The aim of this study was to compare the short-term dental and skeletal effects of a face mask (FM) with those of skeletal anchorage (SA) therapy with intermaxillary elastics in prepubertal patients with skeletal Class III malocclusion. Fifty patients with skeletal Class III malocclusion and maxillary deficiency were divided into two groups. In the FM group, an FM was applied by a bite plate with a force of 400g for each side. In the SA group, mini-plates were placed between mandibular lateral incisors and canines, and mini-implants were inserted between maxillary second premolars and first molars. A bite plate was inserted into the upper arch, and Class III elastics were applied with a force of 200g between each mini-plate and mini-implant. Mean treatment durations were 0.52±0.09 years for FM and 0.76±0.09 years for SA. After the treatment, statistically significant increases in SNA°, ANB°, A-y, 1-NA, SnGoGn°, Co-A, Co-Gn, and A-Nperp, and reductions in SNB° and FH┴N-Pg were observed in both groups, and these changes were similar in both groups. In the FM group, 1-NB decreased significantly, and in the SA group, it increased significantly (P journals.permissions@oup.com.

  17. Which Dimensions of Culture Matter for Long-Run Growth?

    OpenAIRE

    Yuriy Gorodnichenko; Gerard Roland

    2011-01-01

    We present empirical evidence that, among a variety of cultural dimensions, the individualism-collectivism dimension, based on Hofstede's (2001) data, is the most important and robustly significant effect of culture on long run growth. Other dimensions that have a significant effect, albeit less robust, are generally strongly correlated with individualism and convey similar information. We found no significant or robust effect on growth from cultural dimensions that are independent from the i...

  18. SP600125 Induces Src and Type I IGF Receptor Phosphorylation Independent of JNK

    Directory of Open Access Journals (Sweden)

    Qingbin Kong

    2014-09-01

    Full Text Available c-Jun N-terminal kinases (JNK are members of the mitogen-activated protein kinase (MAPK family that have important roles in signal transduction. The small molecule SP600125 is widely used in biochemical studies as a JNK inhibitor. However, recent studies indicate that SP600125 may also act independent of JNK. Here, we report that SP600125 can induce Src, type I insulin-like growth factor receptor (IGF-IR, Akt and Erk1/2 phosphorylation. Notably, these effects are independent of its inhibition of JNK. Inhibition of Src abrogates the stimulation of IGF-IR, Akt and Erk1/2 phosphorylation. IGF-IR knockdown blunts the induction of both Akt and Erk1/2 phosphorylation by SP600125. Moreover, combination of SP600125 and the Src inhibitor saracatinib synergistically inhibits cell proliferation. We conclude that SP600125 can activate Src-IGF-IR-Akt/Erk1/2 signaling pathways independent of JNK.

  19. The influence of social anchorage on the gender difference in the use of mental health services.

    Science.gov (United States)

    Drapeau, Aline; Boyer, Richard; Lesage, Alain

    2009-07-01

    Overall, women are more likely than men to seek professional care when they face light or moderate mental health problems. This difference is usually attributed to culture-related factors, but neither women nor men form a homogeneous cultural group. The help-seeking behavior may reflect not only the cultural values and expectations associated with a specific gender but also those associated with specific social roles endorsed by women and men. In addition, the influence of these culture-related factors on the help-seeking behavior is constrained by barriers to care, which apply similarly to women and men. In consequence, the gender difference in the use of mental health services should vary across social roles and types of service. This hypothesis was tested on data from the cycle 1.2 of the Canadian Community Health Survey. Logistic regression analyses show that, although women are more likely than men to use mental health services, this gender difference is larger for general services than for psychiatric and psychological services whose access in Canada is constrained, respectively, by systemic and financial barriers to care. They also suggest that holding the role of worker tends to foster the use of psychological services in women, especially in married women, and to a lesser degree in men, whereas it tends to hinder the use of general and psychiatric services in men but to exert no or less influence in women. Thus, professional anchorage seems to be an important source of the societal norms that influence the decision of women and men to seek or not to seek medical care for mental health problems.

  20. On the k-independence required by linear probing and minwise independence

    DEFF Research Database (Denmark)

    Pǎtraşcu, Mihai; Thorup, Mikkel

    2016-01-01

    We show that linear probing requires 5-independent hash functions for expected constant-time performance, matching an upper bound of Pagh et al. [2009]. More precisely, we construct a random 4-independent hash function yielding expected logarithmic search time for certain keys. For (1 + ε......)-approximate minwise independence, we show that Ω(lg1 ε)-independent hash functions are required, matching an upper bound of Indyk [2001]. We also show that the very fast 2-independent multiply-shift scheme of Dietzfelbinger [1996] fails badly in both applications....

  1. Modelling the growth of a methanotrophic biofilm

    DEFF Research Database (Denmark)

    Arcangeli, J.-P.; Arvin, E.

    1999-01-01

    This article discusses the growth of methanotrophic biofilms. Several independent biofilm growths scenarios involving different inocula were examined. Biofilm growth, substrate removal and product formation were monitored throughout the experiments. Based on the oxygen consumption it was concluded...... that heterotrophs and nitrifiers co-existed with methanotrophs in the biofilm. Heterotrophic biomass grew on soluble polymers formed by the hydrolysis of dead biomass entrapped in the biofilm. Nitrifier populations developed because of the presence of ammonia in the mineral medium. Based on these experimental...... was performed on this model. It indicated that the most influential parameters were those related to the biofilm (i.e. density; solid-volume fraction; thickness). This suggests that in order to improve the model, further research regarding the biofilm structure and composition is needed....

  2. Impact of radiation history, gender and age on bone quality in sites for orthodontic skeletal anchorage device placement.

    Science.gov (United States)

    Konermann, A; Appel, T; Wenghoefer, M; Sirokay, S; Dirk, C; Jäger, A; Götz, W

    2015-05-01

    Stability of orthodontic miniscrew implants is prerequisite to their success and durability in orthodontic treatment. As investigations revealed a positive correlation of miniscrew stability to periimplant bone quality, it has been the aim of this study to analyze the bone structure of resection preparations of human mandibles histologically by investigating the samples according to age, gender and exposure to radiotherapy. Inflammation- and tumor-free alveolar bone sections from human mandibles (n = 31) with previously diagnosed carcinoma, chronic osteomyelitis or cysts were analyzed histomorphologically and histomorphometrically as to the dimension of trabeculae in cancellous areas. Group A investigated the impact of a history of radiation therapy, group B of gender and group C contrasted biopsies from individuals aging under 60 or over 60 years. Statistics were performed using the Kruskal-Wallis-test. Radiation, gender and age did not significantly influence bone density. The mean bone density averaged 40.7 ± 15.0% of spongiosa for the total collective with a median age of 58.4 years ± 14.7 years. Our findings provide new information on bone quality, thus contributing to a more precise evaluation of the parameters affecting and those not affecting miniscrew implant stability. On the basis of these results, the formulation of clinical guidelines for risk assessment of therapeutic approaches in patients prior to insertion of orthodontic skeletal anchorage devices seems to be conceivable. Copyright © 2014 Elsevier GmbH. All rights reserved.

  3. Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin

    Science.gov (United States)

    Winbanks, Catherine E.; Weeks, Kate L.; Thomson, Rachel E.; Sepulveda, Patricio V.; Beyer, Claudia; Qian, Hongwei; Chen, Justin L.; Allen, James M.; Lancaster, Graeme I.; Febbraio, Mark A.; Harrison, Craig A.; McMullen, Julie R.; Chamberlain, Jeffrey S.

    2012-01-01

    Follistatin is essential for skeletal muscle development and growth, but the intracellular signaling networks that regulate follistatin-mediated effects are not well defined. We show here that the administration of an adeno-associated viral vector expressing follistatin-288aa (rAAV6:Fst-288) markedly increased muscle mass and force-producing capacity concomitant with increased protein synthesis and mammalian target of rapamycin (mTOR) activation. These effects were attenuated by inhibition of mTOR or deletion of S6K1/2. Furthermore, we identify Smad3 as the critical intracellular link that mediates the effects of follistatin on mTOR signaling. Expression of constitutively active Smad3 not only markedly prevented skeletal muscle growth induced by follistatin but also potently suppressed follistatin-induced Akt/mTOR/S6K signaling. Importantly, the regulation of Smad3- and mTOR-dependent events by follistatin occurred independently of overexpression or knockout of myostatin, a key repressor of muscle development that can regulate Smad3 and mTOR signaling and that is itself inhibited by follistatin. These findings identify a critical role of Smad3/Akt/mTOR/S6K/S6RP signaling in follistatin-mediated muscle growth that operates independently of myostatin-driven mechanisms. PMID:22711699

  4. Phosphoribosyl diphosphate synthetase-independent NAD de novo synthesis in Escherichia coli: a new phenotype of phosphate regulon mutants

    DEFF Research Database (Denmark)

    Hove-Jensen, Bjarne

    1996-01-01

    Phosphoribosyl diphosphate-lacking (Δprs) mutant strains of Escherichia coli require NAD, guanosine, uridine, histidine, and tryptophan for growth. NAD is required by phosphoribosyl diphosphate-lacking mutants because of lack of one of the substrates for the quinolinate phosphoribosyltransferase...... reaction, an enzyme of the NAD de novo pathway. Several NAD-independent mutants of a host from which prs had been deleted were isolated; all of them were shown to have lesions in the pstSCAB-phoU operon, in which mutations lead to derepression of the Pho regulon. In addition NAD-independent growth...... was dependent on a functional quinolinate phosphoribosyltransferase. The prs suppressor mutations led to the synthesis of a new phosphoryl compound that may act as a precursor for a new NAD biosynthetic pathway. This compound may be synthesized by the product of an unknown phosphate starvation-inducible gene...

  5. Cross-talk between Integrin α6β4 and Insulin-like Growth Factor-1 Receptor (IGF1R) through Direct α6β4 Binding to IGF1 and Subsequent α6β4-IGF1-IGF1R Ternary Complex Formation in Anchorage-independent Conditions*

    OpenAIRE

    Fujita, Masaaki; Ieguchi, Katsuaki; Davari, Parastoo; Yamaji, Satoshi; Taniguchi, Yukimasa; Sekiguchi, Kiyotoshi; Takada, Yoko K.; Takada, Yoshikazu

    2012-01-01

    Background: Integrin αvβ3-extracellular matrix interaction and/or αvβ3 binding to insulin-like growth factor-1 (IGF1; and integrin-IGF1-IGF1 receptor ternary complex formation) is critical for IGF signaling.

  6. LKB1 promotes metabolic flexibility in response to energy stress.

    Science.gov (United States)

    Parker, Seth J; Svensson, Robert U; Divakaruni, Ajit S; Lefebvre, Austin E; Murphy, Anne N; Shaw, Reuben J; Metallo, Christian M

    2017-09-01

    The Liver Kinase B1 (LKB1) tumor suppressor acts as a metabolic energy sensor to regulate AMP-activated protein kinase (AMPK) signaling and is commonly mutated in various cancers, including non-small cell lung cancer (NSCLC). Tumor cells deficient in LKB1 may be uniquely sensitized to metabolic stresses, which may offer a therapeutic window in oncology. To address this question we have explored how functional LKB1 impacts the metabolism of NSCLC cells using 13 C metabolic flux analysis. Isogenic NSCLC cells expressing functional LKB1 exhibited higher flux through oxidative mitochondrial pathways compared to those deficient in LKB1. Re-expression of LKB1 also increased the capacity of cells to oxidize major mitochondrial substrates, including pyruvate, fatty acids, and glutamine. Furthermore, LKB1 expression promoted an adaptive response to energy stress induced by anchorage-independent growth. Finally, this diminished adaptability sensitized LKB1-deficient cells to combinatorial inhibition of mitochondrial complex I and glutaminase. Together, our data implicate LKB1 as a major regulator of adaptive metabolic reprogramming and suggest synergistic pharmacological strategies for mitigating LKB1-deficient NSCLC tumor growth. Copyright © 2016. Published by Elsevier Inc.

  7. Expression of connective tissue growth factor in tumor tissues is an independent predictor of poor prognosis in patients with gastric cancer.

    Science.gov (United States)

    Liu, Lu-Ying; Han, Yan-Chun; Wu, Shu-Hua; Lv, Zeng-Hua

    2008-04-07

    To examine the expression of connective tissue growth factor (CTGF), also known as CCN2, in gastric carcinoma (GC), and the correlation between the expression of CTGF, clinicopathologic features and clinical outcomes of patients with GC. One hundred and twenty-two GC patients were included in the present study. All patients were followed up for at least 5 years. Proteins of CTGF were detected using the Powervision two-step immunostaining method. Of the specimens from 122 GC patients analyzed for CTGF expression, 58 (58/122, 47.5%) had a high CTGF expression in cytoplasm of gastric carcinoma cells and 64 (64/122, 52.5%) had a low CTGF expression. Patients with a high CTGF expression showed a higher incidence of lymph node metastasis than those with a low CTGF expression (P = 0.032). Patients with a high CTGF expression had significantly lower 5-year survival rate than those with a low CTGF expression (27.6% vs 46.9%, P = 0.0178), especially those staging I + II + III (35.7% vs 65.2%, P = 0.0027). GC patients with an elevated CTGF expression have more lymph node metastases and a shorter survival time. CTGF seems to be an independent prognostic factor for the successful differentiation of high-risk GC patients staging I + II + III. Over-expression of CTGF in human GC cells results in an increased aggressive ability.

  8. Distributed Large Independent Sets in One Round On Bounded-independence Graphs

    OpenAIRE

    Halldorsson , Magnus M.; Konrad , Christian

    2015-01-01

    International audience; We present a randomized one-round, single-bit messages, distributed algorithm for the maximum independent set problem in polynomially bounded-independence graphs with poly-logarithmic approximation factor. Bounded-independence graphs capture various models of wireless networks such as the unit disc graphs model and the quasi unit disc graphs model. For instance, on unit disc graphs, our achieved approximation ratio is O((log(n)/log(log(n)))^2).A starting point of our w...

  9. The hepatic transcriptome of young suckling and aging intrauterine growth restricted male rats.

    Science.gov (United States)

    Freije, William A; Thamotharan, Shanthie; Lee, Regina; Shin, Bo-Chul; Devaskar, Sherin U

    2015-04-01

    Intrauterine growth restriction leads to the development of adult onset obesity/metabolic syndrome, diabetes mellitus, cardiovascular disease, hypertension, stroke, dyslipidemia, and non-alcoholic fatty liver disease/steatohepatitis. Continued postnatal growth restriction has been shown to ameliorate many of these sequelae. To further our understanding of the mechanism of how intrauterine and early postnatal growth affects adult health we have employed Affymetrix microarray-based expression profiling to characterize hepatic gene expression of male offspring in a rat model of maternal nutrient restriction in early and late life. At day 21 of life (p21) combined intrauterine and postnatal calorie restriction treatment led to expression changes in circadian, metabolic, and insulin-like growth factor genes as part of a larger transcriptional response that encompasses 144 genes. Independent and controlled experiments at p21 confirm the early life circadian, metabolic, and growth factor perturbations. In contrast to the p21 transcriptional response, at day 450 of life (d450) only seven genes, largely uncharacterized, were differentially expressed. This lack of a transcriptional response identifies non-transcriptional mechanisms mediating the adult sequelae of intrauterine growth restriction. Independent experiments at d450 identify a circadian defect as well as validate expression changes to four of the genes identified by the microarray screen which have a novel association with growth restriction. Emerging from this rich dataset is a portrait of how the liver responds to growth restriction through circadian dysregulation, energy/substrate management, and growth factor modulation. © 2014 Wiley Periodicals, Inc.

  10. Investigation of Mediational Processes Using Parallel Process Latent Growth Curve Modeling

    Science.gov (United States)

    Cheong, JeeWon; MacKinnon, David P.; Khoo, Siek Toon

    2010-01-01

    This study investigated a method to evaluate mediational processes using latent growth curve modeling. The mediator and the outcome measured across multiple time points were viewed as 2 separate parallel processes. The mediational process was defined as the independent variable influencing the growth of the mediator, which, in turn, affected the growth of the outcome. To illustrate modeling procedures, empirical data from a longitudinal drug prevention program, Adolescents Training and Learning to Avoid Steroids, were used. The program effects on the growth of the mediator and the growth of the outcome were examined first in a 2-group structural equation model. The mediational process was then modeled and tested in a parallel process latent growth curve model by relating the prevention program condition, the growth rate factor of the mediator, and the growth rate factor of the outcome. PMID:20157639

  11. Fibroblast growth factor receptor mediates fibroblast-dependent growth in EMMPRIN-depleted head and neck cancer tumor cells.

    Science.gov (United States)

    Liu, Zhiyong; Hartman, Yolanda E; Warram, Jason M; Knowles, Joseph A; Sweeny, Larissa; Zhou, Tong; Rosenthal, Eben L

    2011-08-01

    Head and neck squamous cell carcinoma tumors (HNSCC) contain a dense fibrous stroma which is known to promote tumor growth, although the mechanism of stroma-mediated growth remains unclear. As dysplastic mucosal epithelium progresses to cancer, there is incremental overexpression of extracellular matrix metalloprotease inducer (EMMPRIN) which is associated with tumor growth and metastasis. Here, we present evidence that gain of EMMPRIN expression allows tumor growth to be less dependent on fibroblasts by modulating fibroblast growth factor receptor-2 (FGFR2) signaling. We show that silencing EMMPRIN in FaDu and SCC-5 HNSCC cell lines inhibits cell growth, but when EMMPRIN-silenced tumor cells were cocultured with fibroblasts or inoculated with fibroblasts into severe combined immunodeficient mice, the growth inhibition by silencing EMMPRIN was blunted by the presence of fibroblasts. Coculture experiments showed fibroblast-dependent tumor cell growth occurred via a paracrine signaling. Analysis of tumor gene expression revealed expression of FGFR2 was inversely related to EMMPRIN expression. To determine the role of FGFR2 signaling in EMMPRIN-silenced tumor cells, ligands and inhibitors of FGFR2 were assessed. Both FGF1 and FGF2 enhanced tumor growth in EMMPRIN-silenced cells compared with control vector-transfected cells, whereas inhibition of FGFR2 with blocking antibody or with a synthetic inhibitor (PD173074) inhibited tumor cell growth in fibroblast coculture, suggesting the importance of FGFR2 signaling in fibroblast-mediated tumor growth. Analysis of xenografted tumors revealed that EMMPRIN-silenced tumors had a larger stromal compartment compared with control. Taken together, these results suggest that EMMPRIN acquired during tumor progression promotes fibroblast-independent tumor growth.

  12. Fibroblast growth factor receptor mediates fibroblast-dependent growth in EMMPRIN depleted head and neck cancer tumor cells

    Science.gov (United States)

    Liu, Zhiyong; Hartman, Yolanda E.; Warram, Jason M.; Knowles, Joseph A.; Sweeny, Larrisa; Zhou, Tong; Rosenthal, Eben L.

    2011-01-01

    Head and neck squamous cell carcinoma tumors (HNSCC) contain a dense fibrous stroma which is known to promote tumor growth, although the mechanism of stroma mediated growth remains unclear. As dysplastic mucosal epithelium progresses to cancer there is incremental overexpression of extracellular matrix metalloprotease inducer (EMMPRIN) which is associated with tumor growth and metastasis. Here we present evidence that gain of EMMPRIN expression allows tumor growth to be less dependent on fibroblasts by modulating fibroblast growth factor receptor-2 (FGFR2) signaling. We show that silencing EMMPRIN in FaDu and SCC-5 HNSCC cell lines inhibits cell growth, but when EMMPRIN-silenced tumor cells were co-cultured with fibroblasts or inoculated with fibroblasts into SCID mice, the growth inhibition by silencing EMMPRIN was blunted by the presence of fibroblasts. Co-culture experiments demonstrated fibroblast-dependent tumor cell growth occurred via a paracrine signaling. Analysis of tumor gene expression revealed expression of FGFR2 was inversely related to EMMPRIN expression. To determine the role of FGFR2 signaling in EMMPRIN silenced tumor cells, ligands and inhibitors of FGFR2 were assessed. Both FGF1 and FGF2 enhanced tumor growth in EMMPRIN silenced cells compared to control vector transfected cells, while inhibition of FGFR2 with blocking antibody or with a synthetic inhibitor (PD173074) inhibited tumor cell growth in fibroblast co-culture, suggesting the importance of FGFR2 signaling in fibroblast mediated tumor growth. Analysis of xenografted tumors revealed EMMPRIN silenced tumors had a larger stromal compartment compared to control. Taken together, these results suggest that EMMPRIN acquired during tumor progression promotes fibroblast independent tumor growth. PMID:21665938

  13. L’ancrage squelettique au passé, présent et futur

    DEFF Research Database (Denmark)

    Melsen, Birte; Dalstra, Michel

    2017-01-01

    INTRODUCTION: Skeletal anchorage was not introduced as an alternative to conventional anchorage modalities. The first skeletal anchorage was a ligature through a hole in the infrazygomatic crest. This was replaced by surgical screws and finally the TADs, which were optimized with respect to the m......INTRODUCTION: Skeletal anchorage was not introduced as an alternative to conventional anchorage modalities. The first skeletal anchorage was a ligature through a hole in the infrazygomatic crest. This was replaced by surgical screws and finally the TADs, which were optimized with respect...

  14. Cheliensisin A (Chel A) induces apoptosis in human bladder cancer cells by promoting PHLPP2 protein degradation.

    Science.gov (United States)

    Zhang, Ruowen; Che, Xun; Zhang, Jingjie; Li, Yang; Li, Jingxia; Deng, Xu; Zhu, Junlan; Jin, Honglei; Zhao, Qinshi; Huang, Chuanshu

    2016-10-11

    Cheliensisin A (Chel A), a styryl-lactone compound extracted from Goniothalamus cheliensis, is reported to have significant anti-cancer effects in various cancer cells. Here we demonstrated that Chel A treatment resulted in apoptosis and an inhibition of anchorage-independent growth in human bladder cancer T24, T24T and U5637 cells. Mechanistic studies showed that such effect is mediated by PH domain and Leucine rich repeat Protein Phosphatases (PHLPP2) protein. Chel A treatment led to PHLPP2 degradation and subsequently increased in c-Jun phosphorylation. Moreover PHLPP2 degradation could be attenuated by inhibition of autophagy, which was mediated by Beclin 1. Collectively, we discover that Chel A treatment induces Beclin-dependent autophagy, consequently mediates PHLPP2 degradation and JNK/C-Jun phosphorylation and activation, further in turn contributing to apoptosis in human bladder cancer cells. Current studies provide a significant insight into understanding of anticancer effect of Chel A in treatment of human bladder cancer.

  15. Acetylshikonin Inhibits Human Pancreatic PANC-1 Cancer Cell Proliferation by Suppressing the NF-κB Activity.

    Science.gov (United States)

    Cho, Seok-Cheol; Choi, Bu Young

    2015-09-01

    Acetylshikonin, a natural naphthoquinone derivative compound, has been used for treatment of inflammation and cancer. In the present study, we have investigated whether acetylshikonin could regulate the NF-κB signaling pathway, thereby leading to suppression of tumorigenesis. We observed that acetylshikonin significantly reduced proliferation of several cancer cell lines, including human pancreatic PANC-1 cancer cells. In addition, acetylshikonin inhibited phorbol 12-myristate 13-acetate (PMA) or tumor necrosis-α (TNF-α)-induced NF-κB reporter activity. Proteome cytokine array and real-time RT-PCR results illustrated that acetylshikonin inhibition of PMA-induced production of cytokines was mediated at the transcriptional level and it was associated with suppression of NF-κB activity and matrix metalloprotenases. Finally, we observed that an exposure of acetylshikonin significantly inhibited the anchorage-independent growth of PANC-1 cells. Together, our results indicate that acetylshikonin could serve as a promising therapeutic agent for future treatment of pancreatic cancer.

  16. Flotillins Regulate Focal Adhesions by Interacting with α-Actinin and by Influencing the Activation of Focal Adhesion Kinase

    Directory of Open Access Journals (Sweden)

    Antje Banning

    2018-04-01

    Full Text Available Cell–matrix adhesion and cell migration are physiologically important processes that also play a major role in cancer spreading. In cultured cells, matrix adhesion depends on integrin-containing contacts such as focal adhesions. Flotillin-1 and flotillin-2 are frequently overexpressed in cancers and are associated with poor survival. Our previous studies have revealed a role for flotillin-2 in cell–matrix adhesion and in the regulation of the actin cytoskeleton. We here show that flotillins are important for cell migration in a wound healing assay and influence the morphology and dynamics of focal adhesions. Furthermore, anchorage-independent growth in soft agar is enhanced by flotillins. In the absence of flotillins, especially flotillin-2, phosphorylation of focal adhesion kinase and extracellularly regulated kinase is diminished. Flotillins interact with α-actinin, a major regulator of focal adhesion dynamics. These findings are important for understanding the molecular mechanisms of how flotillin overexpression in cancers may affect cell migration and, especially, enhance metastasis formation.

  17. Nicotine-mediated suppression of the retinoic acid metabolizing enzyme CYP26A1 limits the oncogenic potential of breast cancer.

    Science.gov (United States)

    Osanai, Makoto; Lee, Gang-Hong

    2011-06-01

    Tobacco smoke influences cancer development in tissues that are not directly exposed, and epidemiological studies have indicated that smoking women might experience decreased risk of breast cancer as a result of antiestrogenic effects. However, it remains to be clarified whether nicotine, one of the major addictive and best-investigated constituents of tobacco smoke, has any effect on breast cancer. Our recent work demonstrated that the retinoic acid metabolizing enzyme CYP26A1 enhances oncogenic and cell survival properties of breast carcinoma cells, implying a role as an oncogene. Here, we present evidence that nicotine significantly suppresses constitutive expression of CYP26A1, and that cells treated with nicotine exhibit enhanced sensitivity to apoptosis. In addition, nicotine may inhibit anchorage independent growth, cellular invasiveness and motility. These data show that nicotine can limit CYP26A1-mediated oncogenic characteristics, and suggest mechanisms by which nicotine might inhibit breast cancer development. © 2011 Japanese Cancer Association.

  18. The effects of baicalein on canine osteosarcoma cell proliferation and death.

    Science.gov (United States)

    Helmerick, E C; Loftus, J P; Wakshlag, J J

    2014-12-01

    Flavonoids are a group of modified triphenolic compounds from plants with medicinal properties. Baicalein, a specific flavone primarily isolated from plant roots (Scutellaria baicalensis), is commonly used in Eastern medicine for its anti-inflammatory and antineoplastic properties. Previous research shows greater efficacy for baicalein than most flavonoids; however, there has been little work examining their effects on sarcoma cells, let alone canine cells. Three canine osteosarcoma cell lines (HMPOS, D17 and OS 2.4) were treated with baicalein to examine cell viability, cell cycle kinetics, anchorage-independent growth and apoptosis. Results showed that osteosarcoma cells were sensitive to baicalein at concentrations from approximately 1 to 25 μM. Modest cell cycle changes were observed in one cell line. Baicalein was effective in inducing apoptosis and did not prevent doxorubicin cell proliferation inhibition in all the cell lines. The mechanism for induction of apoptosis has not been fully elucidated; however, changes in mitochondrial permeability supersede the apoptotic response. © 2012 Blackwell Publishing Ltd.

  19. Ethanol inhibits B16-BL6 melanoma metastasis and cell phenotypes associated with metastasis.

    Science.gov (United States)

    Kushiro, Kyoko; Núñez, Nomelí P

    2012-01-01

    Every year, approximately 68,000 new cases of malignant melanoma are diagnosed in the US. Ethanol consumption inhibits metastasis of melanoma in mice, but the mechanism is not well understood. C57BL/6J ob/+ mice, given either water or 20% ethanol, were injected intravenously with B16-BL6 melanoma cells to determine pulmonary metastasis. The effects of ethanol on cell phenotypes and markers of the epithelial-to-mesenchymal transition were determined in cell culture. In mice, ethanol consumption inhibited experimental pulmonary metastasis. This inhibition was associated with decreased body weight, and levels of systemic leptin, and insulin. In cell culture, ethanol inhibited B16-BL6 cell motility, invasion, and anchorage-independent growth. Additionally, ethanol reduced Snai1 expression and increased E-cadherin expression. Lastly, ethanol increased the expression of Kiss1 metastasis-suppressor and the metastasis suppressor Nm23/nucleoside diphosphate kinase. In both animal and in cell culture conditions, ethanol inhibited the metastatic ability of B16-BL6 melanoma cells.

  20. Media independence and dividend policy

    DEFF Research Database (Denmark)

    Farooq, Omar; Dandoune, Salma

    2012-01-01

    independence and dividend policies in emerging markets. Using a dataset from twenty three emerging markets, we show a significantly negative relationship between dividend policies (payout ratio and decision to pay dividend) and media independence. We argue that independent media reduces information asymmetries...... for stock market participants. Consequently, stock market participants in emerging markets with more independent media do not demand as high and as much dividends as their counterparts in emerging markets with less independent media. We also show that press independence is more important in defining......Can media pressurize managers to disgorge excess cash to shareholders? Do firms in countries with more independent media follow different dividend policies than firms with less independent media? This paper seeks to answer these questions and aims to document the relationship between media...