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Sample records for pten kd hescs

  1. Identification of novel PTEN-binding partners: PTEN interaction with fatty acid binding protein FABP4.

    Science.gov (United States)

    Gorbenko, O; Panayotou, G; Zhyvoloup, A; Volkova, D; Gout, I; Filonenko, V

    2010-04-01

    PTEN is a tumor suppressor with dual protein and lipid-phosphatase activity, which is frequently deleted or mutated in many human advanced cancers. Recent studies have also demonstrated that PTEN is a promising target in type II diabetes and obesity treatment. Using C-terminal PTEN sequence in pEG202-NLS as bait, yeast two-hybrid screening on Mouse Embryo, Colon Cancer, and HeLa cDNA libraries was carried out. Isolated positive clones were validated by mating assay and identified through automated DNA sequencing and BLAST database searches. Sequence analysis revealed a number of PTEN-binding proteins linking this phosphatase to a number of different signaling cascades, suggesting that PTEN may perform other functions besides tumor-suppressing activity in different cell types. In particular, the interplay between PTEN function and adipocyte-specific fatty-acid-binding protein FABP4 is of notable interest. The demonstrable tautology of PTEN to FABP4 suggested a role for this phosphatase in the regulation of lipid metabolism and adipocyte differentiation. This interaction was further studied using coimmunoprecipitation and gel-filtration assays. Finally, based on Biacore assay, we have calculated the K(D) of PTEN-FABP4 complex, which is around 2.8 microM.

  2. Focus on PTEN regulation

    Directory of Open Access Journals (Sweden)

    Miriam eBermudez-Brito

    2015-07-01

    Full Text Available The role of PTEN as a tumour suppressor has been for a long time attributed to its lipid phosphatase activity against PI(3,4,5P3, the phospholipid product of the class I PI3Ks. Besides its traditional role as a lipid phosphatase at the plasma membrane, a wealth of data has shown that PTEN can function independently of its phosphatase activity and that PTEN also exists and plays a role in the nucleus, in cytoplasmic organelles and extracellularly. Accumulating evidence has shed light on diverse physiological functions of PTEN which are accompanied by a complex regulation of its expression and activity. PTEN levels and function are regulated transcriptionally, post-transcriptionally and post-translationally. PTEN is also sensitive to regulation by its interacting proteins and its localization. Herein, we summarize the current knowledge on mechanisms that regulate the expression and enzymatic activity of PTEN and its role in human diseases.

  3. The hESC line Envy expresses high levels of GFP in all differentiated progeny.

    Science.gov (United States)

    Costa, Magdaline; Dottori, Mirella; Ng, Elizabeth; Hawes, Susan M; Sourris, Koula; Jamshidi, Pegah; Pera, Martin F; Elefanty, Andrew G; Stanley, Edouard G

    2005-04-01

    Human embryonic stem cells (hESCs) have been advanced as a potential source of cells for use in cell replacement therapies. The ability to identify hESCs and their differentiated progeny readily in transplantation experiments will facilitate the analysis of hESC potential and function in vivo. We have generated a hESC line designated 'Envy', in which robust levels of green fluorescent protein (GFP) are expressed in stem cells and all differentiated progeny.

  4. PTEN at 18: Still Growing.

    Science.gov (United States)

    Gorbenko, Olena; Stambolic, Vuk

    2016-01-01

    Discovered in 1997, PTEN remains one of the most studied tumor suppressors. In this issue of Methods in Molecular Biology, we assembled a series of papers describing various clinical and experimental approaches to studying PTEN function. Due to its broad expression, regulated subcellular localization, and intriguing phosphatase activity, methodologies aimed at PTEN study have often been developed in the context of mutations affecting various aspects of its regulation, found in patients burdened with PTEN loss-driven tumors. PTEN's extensive posttranslational modifications and dynamic localization pose unique challenges for studying PTEN features in isolation and necessitate considerable development of experimental systems to enable controlled characterization. Nevertheless, ongoing efforts towards the development of PTEN knockout and knock-in animals and cell lines, antibodies, and enzymatic assays have facilitated a huge body of work, which continues to unravel the fascinating biology of PTEN.

  5. hESC expansion and stemness are independent of connexin forty-three-mediated intercellular communication between hESCs and hASC feeder cells.

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    Jin-Su Kim

    Full Text Available BACKGROUND: Human embryonic stem cells (hESCs are a promising and powerful source of cells for applications in regenerative medicine, tissue engineering, cell-based therapies, and drug discovery. Many researchers have employed conventional culture techniques using feeder cells to expand hESCs in significant numbers, although feeder-free culture techniques have recently been developed. In regard to stem cell expansion, gap junctional intercellular communication (GJIC is thought to play an important role in hESC survival and differentiation. Indeed, it has been reported that hESC-hESC communication through connexin 43 (Cx43, one of the major gap junctional proteins is crucial for the maintenance of hESC stemness during expansion. However, the role of GJIC between hESCs and feeder cells is unclear and has not yet been reported. METHODOLOGY/PRINCIPAL FINDINGS: This study therefore examined whether a direct Cx43-mediated interaction between hESCs and human adipose-derived stem cells (hASCs influences the maintenance of hESC stemness. Over 10 passages, hESCs cultured on a layer of Cx43-downregulated hASC feeder cells showed normal morphology, proliferation (colony growth, and stemness, as assessed by alkaline phosphatase (AP, OCT4 (POU5F1-Human gene Nomenclature Database, SOX2, and NANOG expression. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that Cx43-mediated GJIC between hESCs and hASC feeder cells is not an important factor for the conservation of hESC stemness and expansion.

  6. Poly-ADP ribosylation of PTEN by tankyrases promotes PTEN degradation and tumor growth

    OpenAIRE

    Li, Nan; Zhang, Yajie; Han, Xin; Liang, Ke; Wang, Jiadong; Feng, Lin; Wang, Wenqi; Songyang, Zhou; Lin, Chunru; Yang, Liuqing; Yu, Yonghao; Chen, Junjie

    2015-01-01

    Li et al. report ADP-ribosylation as a new post-translational modification of the tumor suppressor PTEN. Tankyrases interact with and ribosylate PTEN, which promotes the recognition of PTEN by a PAR-binding E3 ubiquitin ligase, RNF146, leading to PTEN ubiquitination and degradation. Tankyrases were up-regulated and negatively correlated with PTEN expression in human colon carcinomas.

  7. Adapting collagen/CNT matrix in directing hESC differentiation

    OpenAIRE

    Sridharan, Indumathi; Kim, Taeyoung; Wang, Rong

    2009-01-01

    The lineage selection in human embryonic stem cell (hESC) differentiation relies on both the growth factors and small molecules in the media and the physical characteristics of the micro-environment. In this work, we utilized various materials, including the collagen-carbon nanotube (collagen/CNT) composite material, as cell culture matrices to examine the impact of matrix properties on hESC differentiation. Our AFM analysis indicated that the collagen/CNT formed rigid fibril bundles, which p...

  8. Adapting collagen/CNT matrix in directing hESC differentiation.

    Science.gov (United States)

    Sridharan, Indumathi; Kim, Taeyoung; Wang, Rong

    2009-04-17

    The lineage selection in human embryonic stem cell (hESC) differentiation relies on both the growth factors and small molecules in the media and the physical characteristics of the micro-environment. In this work, we utilized various materials, including the collagen-carbon nanotube (collagen/CNT) composite material, as cell culture matrices to examine the impact of matrix properties on hESC differentiation. Our AFM analysis indicated that the collagen/CNT formed rigid fibril bundles, which polarized the growth and differentiation of hESCs, resulting in more than 90% of the cells to the ectodermal lineage in Day 3 in the media commonly used for spontaneous differentiation. We also observed the differentiated cells followed the coarse alignment of the collagen/CNT matrix. The research not only revealed the responsiveness of hESCs to matrix properties, but also provided a simple yet efficient way to direct the hESC differentiation, and imposed the potential of forming neural-cell based bio-devices for further applications.

  9. Primed to perish: heightened mitochondrial priming explains hESC apoptosis sensitivity

    NARCIS (Netherlands)

    Geijsen, N.

    2013-01-01

    Human embryonic stem cells (hESCs) are hypersensitive to apoptotic stimuli, though the underlying mechanisms are poorly characterized. In this issue of Cell Stem Cell, Liu et al. (2013) report that mitochondria of human ESCs exist in an apoptosis-prone state, ready to act as cellular executioners up

  10. Primed to perish: heightened mitochondrial priming explains hESC apoptosis sensitivity

    NARCIS (Netherlands)

    Geijsen, N.

    2013-01-01

    Human embryonic stem cells (hESCs) are hypersensitive to apoptotic stimuli, though the underlying mechanisms are poorly characterized. In this issue of Cell Stem Cell, Liu et al. (2013) report that mitochondria of human ESCs exist in an apoptosis-prone state, ready to act as cellular executioners up

  11. Primed to perish: heightened mitochondrial priming explains hESC apoptosis sensitivity

    NARCIS (Netherlands)

    Geijsen, N.

    2013-01-01

    Abstract Human embryonic stem cells (hESCs) are hypersensitive to apoptotic stimuli, though the underlying mechanisms are poorly characterized. In this issue of Cell Stem Cell, Liu et al. (2013) report that mitochondria of human ESCs exist in an apoptosis-prone state, ready to act as cellular execut

  12. Primed to perish: heightened mitochondrial priming explains hESC apoptosis sensitivity

    NARCIS (Netherlands)

    Geijsen, N.

    2013-01-01

    Abstract Human embryonic stem cells (hESCs) are hypersensitive to apoptotic stimuli, though the underlying mechanisms are poorly characterized. In this issue of Cell Stem Cell, Liu et al. (2013) report that mitochondria of human ESCs exist in an apoptosis-prone state, ready to act as cellular execut

  13. Genomic rearrangements of PTEN in prostate cancer

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    Sopheap ePhin

    2013-09-01

    Full Text Available The phosphatase and tensin homolog gene on chromosome 10q23.3 (PTEN is a negative regulator of the PIK3/Akt survival pathway and is the most frequently deleted tumor suppressor gene in prostate cancer. Monoallelic loss of PTEN is present in up to 60% of localized prostate cancers and complete loss of PTEN in prostate cancer is linked to metastasis and androgen independent progression. Studies on the genomic status of PTEN in prostate cancer initially used a two-color fluorescence in-situ hybridization (FISH assay for PTEN copy number detection in formalin fixed paraffin embedded tissue preparations. More recently, a four-color FISH assay containing two additional control probes flanking the PTEN locus with a lower false-positive rate was reported. Combined with the detection of other critical genomic biomarkers for prostate cancer such as ERG, AR, and MYC, the evaluation of PTEN genomic status has proven to be invaluable for patient stratification and management. Although less frequent than allelic deletions, point mutations in the gene and epigenetic silencing are also known to contribute to loss of PTEN function, and ultimately to prostate cancer initiation. Overall, it is clear that PTEN is a powerful biomarker for prostate cancer. Used as a companion diagnostic for emerging therapeutic drugs, FISH analysis of PTEN is promisingly moving human prostate cancer closer to more effective cancer management and therapies.

  14. Toda and KdV

    OpenAIRE

    Gieseker, D.

    1999-01-01

    The main object of this paper is to produce a deformation of the KdV hierarchy of partial differential equations. We construct this deformation by taking a certain limit of the Toda hierarchy. This construction also provides a deformation of the Virasoro algebra.

  15. Computational Analysis of PTEN Gene Mutation

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    Siew-Kien Mah

    2012-01-01

    Full Text Available Post-genomic data can be efficiently analyzed using computational tools. It has the advantage over the biochemical and biophysical methods in term of higher coverage. In this research, we adopted a computational analysis on PTEN gene mutation.  Mutation in PTEN is responsible for many human diseases. The results of this research provide insights into the protein domains of PTEN and the distribution of mutation.

  16. PPARγ, PTEN, and the Fight against Cancer

    OpenAIRE

    Teresi, Rosemary E.; Kristin A. Waite

    2008-01-01

    Peroxisome proliferator-activated receptor gamma (PPAR ) is a ligand-activated transcription factor, which belongs to the family of nuclear hormone receptors. Recent in vitro studies have shown that PPAR can regulate the transcription of phosphatase and tensin homolog on chromosome ten (PTEN), a known tumor suppressor. PTEN is a susceptibility gene for a number of disorders, including breast and thyroid cancer. Activation of PPAR through agonists increases functional PTEN protein levels...

  17. The KdV-mKdV equation and series solutions%KdV-mKdV方程及其级数解

    Institute of Scientific and Technical Information of China (English)

    韦敏志; 唐生强

    2012-01-01

    为研究KdV-mKdV方程的级数解,运用扩展的齐次平衡法,将KdV-mKdV方程约化成线性的偏微分方程,得到B(a)cklund变换以及KdV-mKdV方程的自变换解.通过B(a)cklund变换和该偏微分方程的多种级数解,获得丰富的精确解,包括多孤立波解、三角函数解和有理级数解.%The series solutions of the KdV-mKdV equation will be studied by using the extended homogenous balance method,we reduce the KdV-mKdV equation to a linear PDE and obtain Backlund transformation of it. Furthermore, the self-transformation of solutions for the KdV-mKdV equation is obtained. By the Backlund transformation and various series solutions of the PDE,abundant exact solutions of the KdV-mKdV equation are obtained including the multi-solitary wave solution, trigonometric function series solution,rational series solution and solution consisting of the three types of solutions.

  18. Population based model of human embryonic stem cell (hESC differentiation during endoderm induction.

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    Keith Task

    Full Text Available The mechanisms by which human embryonic stem cells (hESC differentiate to endodermal lineage have not been extensively studied. Mathematical models can aid in the identification of mechanistic information. In this work we use a population-based modeling approach to understand the mechanism of endoderm induction in hESC, performed experimentally with exposure to Activin A and Activin A supplemented with growth factors (basic fibroblast growth factor (FGF2 and bone morphogenetic protein 4 (BMP4. The differentiating cell population is analyzed daily for cellular growth, cell death, and expression of the endoderm proteins Sox17 and CXCR4. The stochastic model starts with a population of undifferentiated cells, wherefrom it evolves in time by assigning each cell a propensity to proliferate, die and differentiate using certain user defined rules. Twelve alternate mechanisms which might describe the observed dynamics were simulated, and an ensemble parameter estimation was performed on each mechanism. A comparison of the quality of agreement of experimental data with simulations for several competing mechanisms led to the identification of one which adequately describes the observed dynamics under both induction conditions. The results indicate that hESC commitment to endoderm occurs through an intermediate mesendoderm germ layer which further differentiates into mesoderm and endoderm, and that during induction proliferation of the endoderm germ layer is promoted. Furthermore, our model suggests that CXCR4 is expressed in mesendoderm and endoderm, but is not expressed in mesoderm. Comparison between the two induction conditions indicates that supplementing FGF2 and BMP4 to Activin A enhances the kinetics of differentiation than Activin A alone. This mechanistic information can aid in the derivation of functional, mature cells from their progenitors. While applied to initial endoderm commitment of hESC, the model is general enough to be applicable

  19. Population based model of human embryonic stem cell (hESC) differentiation during endoderm induction.

    Science.gov (United States)

    Task, Keith; Jaramillo, Maria; Banerjee, Ipsita

    2012-01-01

    The mechanisms by which human embryonic stem cells (hESC) differentiate to endodermal lineage have not been extensively studied. Mathematical models can aid in the identification of mechanistic information. In this work we use a population-based modeling approach to understand the mechanism of endoderm induction in hESC, performed experimentally with exposure to Activin A and Activin A supplemented with growth factors (basic fibroblast growth factor (FGF2) and bone morphogenetic protein 4 (BMP4)). The differentiating cell population is analyzed daily for cellular growth, cell death, and expression of the endoderm proteins Sox17 and CXCR4. The stochastic model starts with a population of undifferentiated cells, wherefrom it evolves in time by assigning each cell a propensity to proliferate, die and differentiate using certain user defined rules. Twelve alternate mechanisms which might describe the observed dynamics were simulated, and an ensemble parameter estimation was performed on each mechanism. A comparison of the quality of agreement of experimental data with simulations for several competing mechanisms led to the identification of one which adequately describes the observed dynamics under both induction conditions. The results indicate that hESC commitment to endoderm occurs through an intermediate mesendoderm germ layer which further differentiates into mesoderm and endoderm, and that during induction proliferation of the endoderm germ layer is promoted. Furthermore, our model suggests that CXCR4 is expressed in mesendoderm and endoderm, but is not expressed in mesoderm. Comparison between the two induction conditions indicates that supplementing FGF2 and BMP4 to Activin A enhances the kinetics of differentiation than Activin A alone. This mechanistic information can aid in the derivation of functional, mature cells from their progenitors. While applied to initial endoderm commitment of hESC, the model is general enough to be applicable either to a system of

  20. Donating embryos for human embryonic stem cell (hESC) research: a committee opinion.

    Science.gov (United States)

    2013-10-01

    hESC research is an ethically acceptable use of human embryos that are in excess of those needed to meet the fertility goals of patients. The ethical basis for this view and issues to be considered during the informed consent process for the donation of embryos are developed in this document. This report replaces the Committee's 2009 report, "Donating spare embryos for stem cell research" (Fertil Steril 2009;91:667-70).

  1. New interaction solutions to the combined KdV–mKdV equation from CTE method

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    Hengchun Hu

    2016-10-01

    Full Text Available The consistent tanh expansion (CTE method is developed for the combined KdV–mKdV equation. The combined KdV–mKdV equation is proved to be CTE solvable. New exact interaction solutions such as soliton–cnoidal wave solutions, soliton–periodic wave solutions for the combined KdV–mKdV equation are given out analytically and graphically.

  2. New interaction solutions to the combined KdV–mKdV equation from CTE method

    OpenAIRE

    2016-01-01

    The consistent tanh expansion (CTE) method is developed for the combined KdV–mKdV equation. The combined KdV–mKdV equation is proved to be CTE solvable. New exact interaction solutions such as soliton–cnoidal wave solutions, soliton–periodic wave solutions for the combined KdV–mKdV equation are given out analytically and graphically.

  3. PTEN inhibits BMI1 function independently of its phosphatase activity

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    Kapoor Anil

    2009-11-01

    Full Text Available Abstract Background PTEN is the second most mutated tumor suppressor gene other than p53. It suppresses tumorigenesis by dephosphorylating phosphatidylinositol (3,4,5-triphosphate (PIP3 to phosphatidylinositol (4,5-biphosphate (PIP2, thereby directly inhibiting phosphatidylinositol 3 kinase (PI3K-mediated tumorigenic activities. Consistent with this model of action, cytosolic PTEN is recruited to the plasma membrane to dephosphorylate PIP3. While nuclear PTEN has been shown to suppress tumorigenesis by governing genome integrity, additional mechanisms may also contribute to nuclear PTEN-mediated tumor suppression. The nuclear protein BMI1 promotes stem cell self-renewal and tumorigenesis and PTEN inhibits these events, suggesting that PTEN may suppress BMI1 function. Results We investigated whether PTEN inhibits BMI1 function during prostate tumorigenesis. PTEN binds to BMI1 exclusively in the nucleus. This interaction does not require PTEN's phosphatase activity, as phosphatase-deficient PTEN mutants, PTEN/C124S (CS, PTEN/G129E (GE, and a C-terminal PTEN fragment (C-PTEN excluding the catalytic domain, all associate with BMI1. Furthermore, the residues 186-286 of C-PTEN are sufficient for binding to BMI1. This interaction reduces BMI1's function. BMI1 enhances hTERT activity and reduces p16INK4A and p14ARF expression. These effects were attenuated by PTEN, PTEN(CS, PTEN(GE, and C-PTEN. Furthermore, knockdown of PTEN in DU145 cells increased hTERT promoter activity, which was reversed when BMI1 was concomitantly knocked-down, indicating that PTEN reduces hTERT promoter activity via inhibiting BMI1 function. Conversely, BMI1 reduces PTEN's ability to inhibit AKT activation, which can be attributed to its interaction with PTEN in the nucleus, making PTEN unavailable to dephosphorylate membrane-bound PIP3. Furthermore, BMI1 appears to co-localize with PTEN more frequently in clinical prostate tissue samples from patients diagnosed with PIN

  4. Mutant PTEN in Cancer : Worse Than Nothing

    NARCIS (Netherlands)

    Leslie, Nick R; den Hertog, Jeroen

    2014-01-01

    Tumor suppressors block the development of cancer and are often lost during tumor development. Papa et al. show that partial loss of normal PTEN tumor suppressor function can be compounded by additional disruption caused by the expression of inactive mutant PTEN protein. This has significant

  5. PTEN, Longevity and Age-Related Diseases

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    Izak S. Tait

    2013-12-01

    Full Text Available Since the discovery of PTEN, this protein has been shown to be an effective suppressor of cancer and a contributor to longevity. This report will review, in depth, the associations between PTEN and other molecules, its mutations and regulations in order to present how PTEN can be used to increase longevity. This report will collect recent research of PTEN and use this to discuss PTEN’s role in caloric restriction, antioxidative defense of DNA-damage and the role it plays in suppressing tumors. The report will also discuss that variety of ways that PTEN can be compromised, through mutations, complete loss of alleles and its main antagonist, the PI3K/AKT pathway.

  6. Poly-ADP ribosylation of PTEN by tankyrases promotes PTEN degradation and tumor growth

    Science.gov (United States)

    Li, Nan; Zhang, Yajie; Han, Xin; Liang, Ke; Wang, Jiadong; Feng, Lin; Wang, Wenqi; Songyang, Zhou; Lin, Chunru; Yang, Liuqing; Yu, Yonghao

    2015-01-01

    PTEN [phosphatidylinositol (3,4,5)-trisphosphate phosphatase and tensin homolog deleted from chromosome 10], a phosphatase and critical tumor suppressor, is regulated by numerous post-translational modifications, including phosphorylation, ubiquitination, acetylation, and SUMOylation, which affect PTEN localization and protein stability. Here we report ADP-ribosylation as a new post-translational modification of PTEN. We identified PTEN as a novel substrate of tankyrases, which are members of the poly(ADP-ribose) polymerases (PARPs). We showed that tankyrases interact with and ribosylate PTEN, which promotes the recognition of PTEN by a PAR-binding E3 ubiquitin ligase, RNF146, leading to PTEN ubiquitination and degradation. Double knockdown of tankyrase1/2 stabilized PTEN, resulting in the subsequent down-regulation of AKT phosphorylation and thus suppressed cell proliferation and glycolysis in vitro and tumor growth in vivo. Furthermore, tankyrases were up-regulated and negatively correlated with PTEN expression in human colon carcinomas. Together, our study revealed a new regulation of PTEN and highlighted a role for tankyrases in the PTEN–AKT pathway that can be explored further for cancer treatment. PMID:25547115

  7. PTEN in liver diseases and cancer

    Institute of Scientific and Technical Information of China (English)

    Marion; Peyrou; Lucie; Bourgoin; Michelangelo; Foti

    2010-01-01

    The phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt axis is a key signal transduction node that regulates crucial cellular functions, including insulin and other growth factors signaling, lipid and glucose metabolism, as well as cell survival and apoptosis. In this pathway, PTEN acts as a phosphoinositide phosphatase, which terminates PI3Kpropagated signaling by dephosphorylating PtdIns(3,4)P2 and PtdIns(3,4,5)P3. However, the role of PTEN does not appear to be restricted only to ...

  8. The kd/kd mouse is a model of collapsing glomerulopathy.

    Science.gov (United States)

    Barisoni, Laura; Madaio, Michael P; Eraso, Maria; Gasser, David L; Nelson, Peter J

    2005-10-01

    Collapsing glomerulopathy (CG) is associated with disorders that markedly perturb the phenotype of podocytes. The kd/kd mouse has been studied for immune and genetic causes of microcystic tubulointerstitial nephritis with little attention to its glomerular lesion. Because histologic examination revealed classic morphologic features of CG, the question arises whether podocytes in kd/kd mice exhibit additional phenotypic criteria for CG. Utilizing Tg26 mice as a positive control, immunohistochemical profiling of the podocyte phenotype was conducted simultaneously on both models. Similar to Tg26 kidneys, podocytes in kd/kd kidneys showed de novo cyclin D1, Ki-67, and desmin expression with loss of synaptopodin and WT-1 expression. Electron micrographs showed collapsed capillaries, extensive foot process effacement, and dysmorphic mitochondria in podocytes. These results indicate that the kd/kd mouse is a model of CG and raise the possibility that human equivalents of the kd susceptibility gene may exist in patients with CG.

  9. Pten Regulates Epithelial Cytodifferentiation during Prostate Development

    DEFF Research Database (Denmark)

    Lokody, Isabel B; Francis, Jeffrey C; Gardiner, Jennifer R;

    2015-01-01

    Gene expression and functional studies have indicated that the molecular programmes involved in prostate development are also active in prostate cancer. PTEN has been implicated in human prostate cancer and is frequently mutated in this disease. Here, using the Nkx3.1:Cre mouse strain and a genetic...... deletion approach, we investigate the role of Pten specifically in the developing mouse prostate epithelia. In contrast to its role in other developing organs, this gene is dispensable for the initial developmental processes such as budding and branching. However, as cytodifferentiation progresses...... that are shared with Pten mutant prostate cancer models, including a decrease in androgen receptor regulated genes. In depth analysis of the phenotype of these mice during development revealed that loss of Pten leads to the precocious differentiation of epithelial cells towards a luminal cell fate. This study...

  10. PTEN degradation after ischemic stroke: a double-edged sword.

    Science.gov (United States)

    Li, W; Huang, R; Chen, Z; Yan, L-J; Simpkins, J W; Yang, S-H

    2014-08-22

    Tumor suppressor phosphatase and tensin homolog (PTEN) is highly expressed in neurons and PTEN inhibition has been reported to be neuroprotective against ischemic stroke in experimental models. On the other hand, PTEN deletion has been shown to lead to cognitive impairment. In the current study, we examined the expression and functions of PTEN in an ischemic stroke rodent model. We found rapid S-nitrosylation and degradation of PTEN after cerebral ischemia/reperfusion injury. PTEN degradation leads to activation of Akt. PTEN partial deletion or PTEN inhibition increased the expression of GABAA receptor (GABAAR) γ2 subunit and enhanced GABAA receptor current. After cerebral ischemia, increased expression of GABAAR γ2 subunit was observed in the ischemia region and the penumbra area. We also observed PTEN loss in astrocytes after cerebral ischemia. Astrocytic PTEN partial knockout increased astrocyte activation and exacerbated ischemic damage. We speculated that ischemic stroke induced neuronal PTEN degradation, hence enhanced GABAA receptor-medicated neuronal activity inhibition which could attenuate excitotoxicity and provide neuroprotection during the acute phase after stroke, while inhibiting long-term functional recovery and contributing to vascular cognitive impairment after stroke. On the other hand, ischemic stroke induced astrocytic PTEN loss and enhanced ischemic damage and astrogliosis. Taken together, our study indicates that ischemic stroke induces rapid PTEN degradation in both neurons and astrocytes which play both protective and detrimental action in a spatiotemporal- and cell-type-dependent manner. Our study provides critical insight for targeting PTEN signaling pathway for stroke treatment.

  11. Role of PTEN in the Tumor Microenvironment

    Science.gov (United States)

    2008-06-01

    mouse mammary tumors. Oncogene 24, 6870-6876. 11. Park ES, Lee JS, Woo HG, Zhan F, Shih JH, Shaughnessy JD Jr, Frederic Mushinski J. (2007...between: Pearson : p-value PTEN and ETS2-P (T72) -0.577 < 0.001 PTEN and AKT-P (S473) -0.552 < 0.001 ETS2-P (T72) and AKT-P (S473) 0.947 < 0.001 50μm

  12. Pten Regulates Epithelial Cytodifferentiation during Prostate Development.

    Directory of Open Access Journals (Sweden)

    Isabel B Lokody

    Full Text Available Gene expression and functional studies have indicated that the molecular programmes involved in prostate development are also active in prostate cancer. PTEN has been implicated in human prostate cancer and is frequently mutated in this disease. Here, using the Nkx3.1:Cre mouse strain and a genetic deletion approach, we investigate the role of Pten specifically in the developing mouse prostate epithelia. In contrast to its role in other developing organs, this gene is dispensable for the initial developmental processes such as budding and branching. However, as cytodifferentiation progresses, abnormal luminal cells fill the ductal lumens together with augmented epithelial proliferation. This phenotype resembles the hyperplasia seen in postnatal Pten deletion models that develop neoplasia at later stages. Consistent with this, gene expression analysis showed a number of genes affected that are shared with Pten mutant prostate cancer models, including a decrease in androgen receptor regulated genes. In depth analysis of the phenotype of these mice during development revealed that loss of Pten leads to the precocious differentiation of epithelial cells towards a luminal cell fate. This study provides novel insight into the role of Pten in prostate development as part of the process of coordinating the differentiation and proliferation of cell types in time and space to form a functional organ.

  13. Pten Regulates Epithelial Cytodifferentiation during Prostate Development

    Science.gov (United States)

    Lokody, Isabel B.; Francis, Jeffrey C.; Gardiner, Jennifer R.; Erler, Janine T.; Swain, Amanda

    2015-01-01

    Gene expression and functional studies have indicated that the molecular programmes involved in prostate development are also active in prostate cancer. PTEN has been implicated in human prostate cancer and is frequently mutated in this disease. Here, using the Nkx3.1:Cre mouse strain and a genetic deletion approach, we investigate the role of Pten specifically in the developing mouse prostate epithelia. In contrast to its role in other developing organs, this gene is dispensable for the initial developmental processes such as budding and branching. However, as cytodifferentiation progresses, abnormal luminal cells fill the ductal lumens together with augmented epithelial proliferation. This phenotype resembles the hyperplasia seen in postnatal Pten deletion models that develop neoplasia at later stages. Consistent with this, gene expression analysis showed a number of genes affected that are shared with Pten mutant prostate cancer models, including a decrease in androgen receptor regulated genes. In depth analysis of the phenotype of these mice during development revealed that loss of Pten leads to the precocious differentiation of epithelial cells towards a luminal cell fate. This study provides novel insight into the role of Pten in prostate development as part of the process of coordinating the differentiation and proliferation of cell types in time and space to form a functional organ. PMID:26076167

  14. Role of PTEN in TNFα induced insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Bulger, David A. [Departments of Medicine and Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104 (United States); Wellcome Trust Medical Research Council Institute of Metabolic Science, Cambridge CB2 0QQ (United Kingdom); National Institute of Diabetes & Digestive & Kidney Disease, National Institutes of Health, Bethesda, MD 20892 (United States); Conley, Jermaine [Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104 (United States); Conner, Spencer H.; Majumdar, Gipsy [Departments of Medicine and Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104 (United States); Solomon, Solomon S., E-mail: ssolomon@uthsc.edu [Departments of Medicine and Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104 (United States)

    2015-06-05

    Aims/hypothesis: PTEN may play a reversible role in TNFα induced insulin resistance, which has been linked to obesity-associated insulin resistance (IR). Methods: Western blots for PTEN and p-Akt were performed on H-411E liver cells incubated with insulin, TNFα, and in selected experiments VO-OHpic vanadium complex in the presence and absence of PTEN siRNA. Total PTEN was compared to β-actin loading control and p-Akt was compared to total Akt. Results: Western blot and Real Time RT-PCR experiments showed increased PTEN after TNFα treatment (p = 0.04); slightly decreased PTEN after insulin treatment; and slightly increased PTEN after insulin + TNFα treatment. PTEN siRNA markedly inhibited the TNFα-induced increase in PTEN (p < 0.01) without significantly changing the p-Akt levels. The vanadium complex, exhibiting insulin-like effects, also significantly prevented the TNFα-induced increase in PTEN. Combining insulin and VO-OHpic was additive, providing both proof of concept and insight into mechanism. Discussion: The PTEN increase due to TNFα treatment was reversible by both PTEN siRNA knockdown and VO-OHpic treatment. Thus, PTEN is identified as a potential new therapeutic target for reducing IR in Type 2 DM. - Highlights: • TNFα treatment induced a significant increase in PTEN in H-411E liver cells. • PTEN siRNA knockdown prevented this effect. • VO-OHpic (vanadium complex) treatment, like insulin, decreased PTEN protein levels. • Thus, PTEN is identified as a potential therapeutic target in DM Type 2.

  15. New Complexiton Solutions of the KdV and Coupled KdV Equations

    OpenAIRE

    Pekcan, Aslı

    2016-01-01

    A new approach to double-sub equation method is introduced to construct novel solutions for the nonlinear partial differential equations. It is applied to the Korteweg-de Vries (KdV) equation and yields new complexiton solutions of both the KdV and coupled KdV equations. The graphs of the solutions are also illustrated.

  16. KdV方程和mKdV方程的新奇异解%New Singular Solutions of KdV and mKdV Equations

    Institute of Scientific and Technical Information of China (English)

    刘正荣; 唐昊

    2012-01-01

    This paper deals with the singular solutions of the famous KdV and mKdV equations.In the investigation,first,the corresponding planar systems of these equations are established.Then,through some special orbits of the corresponding planar systems,some new singular solutions of these equations are obtained.Finally,by employing the singular solutions of the mKdV equation and the Miura transformations,other singular solutions of the KdV equation are presented.%研究了著名的KdV方程和mKdV方程的奇异解.首先,建立了与这两个方程相应的平面行波系统.然后,利用行波系统的一些特殊轨道,导出了新奇异解.最后,通过mKdV方程的奇异解以及Miura变换,获得了KdV方程其它的新奇异解.

  17. Inhibition of transfected PTEN on human colon cancer

    Institute of Scientific and Technical Information of China (English)

    Shou-Shui Xu; Wen-Lu Shen; Song-Ying Ouyang

    2004-01-01

    AIM: To study the inhibitory effect of transfected PTEN on LoVo cells.METHODS: Human PTEN cDNA was transferred into LoVo cells via lipofectin and PTEN mRNA levels and its expression were analyzed by Western blot and flow cytometry. Before or after transfection, the effects of 5-Fu on inhibiting cell proliferation and inducing apoptosis were measured by flow cytometry, DNA bands and MTT.RESULTS: PTEN transfection significantly up-regulated PTEN expression in LoVo cells. 5-Fu inhibited cell proliferation and induced apoptosis in transfected LoVo cells.CONCLUSION: Transfected PTEN can remark ably up-regulate PTEN expression in LoVo cells and promote the apoptosis.PTEN transfection is associated with 5-Fu treatment effect and has a cooperatively cytotoxic effect.

  18. Subtle variations in Pten dose determine cancer susceptibility.

    Science.gov (United States)

    Alimonti, Andrea; Carracedo, Arkaitz; Clohessy, John G; Trotman, Lloyd C; Nardella, Caterina; Egia, Ainara; Salmena, Leonardo; Sampieri, Katia; Haveman, William J; Brogi, Edi; Richardson, Andrea L; Zhang, Jiangwen; Pandolfi, Pier Paolo

    2010-05-01

    Cancer susceptibility has been attributed to at least one heterozygous genetic alteration in a tumor suppressor gene (TSG). It has been hypothesized that subtle variations in TSG expression can promote cancer development. However, this hypothesis has not yet been definitively supported in vivo. Pten is a TSG frequently lost in human cancer and mutated in inherited cancer-predisposition syndromes. Here we analyze Pten hypermorphic mice (Pten(hy/+)), expressing 80% normal levels of Pten. Pten(hy/+) mice develop a spectrum of tumors, with breast tumors occurring at the highest penetrance. All breast tumors analyzed here retained two intact copies of Pten and maintained Pten levels above heterozygosity. Notably, subtle downregulation of Pten altered the steady-state biology of the mammary tissues and the expression profiles of genes involved in cancer cell proliferation. We present an alterative working model for cancer development in which subtle reductions in the dose of TSGs predispose to tumorigenesis in a tissue-specific manner.

  19. Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress

    Science.gov (United States)

    Bassi, C; Ho, J; Srikumar, T; Dowling, RJO; Gorrini, C; Miller, SJ; Mak, TW; Neel, BG; Raught, B; Stambolic, V

    2016-01-01

    Loss of function of the Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor gene is associated with many human cancers. In the cytoplasm, PTEN antagonizes the Phosphatidylinositol 3′ kinase (PI3K) signaling pathway. PTEN also accumulates in the nucleus, where its function remains poorly understood. We demonstrate that SUMOylation (SUMO) of PTEN controls its nuclear localization. In cells exposed to genotoxic stress, SUMO-PTEN was rapidly excluded from the nucleus dependent on the protein kinase Ataxia telangiectasia mutated (ATM). Cells lacking nuclear PTEN were hypersensitive to DNA damage, while PTEN-deficient cells were susceptible to killing by a combination of genotoxic stress and a small molecule PI3K inhibitor both in vitro and in vivo. Our findings may have implications for individualized therapy for patients with PTEN-deficient tumors. PMID:23888040

  20. PTEN function: the long and the short of it.

    Science.gov (United States)

    Hopkins, Benjamin D; Hodakoski, Cindy; Barrows, Douglas; Mense, Sarah M; Parsons, Ramon E

    2014-04-01

    Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a phosphatase that is frequently altered in cancer. PTEN has phosphatase-dependent and -independent roles, and genetic alterations in PTEN lead to deregulation of protein synthesis, the cell cycle, migration, growth, DNA repair, and survival signaling. PTEN localization, stability, conformation, and phosphatase activity are controlled by an array of protein-protein interactions and post-translational modifications. Thus, PTEN-interacting and -modifying proteins have profound effects on the tumor suppressive functions of PTEN. Moreover, recent studies identified mechanisms by which PTEN can exit cells, via either exosomal export or secretion, and act on neighboring cells. This review focuses on modes of PTEN protein regulation and ways in which perturbations in this regulation may lead to disease.

  1. Can we accurately report PTEN status in advanced colorectal cancer?

    OpenAIRE

    Hocking, Christopher; Hardingham, Jennifer E.; Broadbridge, Vy; Wrin, Joe; Townsend, Amanda R; Tebbutt, Niall; Cooper, John; Ruszkiewicz, Andrew; Lee, Chee; Price, Timothy J.

    2014-01-01

    Background Loss of phosphatase and tensin homologue (PTEN) function evaluated by loss of PTEN protein expression on immunohistochemistry (IHC) has been reported as both prognostic in metastatic colorectal cancer and predictive of response to anti-EGFR monoclonal antibodies although results remain uncertain. Difficulties in the methodological assessment of PTEN are likely to be a major contributor to recent conflicting results. Methods We assessed loss of PTEN function in 51 colorectal cancer ...

  2. EXPRESSION AND SIGNIFICANCE OF PTEN IN ENDOMETRIAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    GE Xiu-jun; LIU Zhi-hui; LI Ying-yong; Gao Rui-ping

    2005-01-01

    Objective: To investigate the expression of PTEN in endometrial carcinoma and its clinical significance. Methods: Reverse transcriptase-polymerase chain reaction and Western-blot methods were used to detect PTEN expression in 28 cases of endometrial carcinoma. Results: mRNA and protein expression levels of PTEN in endometrial carcinomas were significantly lower than those in normal endometrium (P<0.01). Conclusion: PTEN may play an important role in the tumorigenesis of endometrial carcinoma.

  3. PTEN regulates colorectal epithelial apoptosis through Cdc42 signalling

    OpenAIRE

    Deevi, R; A. Fatehullah; Jagan, I; Nagaraju, M; Bingham, V; Campbell, F C

    2011-01-01

    Background: Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) regulation of the Rho-like GTPase Cdc42 has a central role in epithelial polarised growth, but effects of this molecular network on apoptosis remain unclear. Methods: To investigate the role of Cdc42 in PTEN-dependent cell death, we used flow cytometry, in vitro pull-down assays, poly(ADP ribose) polymerase (PARP) cleavage and other immunoblots in isogenic PTEN-expressing and -deficient colorectal cells (HCT116PTEN+/...

  4. PTEN mosaicism with features of Cowden syndrome.

    Science.gov (United States)

    Gammon, A; Jasperson, K; Pilarski, R; Prior, Tw; Kuwada, S

    2013-12-01

    We present the first known case of somatic PTEN mosaicism causing features of Cowden syndrome (CS) and inheritance in the subsequent generation. A 20-year-old woman presented for genetics evaluation with multiple ganglioneuromas of the colon. On examination, she was found to have a thyroid goiter, macrocephaly, and tongue papules, all suggestive of CS. However, her reported family history was not suspicious for CS. A deleterious PTEN mutation was identified in blood lymphocytes, 966A>G, 967delA. Genetic testing was recommended for her parents. Her 48-year-old father was referred for evaluation and was found to have macrocephaly and a history of Hashimoto's thyroiditis, but no other features of CS. Site-specific genetic testing carried out on blood lymphocytes showed mosaicism for the same PTEN mutation identified in his daughter. Identifying PTEN mosaicism in the proband's father had significant implications for the risk assessment/genetic testing plan for the rest of his family. His result also provides impetus for somatic mosaicism in a parent to be considered when a de novo PTEN mutation is suspected.

  5. Integrable dispersionless KdV hierarchy with sources

    OpenAIRE

    2006-01-01

    An integrable dispersionless KdV hierarchy with sources (dKdVHWS) is derived. Lax pair equations and bi-Hamiltonian formulation for dKdVHWS are formulated. Hodograph solution for the dispersionless KdV equation with sources (dKdVWS) is obtained via hodograph transformation. Furthermore, the dispersionless Gelfand-Dickey hierarchy with sources (dGDHWS) is presented.

  6. Implementation Architecture of KD-RTI

    Institute of Scientific and Technical Information of China (English)

    郝建国; 黄健

    2002-01-01

    This paper describes the architecture of the KD-RTI developed by us. It concentrates on the design decisions that were made that affected the ability of the RTI to improve the performance of federated simulations. The KD-RTI provides a fully distributed infrastructure. The majority of the operations are performed in a peer to peer manner rather than through accessing a central RTI server. This provides considerable runtime benefits through the use of local calls for data transportation and lookup functions. The development of KD-RTI has highlighted key issues should be addressed in most distributed systems.

  7. Feeder-free maintenance of hESCs in mesenchymal stem cell-conditioned media: distinct requirements for TGF-β and IGF-Ⅱ

    Institute of Scientific and Technical Information of China (English)

    Rosa Montes; Gertrudis Ligero; Laura Sanchez; Purificación Catalina; Teresa de la Cueva; Ana Nieto; Gustavo J Melen; Ruth Rubio; Javier García-Castro; Clara Bueno; Pablo Menendez

    2009-01-01

    A paracrine regulation was recently proposed in human embryonic stem cells (hESCs) grown in mouse embryonic fibroblast (MEF)-conditioned media (MEF-CM), where hESCs spontaneously differentiate into autologous fibroblast-like cells to maintain culture homeostasis by producing TGF-β and insulin-like growth factor-Ⅱ (IGF-Ⅱ) in response to basic fibroblast growth factor (bFGF). Although the importance of TGF-β family members in the maintenance of pluripotency of hESCs is widely established, very little is known about the role of IGF-Ⅱ. In order to ease hESC cul-ture conditions and to reduce xenogenic components, we sought (ⅰ) to determine whether hESCs can be maintained stable and pluripotent using CM from human foreskin fibroblasts (HFFs) and human mesenchymal stem cells (hM-SCs) rather than MEF-CM, and (ⅱ) to analyze whether the cooperation of bFGF with TGF-β and IGF-Ⅱ to maintain hESCs in MEF-CM may be extrapolated to hESCs maintained in ailogeneic mesenchymal stem cell (MSC)-CM and HFF-CM. We found that MSCs and HFFs express all FGF receptors (FGFRI-4) and specifically produce TGF-β in response to bFGF. However, HFFs but not MSCs secrete IGF-Ⅱ. Despite the absence of IGF-Ⅱ in MSC-CM, hESC pluripotency and culture homeostasis were successfully maintained in MSC-CM for over 37 passages. Human ESCs derived on MSCs and hESCs maintained in MSC-CM retained hESC morphology, euploidy, expression of surface markers and transcription factors linked to pluripotency and displayed in vitro and in vivo multilineage developmen-tal potential, suggesting that IGF-Ⅱ may be dispensable for hESC pluripotency. In fact, IGF-Ⅱ blocking had no effect on the homeostasis of hESC cultures maintained either on HFF-CM or on MSC-CM. These data indicate that hESCs are successfully maintained feeder-free with IGF-Ⅱ-lacking MSC-CM, and that the previously proposed paracrine mechanism by which bFGF cooperates with TGF-β and IGF-Ⅱ in the maintenance of hESCs in MEF

  8. A functional dissection of PTEN N-terminus : Implications in PTEN subcellular targeting and tumor suppressor activity

    NARCIS (Netherlands)

    Gil, Anabel; Rodríguez-Escudero, Isabel; Stumpf, Miriam; Molina, María; Cid, Víctor J.; Pulido, Rafael

    2015-01-01

    Spatial regulation of the tumor suppressor PTEN is exerted through alternative plasma membrane, cytoplasmic, and nuclear subcellular locations. The N-terminal region of PTEN is important for the control of PTEN subcellular localization and function. It contains both an active nuclear localization

  9. Label-free separation of human embryonic stem cells (hESCs) and their cardiac derivatives using Raman spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Chan, J W; Lieu, D K; Huser, T R; Li, R A

    2008-09-08

    Self-renewable, pluripotent human embryonic stem cells (hESCs) can be differentiated into cardiomyocytes (CMs), providing an unlimited source of cells for transplantation therapies. However, unlike certain cell lineages such as hematopoietic cells, CMs lack specific surface markers for convenient identification, physical separation, and enrichment. Identification by immunostaining of cardiac-specific proteins such as troponin requires permeabilization, which renders the cells unviable and non-recoverable. Ectopic expression of a reporter protein under the transcriptional control of a heart-specific promoter for identifying hESC-derived CMs (hESC-CMs) is useful for research but complicates potential clinical applications. The practical detection and removal of undifferentiated hESCs in a graft, which may lead to tumors, is also critical. Here, we demonstrate a non-destructive, label-free optical method based on Raman scattering to interrogate the intrinsic biochemical signatures of individual hESCs and their cardiac derivatives, allowing cells to be identified and classified. By combining the Raman spectroscopic data with multivariate statistical analysis, our results indicate that hESCs, human fetal left ventricular CMs, and hESC-CMs can be identified by their intrinsic biochemical characteristics with an accuracy of 96%, 98% and 66%, respectively. The present study lays the groundwork for developing a systematic and automated method for the non-invasive and label-free sorting of (i) high-quality hESCs for expansion, and (ii) ex vivo CMs (derived from embryonic or adult stem cells) for cell-based heart therapies.

  10. A Direct Method for Solving the KdV Equation and KdV-Burgers Equation%KdV和KdV-Burgers方程的直接解法

    Institute of Scientific and Technical Information of China (English)

    谢元喜

    2007-01-01

    利用文献中引入的变换,将非线性偏微分方程化为非线性常微分方程,再直接求解该常微分方程,从而简洁地求得了KdV方程和KdV-Burgers方程的若干显式精确解析解,包括孤波解、奇异行波解等.

  11. PTEN function, the long and the short of it

    Science.gov (United States)

    Hopkins, Benjamin D.; Hodakoski, Cindy; Barrows, Doug; Mense, Sarah; Parsons, Ramon E.

    2014-01-01

    Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a phosphatase that is frequently altered in cancer. PTEN has phosphatase-dependent and - independent roles; and genetic alterations in PTEN lead to deregulation of protein synthesis, cell cycle, migration, growth, DNA repair, and survival signaling. PTEN localization, stability, conformation, and phosphatase activity are controlled by an array of protein-protein interactions and post-translational modifications. Thus, PTEN-interacting and modifying proteins have profound effects on PTEN’s tumor suppressive functions. Moreover, recent studies identified mechanisms by which PTEN can exit cells, either via exosomal export or secretion, and act on neighboring cells. This review focuses on modes of PTEN protein regulation and ways in which perturbations in this regulation may lead to disease. PMID:24656806

  12. A novel PTEN gene promoter mutation and untypical Cowden syndrome

    Institute of Scientific and Technical Information of China (English)

    Chen Liu; Guangbing Li; Rongrong Chen; Xiaobo Yang; Xue Zhao; Haitao Zhao

    2013-01-01

    Cowden syndrome (CS),an autosomal dominant disorder,is one of a spectrum of clinical disorders that have been linked to germline mutations in the phosphatase and tensin homolog (PTEN) gene.Although 70-80% of patients with CS have an identifiable germline PTEN mutation,the clinical diagnosis presents many challenges because of the phenotypic and genotypic variations.In the present study,we sequenced the exons and the promoter of PTEN gene,mutations and variations in the promoter and exons were identified,and a PTEN protein expression negative region was determined by immunohistochemistry (IHC).In conclusion,a novel promoter mutation we found in PTEN gene may turn off PTEN protein expression occasionally,leading to the disorder of PTEN and untypical CS manifestations.

  13. The Parvalbumin/Somatostatin Ratio Is Increased in Pten Mutant Mice and by Human PTEN ASD Alleles

    Directory of Open Access Journals (Sweden)

    Daniel Vogt

    2015-05-01

    Full Text Available Mutations in the phosphatase PTEN are strongly implicated in autism spectrum disorder (ASD. Here, we investigate the function of Pten in cortical GABAergic neurons using conditional mutagenesis in mice. Loss of Pten results in a preferential loss of SST+ interneurons, which increases the ratio of parvalbumin/somatostatin (PV/SST interneurons, ectopic PV+ projections in layer I, and inhibition onto glutamatergic cortical neurons. Pten mutant mice exhibit deficits in social behavior and changes in electroencephalogram (EEG power. Using medial ganglionic eminence (MGE transplantation, we test for cell-autonomous functional differences between human PTEN wild-type (WT and ASD alleles. The PTEN ASD alleles are hypomorphic in regulating cell size and the PV/SST ratio in comparison to WT PTEN. This MGE transplantation/complementation assay is efficient and is generally applicable for functional testing of ASD alleles in vivo.

  14. The KdV hierarchy in optics

    CERN Document Server

    Horsley, S A R

    2016-01-01

    There is a well explored relationship between quantum mechanical scattering from a potential and the Korteweg-de Vries (KdV) equation of fluid dynamics: if the potential is 'evolved' according to the KdV equation then it will have the same reflectivity and transmissivity as a function of energy, for each snapshot in time. In this work we explore this connection in optics, where the permittivity plays the role of the potential. We begin by deriving the relationship between the Helmholtz equation and the KdV equation in terms of the current induced in a material when a permittivity profile is changed slightly. It is then shown that the KdV equation can be used to design a plethora of bounded complex potentials that are relfectionless from both sides for all angles of incidence, and planar periodic media that exhibit a real Bloch vector for all angles of propagation. Finally we apply the KdV equation to reduce the reflection of a wave from an interface between two media of differing refractive indices.

  15. The KdV hierarchy in optics

    Science.gov (United States)

    Horsley, S. A. R.

    2016-08-01

    There is a well explored relationship between quantum mechanical scattering from a potential and the Korteweg-de Vries (KdV) equation of fluid dynamics: if the potential is ‘evolved’ according to the KdV equation then it will have the same reflectivity and transmissivity as a function of energy, for each snapshot in time. In this work we explore this connection in optics, where the permittivity plays the role of the potential. We begin by deriving the relationship between the Helmholtz equation and the KdV equation in terms of the current induced in a material when a permittivity profile is changed slightly. It is then shown that the KdV equation can be used to design a plethora of bounded complex potentials that are relfectionless from both sides for all angles of incidence, and planar periodic media that exhibit a real Bloch vector for all angles of propagation. Finally we apply the KdV equation to reduce the reflection of a wave from an interface between two media of differing refractive indices.

  16. Impaired Pten expression in human malignant peripheral nerve sheath tumours.

    Directory of Open Access Journals (Sweden)

    Maren Bradtmöller

    Full Text Available Malignant peripheral nerve sheath tumours (MPNST are aggressive sarcomas that develop in about 10% of patients with the genetic disease neurofibromatosis type 1 (NF1. Molecular alterations contributing to MPNST formation have only partially been resolved. Here we examined the role of Pten, a key regulator of the Pi3k/Akt/mTOR pathway, in human MPNST and benign neurofibromas. Immunohistochemistry showed that Pten expression was significantly lower in MPNST (n=16 than in neurofibromas (n=16 and normal nervous tissue. To elucidate potential mechanisms for Pten down-regulation or Akt/mTOR activation in MPNST we performed further experiments. Mutation analysis revealed absence of somatic mutations in PTEN (n=31 and PIK3CA (n=38. However, we found frequent PTEN promotor methylation in primary MPNST (11/26 and MPNST cell lines (7/8 but not in benign nerve sheath tumours. PTEN methylation was significantly associated with early metastasis. Moreover, we detected an inverse correlation of Pten-regulating miR-21 and Pten protein levels in MPNST cell lines. The examination of NF1-/- and NF1+/+Schwann cells and fibroblasts showed that Pten expression is not regulated by NF1. To determine the significance of Pten status for treatment with the mTOR inhibitor rapamycin we treated 5 MPNST cell lines with rapamycin. All cell lines were sensitive to rapamycin without a significant correlation to Pten levels. When rapamycin was combined with simvastatin a synergistic anti-proliferative effect was achieved. Taken together we show frequent loss/reduction of Pten expression in MPNST and provide evidence for the involvement of multiple Pten regulating mechanisms.

  17. Novel Wronskian Solutions of the KdV Equation%KdV方程的新Wronskian解

    Institute of Scientific and Technical Information of China (English)

    刘金; 邓淑芳

    2003-01-01

    The novel Wronskian solutions of the KdV equation were obtained as limits of the soliton solutions in the Wronskian form.These solutions were verified by direct substitution to satisfy the bilinear derivative form of the KdV equation and its Backlund trans-formation.

  18. KdV shock-like waves as invariant solutions of KdV equation symmetries

    OpenAIRE

    Kudashev, Vadim R.

    1994-01-01

    We consider the following hypothesis: some of KdV equation shock-like waves are invariant with respect to the combination of the Galilean symmetry and KdV equation higher symmetries. Also we demonstrate our approach on the example of Burgers equation.

  19. The Study of the Solution to a Generalized KdV-mKdV Equation

    Directory of Open Access Journals (Sweden)

    Xiumei Lv

    2013-01-01

    Full Text Available A mathematical technique based on an auxiliary equation and the symbolic computation system Matlab is employed to investigate a generalized KdV-mKdV equation which possesses high-order nonlinear terms. Some new solutions including the Jacobi elliptic function solutions, the degenerated soliton-like solutions, and the triangle function solutions to the equation are obtained.

  20. Effect of Chromatin Structure on the Extent and Distribution of DNA Double Strand Breaks Produced by Ionizing Radiation; Comparative Study of hESC and Differentiated Cells Lines.

    Science.gov (United States)

    Venkatesh, Priyanka; Panyutin, Irina V; Remeeva, Evgenia; Neumann, Ronald D; Panyutin, Igor G

    2016-01-02

    Chromatin structure affects the extent of DNA damage and repair. Thus, it has been shown that heterochromatin is more protective against DNA double strand breaks (DSB) formation by ionizing radiation (IR); and that DNA DSB repair may proceed differently in hetero- and euchromatin regions. Human embryonic stem cells (hESC) have a more open chromatin structure than differentiated cells. Here, we study the effect of chromatin structure in hESC on initial DSB formation and subsequent DSB repair. DSB were scored by comet assay; and DSB repair was assessed by repair foci formation via 53BP1 antibody staining. We found that in hESC, heterochromatin is confined to distinct regions, while in differentiated cells it is distributed more evenly within the nuclei. The same dose of ionizing radiation produced considerably more DSB in hESC than in differentiated derivatives, normal human fibroblasts; and one cancer cell line. At the same time, the number of DNA repair foci were not statistically different among these cells. We showed that in hESC, DNA repair foci localized almost exclusively outside the heterochromatin regions. We also noticed that exposure to ionizing radiation resulted in an increase in heterochromatin marker H3K9me3 in cancer HT1080 cells, and to a lesser extent in IMR90 normal fibroblasts, but not in hESCs. These results demonstrate the importance of chromatin conformation for DNA protection and DNA damage repair; and indicate the difference of these processes in hESC.

  1. MicroRNA-302/367 Cluster Governs hESC Self-Renewal by Dually Regulating Cell Cycle and Apoptosis Pathways

    Directory of Open Access Journals (Sweden)

    Zhonghui Zhang

    2015-04-01

    Full Text Available miR-302/367 is the most abundant miRNA cluster in human embryonic stem cells (hESCs and can promote somatic cell reprogramming. However, its role in hESCs remains poorly understood. Here, we studied functional roles of the endogenous miR-302/367 cluster in hESCs by employing specific TALE-based transcriptional repressors. We revealed that miR-302/367 cluster dually regulates hESC cell cycle and apoptosis in dose-dependent manner. Gene profiling and functional studies identified key targets of the miR-302/367 cluster in regulating hESC self-renewal and apoptosis. We demonstrate that in addition to its role in cell cycle regulation, miR-302/367 cluster conquers apoptosis by downregulating BNIP3L/Nix (a BH3-only proapoptotic factor and upregulating BCL-xL expression. Furthermore, we show that butyrate, a natural compound, upregulates miR-302/367 cluster expression and alleviates hESCs from apoptosis induced by knockdown of miR-302/367 cluster. In summary, our findings provide new insights in molecular mechanisms of how miR-302/367 cluster regulates hESCs.

  2. Propofol-induced neurotoxicity in hESCs involved in activation of miR-206/PUMA signal pathway.

    Science.gov (United States)

    Li, Yu; Jia, Changxin; Zhang, Dianlong; Ni, Guangzhen; Miao, Xia; Tu, Ruirong

    2017-08-23

    Studies in developing animals have demonstrated that when anesthetic agents, such as propofol, are early administered in life, it can lead to neuronal cell death and learning disabilities. However, the mechanisms causing these effects remains unknown. A recent report found that propofol could significantly upregulat miR-206 expression in the human ASCs. miR-206 could also induce apoptosis in human malignant cancers. Therefore, in this study, we hypothesized that propofol induces neurotoxicity in human embryonic stem cells (hESCs). hESCs were exposed to propofol (50 μM) for 6 hr and cell death was assessed using TUNEL staining, and cleaved caspase-3 expression. miR-206 was knocked down using antagomir. PUMA was knocked down using a small interfering RNA. microRNA-206 (miR-206) expression was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). PUMA protein expression was detected using western blot assay. hESCs exposed to propofol showed a significant increase in TUNEL positive cells and cleaved caspase-3 expression, followed by the upregulation of miR-206 and PUMA expression. Targeting PUMA inhibits propofol-induced cell apoptosis; miR-206 knockdown decreased propofol-induced cell apoptosis, cleaved caspase-3 and PUMA expression. Propofol induce s cell death in hESC-derived neurons via activation of miR-206/PUMA signal pathway.

  3. Human ESCs predisposition to karyotypic instability: Is a matter of culture adaptation or differential vulnerability among hESC lines due to inherent properties?

    Directory of Open Access Journals (Sweden)

    Bueno Clara

    2008-10-01

    Full Text Available Abstract Background The use of human embryonic stem cells (hESCs in research is increasing and hESCs hold the promise for many biological, clinical and toxicological studies. Human ESCs are expected to be chromosomally stable since karyotypic changes represent a pitfall for potential future applications. Recently, several studies have analysed the genomic stability of several hESC lines maintained after prolonged in vitro culture but controversial data has been reported. Here, we prompted to compare the chromosomal stability of three hESC lines maintained in the same laboratory using identical culture conditions and passaging methods. Results Molecular cytogenetic analyses performed in three different hESC lines maintained in parallel in identical culture conditions revealed significant differences among them in regard to their chromosomal integrity. In feeders, the HS181, SHEF-1 and SHEF-3 hESC lines were chromosomally stable up to 185 passages using either mechanical or enzymatic dissection methods. Despite the three hESC lines were maintained under identical conditions, each hESC line behaved differently upon being transferred to a feeder-free culture system. The two younger hESC lines, HS181 (71 passages and SHEF-3 (51 passages became chromosomally unstable shortly after being cultured in feeder-free conditions. The HS181 line gained a chromosome 12 by passage 17 and a marker by passage 21, characterized as a gain of chromosome 20 by SKY. Importantly, the mosaicism for trisomy 12 gradually increased up to 89% by passage 30, suggesting that this karyotypic abnormality provides a selective advantage. Similarly, the SHEF-3 line also acquired a trisomy of chromosome 14 as early as passage 10. However, this karyotypic aberration did not confer selective advantage to the genetically abnormal cells within the bulk culture and the level of mosaicism for the trisomy 14 remained overtime between 15%–36%. Strikingly, however, a much older hESC line

  4. PTEN status in advanced colorectal cancer treated with cetuximab

    Science.gov (United States)

    Negri, F V; Bozzetti, C; Lagrasta, C A; Crafa, P; Bonasoni, M P; Camisa, R; Pedrazzi, G; Ardizzoni, A

    2009-01-01

    Background: Loss of phosphatase and tensin homologue deleted in chromosome 10 (PTEN) function in advanced colorectal cancer (CRC) may represent one of the resistance mechanisms to cetuximab by interfering with the epidermal growth factor receptor signal transduction pathway. Methods: PTEN expression tested by indirect immunofluorescence was evaluated both on primary (n=43) and on metastatic (n=24) sites in CRC patients treated with cetuximab. Results: The loss of PTEN expression tested on metastatic sites was negatively associated with response (100% progressive disease (PD) in PTEN-negative cases vs 30% PD in PTEN-positive cases; P<0.05), PFS (0.8 vs 8.2 months; P<0.001) and OS (2.9 vs 14.2 months; P<0.001). Conclusion: A potential role of PTEN in the anti-tumour activity of cetuximab could be hypothesised. PMID:19953097

  5. Hamilton Systems of the Compound KdV Equation%组合KdV方程的Hamilton系统

    Institute of Scientific and Technical Information of China (English)

    吕书强; 蔡春; 马青华

    2014-01-01

    In this article, according to Hamilton Systems of the KdV Equation, and proved Hamilton Systems of the Compound KdV Equation.%本文根据KdV方程的Hamilton系统,构造并证明了组合KdV方程的Hamilton系统。

  6. PTEN stabilizes TOP2A and regulates the DNA decatenation.

    Science.gov (United States)

    Kang, Xi; Song, Chang; Du, Xiao; Zhang, Cong; Liu, Yu; Liang, Ling; He, Jinxue; Lamb, Kristy; Shen, Wen H; Yin, Yuxin

    2015-12-10

    PTEN is a powerful tumor suppressor that antagonizes the cytoplasmic PI3K-AKT pathway and suppresses cellular proliferation. PTEN also plays a role in the maintenance of genomic stability in the nucleus. Here we report that PTEN facilitates DNA decatenation and controls a decatenation checkpoint. Catenations of DNA formed during replication are decatenated by DNA topoisomerase II (TOP2), and this process is actively monitored by a decatenation checkpoint in G2 phase. We found that PTEN deficient cells form ultra-fine bridges (UFBs) during anaphase and these bridges are generated as a result of insufficient decatenation. We show that PTEN is physically associated with a decatenation enzyme TOP2A and that PTEN influences its stability through OTUD3 deubiquitinase. In the presence of PTEN, ubiquitination of TOP2A is inhibited by OTUD3. Deletion or deficiency of PTEN leads to down regulation of TOP2A, dysfunction of the decatenation checkpoint and incomplete DNA decatenation in G2 and M phases. We propose that PTEN controls DNA decatenation to maintain genomic stability and integrity.

  7. PTEN Interacts with Histone H1 and Controls Chromatin Condensation

    Directory of Open Access Journals (Sweden)

    Zhu Hong Chen

    2014-09-01

    Full Text Available Chromatin organization and dynamics are integral to global gene transcription. Histone modification influences chromatin status and gene expression. PTEN plays multiple roles in tumor suppression, development, and metabolism. Here, we report on the interplay of PTEN, histone H1, and chromatin. We show that loss of PTEN leads to dissociation of histone H1 from chromatin and decondensation of chromatin. PTEN deletion also results in elevation of histone H4 acetylation at lysine 16, an epigenetic marker for chromatin activation. We found that PTEN and histone H1 physically interact through their C-terminal domains. Disruption of the PTEN C terminus promotes the chromatin association of MOF acetyltransferase and induces H4K16 acetylation. Hyperacetylation of H4K16 impairs the association of PTEN with histone H1, which constitutes regulatory feedback that may reduce chromatin stability. Our results demonstrate that PTEN controls chromatin condensation, thus influencing gene expression. We propose that PTEN regulates global gene transcription profiling through histones and chromatin remodeling.

  8. PTEN Gene: A Model for Genetic Diseases in Dermatology

    Directory of Open Access Journals (Sweden)

    Corrado Romano

    2012-01-01

    Full Text Available PTEN gene is considered one of the most mutated tumor suppressor genes in human cancer, and it’s likely to become the first one in the near future. Since 1997, its involvement in tumor suppression has smoothly increased, up to the current importance. Germline mutations of PTEN cause the PTEN hamartoma tumor syndrome (PHTS, which include the past-called Cowden, Bannayan-Riley-Ruvalcaba, Proteus, Proteus-like, and Lhermitte-Duclos syndromes. Somatic mutations of PTEN have been observed in glioblastoma, prostate cancer, and brest cancer cell lines, quoting only the first tissues where the involvement has been proven. The negative regulation of cell interactions with the extracellular matrix could be the way PTEN phosphatase acts as a tumor suppressor. PTEN gene plays an essential role in human development. A recent model sees PTEN function as a stepwise gradation, which can be impaired not only by heterozygous mutations and homozygous losses, but also by other molecular mechanisms, such as transcriptional regression, epigenetic silencing, regulation by microRNAs, posttranslational modification, and aberrant localization. The involvement of PTEN function in melanoma and multistage skin carcinogenesis, with its implication in cancer treatment, and the role of front office in diagnosing PHTS are the main reasons why the dermatologist should know about PTEN.

  9. Complex solitary waves and soliton trains in KdV and mKdV equations

    Science.gov (United States)

    Modak, Subhrajit; Singh, Akhil Pratap; Panigrahi, Prasanta Kumar

    2016-06-01

    We demonstrate the existence of complex solitary wave and periodic solutions of the Korteweg-de Vries (KdV) and modified Korteweg-de Vries (mKdV) equations. The solutions of the KdV (mKdV) equation appear in complex-conjugate pairs and are even (odd) under the simultaneous actions of parity (𝓟) and time-reversal (𝓣) operations. The corresponding localized solitons are hydrodynamic analogs of Bloch soliton in magnetic system, with asymptotically vanishing intensity. The 𝓟𝓣-odd complex soliton solution is shown to be iso-spectrally connected to the fundamental sech2 solution through supersymmetry. Physically, these complex solutions are analogous to the experimentally observed grey solitons of non-liner Schödinger equation, governing the dynamics of shallow water waves and hence may also find physical verification.

  10. 组合KdV-mKdV方程的一类三角函数解%Exact Solutions of Trigonometric Function to the Combined KdV-mKdV Equation

    Institute of Scientific and Technical Information of China (English)

    张金战

    2007-01-01

    直接假设组合KdV-mKdV方程ut+2αuux+3βu2ux+γuxxx=0的精确解具有三角函数的有理分式形式,利用待定系数法,将求解组合KdV-mKdV方程的问题转化为代数方程组的求解问题,从而获得了组合KdV-mKdV方程的一类三角函数解.

  11. Hypoxia-induced modulation of PTEN activity and EMT phenotypes in lung cancers.

    Science.gov (United States)

    Kohnoh, Takashi; Hashimoto, Naozumi; Ando, Akira; Sakamoto, Koji; Miyazaki, Shinichi; Aoyama, Daisuke; Kusunose, Masaaki; Kimura, Motohiro; Omote, Norihito; Imaizumi, Kazuyoshi; Kawabe, Tsutomu; Hasegawa, Yoshinori

    2016-01-01

    Persistent hypoxia stimulation, one of the most critical microenvironmental factors, accelerates the acquisition of epithelial-mesenchymal transition (EMT) phenotypes in lung cancer cells. Loss of phosphatase and tensin homologue deleted from chromosome 10 (PTEN) expression might accelerate the development of lung cancer in vivo. Recent studies suggest that tumor microenvironmental factors might modulate the PTEN activity though a decrease in total PTEN expression and an increase in phosphorylation of the PTEN C-terminus (p-PTEN), resulting in the acquisition of the EMT phenotypes. Nevertheless, it is not known whether persistent hypoxia can modulate PTEN phosphatase activity or whether hypoxia-induced EMT phenotypes are negatively regulated by the PTEN phosphatase activity. We aimed to investigate hypoxia-induced modulation of PTEN activity and EMT phenotypes in lung cancers. Western blotting was performed in five lung cancer cell lines to evaluate total PTEN expression levels and the PTEN activation. In a xenograft model of lung cancer cells with endogenous PTEN expression, the PTEN expression was evaluated by immunohistochemistry. To examine the effect of hypoxia on phenotypic alterations in lung cancer cells in vitro, the cells were cultured under hypoxia. The effect of unphosphorylated PTEN (PTEN4A) induction on hypoxia-induced EMT phenotypes was evaluated, by using a Dox-dependent gene expression system. Lung cancer cells involving the EMT phenotypes showed a decrease in total PTEN expression and an increase in p-PTEN. In a xenograft model, loss of PTEN expression was observed in the tumor lesions showing tissue hypoxia. Persistent hypoxia yielded an approximately eight-fold increase in the p-PTEN/PTEN ratio in vitro. PTEN4A did not affect stabilization of hypoxia-inducible factor 1α. PTEN4A blunted hypoxia-induced EMT via inhibition of β-catenin translocation into the cytoplasm and nucleus. Our study strengthens the therapeutic possibility that

  12. Bosonization of supersymmetric KdV equation

    Energy Technology Data Exchange (ETDEWEB)

    Gao Xiaonan [Department of Physics, Shanghai Jiao Tong University, Shanghai, 200240 (China); Lou, S.Y., E-mail: sylou@sjtu.edu.cn [Department of Physics, Shanghai Jiao Tong University, Shanghai, 200240 (China); Faculty of Science, Ningbo University, Ningbo, 315211 (China); School of Mathematics, Fudan University, Shanghai, 200433 (China)

    2012-01-16

    Bosonization approach to the classical supersymmetric systems is presented. By introducing the multi-fermionic parameters in the expansions of the superfields, the N=1 supersymmetric KdV (sKdV) system is transformed to a system of coupled bosonic equations. The method can be applied to any fermionic systems. By solving the coupled bosonic equations, some novel types of exact solutions can be explicitly obtained. Especially, the richness of the localized excitations of the supersymmetric integrable system is discovered. The rich multi-soliton solutions obtained here have not yet been obtained by using other methods. However, the traditional known multi-soliton solutions can also not be obtained by the bosonization approach of this Letter. Some open problems on the bosonization of the supersymmetric integrable models are proposed in the both classical and quantum levels.

  13. Immunoflourescence and mRNA analysis of human embryonic stem cells (hESCs) grown under feeder-free conditions

    DEFF Research Database (Denmark)

    Awan, Aashir; Oliveri, Roberto S; Jensen, Pernille L

    2010-01-01

    This chapter describes the procedures in order to do immunofluorescence (IF) microscopy and quantitative PCR (qPCR) analysis of human embryonic stem cells (hESCs) grown specifically under feeder-free conditions. A detailed protocol outlining the steps from initially growing the cells, passaging...... onto 16-well glass chambers, and continuing with the general IF and qPCR steps will be provided. The techniques will be illustrated with new results on cellular localization of transcriptional factors and components of the Hedgehog, Wnt, and PDGF signaling pathways to primary cilia in stem cell...

  14. Genetic and cell biological aspects of PTEN in prostate cancer

    NARCIS (Netherlands)

    P.W. van Duijn (Petra)

    2008-01-01

    textabstractThe dual specific phosphatase PTEN (Phosphatase and TENsin homolog deleted on chromosome 10) is one of the most extensively studied proteins of the last decade. It was the first phosphatase identified as a tumor suppressor and in sporadic cancers PTEN is one of the most frequently altere

  15. MyosinV controls PTEN function and neuronal cell size.

    Science.gov (United States)

    van Diepen, Michiel T; Parsons, Maddy; Downes, C Peter; Leslie, Nicholas R; Hindges, Robert; Eickholt, Britta J

    2009-10-01

    The tumour suppressor PTEN can inhibit cell proliferation and migration as well as control cell growth, in different cell types. PTEN functions predominately as a lipid phosphatase, converting PtdIns(3,4,5)P(3) to PtdIns(4,5)P(2), thereby antagonizing PI(3)K (phosphoinositide 3-kinase) and its established downstream effector pathways. However, much is unclear concerning the mechanisms that regulate PTEN movement to the cell membrane, which is necessary for its activity towards PtdIns(3,4,5)P(3) (Refs 3, 4, 5). Here we show a requirement for functional motor proteins in the control of PI3K signalling, involving a previously unknown association between PTEN and myosinV. FRET (Förster resonance energy transfer) measurements revealed that PTEN interacts directly with myosinV, which is dependent on PTEN phosphorylation mediated by CK2 and/or GSK3. Inactivation of myosinV-transport function in neurons increased cell size, which, in line with known attributes of PTEN-loss, required PI(3)K and mTor. Our data demonstrate a myosin-based transport mechanism that regulates PTEN function, providing new insights into the signalling networks regulating cell growth.

  16. Pten function in zebrafish : Anything but a fish story

    NARCIS (Netherlands)

    Stumpf, Miriam; Choorapoikayil, Suma; den Hertog, J.

    2015-01-01

    Zebrafish is an excellent model system for the analysis of gene function. We and others use zebrafish to investigate the function of the tumor suppressor, Pten, in tumorigenesis and embryonic development. Zebrafish have two pten genes, ptena and ptenb. The recently identified N-terminal extension of

  17. A unified nomenclature and amino acid numbering for human PTEN

    NARCIS (Netherlands)

    Pulido, Rafael; Baker, Suzanne J; Barata, Joao T; Carracedo, Arkaitz; Cid, Victor J; Chin-Sang, Ian D; Davé, Vrushank; den Hertog, Jeroen; Devreotes, Peter; Eickholt, Britta J; Eng, Charis; Furnari, Frank B; Georgescu, Maria-Magdalena; Gericke, Arne; Hopkins, Benjamin; Jiang, Xeujun; Lee, Seung-Rock; Lösche, Mathias; Malaney, Prerna; Matias-Guiu, Xavier; Molina, María; Pandolfi, Pier Paolo; Parsons, Ramon; Pinton, Paolo; Rivas, Carmen; Rocha, Rafael M; Rodríguez, Manuel S; Ross, Alonzo H; Serrano, Manuel; Stambolic, Vuk; Stiles, Bangyan; Suzuki, Akira; Tan, Seong-Seng; Tonks, Nicholas K; Trotman, Lloyd C; Wolff, Nicolas; Woscholski, Rudiger; Wu, Hong; Leslie, Nicholas R

    2014-01-01

    The tumor suppressor PTEN is a major brake for cell transformation, mainly due to its phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] phosphatase activity that directly counteracts the oncogenicity of phosphoinositide 3-kinase (PI3K). PTEN mutations are frequent in tumors and in the germ line

  18. A unified nomenclature and amino acid numbering for human PTEN

    NARCIS (Netherlands)

    Pulido, Rafael; Baker, Suzanne J; Barata, Joao T; Carracedo, Arkaitz; Cid, Victor J; Chin-Sang, Ian D; Davé, Vrushank; den Hertog, Jeroen; Devreotes, Peter; Eickholt, Britta J; Eng, Charis; Furnari, Frank B; Georgescu, Maria-Magdalena; Gericke, Arne; Hopkins, Benjamin; Jiang, Xeujun; Lee, Seung-Rock; Lösche, Mathias; Malaney, Prerna; Matias-Guiu, Xavier; Molina, María; Pandolfi, Pier Paolo; Parsons, Ramon; Pinton, Paolo; Rivas, Carmen; Rocha, Rafael M; Rodríguez, Manuel S; Ross, Alonzo H; Serrano, Manuel; Stambolic, Vuk; Stiles, Bangyan; Suzuki, Akira; Tan, Seong-Seng; Tonks, Nicholas K; Trotman, Lloyd C; Wolff, Nicolas; Woscholski, Rudiger; Wu, Hong; Leslie, Nicholas R

    2014-01-01

    The tumor suppressor PTEN is a major brake for cell transformation, mainly due to its phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] phosphatase activity that directly counteracts the oncogenicity of phosphoinositide 3-kinase (PI3K). PTEN mutations are frequent in tumors and in the germ line

  19. PTEN-PDZ domain interactions: Binding of PTEN to PDZ domains of PTPN13.

    NARCIS (Netherlands)

    Sotelo, N.S.; Schepens, J.T.G.; Valiente, M.; Hendriks, W.J.A.J.; Pulido, R.

    2015-01-01

    Protein modular interactions mediated by PDZ domains are essential for the establishment of functional protein networks controlling diverse cellular functions. The tumor suppressor PTEN possesses a C-terminal PDZ-binding motif (PDZ-BM) that is recognized by a specific set of PDZ domains from scaffol

  20. Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine/threonine kinases.

    Science.gov (United States)

    Valiente, Miguel; Andrés-Pons, Amparo; Gomar, Beatriz; Torres, Josema; Gil, Anabel; Tapparel, Caroline; Antonarakis, Stylianos E; Pulido, Rafael

    2005-08-12

    The tumor suppressor phosphatase PTEN is a key regulator of cell growth and apoptosis that interacts with PDZ domains from regulatory proteins, including MAGI-1/2/3, hDlg, and MAST205. Here we identified novel PTEN-binding PDZ domains within the MAST205-related proteins, syntrophin-associated serine/threonine kinase and MAST3, characterized the regions of PTEN involved in its interaction with distinctive PDZ domains, and analyzed the functional consequences on PTEN of PDZ domain binding. Using a panel of PTEN mutations, as well as PTEN chimeras containing distinct domains of the related protein TPTE, we found that the PTP and C2 domains of PTEN do not affect PDZ domain binding and that the C-terminal tail of PTEN (residues 350-403) provides selectivity to recognize specific PDZ domains from MAGI-2, hDlg, and MAST205. Binding of PTEN to the PDZ-2 domain from MAGI-2 increased PTEN protein stability. Furthermore, binding of PTEN to the PDZ domains from microtubule-associated serine/threonine kinases facilitated PTEN phosphorylation at its C terminus by these kinases. Our results suggest an important role for the C-terminal region of PTEN in the selective association with scaffolding and/or regulatory molecules and provide evidence that PDZ domain binding stabilizes PTEN and targets this tumor suppressor for phosphorylation by microtubule-associated serine/threonine kinases.

  1. KdV-Burgers方程和 KdV-Burgers-Kuramoto方程的精确解%Exact solutions to the KdV-Burgers equation and KdV-Burgers-Kuramoto equation

    Institute of Scientific and Technical Information of China (English)

    谢元喜; 朱曙华

    2007-01-01

    基于对 KdV-Burgers方程和KdV-Burgers-Kuramoto方程特点的分析,提出了一种由Burgers方程的解和 KdV 方程的解通过线性叠加构造 KdV-Burgers 方程的解以及由 KdV 方程的解和Kuramoto-Sivashinsky 方程的解通过线性叠加构造 KdV-Burgers-Kuramoto 方程的解的方法,并用该法求得了 KdV-Burgers 方程和 KdV-Burgers-Kuramoto 方程的若干精确解.

  2. Clinical Implications for Germline PTEN Spectrum Disorders.

    Science.gov (United States)

    Ngeow, Joanne; Sesock, Kaitlin; Eng, Charis

    2017-06-01

    Patients with PTEN hamartoma tumor syndrome (PHTS) may present to a variety of different subspecialties with benign and malignant clinical features. They have increased lifetime risks of breast, endometrial, thyroid, renal, and colon cancers, as well as neurodevelopmental disorders such as autism spectrum disorder. Patients and affected family members can be offered gene-directed surveillance and management. Patients who are unaffected can be spared unnecessary investigations. With longitudinal follow-up, we are likely to identify other non-cancer manifestations associated with PHTS such as metabolic, immunologic, and neurologic features. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Creating, Searching, and Deleting KD Trees Using C++

    Science.gov (United States)

    2014-09-01

    Creating, Searching, and Deleting KD Trees Using C++ by Robert J Yager ARL-TN-0629 September 2014...Deleting KD Trees Using C++ by Robert J Yager Weapons and Materials Research Directorate, ARL...Searching, and Deleting KD Trees Using C++ 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Robert J Yager

  4. A Discrete Lax-Integrable Coupled System Related to Coupled KdV and Coupled mKdV Equations

    Institute of Scientific and Technical Information of China (English)

    LIU Ping; JIA Ma; LOU Sen-Yue

    2007-01-01

    A modified Korteweg-de Vries (mKdV) lattice is found to be also a discrete Korteweg-de Vries (KdV) equation.A discrete coupled system is derived from the single lattice equation and its Lax pair is proposed. The coupled system is shown to be related to the coupled KdV and coupled mKdV systems which are widely used in physics.

  5. Phosphorylation of PTEN at STT motif is associated with DNA damage response

    Energy Technology Data Exchange (ETDEWEB)

    Misra, Sandip; Mukherjee, Ananda; Karmakar, Parimal, E-mail: pkarmakar_28@yahoo.co.in

    2014-12-15

    Highlights: • Phosphorylation PTEN at the C-terminal STT motif is necessary for DNA repair. • DNA damage induces phosphorylation of STT motif of PTEN. • Phospho-PTEN translocates to nucleus after DNA damage. • Phospho-PTEN forms nuclear foci after DNA damage which co localized with γH2AX. - Abstract: Phosphatase and tensin homolog deleted on chromosome Ten (PTEN), a tumor suppressor protein participates in multiple cellular activities including DNA repair. In this work we found a relationship between phosphorylation of carboxy (C)-terminal STT motif of PTEN and DNA damage response. Ectopic expression of C-terminal phospho-mutants of PTEN, in PTEN deficient human glioblastoma cells, U87MG, resulted in reduced viability and DNA repair after etoposide induced DNA damage compared to cells expressing wild type PTEN. Also, after etoposide treatment phosphorylation of PTEN increased at C-terminal serine 380 and threonine 382/383 residues in PTEN positive HEK293T cells and wild type PTEN transfected U87MG cells. One-step further, DNA damage induced phosphorylation of PTEN was confirmed by immunoprecipitation of total PTEN from cellular extract followed by immunobloting with phospho-specific PTEN antibodies. Additionally, phospho-PTEN translocated to nucleus after etoposide treatment as revealed by indirect immunolabeling. Further, phosphorylation dependent nuclear foci formation of PTEN was observed after ionizing radiation or etoposide treatment which colocalized with γH2AX. Additionally, etoposide induced γH2AX, Mre11 and Ku70 foci persisted for a longer period of times in U87MG cells after ectopic expression of PTEN C-terminal phospho-mutant constructs compared to wild type PTEN expressing cells. Thus, our findings strongly suggest that DNA damage induced phosphorylation of C-terminal STT motif of PTEN is necessary for DNA repair.

  6. On a generalized fifth order KdV equations

    Energy Technology Data Exchange (ETDEWEB)

    Kaya, Dogan; El-Sayed, Salah M

    2003-04-07

    In this Letter, we dealt with finding the solutions of a generalized fifth order KdV equation (for short, gfKdV) by using the Adomian decomposition method (for short, ADM). We prove the convergence of ADM applied to the gfKdV equation. Then we obtain the exact solitary-wave solutions and numerical solutions of the gfKdV equation for the initial conditions. The numerical solutions are compared with the known analytical solutions. Their remarkable accuracy are finally demonstrated for the gfKdV equation.

  7. Mesodermal Pten inactivation leads to alveolar capillary dysplasia- like phenotype.

    Science.gov (United States)

    Tiozzo, Caterina; Carraro, Gianni; Al Alam, Denise; Baptista, Sheryl; Danopoulos, Soula; Li, Aimin; Lavarreda-Pearce, Maria; Li, Changgong; De Langhe, Stijn; Chan, Belinda; Borok, Zea; Bellusci, Saverio; Minoo, Parviz

    2012-11-01

    Alveolar capillary dysplasia (ACD) is a congenital, lethal disorder of the pulmonary vasculature. Phosphatase and tensin homologue deleted from chromosome 10 (Pten) encodes a lipid phosphatase controlling key cellular functions, including stem/progenitor cell proliferation and differentiation; however, the role of PTEN in mesodermal lung cell lineage formation remains unexamined. To determine the role of mesodermal PTEN in the ontogeny of various mesenchymal cell lineages during lung development, we specifically deleted Pten in early embryonic lung mesenchyme in mice. Pups lacking Pten died at birth, with evidence of failure in blood oxygenation. Analysis at the cellular level showed defects in angioblast differentiation to endothelial cells and an accompanying accumulation of the angioblast cell population that was associated with disorganized capillary beds. We also found decreased expression of Forkhead box protein F1 (Foxf1), a gene associated with the ACD human phenotype. Analysis of human samples for ACD revealed a significant decrease in PTEN and increased activated protein kinase B (AKT). These studies demonstrate that mesodermal PTEN has a key role in controlling the amplification of angioblasts as well as their differentiation into endothelial cells, thereby directing the establishment of a functional gas exchange interface. Additionally, these mice could serve as a murine model of ACD.

  8. Bifurcation and Solitary Waves of the Combined KdV and KdV Equation

    Institute of Scientific and Technical Information of China (English)

    HUA Cun-Cai; LIU Yan-Zhu

    2002-01-01

    Bifurcation, bistability and solitary waves of the combined KdV and mKdV equation are investigatedsystematically. At first, bifurcation and bistability are analyzed by selecting an integral constant as the bifurcationparameter. Then, different conditions expressed in terms of the bifurcation parameter are obtained for the existence ofbreather-like, algebraic, pulse-like solitary waves, and shock waves. All types of the solitary wave and shock wave solutionsare given by direct integration. Finally, an approximate analytic method by employing the interpolation polynomials iscomplete and the theoretical methods are the simplest hitherto.

  9. WWP2 and its association with PTEN in endometrial cancer

    Directory of Open Access Journals (Sweden)

    Aine E. Clements

    2015-08-01

    We found that in tumors with low PTEN protein but normal mRNA expression there were significantly higher levels of WWP2 expression (p = 0.0017. Increased WWP2 expression was not associated with clinical prognostic factors including lymphovascular space invasion, ≥50% myometrial invasion, grade, stage or recurrence. WWP2 expression was not different statistically between tumors and normal controls (p = NS. Therefore, in this cohort, tumors with low PTEN protein but normal mRNA expression had elevated levels of WWP2 expression. This suggests that WWP2 may be playing a role in PTEN degradation in endometrial cancer.

  10. DNA methylation of PTEN gene promoter region is not correlated ...

    African Journals Online (AJOL)

    Yomi

    2012-02-23

    Feb 23, 2012 ... Key words: PTEN, promoter methylation, bladder cancer. INTRODUCTION ... al., 2005), pancreatic cancer (Asano et al., 2004), thyroid cancer (Frisk et al., ..... papillary mucinous neoplasms of the pancreas. J. Hepatobiliary.

  11. What controls PTEN and what it controls (in prostate cancer)

    Institute of Scientific and Technical Information of China (English)

    Paramita M Ghosh

    2012-01-01

    The standard of care for metastatic prostate cancer (PCa) is androgen deprivation therapy since almost all PCa growth is initially reliant on the androgen receptor (AR).However,almost all patients develop resistance to this therapy within 18-24months,and current treatment for castration-resistant prostate cancer (CRPC) is extremely limited,despite the advent of new drugs that target the AR,such as ahiraterone and MDV3100.1 Multiple studies have associated the loss of phosphatase and tensin homolog deleted on chromosome 10(PTEN),a dual lipid and protein phosphatase that is frequently lost in prostate cancer,with the development of CRPC.2,3 Yet,multiple studies have shown that at least 20%-40%of primary PCa,which are almost always androgen sensitive,experience a loss of PTEN,4,5 while as many as 30% of CRPC tumors are PTEN-positive.6 The broad questions then facing researchers are:(i) How does PTEN loss cause CRPC?;(ii) What is the mechanism of CRPC development in PTEN+/+ tumors?;and (iii) How can CRPC tumors be inhibited in PTEN-null cells?Three new publications in recent times have come up with mechanisms that answer these questions.7-9 Two of these,both in Cancer Cell eadier this year,from the laboratories of Dr Charles Sawyers and Dr Hong Wu,address a novel negative feedback regulation between AR and PTEN,and all three,including the one from Dr Damu Tang,show that the loss of PTEN function is likely the first step towards the development of CRPC.

  12. Caffeine activates tumor suppressor PTEN in sarcoma cells

    OpenAIRE

    Miwa, Shinji; Sugimoto, Naotoshi; Shirai, Toshiharu; Hayashi, Katsuhiro; Nishida, Hideji; Ohnari, Issei; Takeuchi, Akihiko; Yachie, Akihiro; Tsuchiya, Hiroyuki

    2011-01-01

    The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a negative regulator of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Akt activation exerts a strong anti-apoptotic effect and inhibits key pro-apoptotic proteins. We investigated the effect of caffeine in the prevention of tumor cell proliferation and induction of cell death. We found that caffeine induced increased intracellular cAMP levels, PTEN activation and Akt inactivation, which to...

  13. Numerical study on generalized KdV equations and Ito-type coupled KdV equations%广义KdV方程和Ito型耦合KdV方程的数值研究

    Institute of Scientific and Technical Information of China (English)

    李佩玲; 刘儒勋

    2008-01-01

    An implicit compact difference Padé scheme was improved to solve the fully nonlinear Korteweg-de Vries (KdV) equations and Ito-type coupled KdV equations. Particularly, this method was applied to study the behaviors of solutions of compacton and Ito-type coupled KdV equations. Numerical results show the effectiveness of this scheme.%采用隐式紧差分Padé方法解完全非线性KdV方程和Ito型耦合KdV方程.特别地,应用这种方法研究了compacton和Ito型耦合KdV方程的解特性.数值结果证明了这种方法的效果.

  14. Molecular Analysis of AFP and HSA Interactions with PTEN Protein.

    Science.gov (United States)

    Zhu, Mingyue; Lin, Bo; Zhou, Peng; Li, Mengsen

    2015-01-01

    Human cytoplasmic alpha-fetoprotein (AFP) has been classified as a member of the albuminoid gene family. The protein sequence of AFP has significant homology to that of human serum albumin (HSA), but its biological characteristics are vastly different from HSA. The AFP functions as a regulator in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway, but HSA plays a key role as a transport protein. To probe their molecular mechanisms, we have applied colocalization, coimmunoprecipitation (co-IP), and molecular docking approaches to analyze the differences between AFP and HSA. The data from colocalization and co-IP displayed a strong interaction between AFP and PTEN (phosphatase and tensin homolog), demonstrating that AFP did bind to PTEN, but HSA did not. The molecular docking study further showed that the AFP domains I and III could contact with PTEN. In silicon substitutions of AFP binding site residues at position 490M/K and 105L/R corresponding to residues K490 and R105 in HSA resulted in steric clashes with PTEN residues R150 and K46, respectively. These steric clashes may explain the reason why HSA cannot bind to PTEN. Ultimately, the experimental results and the molecular modeling data from the interactions of AFP and HSA with PTEN will help us to identify targets for designing drugs and vaccines against human hepatocellular carcinoma.

  15. Subtle variations in Pten dose determine cancer susceptibility

    Science.gov (United States)

    Alimonti, Andrea; Carracedo, Arkaitz; Clohessy, John G; Trotman, Lloyd C; Nardella, Caterina; Egia, Ainara; Salmena, Leonardo; Sampieri, Katia; Haveman, William J; Brogi, Edi; Richardson, Andrea L; Zhang, Jiangwen; Pandolfi, Pier Paolo

    2010-01-01

    Cancer susceptibility has been attributed to at least one heterozygous genetic alteration in a tumor suppressor gene (TSG)1. It has been hypothesized that subtle variations in TSG expression can promote cancer development2,3. However, this hypothesis has not yet been definitively supported in vivo. PTEN is a TSG frequently lost in human cancer and mutated in inherited cancer-predisposition syndromes4. Here, we analyze Pten hypermorphic mice (Ptenhy/+), expressing 80% normal levels of Pten. Ptenhy/+ mice develop a spectrum of tumors, with breast tumors occurring at the highest penetrance. All breast tumors analyzed here retained two intact copies of Pten and maintained Pten levels above heterozygosis. Notably, subtle downregulation of Pten altered the steady-state biology of the mammary tissues and the expression profiles of genes involved in cancer cell proliferation. We present an alterative working model for cancer development in which subtle reductions in the dose of TSGs predispose to tumorigenesis in a tissue-specific manner. PMID:20400965

  16. Methods to Study PTEN in Mitochondria and Endoplasmic Reticulum.

    Science.gov (United States)

    Missiroli, Sonia; Morganti, Claudia; Giorgi, Carlotta; Pinton, Paolo

    2016-01-01

    Although PTEN has been widely described as a nuclear and cytosolic protein, in the last 2 years, alternative organelles, such as the endoplasmic reticulum (ER), pure mitochondria, and mitochondria-associated membranes (MAMs), have been recognized as pivotal targets of PTEN activity.Here, we describe different methods that have been used to highlight PTEN subcellular localization.First, a protocol to extract nuclear and cytosolic fractions has been described to assess the "canonical" PTEN localization. Moreover, we describe a protocol for mitochondria isolation with proteinase K (PK) to further discriminate whether PTEN associates with the outer mitochondrial membrane (OMM) or resides within the mitochondria. Finally, we focus our attention on a subcellular fractionation protocol of cells that permits the isolation of MAMs containing unique regions of ER membranes attached to the outer mitochondrial membrane (OMM) and mitochondria without contamination from other organelles. In addition to biochemical fractionations, immunostaining can be used to determine the subcellular localization of proteins; thus, a detailed protocol to obtain good immunofluorescence (IF) is described. The employment of these methodological approaches could facilitate the identification of different PTEN localizations in several physiopathological contexts.

  17. Antibody Phage Library Screening Efficiency Measured by KD Values

    Institute of Scientific and Technical Information of China (English)

    WANG Hui-tang; SHAN Ya-ming; TANG Li-li; GAO Li-zeng; WANG Li-ping; LI Wei; LI Yu-xin

    2005-01-01

    An antibody phage library was screened with two target molecules, IFNα-2a and FGFR-GST, and the KD value of each round of panning was measured. It was found that the apparent KD values decreased along with each additional panning round, which indicates the increase of the binding affinity between the phage and the target molecules.This result shows that the KD value is a reliable intrinsic parameter and a new method for screening efficiency detection is thus provided.

  18. Bilinear approach to N=2 supersymmetric KdV equations

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The N=2 supersymmetric KdV equations are studied within the framework of Hirota bilinear method. For two such equations, namely N=2, a=4 and N=2, a=1 supersymmetric KdV equations, we obtain the corresponding bilinear formulations. Using them, we construct particular solutions for both cases. In particular, a bilinear Bcklund transformation is given for the N=2, a=1 supersymmetric KdV equation.

  19. The mKdV Hierarchy With Integral Source

    Institute of Scientific and Technical Information of China (English)

    叶硕

    2002-01-01

    @@ 1 IntroductionThe nonlinear Schrodinger equation with integral source (NLSEIS) and the KdV equation with integral source (KdVIS) were integrated by inverse scattering method in [1,2] and -method in [3].However,since the evolution equations for eigenfunction in Lax representation for NLSEIS and KdVIS were not obtained,the determining scatterging data in [1-3] was quite complicated and required some skill.

  20. Soliton solutions of a generalized discrete KdV equation

    CERN Document Server

    Kanki, Masataka; Tokihiro, Tetsuji

    2012-01-01

    We investigate the multi-soliton solutions to the generalized discrete KdV equation. In some cases a soliton with smaller amplitude moves faster than that with larger amplitude unlike the soliton solutions of the KdV equation. This phenomenon is intuitively understood from its ultradiscrete limit, where the system turns to the box ball system with a carrier. KEYWORDS: soliton, integrable equation, nonlinear system, discrete KdV equation, cellular automaton

  1. On some classes of mKdV periodic solutions

    Energy Technology Data Exchange (ETDEWEB)

    Kevrekidis, P G [Department of Mathematics and Statistics, University of Massachusetts, Amherst, MA 01003-4515 (United States); Khare, Avinash [Institute of Physics, Bhubaneswar, Orissa 751005 (India); Saxena, A [Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Herring, G [Department of Mathematics and Statistics, University of Massachusetts, Amherst, MA 01003-4515 (United States)

    2004-11-12

    We obtain exact periodic solutions of the positive and negative modified Kortweg-de Vries (mKdV) equations. We examine the dynamical stability of these solitary wave lattices through direct numerical simulations. While the positive mKdV breather lattice solutions are found to be unstable, the two-soliton lattice solution of the same equation is found to be stable. Similarly, a negative mKdV lattice solution is found to be stable. We also touch upon the implications of these results for the KdV equation.

  2. Symbolic computation and abundant travelling wave solutions to KdV–mKdV equation

    Indian Academy of Sciences (India)

    SYED TAHIR RAZA RIZVI; KASHIF ALI; ALI SARDAR; MUHAMMAD YOUNIS; AHMET BEKIR

    2017-01-01

    In this article, the novel $(G'/G)$-expansion method is successfully applied to construct the abundant travelling wave solutions to the KdV–mKdV equation with the aid of symbolic computation. This equation is one of the most popular equation in soliton physics and appear in many practical scenarios like thermal pulse, wave propagation of bound particle, etc. The method is reliable and useful, and gives more general exact travelling wave solutions than the existing methods. The solutions obtained are in the form of hyperbolic, trigonometricand rational functions including solitary, singular and periodic solutions which have many potential applications in physical science and engineering. Many of these solutions are new and some have already been constructed. Additionally, the constraint conditions, for the existence of the solutions are also listed.

  3. Symbolic computation and abundant travelling wave solutions to KdV-mKdV equation

    Science.gov (United States)

    Raza Rizvi, Syed Tahir; Ali, Kashif; Sardar, Ali; Younis, Muhammad; Bekir, Ahmet

    2017-01-01

    In this article, the novel ( G '/ G)-expansion method is successfully applied to construct the abundant travelling wave solutions to the KdV-mKdV equation with the aid of symbolic computation. This equation is one of the most popular equation in soliton physics and appear in many practical scenarios like thermal pulse, wave propagation of bound particle, etc. The method is reliable and useful, and gives more general exact travelling wave solutions than the existing methods. The solutions obtained are in the form of hyperbolic, trigonometric and rational functions including solitary, singular and periodic solutions which have many potential applications in physical science and engineering. Many of these solutions are new and some have already been constructed. Additionally, the constraint conditions, for the existence of the solutions are also listed.

  4. Classification of Multiply Travelling Wave Solutions for Coupled Burgers, Combined KdV-Modified KdV, and Schrödinger-KdV Equations

    Directory of Open Access Journals (Sweden)

    A. R. Seadawy

    2015-01-01

    Full Text Available Some explicit travelling wave solutions to constructing exact solutions of nonlinear partial differential equations of mathematical physics are presented. By applying a theory of Frobenius decompositions and, more precisely, by using a transformation method to the coupled Burgers, combined Korteweg-de Vries- (KdV- modified KdV and Schrödinger-KdV equation is written as bilinear ordinary differential equations and two solutions to describing nonlinear interaction of travelling waves are generated. The properties of the multiple travelling wave solutions are shown by some figures. All solutions are stable and have applications in physics.

  5. Genomic Analysis of hESC Pedigrees Identifies De Novo Mutations and Enables Determination of the Timing and Origin of Mutational Events

    Directory of Open Access Journals (Sweden)

    Dalit Ben-Yosef

    2013-09-01

    Full Text Available Given the association between mutational load and cancer, the observation that genetic aberrations are frequently found in human pluripotent stem cells (hPSCs is of concern. Prior studies in human induced pluripotent stem cells (hiPSCs have shown that deletions and regions of loss of heterozygosity (LOH tend to arise during reprogramming and early culture, whereas duplications more frequently occur during long-term culture. For the corresponding experiments in human embryonic stem cells (hESCs, we studied two sets of hESC lines: one including the corresponding parental DNA and the other generated from single blastomeres from four sibling embryos. Here, we show that genetic aberrations observed in hESCs can originate during preimplantation embryo development and/or early derivation. These early aberrations are mainly deletions and LOH, whereas aberrations arising during long-term culture of hESCs are more frequently duplications. Our results highlight the importance of close monitoring of genomic integrity and the development of improved methods for derivation and culture of hPSCs.

  6. A novel stem cell associated marker identified by monoclonal antibody HESC5:3 differentiates between neoplastic lesions in follicular thyroid neoplasms.

    Science.gov (United States)

    Heikkilä, Annukka; Fermér, Christian; Hagström, Jaana; Louhimo, Johanna; Mäenpää, Hanna; Siironen, Päivi; Heiskanen, Ilkka; Nilsson, Olle; Arola, Johanna; Haglund, Caj

    2015-07-01

    Follicular thyroid lesions are the bane of cytopathology. Differentiation between adenoma and carcinoma is impossible, and often these neoplasms are indistinguishable even from uninodular goitre. In other cancers as well, a theory of stem cells as the origin of cancer has been discussed in thyroid carcinogenesis. We aimed to examine a novel stem cell associated marker identified by monoclonal antibody HESC5:3 in follicular lesions in an attempt to find a marker for differential diagnosis in thyroid cytopathology. HESC5:3 was raised against and is specific for undifferentiated human embryonic stem cells. The epitope of this novel antibody is to be defined. Immunohistochemical expression of HESC5:3 was examined in clinical material comprised of follicular neoplasms (83 adenomas, 43 carcinomas) and non-neoplastic lesions (41 goitrous, 22 hyperplastic, 23 normal tissue specimens). Staining differed significantly between neoplastic and non-neoplastic lesions. Nuclear staining was increased in non-neoplastic cells, whereas in neoplastic cells expression was mainly cytoplasmic. There was no difference between benign and malignant lesions, suggesting a role in early tumourigenesis. In conclusion, the HESC5:3 epitope may be of benefit as a neoplasia marker in distinguishing between uninodular goitre and neoplasia. Characterization of the epitope would increase the interest in this promising new stem cell associated marker.

  7. A role for Pten in paediatric intestinal dysmotility disorders.

    LENUS (Irish Health Repository)

    O'Donnell, Anne-Marie

    2012-02-01

    PURPOSE: The enteric nervous system (ENS) is a network of neurons and glia that lies within the gut wall. It is responsible for the normal regulation of gut motility and secretory activities. Hirschsprung\\'s disease (HD) is a congenital defect of the ENS, characterised by an absence of ganglia in the distal colon. Intestinal neuronal dysplasia (IND) is a condition that clinically resembles HD, characterised by hyperganglionosis, giant and ectopic ganglia, resulting in intestinal dysmotility. Intestinal ganglioneuromatosis is characterised by hyperplasia and hypertrophy of enteric neuronal cells and causes chronic intestinal pseudo-obstruction (CIPO). Phosphatase and tensin homolog deleted on chromosome 10 (Pten) is a phosphatase that is critical for controlling cell growth, proliferation and cell death. A recent study of Pten knockout mice showed evidence of ganglioneuromatosis in the ENS suggesting a role for this protein in ENS development. Ganglioneuromatosis patients have also been shown to have a decreased level of Pten expression in the colon. The aim of our study was to investigate Pten expression in the ENS of HD and IND patients compared to normal controls. METHODS: Resected tissue from 10 HD and 10 IND type B patients was fixed and embedded in paraffin wax. Normal control colon tissue was obtained from ten patients who underwent a colostomy closure for imperforate anus. Sections were cut and immunohistochemistry was carried out using a Pten antibody. Results were analysed by light microscopy. RESULTS: Staining showed that Pten was strongly expressed in ganglia of both the submucosal and myenteric plexus of normal and HD specimens from the ganglionic colon. Pten expression was significantly reduced in the giant ganglia in IND patients in both the myenteric and submucosal plexuses compared to the normal controls. Specimens from the aganglionic region of HD did not show Pten expression. CONCLUSION: To the best of our knowledge, this is the first study

  8. A Novel PTEN/Mutant p53/c-Myc/Bcl-XL Axis Mediates Context-Dependent Oncogenic Effects of PTEN with Implications for Cancer Prognosis and Therapy

    Directory of Open Access Journals (Sweden)

    Xiaoping Huang

    2013-08-01

    Full Text Available Phosphatase and tensin homolog located on chromosome 10 (PTEN is one of the most frequently mutated tumor suppressors in human cancer including in glioblastoma. Here, we show that PTEN exerts unconventional oncogenic effects in glioblastoma through a novel PTEN/mutant p53/c-Myc/Bcl-XL molecular and functional axis. Using a wide array of molecular, genetic, and functional approaches, we demonstrate that PTEN enhances a transcriptional complex containing gain-of-function mutant p53, CBP, and NFY in human glioblastoma cells and tumor tissues. The mutant p53/CBP/NFY complex transcriptionally activates the oncogenes c-Myc and Bcl-XL, leading to increased cell proliferation, survival, invasion, and clonogenicity. Disruption of the mutant p53/c-Myc/Bcl-XL axis or mutant p53/CBP/NFY complex reverses the transcriptional and oncogenic effects of PTEN and unmasks its tumor-suppressive function. Consistent with these data, we find that PTEN expression is associated with worse patient survival than PTEN loss in tumors harboring mutant p53 and that a small molecule modulator of p53 exerts greater antitumor effects in PTEN-expressing cancer cells. Altogether, our study describes a new signaling pathway that mediates context-dependent oncogenic/tumor-suppressive role of PTEN. The data also indicate that the combined mutational status of PTEN and p53 influences cancer prognosis and anticancer therapies that target PTEN and p53.

  9. A new pathway of glucocorticoid action for asthma treatment through the regulation of PTEN expression

    Directory of Open Access Journals (Sweden)

    Chen Qingge

    2011-04-01

    Full Text Available Abstract Background "Phosphatase and tensin homolog deleted on chromosome 10" (PTEN is mostly considered to be a cancer-related gene, and has been suggested to be a new pathway of pathogenesis of asthma. The purpose of this study was to investigate the effects of the glucocorticoid, dexamethasone, on PTEN regulation. Methods OVA-challenged mice were used as an asthma model to investigate the effect of dexamethasone on PTEN regulation. Immunohistochemistry was used to detect expression levels of PTEN protein in lung tissues. The human A549 cell line was used to explore the possible mechanism of action of dexamethasone on human PTEN regulation in vitro. A luciferase reporter construct under the control of PTEN promoter was used to confirm transcriptional regulation in response to dexamethasone. Results PTEN protein was found to be expressed at low levels in lung tissues in asthmatic mice; but the expression was restored after treatment with dexamethasone. In A549 cells, human PTEN was up-regulated by dexamethasone treatment. The promoter-reporter construct confirmed that dexamethasone could regulate human PTEN transcription. Treatment with the histone deacetylase inhibitor, TSA, could increase PTEN expression in A549 cells, while inhibition of histone acetylase (HAT by anacardic acid attenuated dexamethasone-induced PTEN expression. Conclusions Based on the data a new mechanism is proposed where glucocorticoids treat asthma partly through up-regulation of PTEN expression. The in vitro studies also suggest that the PTEN pathway may be involved in human asthma.

  10. Identification of nucleolus-localized PTEN and its function in regulating ribosome biogenesis.

    Science.gov (United States)

    Li, Pingdong; Wang, Danni; Li, Haiyang; Yu, Zhenkun; Chen, Xiaohong; Fang, Jugao

    2014-10-01

    The tumor suppressor PTEN is a lipid phosphatase that is found mutated in different types of human cancers. PTEN suppresses cell proliferation by inhibiting the PI3K-Akt signaling pathway at the cell membrane. However, PTEN is also demonstrated to localize in the cell nucleus where it exhibits tumor suppressive activity via a different, unknown mechanism. In this study we report that PTEN also localizes to the nucleolus and that nucleolar PTEN plays an important role in regulating nucleolar homeostasis and maintaining nucleolar morphology. Overexpression of nuclear PTEN in PTEN null cells inhibits Akt phosphorylation and reduces cell size. Knockdown of PTEN in PTEN positive cells leads to nucleolar morphologic changes and an increase in the proportion of cells with a greater number of nucleoli. In addition, knockdown of PTEN in PTEN positive cells increased ribosome biogenesis. These findings expand current understanding of function and relevance of nuclear localized PTEN and provide a foundation for the development of novel therapies targeting PTEN.

  11. Study on Double Wronskian Solutions of the KdV Equation%KdV方程的双Wronskian解研究

    Institute of Scientific and Technical Information of China (English)

    艾玉波

    2012-01-01

    The problem of double Wronskian solution is studied in this article, the modified KdV equation is solved using the double Wronskian technique, rational solution to the modified KdV equation is given with double Wronskian, and the double Wronskian determinant elements of expression are specifically solved.%在研究双Wronskian解的问题上,利用双Wronskian技巧对修正KdV方程求解,给出修正KdV方程双Wronskian形式的有理解,具体求解了双Wronskian行列式元素的表达式.

  12. Non-autonomous Degenerate KdV Systems

    OpenAIRE

    Turhan, Refik

    2002-01-01

    Non-autonomous degenerate KdV systems in (1+1) dimensions are considered for integrability classification. Integrability of the systems is associated with the existence of a recursion operator. Some new non-autonomous degenerate two-component KdV systems are found.

  13. Novel Wronskian Solutions of the KdV Equation

    Institute of Scientific and Technical Information of China (English)

    刘金; 邓淑芳

    2003-01-01

    The novel Wronskian solutions of the KdV equation were obtained as limits of the soliton solutions in the Wronskian form.These solutions were verified by direct substitution to satisfy the bilinear derivative form of the KdV equation and its Backlund trans-formation.

  14. Division algebras and extended super KdVs

    Energy Technology Data Exchange (ETDEWEB)

    Toppan, F. [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil). Coordenacao de Teoria de Campos e Particulas]. E-mail: toppan@cbpf.br

    2001-05-01

    The division algebras R, C, H, O are used to construct and analyze the N = 1, 2, 4, 8 supersymmetric extensions of the KdV hamiltonian equation. In particular a global N = 8 super-KdV system is introduced and shown to admit a Poisson bracket structure given by the 'Non-Associate N = 8 Superconformal Algebra'. (author)

  15. 7 CFR 29.1080 - Variegated dark red (KD).

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Variegated dark red (KD). 29.1080 Section 29.1080 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards..., 13, 14 and Foreign Type 92) § 29.1080 Variegated dark red (KD). A dark brownish-red...

  16. Homotopy analysis method for solving KdV equations

    Directory of Open Access Journals (Sweden)

    Hossein Jafari

    2010-06-01

    Full Text Available A scheme is developed for the numerical study of the Korteweg-de Vries (KdV and the Korteweg-de Vries Burgers (KdVB equations with initial conditions by a homotopy approach. Numerical solutions obtained by homotopy analysis method are compared with exact solution. The comparison shows that the obtained solutions are in excellent agreement.

  17. PTEN: a default gate-keeping tumor suppressor with a versatile tail

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The tumor suppressor PTEN controls a variety of biological processes including cell proliferation, growth, migration, and death. As a master cellular regulator, PTEN itself is also subjected to deliberated regulation to ensure its proper function. Defects in PTEN regulation have a profound impact on carcinogenesis. In this review, we briefly discuss recent advances concerning PTEN regulation and how such knowledge facilitates our understanding and further exploration of PTEN biology. The carboxyl-tail of PTEN, which appears to be associated with multiple types of posttranslational regulation, will be under detailed scrutiny. Further, a comparative analysis of PTEN and p53 suggests while p53 needs to be activated to suppress tumorigenesis (a dormant gatekeeper), PTEN is probably a constitutive surveillant against cancer development, thus a default gatekeeper.

  18. Hamiltonian formulation of SL(3) Ur-KdV equation

    CERN Document Server

    Chung, B K; Nam, S; Nam, Soonkeon

    1993-01-01

    We give a unified view of the relation between the $SL(2)$ KdV, the mKdV, and the Ur-KdV equations through the Fr\\'{e}chet derivatives and their inverses. For this we introduce a new procedure of obtaining the Ur-KdV equation, where we require that it has no non-local operators. We extend this method to the $SL(3)$ KdV equation, i.e., Boussinesq(Bsq) equation and obtain the hamiltonian structure of Ur-Bsq equationin a simple form. In particular, we explicitly construct the hamiltonian operator of the Ur-Bsq system which defines the poisson structure of the system, through the Fr\\'{e}chet derivative and its inverse.

  19. Reduced Expression of PTEN Protein and Its Prognostic Significance in the Gastrointestinal Stromal Tumor

    Institute of Scientific and Technical Information of China (English)

    张永红; 于冬冬; 李小兰; 胡俊波; 龚建平

    2010-01-01

    Little is reported about the role of PTEN gene in the progression and prognosis of GISTs.This study examined the clinical implications of the tumor suppressor gene PTEN as a prognostic factor in the GISTs.Immunohistological staining and immunoblotting were employed to examine the PTEN protein expression,and its association with clinical measures.Clinicopathological features were reviewed by a retrospective examination of medical records.Reduced PTEN expression was significantly associated with tumor diamete...

  20. Phosphorylation of PTEN at STT motif is associated with DNA damage response.

    Science.gov (United States)

    Misra, Sandip; Mukherjee, Ananda; Karmakar, Parimal

    2014-12-01

    Phosphatase and tensin homolog deleted on chromosome Ten (PTEN), a tumor suppressor protein participates in multiple cellular activities including DNA repair. In this work we found a relationship between phosphorylation of carboxy (C)-terminal STT motif of PTEN and DNA damage response. Ectopic expression of C-terminal phospho-mutants of PTEN, in PTEN deficient human glioblastoma cells, U87MG, resulted in reduced viability and DNA repair after etoposide induced DNA damage compared to cells expressing wild type PTEN. Also, after etoposide treatment phosphorylation of PTEN increased at C-terminal serine 380 and threonine 382/383 residues in PTEN positive HEK293T cells and wild type PTEN transfected U87MG cells. One-step further, DNA damage induced phosphorylation of PTEN was confirmed by immunoprecipitation of total PTEN from cellular extract followed by immunobloting with phospho-specific PTEN antibodies. Additionally, phospho-PTEN translocated to nucleus after etoposide treatment as revealed by indirect immunolabeling. Further, phosphorylation dependent nuclear foci formation of PTEN was observed after ionizing radiation or etoposide treatment which colocalized with γH2AX. Additionally, etoposide induced γH2AX, Mre11 and Ku70 foci persisted for a longer period of times in U87MG cells after ectopic expression of PTEN C-terminal phospho-mutant constructs compared to wild type PTEN expressing cells. Thus, our findings strongly suggest that DNA damage induced phosphorylation of C-terminal STT motif of PTEN is necessary for DNA repair. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. PTEN inhibition and axon regeneration and neural repair

    Institute of Scientific and Technical Information of China (English)

    Yosuke Ohtake; Umar Hayat; Shuxin Li

    2015-01-01

    The intrinsic growth ability of all the neurons declines during development although some may grow better than others. Numerous intracellular signaling proteins and transcription factors have been shown to regulate the intrinsic growth capacity in mature neurons. Among them, PI3 kinase/Akt pathway is important for controlling axon elongation. As a negative regulator of this pathway, the tumor suppressor phosphatase and tensin homolog (PTEN) appears critical to con-trol the regenerative ability of young and adult neurons. This review will focus on recent research progress in axon regeneration and neural repair by PTEN inhibition and therapeutic potential of blocking this phosphatase for neurological disorders. Inhibition of PTEN by deletion in con-ditional knockout mice, knockdown by short-hairpin RNA, or blockade by pharmacological approaches, including administration of selective PTEN antagonist peptides, stimulates various degrees of axon regrowth in juvenile or adult rodents with central nervous system injuries. Im-portantly, post-injury PTEN suppression could enhance axonal growth and functional recovery in adult central nervous system after injury.

  2. On "new travelling wave solutions" of the KdV and the KdV-Burgers equations

    NARCIS (Netherlands)

    Kudryashov, Nikolai A.

    2009-01-01

    The Korteweg-de Vries and the Korteweg-de Vries-Burgers equations are considered. Using the travelling wave the general solutions of these equations are presented. "New travelling wave solutions" of the KdV and the KdV-Burgers equations by Wazzan [Wazzan L Commun Nonlinear Sci Numer Simulat 2009:14:

  3. Multi-symplectic method for the generalized (2+1)-dimensional KdV-mKdV equation

    Institute of Scientific and Technical Information of China (English)

    Wei-Peng Hu; Zi-Chen Deng; Yu-Yue Qin; Wen-Rong Zhang

    2012-01-01

    In the present paper,a general solution involving three arbitrary functions for the generalized (2+1)-dimensional KdV-mKdV equation,which is derived from the generalized (l+l)-dimensional KdV-mKdV equation,is first introduced by means of the Wiess,Tabor,Carnevale (WTC) truncation method.And then multisymplectic fonmulations with several conservation laws taken into account are presented for the generalized (2+1)-dimensional KdV-mKdV equation based on the multisymplectic theory of Bridges.Subsequently,in order to simulate the periodic wave solutions in terms of rational functions of the Jacobi elliptic functions derived from the general solution,a semi-implicit multi-symplectic scheme is constructed that is equivalent to the Preissmann scheme.From the results of the numerical experiments,we can conclude that the multi-symplectic schemes can accurately simulate the periodic wave solutions of the generalized (2+ 1)-dimensional KdV-mKdV equation while preserve approximately the conservation laws.

  4. Suppression of gastric cancer growth by adenovirus-mediated transfer of the PTEN gene

    Institute of Scientific and Technical Information of China (English)

    Ying Hang; Yong-Chen Zheng; Yan Cao; Qing-Shan Li; Yu-Jie Sui

    2005-01-01

    AIM: To investigate the tumor-suppressive effect of the phosphatase and tensin homologue deleted from chromosome (PTEN) in human gastric cancer cells th atwere wild type for PTEN.METHODS: Adenoviruses expressing PTEN or luciferase as a control were introduced into gastric cancer cells.The effect of exogenous PTEN gene on the growth and apoptosis of gastric cancer cells that are wtPTEN were examined in vitro and in vivo.RESULTS: Adenovirus-mediated transfer of PTEN (AdPTEN) suppressed cell growth and induced apoptosis significantly in gastric cancer cells (MGC-803, SGC-7901)carrying wtPTEN in comparison with that in normal gastric epithelial cells (GES-1) carrying wtPTEN. This suppression was induced through downregulation of the Akt/PKB pathway, dephosphorylation of focal adhesion kinase and mitogen-activated protein kinase and cell-cycle arrest at the G2/M phase but not at the G1 phase. Furthermore,treatment of human gastric tumor xenografts (MGC-803,SGC-7901) with Ad-PTEN resulted in a significant (P<0.01)suppression of tumor growth.CONCLUSION: These results indicate a significant tumorsuppressive effect of Ad-PTEN against human gastric cancer cells. Thus, Ad-PTEN may be used as a potential therapeutic strategy for treatment of gastric cancers.

  5. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Zhen [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Gan, Ye-Hua, E-mail: kqyehuagan@bjmu.edu.cn [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China)

    2015-05-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-2 inhibitor, celecoxib, could enhance radiosensitization. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-2 inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-2 inhibitor enhanced radiosensitization through activating PTEN.

  6. Differentiation of stem cells upon deprivation of exogenous FGF2: a general approach to study spontaneous differentiation of hESCs in vitro.

    Science.gov (United States)

    Kjartansdóttir, Kristín Rós; Gabrielsen, Anette; Reda, Ahmed; Söder, Olle; Bergström-Tengzelius, Rosita; Andersen, Claus Yding; Hovatta, Outi; Stukenborg, Jan-Bernd; Fedder, Jens

    2012-12-01

    Establishing a model for in vitro differentiation of human embryonic stem cells (hESCs) towards the germ cell lineage could be used to identify molecular mechanisms behind germ cell differentiation that may help in understanding human infertility. Here, we evaluate whether a lack of exogenous fibroblast growth factor 2 (FGF2) is supporting spontaneous differentiation of hESCs cultured on human foreskin fibroblast (hFF) monolayers towards germ cell lineage. Additionally to depriving the hESCs of exogenous FGF2, cells were stimulated with all-trans retinoic acid (ATRA). To get a more comprehensive impression on effects of removal of FGF2 and stimulation with ATRA, we combined the results of three cell lines for each experimental setting. When combining gene expression profiles of three cell lines for 96 genes, only 6 genes showed a significant up-regulation in all cell lines, when no FGF2 was added to the media for 12 weeks. None of these genes are related to the germ lineage, whereas genes for neuronal cells (PAX6 and NR6A1) and endothelial cells (FLT-1 and PTF1A) were up-regulated. To induce and support the differentiation towards the germ lineage we stimulated hESCs with different concentrations of ATRA for 7 and 14 days. We observed no significant difference in gene expression on RNA level when combining all cell lines. Whereas, the overall outcome was negative, one of these cell lines demonstrated an up-regulation of DDX4 on RNA and protein level after 7 days of ATRA stimulation. In summary, our data showed that the lack of exogenous FGF2 results in up-regulation of genes crucial for neuronal and endothelial cell differentiation of hESCs, but not in the up-regulation of genes related to germ cell differentiation when cultured on hFFs. Additionally, we demonstrated that ATRA supplementation did not result in a general specific direction of hESCs towards the germ lineage.

  7. Decreasing Kd uncertainties through the application of thermodynamic sorption models.

    Science.gov (United States)

    Domènech, Cristina; García, David; Pękala, Marek

    2015-09-15

    Radionuclide retardation processes during transport are expected to play an important role in the safety assessment of subsurface disposal facilities for radioactive waste. The linear distribution coefficient (Kd) is often used to represent radionuclide retention, because analytical solutions to the classic advection-diffusion-retardation equation under simple boundary conditions are readily obtainable, and because numerical implementation of this approach is relatively straightforward. For these reasons, the Kd approach lends itself to probabilistic calculations required by Performance Assessment (PA) calculations. However, it is widely recognised that Kd values derived from laboratory experiments generally have a narrow field of validity, and that the uncertainty of the Kd outside this field increases significantly. Mechanistic multicomponent geochemical simulators can be used to calculate Kd values under a wide range of conditions. This approach is powerful and flexible, but requires expert knowledge on the part of the user. The work presented in this paper aims to develop a simplified approach of estimating Kd values whose level of accuracy would be comparable with those obtained by fully-fledged geochemical simulators. The proposed approach consists of deriving simplified algebraic expressions by combining relevant mass action equations. This approach was applied to three distinct geochemical systems involving surface complexation and ion-exchange processes. Within bounds imposed by model simplifications, the presented approach allows radionuclide Kd values to be estimated as a function of key system-controlling parameters, such as the pH and mineralogy. This approach could be used by PA professionals to assess the impact of key geochemical parameters on the variability of radionuclide Kd values. Moreover, the presented approach could be relatively easily implemented in existing codes to represent the influence of temporal and spatial changes in geochemistry

  8. Numerical simulation of a solitonic gas in KdV and KdV–BBM equations

    Energy Technology Data Exchange (ETDEWEB)

    Dutykh, Denys, E-mail: Denys.Dutykh@univ-savoie.fr [LAMA, UMR 5127 CNRS, Université de Savoie, Campus Scientifique, 73376 Le Bourget-du-Lac Cedex (France); Pelinovsky, Efim, E-mail: pelinovsky@hydro.appl.sci-nnov.ru [Department of Nonlinear Geophysical Processes, Institute of Applied Physics, Nizhny Novgorod (Russian Federation); Department of Applied Mathematics, Nizhny Novgorod State Technical University (Russian Federation); National Research University – Higher School of Economics (Russian Federation)

    2014-08-28

    The collective behaviour of soliton ensembles (i.e. the solitonic gas) is studied using the methods of the direct numerical simulation. Traditionally this problem was addressed in the context of integrable models such as the celebrated KdV equation. We extend this analysis to non-integrable KdV–BBM type models. Some high resolution numerical results are presented in both integrable and nonintegrable cases. Moreover, the free surface elevation probability distribution is shown to be quasi-stationary. Finally, we employ the asymptotic methods along with the Monte Carlo simulations in order to study quantitatively the dependence of some important statistical characteristics (such as the kurtosis and skewness) on the Stokes–Ursell number (which measures the relative importance of nonlinear effects compared to the dispersion) and also on the magnitude of the BBM term. - Highlights: • High-resolution simulations of a solitonic gas are presented. • Integrable and non-integrable cases are considered. • The effect of integrability was shown to be negligible. • Dependence of the statistical characteristics on the model parameters was studied.

  9. PTEN overexpression improves cisplatin-resistance of human ovarian cancer cells through upregulating KRT10 expression

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Huijuan; Wang, Ke; Liu, Wenxin; Hao, Quan, E-mail: quan_haotj@126.com

    2014-02-07

    Highlights: • Overexpression of PTEN enhanced the sensitivity of C13K cells to cisplatin. • KRT10 is a downstream molecule of PTEN involved in the resistance-reversing effect. • Overexpression of KRT10 enhanced the chemosensitivity of C13K cells to cisplatin. - Abstract: Multi-drug resistance (MDR) is a common cause of the failure of chemotherapy in ovarian cancer. PTEN, a tumor suppressor gene, has been demonstrated to be able to reverse cisplatin-resistance in ovarian cancer cell line C13K. However, the downstream molecules of PTEN involved in the resistance-reversing effect have not been completely clarified. Therefore, we screened the downstream molecules of PTEN and studied their interactions in C13K ovarian cancer cells using a 3D culture model. Firstly, we constructed an ovarian cancer cell line stably expressing PTEN, C13K/PTEN. MTT assay showed that overexpression of PTEN enhanced the sensitivity of C13K cells to cisplatin, but not to paclitaxel. Then we examined the differently expressed proteins that interacted with PTEN in C13K/PTEN cells with or without cisplatin treatment by co-immunoprecipitation. KRT10 was identified as a differently expressed protein in cisplatin-treated C13K/PTEN cells. Further study confirmed that cisplatin could induce upregulation of KRT10 mRNA and protein in C13K/PTEN cells and there was a directly interaction between KRT10 and PTEN. Forced expression of KRT10 in C13K cells also enhanced cisplatin-induced proliferation inhibition and apoptosis of C13K cells. In addition, KRT10 siRNA blocked cisplatin-induced proliferation inhibition of C13K/PTEN cells. In conclusion, our data demonstrate that KRT10 is a downstream molecule of PTEN which improves cisplatin-resistance of ovarian cancer and forced KRT10 overexpression may also act as a therapeutic method for overcoming MDR in ovarian cancer.

  10. Lagrangian Approach to Dispersionless KdV Hierarchy

    Directory of Open Access Journals (Sweden)

    Amitava Choudhuri

    2007-09-01

    Full Text Available We derive a Lagrangian based approach to study the compatible Hamiltonian structure of the dispersionless KdV and supersymmetric KdV hierarchies and claim that our treatment of the problem serves as a very useful supplement of the so-called r-matrix method. We suggest specific ways to construct results for conserved densities and Hamiltonian operators. The Lagrangian formulation, via Noether's theorem, provides a method to make the relation between symmetries and conserved quantities more precise. We have exploited this fact to study the variational symmetries of the dispersionless KdV equation.

  11. The Application of kd-tree in Astronomy

    CERN Document Server

    Gao, Dan; Zhao, Yongheng

    2008-01-01

    The basic idea of the kd-tree algorithm is to recursively partition a point set P by hyperplanes, and to store the obtained partitioning in a binary tree. Due to its immense popularity, many applications in astronomy have been implemented. The algorithm can been used to solve a near neighbor problem for cross-identification of huge catalogs and realize the classification of astronomical objects. Since kd-tree can speed up query and partition spaces, some approaches based on it have been applied for photometric redshift measurement. We give the case studies of kd-tree in astronomy to show its importance and performance.

  12. [Inhibitory effects of tumor suppressor gene PTEN on proliferation and metastasis of breast cancer ZR-75-1 cells].

    Science.gov (United States)

    Lin, Guan-Ping; Li, Xiang-Yong; Huang, Jin-Wen; Xiong, Liang; Zhou, Ke-Yuan

    2007-10-01

    Tumor suppressor gene PTEN could not only inhibit the proliferation of cancer cells, but also inhibit their metastasis. However, the mechanism is still unclear. This study was to investigate the effects of PTEN gene on the proliferation and metastasis of human breast cancer ZR-75-1 cells, and explore the mechanisms. Wild-type PTEN (wt-PTEN) plasmid and phosphatase-defective PTEN (G129R-PTEN) plasmid were transfected into ZR-75-1 cells by liposome, respectively. Cell proliferation was detected by MTT assay. Transfected cells were selected by puromycin. The expression of PTEN protein was detected by Western blot. Cell adhesion and invasion were tested by adhesion test and invasion test. The proliferation inhibition rate was significantly higher in wt-PTEN-transfected ZR-75-1 cells than in untransfected cells and G129R-PTEN-transfected cells (42.7% vs. 0% and 2.7%, P0.05). The proliferation inhibition of ZR-75-1 cells was enhanced along with the increase of culture time and concentration of wt-PTEN. wt-PTEN also induced cell apoptosis. PTEN protein was expressed efficiently in the cells transfected with either wt-PTEN or G129R-PTEN. The inhibition rates of adhesion and invasion were significantly higher in wt-PTEN-transfected cells than in G129R-PTEN-transfected cells (65.7% vs. 8.8%, 70.4% vs. 6.9%, PZR-75-1 cells.

  13. Molecular Mechanism of Nkx3.1 Deregulation and its Function in Murine Pten Prostate Cancer Model

    Science.gov (United States)

    2006-09-01

    hybridization , post hybridization , and analyses following standard laboratory procedure. The probe cocktail contained 20 differentially labeled chromosome...contain near tetraploid chromosome number, with 65-84 chromosomes in PTEN-P2 and 76-80 chromosomes in PTEN-CaP2; PTEN- P8 and PTEN-CaP8 have near 6N

  14. Solving the Burgers-KdV equation by a combination method%用组合法求解Burgers-KdV方程

    Institute of Scientific and Technical Information of China (English)

    谢元喜

    2009-01-01

    通过分析Burgers方程、KdV方程和Burgers-KdV方程的特点,提出了一种由Burgers方程的解和KdV方程的解构造Burgers-KdV方程解的组合法,并由此求得了Burgers-KdV方程的若干显式精确解.%In view of the analysis on the characteristics of the Burgers equation,KdV equation and Burgers-KdV equation,aacombination method is presented to construct the solutions of the Burgers-KdV equation by combining with those of the Burgers equation and KdV equation.As a result,many explicit and exact solutions of the Burgers-KdV equation are successfully derived by this technique.

  15. Strain-Specific Spontaneous and NNK-Mediated Tumorigenesis in Pten+/− Mice

    Directory of Open Access Journals (Sweden)

    Mary Christine Hollander

    2008-08-01

    Full Text Available Pten is a negative regulator of the Akt pathway, and its inactivation is believed to be an etiological factor in many tumor types. Pten+/- mice are susceptible to a variety of spontaneous tumor types, depending on strain background. Pten+/- mice, in lung tumor-sensitive and -resistant background strains, were treated with a tobacco carcinogen, 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK, to determine whether allelic Pten deletion can cooperate with NNK in carcinogenesis in lung or other tissues. In lung tumor-resistant C57BL/6 Pten+/- or +/+ mice, NNK treatment did not lead to any lung tumors and did not increase the incidence or severity of tumors previously reported for this strain. In contrast, in a lung tumor-susceptible pseudo-A/J strain, there was a dose-dependent increase in lung tumor size in Pten+/- compared with +/+ mice, although there was no increase in multiplicity. No other tumor types were observed in pseudo-A/J Pten+/- mice regardless of NNK treatment. Lung tumors from these Pten+/- mice had K-ras mutations, retained Pten expression and had similar Akt pathway activation as lung tumors from +/+ mice. Therefore, deletion of a single copy of Pten does not substantially add to the lung tumor phenotype conferred by mutation of K-ras by NNK, and there is likely no selective advantage for loss of the second Pten allele in lung tumor initiation.

  16. Subcellular targeting and dynamic regulation of PTEN: Implications for neuronal cells and neurological disorders

    Directory of Open Access Journals (Sweden)

    Patricia eKreis

    2014-04-01

    Full Text Available PTEN is a lipid and protein phosphatase that regulates a diverse range of cellular mechanisms. PTEN is mainly present in the cytosol and transiently associates with the plasma membrane to dephosphorylate PI(3,4,5P3, thereby antagonizing the PI3-Kinase signaling pathway. Recently, PTEN has been shown to associate also with organelles such as the endoplasmic reticulum, the mitochondria or the nucleus, and to be secreted outside of the cell. In addition, PTEN dynamically localizes to specialized sub-cellular compartments such as the neuronal growth cone or dendritic spines. The diverse localizations of PTEN imply a tight temporal and spatial regulation, orchestrated by mechanisms such as posttranslational modifications, formation of distinct protein-protein interactions or the activation/recruitment of PTEN downstream of external cues. The regulation of PTEN function is thus not only important at the enzymatic activity level, but is also associated to its spatial distribution. In this review we will summarize (i recent findings that highlight mechanisms controlling PTEN movement and sub-cellular localization, and (ii current understanding of how PTEN localization is achieved by mechanisms controlling posttranslational modification, by association with binding partners and by PTEN structural or activity requirements. Finally, we will discuss the possible roles of compartmentalized PTEN in developing and mature neurons in health and disease.

  17. Nuclear trafficking of Pten after brain injury leads to neuron survival not death.

    Science.gov (United States)

    Goh, Choo-Peng; Putz, Ulrich; Howitt, Jason; Low, Ley-Hian; Gunnersen, Jenny; Bye, Nicole; Morganti-Kossmann, Cristina; Tan, Seong-Seng

    2014-02-01

    There is controversy whether accumulation of the tumor suppressor PTEN protein in the cell nucleus under stress conditions such as trauma and stroke causes cell death. A number of in vitro studies have reported enhanced apoptosis in neurons possessing nuclear PTEN, with the interpretation that its nuclear phosphatase activity leads to reduction of the survival protein phospho-Akt. However, there have been no in vivo studies to show that nuclear PTEN in neurons under stress is detrimental. Using a mouse model of injury, we demonstrate here that brain trauma altered the nucleo-cytoplasmic distribution of Pten, resulting in increased nuclear Pten but only in surviving neurons near the lesion. This event was driven by Ndfip1, an adaptor and activator of protein ubiquitination by Nedd4 E3 ligases. Neurons next to the lesion with nuclear PTEN were invariably negative for TUNEL, a marker for cell death. These neurons also showed increased Ndfip1 which we previously showed to be associated with neuron survival. Biochemical assays revealed that overall levels of Pten in the affected cortex were unchanged after trauma, suggesting that Pten abundance globally had not increased but rather Pten subcellular location in affected neurons had changed. Following experimental injury, the number of neurons with nuclear Pten was reduced in heterozygous mice (Ndfip1(+/-)) although lesion volumes were increased. We conclude that nuclear trafficking of Pten following injury leads to neuron survival not death.

  18. Invariance of the KdV Equation%一个有关KdV方程的不变性

    Institute of Scientific and Technical Information of China (English)

    南志杰; 余立海

    2011-01-01

    通过对KdV方程的B(a)cklund变换的分析,将其改造成一个Ricatti系统,并求解此系统,以此为基础,利用“不变性求解法”研究KdV方程的一类解的递推公式,从而由KdV方程的一对显然解出发计算出了它的更复杂的精确解.

  19. Coordinate suppression of B cell lymphoma by PTEN and SHIP phosphatases

    DEFF Research Database (Denmark)

    Miletic, Ana V; Anzelon-Mills, Amy N; Mills, David M

    2010-01-01

    results in lethal T cell lymphomas, we find that animals lacking PTEN or SHIP in B cells show no evidence of malignancy. However, concomitant deletion of PTEN and SHIP (bPTEN/SHIP(-/-)) results in spontaneous and lethal mature B cell neoplasms consistent with marginal zone lymphoma or, less frequently......, follicular or centroblastic lymphoma. bPTEN/SHIP(-/-) B cells exhibit enhanced survival and express more MCL1 and less Bim. These cells also express low amounts of p27(kip1) and high amounts of cyclin D3 and thus appear poised to undergo proliferative expansion. Unlike normal B cells, bPTEN/SHIP(-/-) B cells...... proliferate to the prosurvival factor B cell activating factor (BAFF). Interestingly, although BAFF availability may promote lymphoma progression, we demonstrate that BAFF is not required for the expansion of transferred bPTEN/SHIP(-/-) B cells. This study reveals that PTEN and SHIP act cooperatively...

  20. On complexly coupled modified KdV equations

    Indian Academy of Sciences (India)

    Amitava Choudhuri

    2010-10-01

    We introduced complexly coupled modified KdV (ccmKdV) equations, which could be derived from a two-layer fluid model [Yang and Mao, Chin. Phys. Lett. 25, 1527 (2008); Hu, J. Phys. A: Math. Theor. 43, 185207 (2009)], and used the Miura transformation to construct expressions for their alternative Lax pair representations. We derived a Lagrangian-based approach to study the Hamiltonian structures of the ccmKdV equations and observed that the complexly coupled mKdV equations have an additional analytic structure. The coupled equations were characterized by two alternative Lagrangians not connected by a gauge term. We examined how the alternative Lagrangian descriptions of the system affect the bi-Hamiltonian structures.

  1. Exact Solutions of Bogoyavlenskii Coupled KdV Equations

    Institute of Scientific and Technical Information of China (English)

    HUHeng-Chun; LOUSen-Yue

    2004-01-01

    The special soliton solutions of Bogoyavlenskii coupled KdV equations are obtained by means of the standard Weiss-Tabor -Carnvale Painleve' truncation expansion and the nonstandard truncation of a modified Conte's invariant Painlevé expansion.

  2. Hamiltonian Structures for the Generalized Dispersionless KdV Hierarchy

    OpenAIRE

    Brunelli, J. C.

    1996-01-01

    We study from a Hamiltonian point of view the generalized dispersionless KdV hierarchy of equations. From the so called dispersionless Lax representation of these equations we obtain three compatible Hamiltonian structures. The second and third Hamiltonian structures are calculated directly from the r-matrix approach. Since the third structure is not related recursively with the first two ones the generalized dispersionless KdV hierarchy can be characterized as a truly tri-Hamiltonian system.

  3. Symmetries of KdV and loop groups

    CERN Document Server

    Schiff, J; Schiff, Jeremy; Sci, Comp

    1996-01-01

    A simple version of the Segal-Wilson map from the SL(2,C) loop group to a class of solutions of the KdV hierarchy is given, clarifying certain aspects of this map. It is explained how the known symmetries, including Backlund transformations, of KdV arise from simple, field independent, actions on the loop group. A variety of issues in understanding the algebraic structure of Backlund transformations are thus resolved.

  4. Adiabatic invariants of the extended KdV equation

    CERN Document Server

    Karczewska, Anna; Infeld, Eryk; Rowlands, George

    2015-01-01

    When the Euler equations for shallow water are taken to the next order, beyond KdV, $\\eta^2$ is no longer an invariant. (It would seem that $\\eta$ is the only one.) However, two adiabatic invariants akin to $\\eta^2$ can be found. Here we present and test them. When the KdV expansion parameters are zero, $\\eta^2$ is recovered from both adiabatic invariants.

  5. The mechanism involved in the loss of PTEN expression in NSCLC tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Gang; Zhao, Jingfeng; Peng, Xianjing [Department of Radiology, Xiangya Hospital, Central South University, Changsha 410008 (China); Liang, Jian; Deng, Xin [Ruikang Hospital, Guangxi University of Traditional Chinese Medicine, Nanning 530003 (China); Chen, Yuxiang, E-mail: chenyx008@yahoo.cn [Department of Radiology, Xiangya Hospital, Central South University, Changsha 410008 (China); School of Biological Science and Technology, Central South University, Changsha 410008 (China)

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer Radiation stimulates PTEN reexpression in NSCLC independent of p53 activation. Black-Right-Pointing-Pointer PTEN reexpression is mediated by miR-29b overexpression. Black-Right-Pointing-Pointer miR-29b regulates Dnmts expression in NSCLC tumor cells. Black-Right-Pointing-Pointer Target therapy could be established by overexpressing miR-29b expression. -- Abstract: Loss of PTEN expression is observed in most non-small cell lung cancers (NSCLC). However, the mechanism by which PTEN expression is regulated in NSCLC has not been fully elucidated. In this study, we investigated the role of DNA methyltransferases (Dnmts), microRNA-29b (miR-29b), and anti-miR-29b inhibitor in PTEN promoter methylation and PTEN gene expression in H358 NSCLC cells in vitro and in vivo. PTEN mRNA was measured by RT-PCR. PTEN and Dnmts protein levels were measured by Western blot. miR-29b expression was detected by Northern blot. A xenograft H358 tumor mouse model was established by subcutaneously inoculating H358 cells into the right hind limbs of nude mice. We found that radiation induced cell apoptosis and hypomethylation in PTEN promoter, PTEN and miR-29b expression, and downregulation of Dnmt1, 3a and 3b expression in H358 tumor cells. The effect of radiation on gene expression and apoptosis was blocked by anti-miR-29b inhibitor. In the xenograft H358 tumor model, anti-miR-29b inhibitor reversed radiation-induced tumor growth delay, PTEN reexpression and downregulation of Dnmts expression. Our study suggested that miR-29b is an upstream molecule of PTEN. miR-29b regulates PTEN gene expression through downregulating Dnmts expression and subsequently induces hypomethylation in PTEN promoter. Targeting therapy could be established in NSCLC by upregulating miR-29b expression.

  6. Characterization of a novel PTEN mutation in MDA-MB-453 breast carcinoma cell line

    Directory of Open Access Journals (Sweden)

    Singh Gobind

    2011-11-01

    Full Text Available Abstract Background Cowden Syndrome (CS patients with germ line point mutations in the PTEN gene are at high risk for developing breast cancer. It is believed that cells harboring these mutant PTEN alleles are predisposed to malignant conversion. This article will characterize the biochemical and biological properties of a mutant PTEN protein found in a commonly used metastatic breast cancer cell line. Methods The expression of PTEN in human breast carcinoma cell lines was evaluated by Western blotting analysis. Cell line MDA-MB-453 was selected for further analysis. Mutation analysis of the PTEN gene was carried out using DNA isolated from MDA-MB-453. Site-directed mutagenesis was used to generate a PTEN E307K mutant cDNA and ectopic expressed in PC3, U87MG, MCF7 and Pten-/- mouse embryo fibroblasts (MEFS. Histidine (His-tagged PTEN fusion protein was generated in Sf9 baculovirus expression system. Lipid phosphatase and ubiquitination assays were carried out to characterize the biochemical properties of PTEN E307K mutant. The intracellular localization of PTEN E307K was determined by subcellular fractionation experiments. The ability of PTEN E307K to alter cell growth, migration and apoptosis was analyzed in multiple PTEN-null cell lines. Results We found a mutation in the PTEN gene at codon 307 in MDA-MB-453 cell line. The glutamate (E to lysine (K substitution rendered the mutant protein to migrate with a faster mobility on SDS-PAGE gels. Biochemically, the PTEN E307K mutant displayed similar lipid phosphatase and growth suppressing activities when compared to wild-type (WT protein. However, the PTEN E307K mutant was present at higher levels in the membrane fraction and suppressed Akt activation to a greater extent than the WT protein. Additionally, the PTEN E307K mutant was polyubiquitinated to a greater extent by NEDD4-1 and displayed reduced nuclear localization. Finally, the PTEN E307K mutant failed to confer chemosensitivity to

  7. The PTEN/NRF2 Axis Promotes Human Carcinogenesis

    DEFF Research Database (Denmark)

    Rojo, Ana I; Rada, Patricia; Mendiola, Marta;

    2014-01-01

    UNLABELLED: Abstract Aims: A recent study conducted in mice reported that liver-specific knockout of tumor suppressor Pten augments nuclear factor (erythroid-derived 2)-like 2 (NRF2) transcriptional activity. Here, we further investigated how phosphatase and tensin homolog deleted on chromosome 1...

  8. TMPRSS2-ERG and PTEN loss in prostate cancer.

    Science.gov (United States)

    Squire, Jeremy A

    2009-05-01

    Two studies show that the common recurrent gene fusion between TMPRSS2 and ERG promotes prostate cancer in both mouse and humans when PTEN is concurrently lost. In human prostate cancer, the presence of both these aberrations may be indicative of poor prognosis, suggesting that preclinical therapeutic research should target both of these pathways.

  9. Self-similar solutions for some nonlinear evolution equations: KdV, mKdV and Burgers equations

    Directory of Open Access Journals (Sweden)

    S.A. El-Wakil

    2016-02-01

    Full Text Available A method for solving three types of nonlinear evolution equations namely KdV, modified KdV and Burgers equations, with self-similar solutions is presented. The method employs ideas from symmetry reduction to space and time variables and similarity reductions for nonlinear evolution equations are performed. The obtained self-similar solutions of KdV and mKdV equations are related to Bessel and Airy functions whereas those of Burgers equation are related to the error and Hermite functions. These solutions appear as new types of solitary, shock and periodic waves. Also, the method can be applied to other nonlinear evolution equations in mathematical physics.

  10. Exact Wave Solutions to Inverse-KdV Equation%Inverse-KdV方程的精确行波解

    Institute of Scientific and Technical Information of China (English)

    何应辉

    2013-01-01

    利用F-展开法对Inverse-KdV方程进行研究,获得了一些新的精确行波解,其中包含孤波解和周期波解,丰富了Inverse-KdV的精确解的结构,并使相关文献中的结论得到了有效推广.

  11. Numerical simulation of KdV and mKdV equations with initial conditions by the variational iteration method

    Energy Technology Data Exchange (ETDEWEB)

    Inc, Mustafa [Department of Mathematics, Firat University, 23119 Elazig (Turkey)]. E-mail: minc@firat.edu.tr200

    2007-11-15

    A scheme is developed for the numerical study of the Korteweg-de Vries (KdV) and the modified Korteweg-de Vries (mKdV) equations with initial conditions by a variational approach. The exact and numerical solutions obtained by variational iteration method are compared with those obtained by Adomian decomposition method. The comparison shows that the obtained solutions are in excellent agreement.

  12. Characterization of novel non-clonal intrachromosomal rearrangements between the H4 and PTEN genes (H4/PTEN) in human thyroid cell lines and papillary thyroid cancer specimens

    Energy Technology Data Exchange (ETDEWEB)

    Puxeddu, Efisio [Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, PO Box 670547, Cincinnati, OH 45267-0547 (United States); Zhao Guisheng [Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, PO Box 670547, Cincinnati, OH 45267-0547 (United States); Stringer, James R. [Department of Molecular Genetics, University of Cincinnati College of Medicine, PO Box 670547, Cincinnati, OH 45267-0547 (United States); Medvedovic, Mario [Center for Biostatistic Service, University of Cincinnati College of Medicine, PO Box 670547, Cincinnati, OH 45267-0547 (United States); Moretti, Sonia [Dipartimento di Medicina Interna, Universita degli Studi di Perugia, Via E. dal Pozzo, Perugia 06126, (Italy); Fagin, James A. [Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, PO Box 670547, Cincinnati, OH 45267-0547 (United States)]. E-mail: james.fagin@uc.edu

    2005-02-15

    The two main forms of RET rearrangement in papillary thyroid carcinomas (PTC) arise from intrachromosomal inversions fusing the tyrosine kinase domain of RET with either the H4 (RET/PTC1) or the ELE1/RFG genes (RET/PTC3). PTEN codes for a dual-specificity phosphatase and maps to chromosome 10q22-23. Germline mutations confer susceptibility to Cowden syndrome whereas somatic mutations or deletions are common in several sporadic human tumors. Decreased PTEN expression has been implicated in thyroid cancer development. We report the characterization of a new chromosome 10 rearrangement involving H4 and PTEN. The initial H4/PTEN rearrangement was discovered as a non-specific product of RT-PCR for RET/PTC1 in irradiated thyroid cell lines. Sequencing revealed a transcript consisting of exon 1 and 2 of H4 fused with exons 3-6 of PTEN. Nested RT-PCR with specific primers bracketing the breakpoints confirmed the H4/PTEN rearrangements in irradiated KAT-1 and KAT-50 cells. Additional H4/PTEN variants, generated by recombination of either exon 1 or exon 2 of H4 with exon 6 of PTEN, were found in non-irradiated KAK-1, KAT-50, ARO and NPA cells. Their origin through chromosomal recombination was confirmed by detection of the reciprocal PTEN/H4 product. H4/PTEN recombination was not a clonal event in any of the cell lines, as Southern blots with appropriate probes failed to demonstrate aberrant bands, and multicolor FISH of KAK1 cells with BAC probes for H4 and PTEN did not show a signal overlap in all cells. Based on PCR of serially diluted samples, the minimal frequency of spontaneous recombination between these loci was estimated to be approximately 1/10{sup 6} cells. H4/PTEN products were found by nested RT-PCR in 4/14 normal thyroid tissues (28%) and 14/18 PTC (78%) (P < 0.01). H4/PTEN is another example of recombination involving the H4 locus, and points to the high susceptibility of thyroid cells to intrachromosomal gene rearrangements. As this also represents a

  13. Heterozygosity for Pten promotes tumorigenesis in a mouse model of medulloblastoma.

    Directory of Open Access Journals (Sweden)

    Robert C Castellino

    Full Text Available BACKGROUND: Recent publications have described an important role for cross talk between PI-3 kinase and sonic hedgehog signaling pathways in the pathogenesis of medulloblastoma. METHODOLOGY/PRINCIPAL FINDINGS: We crossed mice with constitutive activation of Smoothened, SmoA1, with Pten deficient mice. Both constitutive and conditional Pten deficiency doubled the incidence of mice with symptoms of medulloblastoma and resulted in decreased survival. Analysis revealed a clear separation of gene signatures, with up-regulation of genes in the PI-3 kinase signaling pathway, including downstream activation of angiogenesis in SmoA1+/-; Pten +/- medulloblastomas. Western blotting and immunohistochemistry confirmed reduced or absent Pten, Akt activation, and increased angiogenesis in Pten deficient tumors. Down-regulated genes included genes in the sonic hedgehog pathway and tumor suppressor genes. SmoA1+/-; Pten +/+ medulloblastomas appeared classic in histology with increased proliferation and diffuse staining for apoptosis. In contrast, Pten deficient tumors exhibited extensive nodularity with neuronal differentiation separated by focal areas of intense staining for proliferation and virtually absent apoptosis. Examination of human medulloblastomas revealed low to absent PTEN expression in over half of the tumors. Kaplan-Meier analysis confirmed worse overall survival in patients whose tumor exhibited low to absent PTEN expression. CONCLUSIONS/SIGNIFICANCE: This suggests that PTEN expression is a marker of favorable prognosis and mouse models with activation of PI-3 kinase pathways may be important tools for preclinical evaluation of promising agents for the treatment of medulloblastoma.

  14. 广义KdV方程的精确行波解%Exact Traveling Wave Solutions to Generalized KdV Equations

    Institute of Scientific and Technical Information of China (English)

    胡建兰

    2002-01-01

    The exact traveling wave solutions to some nonlinear evolution physical models of KdV type, such as the generalized odd order KdV equations and generalized KdV-Burgerse quations, are explicitly established by using two-step hypothesis method.%采用两步假设法,得到非线性物理模型中的KdV型方程的精确行波解. 如广义奇数阶(五阶、七阶)KdV方程和广义KdV-Barges方程.

  15. Coenzyme Q10 supplementation rescues renal disease in Pdss2kd/kd mice with mutations in prenyl diphosphate synthase subunit 2.

    Science.gov (United States)

    Saiki, Ryoichi; Lunceford, Adam L; Shi, Yuchen; Marbois, Beth; King, Rhonda; Pachuski, Justin; Kawamukai, Makoto; Gasser, David L; Clarke, Catherine F

    2008-11-01

    Homozygous mice carrying kd (kidney disease) mutations in the gene encoding prenyl diphosphate synthase subunit 2 (Pdss2kd/kd) develop interstitial nephritis and eventually die from end-stage renal disease. The PDSS2 polypeptide in concert with PDSS1 synthesizes the polyisoprenyl tail of coenzyme Q (Q or ubiquinone), a lipid quinone required for mitochondrial respiratory electron transport. We have shown that a deficiency in Q content is evident in Pdss2kd/kd mouse kidney lipid extracts by 40 days of age and thus precedes the onset of proteinuria and kidney disease by several weeks. The presence of the kd (V117M) mutation in PDSS2 does not prevent its association with PDSS1. However, heterologous expression of the kd mutant form of PDSS2 together with PDSS1 in Escherichia coli recapitulates the Q deficiency observed in the Pdss2kd/kd mouse. Dietary supplementation with Q10 provides a dramatic rescue of both proteinuria and interstitial nephritis in the Pdss2kd/kd mutant mice. The results presented suggest that Q may be acting as a potent lipid-soluble antioxidant, rather than by boosting kidney mitochondrial respiration. Such Q10 supplementation may have profound and beneficial effects in treatment of certain forms of focal segmental glomerulosclerosis that mirror the renal disease of the Pdss2kd/kd mouse.

  16. Beyond the KdV: Post-explosion development.

    Science.gov (United States)

    Ostrovsky, L; Pelinovsky, E; Shrira, V; Stepanyants, Y

    2015-09-01

    Several threads of the last 25 years' developments in nonlinear wave theory that stem from the classical Korteweg-de Vries (KdV) equation are surveyed. The focus is on various generalizations of the KdV equation which include higher-order nonlinearity, large-scale dispersion, and a non-local integral dispersion. We also discuss how relatively simple models can capture strongly nonlinear dynamics and how various modifications of the KdV equation lead to qualitatively new, non-trivial solutions and regimes of evolution observable in the laboratory and in nature. As the main physical example, we choose internal gravity waves in the ocean for which all these models are applicable and have genuine importance. We also briefly outline the authors' view of the future development of the chosen lines of nonlinear wave theory.

  17. On the Convexity of the KdV Hamiltonian

    Science.gov (United States)

    Kappeler, Thomas; Maspero, Alberto; Molnar, Jan; Topalov, Peter

    2016-08-01

    Motivated by perturbation theory, we prove that the nonlinear part {H^{*}} of the KdV Hamiltonian {H^{kdv}}, when expressed in action variables {I = (In)_{n ≥slant 1}}, extends to a real analytic function on the positive quadrant {ℓ2+({N})} of {ℓ2({N})} and is strictly concave near {0}. As a consequence, the differential of {H^{*}} defines a local diffeomorphism near 0 of {ℓ_{{C}}2({N})}. Furthermore, we prove that the Fourier-Lebesgue spaces {{F}{L}^{s,p}} with {-1/2 ≤slant s ≤slant 0} and {2 ≤slant p KdV-Birkhoff coordinates. In particular, it means that {ℓ2_+({N})} is the space of action variables of the underlying phase space {{F}{L}^{-1/2,4}} and that the KdV equation is globally in time {C0}-well-posed on {{F}{L}^{-1/2,4}}.

  18. Global Smoothing for the Periodic KdV Evolution

    CERN Document Server

    Erdogan, Burak

    2011-01-01

    The Korteweg-de Vries (KdV) equation with periodic boundary conditions is considered. It is shown that for $H^s$ initial data, $s>-1/2$, and for any $s_1<\\min(3s+1,s+1)$, the difference of the nonlinear and linear evolutions is in $H^{s_1}$ for all times, with at most polynomially growing $H^{s_1}$ norm. The result also extends to KdV with a smooth, mean zero, time-dependent potential in the case $s\\geq 0$. Our result and a theorem of Oskolkov for the Airy evolution imply that if one starts with continuous and bounded variation initial data then the solution of KdV (given by the $L^2$ theory of Bourgain) is a continuous function of space and time.

  19. Efficient Delaunay Tessellation through K-D Tree Decomposition

    Energy Technology Data Exchange (ETDEWEB)

    Morozov, Dmitriy; Peterka, Tom

    2017-08-21

    Delaunay tessellations are fundamental data structures in computational geometry. They are important in data analysis, where they can represent the geometry of a point set or approximate its density. The algorithms for computing these tessellations at scale perform poorly when the input data is unbalanced. We investigate the use of k-d trees to evenly distribute points among processes and compare two strategies for picking split points between domain regions. Because resulting point distributions no longer satisfy the assumptions of existing parallel Delaunay algorithms, we develop a new parallel algorithm that adapts to its input and prove its correctness. We evaluate the new algorithm using two late-stage cosmology datasets. The new running times are up to 50 times faster using k-d tree compared with regular grid decomposition. Moreover, in the unbalanced data sets, decomposing the domain into a k-d tree is up to five times faster than decomposing it into a regular grid.

  20. On the K^+D Interaction at Low Energies

    CERN Document Server

    Tarasov, V E; Kudryavtsev, A E; Weinberg, V M

    2007-01-01

    The Kd reactions are considered in the impulse approximation with NN final-state interactions (NN FSI) taken into account. The realistic parameters for the KN phase shifts are used. The "quasi-elastic" energy region, in which the elementary KN interaction is predominantly elastic, is considered. The theoretical predictions are compared with the data on the K^+d->K^+pn, K^+d->K^0pp, K^+d->K^+d and K^+d total cross sections. The NN FSI effect in the reaction K^+d->K^+pn has been found to be large. The predictions for the Kd cross sections are also given for slow kaons, produced from phi(1020) decays, as the functions of the isoscalar KN scattering length a_0. These predictions can be used to extract the value of a_0 from the data.

  1. Conservation Laws and Lax Pair of the Variable Coefficient KdV Equation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Da-Jun

    2007-01-01

    By a transformation between a Painlevé integrable variable coefficient KdV equation and the standard KdV equation, we derive the Lax pair and infinitely many conservation laws of the variable coefficient KdV equation from the counterparts of the KdV equation.

  2. CLINICOPATHOLOGICAL SIGNIFICANCE OF PTEN AND CASPASE-3 EXPRESSIONS IN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    Xue-fei Yang; Yan Xin; Li-li Mao

    2008-01-01

    Objective To investigate the expressions of PTEN and Caspase-3 proteins in human breast carcinoma, and to evaluate their clinicopathological implications during the tumorigenesis and progression of breast cancer.Methods The expressions of PTEN and Caspase-3 proteins in 95 cases of breast cancer and 15 cases of benignbreast diseases were investigated immunohistochemically. Correlations between the expression of PTEN protein,Caspase-3 protein, and clinicopathological features of breast cancers were analyzed.Results The loss expression rate of PTEN protein in tumor tissues was significantly higher than that in benignbreast diseases (33.7% vs. 0, P 0. 05). In addition,the expression of PTEN protein had significantly positive correlation with the expression of Caspase-3 protein in breast cancer (P <0.01 ).Conclusion The combination detection of PTEN and Caspase-3 may serve as an important index to estimate the pathobiological behavior and pognosis of breast cancer.

  3. Hydrocephalus caused by conditional ablation of the Pten or beta-catenin gene

    Directory of Open Access Journals (Sweden)

    Ohtoshi Akihira

    2008-10-01

    Full Text Available Abstract To investigate the roles of Pten and β-Catenin in the midbrain, either the Pten gene or the β-catenin gene was conditionally ablated, using Dmbx1 (diencephalon/mesencephalon-expressed brain homeobox gene 1-Cre mice. Homozygous disruption of the Pten or β-catenin gene in Dmbx1-expressing cells caused severe hydrocephalus and mortality during the postnatal period. Conditional deletion of Pten resulted in enlargement of midbrain structures. β-catenin conditional mutant mice showed malformation of the superior and inferior colliculi and stenosis of the midbrain aqueduct. These results demonstrate that both Pten and β-Catenin are essential for proper midbrain development, and provide the direct evidence that mutations of both Pten and β-catenin lead to hydrocephalus.

  4. PTEN functions to 'prioritize' chemotactic cues and prevent 'distraction' in migrating neutrophils.

    Science.gov (United States)

    Heit, Bryan; Robbins, Stephen M; Downey, Charlene M; Guan, Zhiwen; Colarusso, Pina; Miller, B Joan; Jirik, Frank R; Kubes, Paul

    2008-07-01

    Neutrophils encounter and 'prioritize' many chemoattractants in their pursuit of bacteria. Here we tested the possibility that the phosphatase PTEN is responsible for the prioritization of chemoattractants. Neutrophils induced chemotaxis by two separate pathways, the phosphatidylinositol-3-OH kinase (PI(3)K) phosphatase and tensin homolog (PTEN) pathway, and the p38 mitogen-activated protein kinase pathway, with the p38 pathway dominating over the PI(3)K pathway. Pten(-/-) neutrophils could not prioritize chemoattractants and were 'distracted' by chemokines when moving toward bacterial chemoattractants. In opposing gradients, PTEN became distributed throughout the cell circumference, which inhibited all PI(3)K activity, thus permitting 'preferential' migration toward bacterial products via phospholipase A(2) and p38. Such prioritization was defective in Pten(-/-) neutrophils, which resulted in defective bacterial clearance in vivo. Our data identify a PTEN-dependent mechanism in neutrophils to prioritize, 'triage' and integrate responses to multiple chemotactic cues.

  5. Gene expression profile of neuronal progenitor cells derived from hESCs: activation of chromosome 11p15.5 and comparison to human dopaminergic neurons.

    Directory of Open Access Journals (Sweden)

    William J Freed

    Full Text Available BACKGROUND: We initiated differentiation of human embryonic stem cells (hESCs into dopamine neurons, obtained a purified population of neuronal precursor cells by cell sorting, and determined patterns of gene transcription. METHODOLOGY: Dopaminergic differentiation of hESCs was initiated by culturing hESCs with a feeder layer of PA6 cells. Differentiating cells were then sorted to obtain a pure population of PSA-NCAM-expressing neuronal precursors, which were then analyzed for gene expression using Massive Parallel Signature Sequencing (MPSS. Individual genes as well as regions of the genome which were activated were determined. PRINCIPAL FINDINGS: A number of genes known to be involved in the specification of dopaminergic neurons, including MSX1, CDKN1C, Pitx1 and Pitx2, as well as several novel genes not previously associated with dopaminergic differentiation, were expressed. Notably, we found that a specific region of the genome located on chromosome 11p15.5 was highly activated. This region contains several genes which have previously been associated with the function of dopaminergic neurons, including the gene for tyrosine hydroxylase (TH, the rate-limiting enzyme in catecholamine biosynthesis, IGF2, and CDKN1C, which cooperates with Nurr1 in directing the differentiation of dopaminergic neurons. Other genes in this region not previously recognized as being involved in the functions of dopaminergic neurons were also activated, including H19, TSSC4, and HBG2. IGF2 and CDKN1C were also found to be highly expressed in mature human TH-positive dopamine neurons isolated from human brain samples by laser capture. CONCLUSIONS: The present data suggest that the H19-IGF2 imprinting region on chromosome 11p15.5 is involved in the process through which undifferentiated cells are specified to become neuronal precursors and/or dopaminergic neurons.

  6. Integrable quartic potentials and coupled KdV equations

    CERN Document Server

    Baker, S; Fordy, A P; Enolskii, V Z; Fordy, A P

    1995-01-01

    We show a surprising connection between known integrable Hamiltonian systems with quartic potential and the stationary flows of some coupled KdV systems related to fourth order Lax operators. In particular, we present a connection between the Hirota-Satsuma coupled KdV system and (a generalisation of) the 1:6:1 integrable case quartic potential. A generalisation of the 1:6:8 case is similarly related to a different (but gauge related) fourth order Lax operator. We exploit this connection to derive a Lax representation for each of these integrable systems. In this context a canonical transformation is derived through a gauge transformation.

  7. Molecular cloning and characterization of PTEN in the orange-spotted grouper (Epinephelus coioides).

    Science.gov (United States)

    Luo, Sheng-Wei; Wang, Wei-Na; Xie, Ren-Chong; Xie, Fu-Xing; Kong, Jing-Rong; Xiao, Yu-Chao; Huang, Di; Sun, Zuo-Ming; Liu, Yuan; Wang, Cong

    2016-11-01

    PTEN is a key tumor suppressor gene that can play a regulatory role in the cellular proliferation, survival and apoptosis. In this study, the full-length PTEN (EcPTEN) was obtained, containing a 5'UTR of 745 bp, an ORF of 1269 bp and a 3'UTR of 106 bp. The EcPTEN gene encoded a polypeptide of 422 amino acids with an estimated molecular mass of 49.14 KDa and a predicted isoelectric point (pI) of 6.34. The deduced amino acid sequence analysis showed that EcPTEN comprised the conserved residues and the characteristic domains known to the critical functionality of PTEN. qRT-PCR analysis revealed that EcPTEN mRNA was broadly expressed in all the examined tissues, while the highest expression level was observed in liver, followed by the expression in blood, kidney, spleen, heart, gill, muscle and intestine. The groupers challenged with Vibrio alginolyticus showed a sharp increase of EcPTEN mRNA expression in immune tissues. In addition, western blotting analysis confirmed that the up-regulation of EcPTEN protein expression was steadily induced in liver. Subcellular localization analysis indicated that EcPTEN was localized in both nucleus and cytoplasm. Overexpression of EcPTEN can activate the apoptotic cascade and abrogate NF-kB, AP-1, Stat3 and Myc promoter activity in Hela cells. These results indicated that EcPTEN harboring highly-conserved domains with a close sequence similarity to those of PTP superfamily may disrupt the mammalian signalings and play a regulatory role in the apoptotic process.

  8. Adenovirus mediated homozygous endometrial epithelial Pten deletion results in aggressive endometrial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Ayesha; Ellenson, Lora Hedrick, E-mail: lora.ellenson@med.cornell.edu

    2011-07-01

    Pten is the most frequently mutated gene in uterine endometriod carcinoma (UEC) and its precursor complex atypical hyperplasia (CAH). Because the mutation frequency is similar in CAH and UEC, Pten mutations are thought to occur relatively early in endometrial tumorigenesis. Previous work from our laboratory using the Pten{sup +/-} mouse model has demonstrated somatic inactivation of the wild type allele of Pten in both CAH and UEC. In the present study, we injected adenoviruses expressing Cre into the uterine lumen of adult Pten floxed mice in an attempt to somatically delete both alleles of Pten specifically in the endometrium. Our results demonstrate that biallelic inactivation of Pten results in an increased incidence of carcinoma as compared to the Pten{sup +/-} mouse model. In addition, the carcinomas were more aggressive with extension beyond the uterus into adjacent tissues and were associated with decreased expression of nuclear ER{alpha} as compared to associated CAH. Primary cultures of epithelial and stromal cells were prepared from uteri of Pten floxed mice and Pten was deleted in vitro using Cre expressing adenovirus. Pten deletion was evident in both the epithelial and stromal cells and the treatment of the primary cultures with estrogen had different effects on Akt activation as well as Cyclin D3 expression in the two purified components. This study demonstrates that somatic biallelic inactivation of Pten in endometrial epithelium in vivo results in an increased incidence and aggressiveness of endometrial carcinoma compared to mice carrying a germline deletion of one allele and provides an important in vivo and in vitro model system for understanding the genetic underpinnings of endometrial carcinoma.

  9. Germline disruption of Pten localization causes enhanced sex-dependent social motivation and increased glial production.

    Science.gov (United States)

    Tilot, Amanda K; Gaugler, Mary K; Yu, Qi; Romigh, Todd; Yu, Wanfeng; Miller, Robert H; Frazier, Thomas W; Eng, Charis

    2014-06-15

    PTEN Hamartoma Tumor Syndrome (PHTS) is an autosomal-dominant genetic condition underlying a subset of autism spectrum disorder (ASD) with macrocephaly. Caused by germline mutations in PTEN, PHTS also causes increased risks of multiple cancers via dysregulation of the PI3K and MAPK signaling pathways. Conditional knockout models have shown that neural Pten regulates social behavior, proliferation and cell size. Although much is known about how the intracellular localization of PTEN regulates signaling in cancer cell lines, we know little of how PTEN localization influences normal brain physiology and behavior. To address this, we generated a germline knock-in mouse model of cytoplasm-predominant Pten and characterized its behavioral and cellular phenotypes. The homozygous Pten(m3m4) mice have decreased total Pten levels including a specific drop in nuclear Pten and exhibit region-specific increases in brain weight. The Pten(m3m4) model displays sex-specific increases in social motivation, poor balance and normal recognition memory-a profile reminiscent of some individuals with high functioning ASD. The cytoplasm-predominant protein caused cellular hypertrophy limited to the soma and led to increased NG2 cell proliferation and accumulation of glia. The animals also exhibit significant astrogliosis and microglial activation, indicating a neuroinflammatory phenotype. At the signaling level, Pten(m3m4) mice show brain region-specific differences in Akt activation. These results demonstrate that differing alterations to the same autism-linked gene can cause distinct behavioral profiles. The Pten(m3m4) model is the first murine model of inappropriately elevated social motivation in the context of normal cognition and may expand the range of autism-related behaviors replicated in animal models.

  10. PTEN encoding product: a marker for tumorigenesis and progression of gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Lin Yang; Li-Ge Kuang; Hua-Chuan Zheng; Jin-Yi Li; Dong-Ying Wu; Su-Min Zhang; Yan Xin

    2003-01-01

    AIM: To detect the expression of PTEN encoding productin normal mucosa, intestinal metaplasia (IM), dysplasia andcarcinoma of the stomach, and to investigate its clinicalimplication in tumorigenesis and progression of gastriccarcinoma.METHODS: Formalin-fixed paraffin embedded specimens from184 cases of gastric carcinoma, their adjacent normal mucosa,IM and dysplasia were evaluated for PTEN protein expressionby SABC immunohistochemistry. PTEN expression wascompared with tumor stage, lymph node metastasis, Lauren'sand WHO's histological classification of gastric carcinoma.Expression of VEGF was also detected in 60 cases of gastriccarcinoma and its correlation with PTEN was concerned.RESULTS: The positive rates of PTEN protein were 100 %(102/102), 98.5 %(65/66), 66.7 % (4/6) and 47.8 %(88/184)in normal mucosa, IM, dysplasia and carcinoma of the stomach,respectively. The positive rates in dysplasia and carcinomawere lower than in normal mucosa and IM (P<0.01).Advanced gastric cancers expressed less frequent PTEN thanearly gastric cancer (42.9 % v567.6 %, P<0.01). The positiverate of PTEN protein was lower in gastric cancer with thanwithout lymph node metastasis (40.3 % v563.3 %, P<0.01).PTEN was less expressed in diffuse-type than in intestinal-type gastric cancer (41.5 % v557.8 %,P<0.05). Signet ringcell carcinoma showed the expression of PTEN at the lowestlevel (25.0 %, 7/28); less than well and moderatelydifferentiated ones (P<0.01). Expression of PTEN was notcorrelated with expression of VEGF (P>0.05).CONCLUSION: Loss or reduced expression of PTEN proteinoccures commonly in tumorigenesis and progression of gastriccarcinoma. It is suggested that PTEN can be an objective markerfor pathologically biological behaviors of gastric carcinoma.

  11. Dysregulation of AKT Pathway by SMYD2-Mediated Lysine Methylation on PTEN

    OpenAIRE

    Makoto Nakakido; Zhenzhong Deng; Takehiro Suzuki; Naoshi Dohmae; Yusuke Nakamura; Ryuji Hamamoto

    2015-01-01

    Phosphatase and tensin homologue (PTEN), one of the well-characterized tumor suppressor proteins, counteracts the phosphatidylinositol 3-kinase-AKT pathway through its unique lipid phosphatase activity. The functions of PTEN are regulated by a variety of posttranslational modifications such as acetylation, oxidation, ubiquitylation, phosphorylation, and SUMOylation. However, methylation of PTEN has not been reported so far. In this study, we demonstrated that the oncogenic protein lysine meth...

  12. Tumor suppressor PTEN affects tau phosphorylation: deficiency in the phosphatase activity of PTEN increases aggregation of an FTDP-17 mutant Tau

    Directory of Open Access Journals (Sweden)

    Zhang Xue

    2006-07-01

    Full Text Available Abstract Background Aberrant hyperphosphorylation of tau protein has been implicated in a variety of neurodegenerative disorders. Although a number of protein kinases have been shown to phosphorylate tau in vitro and in vivo, the molecular mechanisms by which tau phosphorylation is regulated pathophysiologically are largely unknown. Recently, a growing body of evidence suggests a link between tau phosphorylation and PI3K signaling. In this study, phosphorylation, aggregation and binding to the microtubule of a mutant frontal temporal dementia and parkinsonism linked to chromosome 17 (FTDP-17 tau in the presence of tumor suppressor PTEN, a major regulatory component in PI3K signaling, were investigated. Results Phosphorylation of the human mutant FTDP-17 tau, T40RW, was evaluated using different phospho-tau specific antibodies in the presence of human wild-type or phosphatase activity null mutant PTEN. Among the evaluated phosphorylation sites, the levels of Ser214 and Thr212 phospho-tau proteins were significantly decreased in the presence of wild-type PTEN, and significantly increased when the phosphatase activity null mutant PTEN was ectopically expressed. Fractionation of the mutant tau transfected cells revealed a significantly increased level of soluble tau in cytosol when wild-type PTEN was expressed, and an elevated level of SDS-soluble tau aggregates in the presence of the mutant PTEN. In addition, the filter/trap assays detected more SDS-insoluble mutant tau aggregates in the cells overexpressing the mutant PTEN compared to those in the cells overexpressing wild-type PTEN and control DNA. This notion was confirmed by the immunocytochemical experiment which demonstrated that the overexpression of the phosphatase activity null mutant PTEN caused the mutant tau to form aggregates in the COS-7 cells. Conclusion Tumor suppressor PTEN can alleviate the phosporylation of the mutant FTDP-17 tau at specific sites, and the phosphatase activity

  13. PTEN, Stem Cells, and Cancer Stem Cells*S⃞

    OpenAIRE

    Hill, Reginald; Wu, Hong

    2009-01-01

    Like normal stem cells, “cancer stem cells” have the capacity for indefinite proliferation and generation of new cancerous tissues through self-renewal and differentiation. Among the major intracellular signaling pathways, WNT, SHH, and NOTCH are known to be important in regulating normal stem cell activities, and their alterations are associated with tumorigenesis. It has become clear recently that PTEN (phosphatase and tensin homologue) is also critical for stem cell...

  14. Bell Polynomial Approach and N-Soliton Solutions for a Coupled KdV-mKdV System

    Institute of Scientific and Technical Information of China (English)

    覃翌; 高以天; 于鑫; 蒙高庆

    2012-01-01

    In fluid dynamics, plasma physics and nonlinear optics, Korteweg-de Vries (KdV)-type equations are used to describe certain phenomena. In this paper, a coupled KdV-modified KdV system is investigated. Based on the Bell polynomials and symbolic computation, the bilinear form of such system is derived, and its analytic N-soliton solutions are constructed through the Hirota method. Two types of multi-soliton interactions are found, one with the reverse of solitonic shapes, and the other, without. Both the two types can be considered elastic. For a pair of solutions to such system, u and v, with the number of solitons N even, the soliton shapes of u stay unvaried while those of v reverse after the interaction; with N odd, the soliton shapes of both u and v keep unchanged after the interaction.

  15. The superposition method in seeking the solitary wave solutions to the KdV-Burgers equation

    Indian Academy of Sciences (India)

    Yuanxi Xie; Jilashi Tang

    2006-03-01

    In this paper, starting from the careful analysis on the characteristics of the Burgers equation and the KdV equation as well as the KdV-Burgers equation, the superposition method is put forward for constructing the solitary wave solutions of the KdV-Burgers equation from those of the Burgers equation and the KdV equation. The solitary wave solutions for the KdV-Burgers equation are presented successfully by means of this method.

  16. Expression of PPARγ and PTEN in human colorectal cancer: An immunohistochemical study using tissue microarray methodology.

    Science.gov (United States)

    Lin, Mao Song; Huang, Jun Xing; Chen, Wei Chang; Zhang, Bao Feng; Fang, Jing; Zhou, Qiong; Hu, Ying; Gao, Heng Jun

    2011-11-01

    Although aberrations of peroxisome proliferator-activated receptor γ (PPARγ) and phosphatase and tensin homolog (PTEN) expression have been identified in several other cancer types, certain previous studies have revealed that PPARγ is abundant in normal and malignant tissue in the colon. The question of whether aberrant PTEN is involved in the initial stage or is a later event during colorectal carcinogenesis remains controversial. Relatively few studies have focused on the correlation of expression of PPARγ and PTEN in various tissues. In the present study, paraffin-embedded blocks from 139 patients with CRC, 18 adenomatous polyps and 50 paired paracancerous benign mucosas were selected and analysed in 4 tissue microarray (TMA) blocks comprising 104, 72, 130 and 54 cores, respectively. Expression of PPARγ and PTEN was examined using immunohistochemical staining on TMAs. There were no significant differences in the expression of PPARγ (P=0.055) and PTEN (P=0.100) between the colorectal cancers, adenomas and paracancerous mucosas. However, correlations of PPARγ expression with clinical stage (P=0.004) and PTEN expression with histological grade (P=0.006) and distant metastasis (P=0.015) were demonstrated in the CRC specimens. Although the differences in PPARγ and PTEN protein expression in human colorectal cancer may not be considered as early diagnostic markers, our results indicate that CRCs with a low expression or deletion of PTEN may progress towards invasion and even metastasis; thus, PTEN may have potential as a prognostic marker in human CRC.

  17. Selective neuronal PTEN deletion: can we take the brakes off of growth without losing control?

    Science.gov (United States)

    Gutilla, Erin A; Steward, Oswald

    2016-08-01

    The limited ability for injured adult axons to regenerate is a major cause for limited functional recovery after injury to the nervous system, motivating numerous efforts to uncover mechanisms capable of enhancing regeneration potential. One promising strategy involves deletion or knockdown of the phosphatase and tensin (PTEN) gene. Conditional genetic deletion of PTEN before, immediately following, or several months after spinal cord injury enables neurons of the corticospinal tract (CST) to regenerate their axons across the lesion, which is accompanied by enhanced recovery of skilled voluntary motor functions mediated by the CST. Although conditional genetic deletion or knockdown of PTEN in neurons enables axon regeneration, PTEN is a well-known tumor suppressor and mutations of the PTEN gene disrupt brain development leading to neurological abnormalities including macrocephaly, seizures, and early mortality. The long-term consequences of manipulating PTEN in the adult nervous system, as would be done for therapeutic intervention after injury, are only now being explored. Here, we summarize evidence indicating that long-term deletion of PTEN in mature neurons does not cause evident pathology; indeed, cortical neurons that have lived without PTEN for over 1 year appear robust and healthy. Studies to date provide only a first look at potential negative consequences of PTEN deletion or knockdown, but the absence of any detectable neuropathology supports guarded optimism that interventions to enable axon regeneration after injury are achievable.

  18. Selective neuronal PTEN deletion: can we take the brakes off of growth without losing control?

    Directory of Open Access Journals (Sweden)

    Erin A Gutilla

    2016-01-01

    Full Text Available The limited ability for injured adult axons to regenerate is a major cause for limited functional recovery after injury to the nervous system, motivating numerous efforts to uncover mechanisms capable of enhancing regeneration potential. One promising strategy involves deletion or knockdown of the phosphatase and tensin (PTEN gene. Conditional genetic deletion of PTEN before, immediately following, or several months after spinal cord injury enables neurons of the corticospinal tract (CST to regenerate their axons across the lesion, which is accompanied by enhanced recovery of skilled voluntary motor functions mediated by the CST. Although conditional genetic deletion or knockdown ofPTEN in neurons enables axon regeneration, PTEN is a well-known tumor suppressor and mutations of the PTEN gene disrupt brain development leading to neurological abnormalities including macrocephaly, seizures, and early mortality. The long-term consequences of manipulating PTEN in the adult nervous system, as would be done for therapeutic intervention after injury, are only now being explored. Here, we summarize evidence indicating that long-term deletion of PTEN in mature neurons does not cause evident pathology; indeed, cortical neurons that have lived without PTEN for over 1 year appear robust and healthy. Studies to date provide only a first look at potential negative consequences of PTEN deletion or knockdown, but the absence of any detectable neuropathology supports guarded optimism that interventions to enable axon regeneration after injury are achievable.

  19. Travelling Wave Solutions to the m-KdV-Sine-Gordon Equation and the m-KdV-Sinh-Gordon Equation

    Institute of Scientific and Technical Information of China (English)

    LI Er-qiang; CHEN Jin-lan

    2013-01-01

    By using the function transformation and proper Sub-ODE,exact travelling wave solutions of the m-KdV-Sine-Gordon and the m-KdV-Sinh-Gordon equation are obtained,from which exact travelling wave solutions of the m-KdV equation,the Sine-Gordon equation and the Sinh-Gordon equation are derived.

  20. Quantitative and dynamic analysis of PTEN phosphorylation by NMR.

    Science.gov (United States)

    Cordier, Florence; Chaffotte, Alain; Wolff, Nicolas

    2015-05-01

    The dual lipid and protein phosphatase PTEN is a tumor suppressor controlling key biological processes, such as cell growth, proliferation and neuro-survival. Its activity and intracellular trafficking is finely regulated notably by multi-site phosphorylation of its C-terminal tail. The reversible and highly dynamic character of these regulatory events confers a temporal dimension to the cell for triggering crucial decisions. In this review, we describe how a recently developed time-resolved NMR spectroscopy approach unveils the dynamic establishment of the phosphorylation events of PTEN C-terminal tail controlled by CK2 and GSK3β kinases. Two cascades of reactions have been identified, in vitro and in extracts of human neuroblastoma cells. They are triggered independently on two nearby clusters of sites (S380-S385 and S361-S370) and occur on different timescales. In each cascade, the reactions follow an ordered model with a distributive kinetic mechanism. The vision of these cascades as two delay timers activating distinct or time-delayed regulatory responses gives a temporal dimension on PTEN regulation and is discussed in relation to the known functional roles of each cluster. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. The Two-Variable (′/,1/-Expansion Method for Solving the Nonlinear KdV-mKdV Equation

    Directory of Open Access Journals (Sweden)

    E. M. E. Zayed

    2012-01-01

    Full Text Available We apply the two-variable (/, 1/-expansion method to construct new exact traveling wave solutions with parameters of the nonlinear (1+1-dimensional KdV-mKdV equation. This method can be thought of as the generalization of the well-known (/-expansion method given recently by M. Wang et al. When the parameters are replaced by special values, the well-known solitary wave solutions of this equation are rediscovered from the traveling waves. It is shown that the proposed method provides a more general powerful mathematical tool for solving nonlinear evolution equations in mathematical physics.

  2. Exact Solutions for the Modified KdV and the Generalized KdV Equations via Exp-Function Method

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    J. Manafian Heris

    2010-06-01

    Full Text Available An application of the Exp-function method (EFM to search for exact solutions of nonlinear partial differential equations is analyzed. This method is used for the modified KdV equation and the generalized KdV equation. The EFM was used to construct periodic wave and solitary wave solutions of nonlinear evolution equations (NLEEs. This method is developed for searching exact travelling wave solutions of nonlinear partial differential equations. It is shown that the Exp-function method, with the help of symbolic computation, provides a straightforward and powerful mathematical tool for solving nonlinear evolution equations in mathematical physics and applied mathematics.

  3. Convective Wave Breaking in the KdV Equation

    CERN Document Server

    Brun, Mats K

    2016-01-01

    The KdV equation is a model equation for waves at the surface of an inviscid incompressible fluid, and it is well known that the equation describes the evolution of unidirectional waves of small amplitude and long wavelength fairly accurately if the waves fall into the Boussinesq regime. The KdV equation allows a balance of nonlinear steepening effects and dispersive spreading which leads to the formation of steady wave profiles in the form of solitary waves and cnoidal waves. While these wave profiles are solutions of the KdV equation for any amplitude, it is shown here that there for both the solitary and the cnoidal waves, there are critical amplitudes for which the horizontal component of the particle velocity matches the phase velocity of the wave. Solitary or cnoidal solutions of the KdV equation which surpass these amplitudes feature incipient wave breaking as the particle velocity exceeds the phase velocity near the crest of the wave, and the model breaks down due to violation of the kinematic surface...

  4. Effects of Bacillus subtilis KD1 on broiler intestinal flora.

    Science.gov (United States)

    Wu, B Q; Zhang, T; Guo, L Q; Lin, J F

    2011-11-01

    A novel Bacillus subtilis KD1 strain was isolated and identified from healthy broilers, and its phylogenetic classification was subsequently analyzed. To evaluate its probiotic availability, its growth characteristics and tolerance for the gut environment were evaluated in vitro. The results suggest that B. subtilis KD1 is superior in secreting neutral protease and is highly tolerant of gastric acid and bile salt. In the logarithmic growth phase, the neutral protease reached a maximum of 1,369.3 U/mL. When all live bacteria had become spores in the broth, B. subtilis KD1 was freeze dried and fed to broilers at 10(9), 5 × 10(9), and 10(10) bacilli/kg of feed. The animal trial results suggest that the addition of the new strain significantly improved intestinal flora by increasing lactobacilli and reducing Escherichia coli (P < 0.05) as compared with the control; hence, B. subtilis KD1 is a promising probiotic organism in broilers.

  5. KdV solitons in a cold quark gluon plasma

    CERN Document Server

    Fogaça, D A; Filho, L G Ferreira

    2011-01-01

    The relativistic heavy ion program developed at RHIC and now at LHC motivated a deeper study of the properties of the quark gluon plasma (QGP) and, in particular, the study of perturbations in this kind of plasma. We are interested on the time evolution of perturbations in the baryon and energy densities. If a localized pulse in baryon density could propagate throughout the QGP for long distances preserving its shape and without loosing localization, this could have interesting consequences for relativistic heavy ion physics and for astrophysics. A mathematical way to proove that this can happen is to derive (under certain conditions) from the hydrodynamical equations of the QGP a Korteveg-de Vries (KdV) equation. The solution of this equation describes the propagation of a KdV soliton. The derivation of the KdV equation depends crucially on the equation of state (EOS) of the QGP. The use of the simple MIT bag model EOS does not lead to KdV solitons. Recently we have developed an EOS for the QGP which include...

  6. Classification of Dark Modified KdV Equation

    Science.gov (United States)

    Xiong, Na; Lou, Sen-Yue; Li, Biao; Chen, Yong

    2017-07-01

    The dark Korteweg-de Vries (KdV) systems are defined and classified by Kupershmidt sixteen years ago. However, there is no other classifications for other kinds of nonlinear systems. In this paper, a complete scalar classification for dark modified KdV (MKdV) systems is obtained by requiring the existence of higher order differential polynomial symmetries. Different to the nine classes of the dark KdV case, there exist twelve independent classes of the dark MKdV equations. Furthermore, for the every class of dark MKdV system, there is a free parameter. Only for a fixed parameter, the dark MKdV can be related to dark KdV via suitable Miura transformation. The recursion operators of two classes of dark MKdV systems are also given. Supported by the Global Change Research Program of China under Grant No. 2015Cb953904, National Natural Science Foundation of China under Grant Nos. 11675054, 11435005, 11175092, and 11205092 and Shanghai Knowledge Service Platform for Trustworthy Internet of Things (No. ZF1213) and K. C. Wong Magna Fund in Ningbo University

  7. On the nonlinear stability of mKdV breathers

    DEFF Research Database (Denmark)

    Alejo Plana, Miguel Angel; Muñoz, Claudio

    2012-01-01

    Breather modes of the mKdV equation on the real line are known to be elastic under collisions with other breathers and solitons. This fact indicates very strong stability properties of breathers. In this communication we describe a rigorous, mathematical proof of the stability of breathers under...

  8. Nonholonomic deformation of generalized KdV-type equations

    Science.gov (United States)

    Guha, Partha

    2009-08-01

    Karasu-Kalkani et al (2008 J. Math. Phys. 49 073516) recently derived a new sixth-order wave equation KdV6, which was shown by Kupershmidt (2008 Phys. Lett. 372A 2634) to have an infinite commuting hierarchy with a common infinite set of conserved densities. Incidentally, this equation was written for the first time by Calogero and is included in the book by Calogero and Degasperis (1982 Lecture Notes in Computer Science vol 144 (Amsterdam: North-Holland) p 516). In this paper, we give a geometric insight into the KdV6 equation. Using Kirillov's theory of coadjoint representation of the Virasoro algebra, we show how to obtain a large class of KdV6-type equations equivalent to the original equation. Using a semidirect product extension of the Virasoro algebra, {\\widehat{Vir \\ltimes C^{\\infty}(S^1)}} , we propose the nonholonomic deformation of the Ito equation. We also show that the Adler-Kostant-Symes scheme provides a geometrical method for constructing nonholonomic deformed integrable systems. Applying the Adler-Kostant-Symes scheme to loop algebra, we construct a new nonholonomic deformation of the coupled KdV equation.

  9. High-Fidelity Reprogrammed Human IPSCs Have a High Efficacy of DNA Repair and Resemble hESCs in Their MYC Transcriptional Signature

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    Pratik K. Nagaria

    2016-01-01

    Full Text Available Human induced pluripotent stem cells (hiPSCs are reprogrammed from adult or progenitor somatic cells and must make substantial adaptations to ensure genomic stability in order to become “embryonic stem cell- (ESC- like.” The DNA damage response (DDR is critical for maintenance of such genomic integrity. Herein, we determined whether cell of origin and reprogramming method influence the DDR of hiPSCs. We demonstrate that hiPSCs derived from cord blood (CB myeloid progenitors (i.e., CB-iPSC via an efficient high-fidelity stromal-activated (sa method closely resembled hESCs in DNA repair gene expression signature and irradiation-induced DDR, relative to hiPSCs generated from CB or fibroblasts via standard methods. Furthermore, sa-CB-iPSCs also more closely resembled hESCs in accuracy of nonhomologous end joining (NHEJ, DNA double-strand break (DSB repair, and C-MYC transcriptional signatures, relative to standard hiPSCs. Our data suggests that hiPSCs derived via more efficient reprogramming methods possess more hESC-like activated MYC signatures and DDR signaling. Thus, an authentic MYC molecular signature may serve as an important biomarker in characterizing the genomic integrity in hiPSCs.

  10. Relationship between PTEN, DNA mismatch repair, and tumor histotype in endometrial carcinoma: retained positive expression of PTEN preferentially identifies sporadic non-endometrioid carcinomas.

    Science.gov (United States)

    Djordjevic, Bojana; Barkoh, Bedia A; Luthra, Rajyalakshmi; Broaddus, Russell R

    2013-10-01

    Loss of PTEN (phosphatase and tensin homolog) expression and microsatellite instability are two of the more common molecular alterations in endometrial carcinoma. From the published literature, it is controversial as to whether there is a relationship between these different molecular mechanisms. Therefore, a cohort of 187 pure endometrioid and non-endometrioid endometrial carcinomas, carefully characterized as to clinical and pathological features, was examined for PTEN sequence abnormalities and the immunohistochemical expression of PTEN and the DNA mismatch repair proteins MLH1, MSH2, MSH6, and PMS2. MLH1 methylation analysis was performed when tumors had loss of MLH1 protein. Mismatch repair protein loss was more frequent in endometrioid carcinomas compared with non-endometrioid carcinomas, a difference primarily attributable to the presence of MLH1 methylation in a greater proportion of endometrioid tumors. Among the non-endometrioid group, mixed endometrioid/non-endometrioid carcinomas were the histotype that most commonly had loss of a mismatch repair protein. In endometrioid tumors, the frequency of PTEN loss measured by immunohistochemistry and mutation did not differ significantly between the mismatch repair protein intact or mismatch repair protein loss groups, suggesting that PTEN loss is independent of mismatch protein repair status in this group. However, in non-endometrioid carcinomas, both intact positive PTEN immunohistochemical expression and PTEN wild type were highly associated with retained positive expression of mismatch repair proteins in the tumor. Relevant to screening endometrial cancers for Lynch Syndrome, an initial PTEN immunohistochemistry determination may be able to replace the use of four mismatch repair immunohistochemical markers in 63% of patients with non-endometrioid endometrial carcinoma. Therefore, PTEN immunohistochemistry, in combination with tumor histotype, is a useful adjunct in the clinical evaluation of endometrial

  11. Cell-Type Specific Roles for PTEN in Establishing a Functional Retinal Architecture

    Science.gov (United States)

    Cantrup, Robert; Dixit, Rajiv; Palmesino, Elena; Bonfield, Stephan; Shaker, Tarek; Tachibana, Nobuhiko; Zinyk, Dawn; Dalesman, Sarah; Yamakawa, Kazuhiro; Stell, William K.; Wong, Rachel O.; Reese, Benjamin E.; Kania, Artur; Sauvé, Yves; Schuurmans, Carol

    2012-01-01

    Background The retina has a unique three-dimensional architecture, the precise organization of which allows for complete sampling of the visual field. Along the radial or apicobasal axis, retinal neurons and their dendritic and axonal arbors are segregated into layers, while perpendicular to this axis, in the tangential plane, four of the six neuronal types form patterned cellular arrays, or mosaics. Currently, the molecular cues that control retinal cell positioning are not well-understood, especially those that operate in the tangential plane. Here we investigated the role of the PTEN phosphatase in establishing a functional retinal architecture. Methodology/Principal Findings In the developing retina, PTEN was localized preferentially to ganglion, amacrine and horizontal cells, whose somata are distributed in mosaic patterns in the tangential plane. Generation of a retina-specific Pten knock-out resulted in retinal ganglion, amacrine and horizontal cell hypertrophy, and expansion of the inner plexiform layer. The spacing of Pten mutant mosaic populations was also aberrant, as were the arborization and fasciculation patterns of their processes, displaying cell type-specific defects in the radial and tangential dimensions. Irregular oscillatory potentials were also observed in Pten mutant electroretinograms, indicative of asynchronous amacrine cell firing. Furthermore, while Pten mutant RGC axons targeted appropriate brain regions, optokinetic spatial acuity was reduced in Pten mutant animals. Finally, while some features of the Pten mutant retina appeared similar to those reported in Dscam-mutant mice, PTEN expression and activity were normal in the absence of Dscam. Conclusions/Significance We conclude that Pten regulates somal positioning and neurite arborization patterns of a subset of retinal cells that form mosaics, likely functioning independently of Dscam, at least during the embryonic period. Our findings thus reveal an unexpected level of cellular

  12. Cell-type specific roles for PTEN in establishing a functional retinal architecture.

    Directory of Open Access Journals (Sweden)

    Robert Cantrup

    Full Text Available BACKGROUND: The retina has a unique three-dimensional architecture, the precise organization of which allows for complete sampling of the visual field. Along the radial or apicobasal axis, retinal neurons and their dendritic and axonal arbors are segregated into layers, while perpendicular to this axis, in the tangential plane, four of the six neuronal types form patterned cellular arrays, or mosaics. Currently, the molecular cues that control retinal cell positioning are not well-understood, especially those that operate in the tangential plane. Here we investigated the role of the PTEN phosphatase in establishing a functional retinal architecture. METHODOLOGY/PRINCIPAL FINDINGS: In the developing retina, PTEN was localized preferentially to ganglion, amacrine and horizontal cells, whose somata are distributed in mosaic patterns in the tangential plane. Generation of a retina-specific Pten knock-out resulted in retinal ganglion, amacrine and horizontal cell hypertrophy, and expansion of the inner plexiform layer. The spacing of Pten mutant mosaic populations was also aberrant, as were the arborization and fasciculation patterns of their processes, displaying cell type-specific defects in the radial and tangential dimensions. Irregular oscillatory potentials were also observed in Pten mutant electroretinograms, indicative of asynchronous amacrine cell firing. Furthermore, while Pten mutant RGC axons targeted appropriate brain regions, optokinetic spatial acuity was reduced in Pten mutant animals. Finally, while some features of the Pten mutant retina appeared similar to those reported in Dscam-mutant mice, PTEN expression and activity were normal in the absence of Dscam. CONCLUSIONS/SIGNIFICANCE: We conclude that Pten regulates somal positioning and neurite arborization patterns of a subset of retinal cells that form mosaics, likely functioning independently of Dscam, at least during the embryonic period. Our findings thus reveal an unexpected

  13. Rescue of glandular dysmorphogenesis in PTEN-deficient colorectal cancer epithelium by PPARγ-targeted therapy.

    Science.gov (United States)

    Jagan, I; Fatehullah, A; Deevi, R K; Bingham, V; Campbell, F C

    2013-03-07

    Disruption of glandular architecture associates with poor clinical outcome in high-grade colorectal cancer (CRC). Phosphatase and tensin homolog deleted on chromosome ten (PTEN) regulates morphogenic growth of benign MDCK (Madin Darby Canine Kidney) cells through effects on the Rho-like GTPase cdc42 (cell division cycle 42). This study investigates PTEN-dependent morphogenesis in a CRC model. Stable short hairpin RNA knockdown of PTEN in Caco-2 cells influenced expression or localization of cdc42 guanine nucleotide exchange factors and inhibited cdc42 activation. Parental Caco-2 cells formed regular hollow gland-like structures (glands) with a single central lumen, in three-dimensional (3D) cultures. Conversely, PTEN-deficient Caco-2 ShPTEN cells formed irregular glands with multiple abnormal lumens as well as intra- and/or intercellular vacuoles evocative of the high-grade CRC phenotype. Effects of targeted treatment were investigated. Phosphatidinylinositol 3-kinase (PI3K) modulating treatment did not affect gland morphogenesis but did influence gland number, gland size and/or cell size within glands. As PTEN may be regulated by the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ), cultures were treated with the PPARγ ligand rosiglitazone. This treatment enhanced PTEN expression, cdc42 activation and rescued dysmorphogenesis by restoring single lumen formation in Caco-2 ShPTEN glands. Rosiglitazone effects on cdc42 activation and Caco-2 ShPTEN gland development were attenuated by cotreatment with GW9662, a PPARγ antagonist. Taken together, these studies show PTEN-cdc42 regulation of lumen formation in a 3D model of human CRC glandular morphogenesis. Treatment by the PPARγ ligand rosiglitazone, but not PI3K modulators, rescued colorectal glandular dysmorphogenesis of PTEN deficiency.

  14. Hyperactivity of Newborn Pten Knock-out Neurons Results from Increased Excitatory Synaptic Drive

    Science.gov (United States)

    Williams, Michael R.; DeSpenza, Tyrone; Li, Meijie; Gulledge, Allan T.

    2015-01-01

    Developing neurons must regulate morphology, intrinsic excitability, and synaptogenesis to form neural circuits. When these processes go awry, disorders, including autism spectrum disorder (ASD) or epilepsy, may result. The phosphatase Pten is mutated in some patients having ASD and seizures, suggesting that its mutation disrupts neurological function in part through increasing neuronal activity. Supporting this idea, neuronal knock-out of Pten in mice can cause macrocephaly, behavioral changes similar to ASD, and seizures. However, the mechanisms through which excitability is enhanced following Pten depletion are unclear. Previous studies have separately shown that Pten-depleted neurons can drive seizures, receive elevated excitatory synaptic input, and have abnormal dendrites. We therefore tested the hypothesis that developing Pten-depleted neurons are hyperactive due to increased excitatory synaptogenesis using electrophysiology, calcium imaging, morphological analyses, and modeling. This was accomplished by coinjecting retroviruses to either “birthdate” or birthdate and knock-out Pten in granule neurons of the murine neonatal dentate gyrus. We found that Pten knock-out neurons, despite a rapid onset of hypertrophy, were more active in vivo. Pten knock-out neurons fired at more hyperpolarized membrane potentials, displayed greater peak spike rates, and were more sensitive to depolarizing synaptic input. The increased sensitivity of Pten knock-out neurons was due, in part, to a higher density of synapses located more proximal to the soma. We determined that increased synaptic drive was sufficient to drive hypertrophic Pten knock-out neurons beyond their altered action potential threshold. Thus, our work contributes a developmental mechanism for the increased activity of Pten-depleted neurons. PMID:25609613

  15. Cdc6 and Cyclin E2 Are PTEN-Regulated Genes Associated with Human Prostate Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    Zhong Wu

    2009-01-01

    Full Text Available Phosphatase and tensin homolog deleted on chromosome 10 (PTEN is frequently inactivated in metastatic prostate cancer, yet the molecular consequences of this and their association with the metastatic phenotype are incompletely understood. We performed transcriptomic analysis and identified genes altered by conditional PTEN reexpression in C4-2, a human metastatic prostate cancer cell line with inactive PTEN. PTEN-regulated genes were disproportionately represented among genes altered in human prostate cancer progression and metastasis but not among those associated with tumorigenesis. From the former set, we identified two novel putative PTEN targets, cdc6 and cyclin E2, which were overexpressed in metastatic human prostate cancer and up-regulated as a function of PTEN depletion in poorly metastatic DU145 human prostate cancer cells harboring a wild type PTEN. Inhibition of cdc6 and cyclin E2 levels as a consequence of PTEN expression was associated with cell cycle G1 arrest, whereas use of PTEN activity mutants revealed that regulation of these genes was dependent on PTEN lipid phosphatase activity. Computational and promoter-reporter evaluations implicated the E2F transcription factor in PTEN regulation of cdc6 and cyclin E2 expression. Our results suggest a hypothetical model whereby PTEN loss upregulates cell cycle genes such as cdc6 and cyclin E2 that in turn promote metastatic colonization at distant sites.

  16. Soy peptide lunasin induces pten-mediated apoptosis in human breast cancer cells

    Science.gov (United States)

    The tumor suppressor PTEN inhibits the AKT signaling pathway whose unrestrained activity underlies many human malignancies. Previously we showed that dietary intake of soy protein isolate (SPI) enhanced PTEN expression in mammary tissue of rats with lower NMU-induced mammary tumor incidence relative...

  17. Studies of variability in the PTEN gene among Danish caucasian patients with Type II diabetes mellitus

    DEFF Research Database (Denmark)

    Hansen, L; Jensen, J N; Ekstrøm, C T

    2001-01-01

    Phosphatase and tensin homologue deleted from chromosome ten (PTEN) has recently been characterized as a novel member in the expanding network of proteins regulating the intracellular effects of insulin. By dephosphorylation of phosphatidyl-inositol-(3, 4, 5)-trisphosphate (PIP3) the PTEN protein...

  18. Planarian PTEN homologs regulate stem cells and regeneration through TOR signaling.

    Science.gov (United States)

    Oviedo, Néstor J; Pearson, Bret J; Levin, Michael; Sánchez Alvarado, Alejandro

    2008-01-01

    We have identified two genes, Smed-PTEN-1 and Smed-PTEN-2, capable of regulating stem cell function in the planarian Schmidtea mediterranea. Both genes encode proteins homologous to the mammalian tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Inactivation of Smed-PTEN-1 and -2 by RNA interference (RNAi) in planarians disrupts regeneration, and leads to abnormal outgrowths in both cut and uncut animals followed soon after by death (lysis). The resulting phenotype is characterized by hyperproliferation of neoblasts (planarian stem cells), tissue disorganization and a significant accumulation of postmitotic cells with impaired differentiation capacity. Further analyses revealed that rapamycin selectively prevented such accumulation without affecting the normal neoblast proliferation associated with physiological turnover and regeneration. In animals in which PTEN function is abrogated, we also detected a significant increase in the number of cells expressing the planarian Akt gene homolog (Smed-Akt). However, functional abrogation of Smed-Akt in Smed-PTEN RNAi-treated animals does not prevent cell overproliferation and lethality, indicating that functional abrogation of Smed-PTEN is sufficient to induce abnormal outgrowths. Altogether, our data reveal roles for PTEN in the regulation of planarian stem cells that are strikingly conserved to mammalian models. In addition, our results implicate this protein in the control of stem cell maintenance during the regeneration of complex structures in planarians.

  19. Characterization of cryptic splicing in germline PTEN intronic variants in Cowden syndrome.

    Science.gov (United States)

    Chen, Hannah Jinlian; Romigh, Todd; Sesock, Kaitlin; Eng, Charis

    2017-10-01

    Germline mutations in the tumor-suppressor gene PTEN predispose to subsets of Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, and autism. Evidence-based classification of PTEN variants as either deleterious or benign is urgently needed for accurate molecular diagnosis and gene-informed genetic counseling. We studied 34 different germline PTEN intronic variants from 61 CS patients, characterized their PTEN mRNA processing, and analyzed PTEN expression and downstream readouts of P-AKT and P-ERK1/2. While we found that many mutations near splice junctions result in exon skipping, we also identified the presence of cryptic splicing that resulted in premature termination or a shift in isoform usage. PTEN protein expression is significantly lower in the group with splicing changes while P-AKT, but not P-ERK1/2, is significantly increased. Our observations of these PTEN intronic variants should contribute to the determination of pathogenicity of PTEN intronic variants and aid in genetic counseling. © 2017 The Authors. Human Mutation published by Wiley Periodicals, Inc.

  20. Cancer risk and genotype-phenotype correlations in PTEN hamartoma tumor syndrome

    NARCIS (Netherlands)

    Nieuwenhuis, M.H.; Kets, C.M.; Murphy-Ryan, M.; Yntema, H.G.; Evans, D.G.; Colas, C.; Moller, P.; Hes, F.J.; Hodgson, S.V.; Olderode-Berends, M.J.; Aretz, S.; Heinimann, K.; Garcia, E.B.; Douglas, F.; Spigelman, A.; Timshel, S.; Lindor, N.M.; Vasen, H.F.

    2014-01-01

    Patients with germline PTEN mutations are at high risk of developing benign and malignant tumours. We aimed to evaluate the cumulative risk of several types of cancer and of dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease, LDD). In addition, genotype-phenotype correlations in PTEN hama

  1. Systematic analysis of the PTEN 5' leader identifies a major AUU initiated proteoform.

    Science.gov (United States)

    Tzani, Ioanna; Ivanov, Ivaylo P; Andreev, Dmitri E; Dmitriev, Ruslan I; Dean, Kellie A; Baranov, Pavel V; Atkins, John F; Loughran, Gary

    2016-05-01

    Abundant evidence for translation within the 5' leaders of many human genes is rapidly emerging, especially, because of the advent of ribosome profiling. In most cases, it is believed that the act of translation rather than the encoded peptide is important. However, the wealth of available sequencing data in recent years allows phylogenetic detection of sequences within 5' leaders that have emerged under coding constraint and therefore allow for the prediction of functional 5' leader translation. Using this approach, we previously predicted a CUG-initiated, 173 amino acid N-terminal extension to the human tumour suppressor PTEN. Here, a systematic experimental analysis of translation events in the PTEN 5' leader identifies at least two additional non-AUG-initiated PTEN proteoforms that are expressed in most human cell lines tested. The most abundant extended PTEN proteoform initiates at a conserved AUU codon and extends the canonical AUG-initiated PTEN by 146 amino acids. All N-terminally extended PTEN proteoforms tested retain the ability to downregulate the PI3K pathway. We also provide evidence for the translation of two conserved AUG-initiated upstream open reading frames within the PTEN 5' leader that control the ratio of PTEN proteoforms.

  2. Opening the conformation is a master switch for the dual localization and phosphatase activity of PTEN

    Science.gov (United States)

    Nguyen, Hoai-Nghia; Yang, Jr-Ming; Miyamoto, Takafumi; Itoh, Kie; Rho, Elmer; Zhang, Qiang; Inoue, Takanari; Devreotes, Peter N.; Sesaki, Hiromi; Iijima, Miho

    2015-01-01

    Tumor suppressor PTEN mainly functions at two subcellular locations, the plasma membrane and the nucleus. At the plasma membrane, PTEN dephosphorylates the tumorigenic second messenger PIP3, which drives cell proliferation and migration. In the nucleus, PTEN controls DNA repair and genome stability independently of PIP3. Whereas the concept that a conformational change regulates protein function through post-translational modifications has been well established in biology, it is unknown whether a conformational change simultaneously controls dual subcellular localizations of proteins. Here, we discovered that opening the conformation of PTEN is the crucial upstream event that determines its key dual localizations of this crucial tumor suppressor. We identify a critical conformational switch that regulates PTEN’s localization. Most PTEN molecules are held in the cytosol in a closed conformation by intramolecular interactions between the C-terminal tail and core region. Dephosphorylation of the tail opens the conformation and exposes the membrane-binding regulatory interface in the core region, recruiting PTEN to the membrane. Moreover, a lysine at residue 13 is also exposed and when ubiquitinated, transports PTEN to the nucleus. Thus, opening the conformation of PTEN is a key mechanism that enhances its dual localization and enzymatic activity, providing a potential therapeutic strategy in cancer treatments. PMID:26216063

  3. Reprogramming of the Tumor Microenvironment by Stromal Pten-regulated miR-320

    Science.gov (United States)

    Bronisz, A; Godlewski, J; Wallace, JA; Merchant, AS; Nowicki, MO; Mathsyaraja, H; Srinivasan, R; Trimboli, AJ; Martin, CK; Li, F; Yu, L; Fernandez, SA; Pécot, T; Rosol, TJ; Cory, S; Hallett, M; Park, M; Piper, MG; Marsh, CB; Yee, LD; Jimenez, RE; Nuovo, G; Lawler, SE; Chiocca, EA; Leone, G; Ostrowski, MC

    2011-01-01

    Phosphatase and tensin homolog deleted on chromosome ten (Pten) in stromal fibroblasts suppresses epithelial mammary tumors, but the underlying molecular mechanisms remain unknown. Using proteomic and expression profiling, we show that Pten loss from mammary stromal fibroblasts activates an oncogenic secretome that orchestrates the transcriptional reprogramming of other cell types in the microenvironment. Downregulation of miR-320 and upregulation of one of its direct targets, ETS2, are critical events in Pten-deleted stromal fibroblasts responsible for inducing this oncogenic secretome, which in turn promotes tumor angiogenesis and tumor cell invasion. Expression of the Pten-miR-320-Ets2 regulated secretome distinguished human normal breast stroma from tumor stroma and robustly correlated with recurrence in breast cancer patients. This work reveals miR-320 as a critical component of the Pten tumor suppressor axis that acts in stromal fibroblasts to reprogram the tumor microenvironment and curtail tumor progression. PMID:22179046

  4. Function of PTEN during the formation and maintenance of neuronal circuits in the brain.

    Science.gov (United States)

    van Diepen, Michiel T; Eickholt, Britta J

    2008-01-01

    PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumor suppressor that can inhibit proliferation and migration and controls apoptosis in a number of cell types, mainly through inhibition of the phosphoinositide 3-kinase (PI3K) signaling pathway. Patients carrying inactivating mutations of PTEN show a prevalence to develop tumors that can coincide with neurological defects such as mental retardation, ataxia and seizures. A number of in vitro and in vivo studies were instrumental in uncovering a direct correlation between deregulated PI3K/PTEN signaling and changes in neuronal morphogenesis, which is likely to have profound bearings upon the pathogenesis of neurological symptoms. This review outlines recent work on the function of PTEN during vertebrate brain development and the current understanding of the signaling pathways downstream of PTEN that control neuronal connectivity in the brain.

  5. KD4v: Comprehensible Knowledge Discovery System for Missense Variant.

    Science.gov (United States)

    Luu, Tien-Dao; Rusu, Alin; Walter, Vincent; Linard, Benjamin; Poidevin, Laetitia; Ripp, Raymond; Moulinier, Luc; Muller, Jean; Raffelsberger, Wolfgang; Wicker, Nicolas; Lecompte, Odile; Thompson, Julie D; Poch, Olivier; Nguyen, Hoan

    2012-07-01

    A major challenge in the post-genomic era is a better understanding of how human genetic alterations involved in disease affect the gene products. The KD4v (Comprehensible Knowledge Discovery System for Missense Variant) server allows to characterize and predict the phenotypic effects (deleterious/neutral) of missense variants. The server provides a set of rules learned by Induction Logic Programming (ILP) on a set of missense variants described by conservation, physico-chemical, functional and 3D structure predicates. These rules are interpretable by non-expert humans and are used to accurately predict the deleterious/neutral status of an unknown mutation. The web server is available at http://decrypthon.igbmc.fr/kd4v.

  6. Operator splitting for the KdV equation

    CERN Document Server

    Holden, Helge; Risebro, Nils Henrik; Tao, Terence

    2009-01-01

    We provide a new analytical approach to operator splitting for equations of the type $u_t=Au+B(u)$ where $A$ is a linear operator and $B$ is quadratic. A particular example is the Korteweg-de Vries (KdV) equation $u_t-u u_x+u_{xxx}=0$. We show that the Godunov and Strang splitting methods converge with the expected rates if the initial data are sufficiently regular.

  7. Similarity Reductions of Nearly Concentric KdV Equation

    Institute of Scientific and Technical Information of China (English)

    WANG Jia; LI Biao

    2009-01-01

    Basing on the direct method developed by Clarkson and Kruskal, the nearly concentric Korteweg-de Vries (ncKdV) equation can be reduced to three types of (1+1)-dimensional variable coefficients partial differential equations (PDEs) and three types of variable coefficients ordinary differential equation. Furthermore, three types of (1+1)-dimensional variable coefficients PDEs are all reduced to constant coefficients PDEs by some transformations.

  8. On exact solutions of modified KdV-ZK equation

    Directory of Open Access Journals (Sweden)

    Syed Tauseef Mohyud-Din

    2016-12-01

    Full Text Available In this work, we established some exact particular solutions with parameters for Modified KdV-ZK Equation. The improved tanϕ(ξ2-expansion method is introduced to construct exact particular solutions of nonlinear evolution equations. The exact particular solutions contain four types: hyperbolic function solution, trigonometric function solution, exponential solution, and rational solution. The method appears to be effective mathematical tool for solving nonlinear evolution equations (NLEEs in applied mathematics and engineering.

  9. Conservative Linear Difference Scheme for Rosenau-KdV Equation

    Directory of Open Access Journals (Sweden)

    Jinsong Hu

    2013-01-01

    Full Text Available A conservative three-level linear finite difference scheme for the numerical solution of the initial-boundary value problem of Rosenau-KdV equation is proposed. The difference scheme simulates two conservative quantities of the problem well. The existence and uniqueness of the difference solution are proved. It is shown that the finite difference scheme is of second-order convergence and unconditionally stable. Numerical experiments verify the theoretical results.

  10. Finite Element Method for Stochastic Extended KdV Equations

    CERN Document Server

    Karczewska, Anna; Rozmej, Piotr; Boguniewicz, Bartosz

    2016-01-01

    The finite element method is applied to obtain numerical solutions to the recently derived nonlinear equation for shallow water wave problem for several cases of bottom shapes. Results for time evolution of KdV solitons and cnoidal waves under stochastic forces are presented. Though small effects originating from second order dynamics may be obscured by stochastic forces, the main waves, both cnoidal and solitary ones, remain very robust against any distortions.

  11. Characterization of Heterogeneous Prostate Tumors in Targeted Pten Knockout Mice.

    Directory of Open Access Journals (Sweden)

    Hanneke Korsten

    Full Text Available Previously, we generated a preclinical mouse prostate tumor model based on PSA-Cre driven inactivation of Pten. In this model homogeneous hyperplastic prostates (4-5m developed at older age (>10m into tumors. Here, we describe the molecular and histological characterization of the tumors in order to better understand the processes that are associated with prostate tumorigenesis in this targeted mouse Pten knockout model. The morphologies of the tumors that developed were very heterogeneous. Different histopathological growth patterns could be identified, including intraductal carcinoma (IDC, adenocarcinoma and undifferentiated carcinoma, all strongly positive for the epithelial cell marker Cytokeratin (CK, and carcinosarcomas, which were negative for CK. IDC pattern was already detected in prostates of 7-8 month old mice, indicating that it could be a precursor stage. At more than 10 months IDC and carcinosarcoma were most frequently observed. Gene expression profiling discriminated essentially two molecular subtypes, denoted tumor class 1 (TC1 and tumor class 2 (TC2. TC1 tumors were characterized by high expression of epithelial markers like Cytokeratin 8 and E-Cadherin whereas TC2 tumors showed high expression of mesenchyme/stroma markers such as Snail and Fibronectin. These molecular subtypes corresponded with histological growth patterns: where TC1 tumors mainly represented adenocarcinoma/intraductal carcinoma, in TC2 tumors carcinosarcoma was the dominant growth pattern. Further molecular characterization of the prostate tumors revealed an increased expression of genes associated with the inflammatory response. Moreover, functional markers for senescence, proliferation, angiogenesis and apoptosis were higher expressed in tumors compared to hyperplasia. The highest expression of proliferation and angiogenesis markers was detected in TC2 tumors. Our data clearly showed that in the genetically well-defined PSA-Cre;Pten-loxP/loxP prostate tumor

  12. Construction and Expression of Human PTEN Tumor Suppressor Gene Recombinant Adenovirus Vector

    Institute of Scientific and Technical Information of China (English)

    CHEN Qingyong; WANG Chunyou; CHEN Daoda; CHEN Jianying; JIANG Chunfang; ZHENG Hai

    2006-01-01

    The recombinant defective adenovirus vector carrying human PTEN tumor suppres sor gene was constructed by using AdEasy-1 system and its expression was detected in human breast cancer cell line MDA-MB-468. Human PTEN cDNA was cloned into adenovirus shuttle plasmid pAdTrack-CMV to generate a recombinant plasmid pAdTrack-CMV-PTEN, then homologeous recombination was carried out in the E. coli BJ5183 by contransforming linearized shuttle vector with adenovirus backbone plasmid pAdEasy-1. The newly recombined defective adenovirus vector AdPTEN containing green fluorescent protein (GFP) was packaged and propagated in 293 cells. After being purified by cesium chloride gradient centrifugation, the adenovirus was transfected into human breast cancer cell line MDA-MB-468 in vitro. The expression of PTEN mRNA and protein in infected human breast cancer cell line MDA-MB-468 was detected by RT-PCR and Western blot respectively. The recombinant defective adenovirus vector carrying PTEN gene was constructed successfully. The viral titer of purified adenovirus was 2.5×1010 pfu/mL, and about 70 % breast cancer cells were infected with Ad PTEN when multiplicity of infection (MOI) reached 50. The exogenous PTEN mRNA and protein were expressed in MDA-MB-468 cells infected with Ad-PTEN by RT-PCR and Western blot. The recombinant defective adenovirus vector of PTEN gene was constructed successfully using AdEasy-1 system rapidly, which paved a sound foundation for gene study of breast cancer.

  13. The role of PTEN in chronic growth hormone-induced hepatic insulin resistance.

    Science.gov (United States)

    Gao, Yuan; Su, Peizhu; Wang, Chuqiong; Zhu, Kongqin; Chen, Xiaolan; Liu, Side; He, Jiman

    2013-01-01

    Chronic growth hormone (GH) therapy has been shown to cause insulin resistance, but the mechanism remains unknown. PTEN, a tumor suppressor gene, is a major negative regulator of insulin signaling. In this study, we explored the effect of chronic GH on insulin signaling in the context of PTEN function. Balb/c healthy mice were given recombinant human or bovine GH intraperitoneally for 3 weeks. We found that phosphorylation of Akt was significantly decreased in chronic GH group and the expression of PTEN was significantly increased. We further examined this effect in the streptozotocin-induced Type I diabetic mouse model, in which endogenous insulin secretion was disrupted. Insulin/PI3K/Akt signaling was impaired. However, different from the observation in healthy mice, the expression of PTEN did not increase. Similarly, PTEN expression did not significantly increase in chronic GH-treated mice with hypoinsulinemia induced by prolonged fasting. We conducted in-vitro experiments in HepG2 cells to validate our in-vivo findings. Long-term exposure to GH caused similar resistance of insulin/PI3K/Akt signaling in HepG2 cells; and over-expression of PTEN enhanced the impairment of insulin signaling. On the other hand, disabling the PTEN gene by transfecting the mutant PTEN construct C124S or siPTEN, disrupted the chronic GH induced insulin resistance. Our data demonstrate that PTEN plays an important role in chronic-GH-induced insulin resistance. These findings may have implication in other pathological insulin resistance.

  14. Molecular characterization and function of a PTEN gene from Litopenaeus vannamei after Vibrio alginolyticus challenge.

    Science.gov (United States)

    Xie, C-y; Kong, J-r; Zhao, C-s; Xiao, Y-c; Peng, T; Liu, Y; Wang, W-n

    2016-06-01

    PTEN, a tumor suppressor gene, suppresses cell survival, growth, apoptosis, cell migration and DNA damage repair by inhibiting the PI3K/AKT signaling pathway. In this study, the full-length Litopenaeus vannamei PTEN (LvPTEN) cDNA was obtained, containing a 5'UTR of 59bp, an ORF of 1269bp and a 3'UTR of 146bp besides the poly (A) tail. The PTEN gene encoded a protein of 422 amino acids with an estimated molecular mass of 48.3 KDa and a predicted isoelectric point (pI) of 7.6. Subcellular localization analysis revealed that LvPTEN was distributed in both cytoplasm and nucleus, and the tissue distribution patterns showed that LvPTEN was ubiquitously expressed in all the examined tissues. Vibrio alginolyticus challenge induced upregulation of LvPTEN expression. Moreover, RNAi knock-down of LvPTEN in vivo significantly increased the expression of LvAKT mRNA, while reducing that of the downstream apoptosis genes LvP53 and LvCaspase3. LvPTEN knock-down also caused a sharp increase in cumulative mortality, bacterial numbers, and DNA damage in the hemolymph of L. vannamei following V. alginolyticus challenge, together with a sharp decrease in the total hemocyte count (THC). These results suggested that LvPTEN may participate in apoptosis via the PI3K/AKT signaling pathway in L. vannamei, and play an important role in shrimp innate immunity.

  15. Downregulation of PTEN at Corneal Wound Sites Accelerates Wound Healing through Increased Cell Migration

    Science.gov (United States)

    Cao, Lin; Graue-Hernandez, Enrique O.; Tran, Vu; Reid, Brian; Pu, Jin; Mannis, Mark J.

    2011-01-01

    Purpose. The PI3K/Akt pathway is required for cell polarization and migration, whereas the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has inhibitory effects on the PI3K/Akt pathway. The authors therefore hypothesized that wounding would downregulate PTEN and that this downregulation would enhance wound healing. Methods. In human corneal epithelial (HCE) cell monolayer and rat cornea scratch wound models, the authors investigated PTEN and Akt expression using Western blot and immunofluorescence analyses. The effects of PTEN and PI3K inhibitors dipotassium bisperoxo (picolinato) oxovanadate (bpv(pic)) and LY294002 on cell migration and wound closure were investigated using time-lapse imaging. Finally, the authors investigated the effect of PTEN inhibition on wound healing in whole rat eyes. Results. In HCE cell monolayer and rat cornea, PTEN was downregulated at the wound edges within 30 minutes of wounding. The downregulation of PTEN was causal in a simultaneous increase in Akt activation, which was responsible for a significant increase in individual cell migration rate from 8.8 μm/h to 17.3 μm/h. An increased migration rate was maintained for 20 hours. PTEN inhibition significantly enhanced the wound healing rate in the HCE cell monolayer from 10 minutes onward after treatment and reduced the healing time in eye organ culture from 30 to 20 hours. Conclusions. Injury to the corneal epithelium downregulates the expression of PTEN at wound edges, allowing increased PI3K/Akt signaling, thereby contributing to a significant enhancement of cell migration and wound healing. These results suggest that PTEN inhibition may be an effective treatment for corneal injury. PMID:21212174

  16. Loss of PTEN causes SHP2 activation, making lung cancer cells unresponsive to IFN-γ

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chia-Ling [Translational Research Center, Taipei Medical University, Taipei 110, Taiwan (China); Chiang, Tzu-Hui; Tseng, Po-Chun [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); Wang, Yu-Chih [Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan (China); Lin, Chiou-Feng, E-mail: cflin2014@tmu.edu.tw [Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan (China); Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan (China)

    2015-10-23

    Src homology-2 domain-containing phosphatase (SHP) 2, an oncogenic phosphatase, inhibits type II immune interferon (IFN)-γ signaling by subverting signal transducers and activators of transcription 1 tyrosine phosphorylation and activation. For cancer immunoediting, this study aimed to investigate the decrease of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor protein, leading to cellular impairment of IFN-γ signaling. In comparison with human lung adenocarcinoma A549 cells, the natural PTEN loss in another human lung adenocarcinoma line, PC14PE6/AS2 cells, presents reduced responsiveness in IFN-γ-induced IFN regulatory factor 1 activation and CD54 expression. Artificially silencing PTEN expression in A549 cells also caused cells to be unresponsive to IFN-γ without affecting IFN-γ receptor expression. IFN-γ-induced inhibition of cell proliferation and cytotoxicity were demonstrated in A549 cells but were defective in PC14PE6/AS2 cells and in PTEN-deficient A549 cells. Aberrant activation of SHP2 by ROS was specifically shown in PC14PE6/AS2 cells and PTEN-deficient A549 cells. Inhibiting ROS and SHP2 rescued cellular responses to IFN-γ-induced cytotoxicity and inhibition of cell proliferation in PC14PE6/AS2 cells. These results demonstrate that a decrease in PTEN facilitates ROS/SHP2 signaling, causing lung cancer cells to become unresponsive to IFN-γ. - Highlights: • This study demonstrates that PTEN decrease causes cellular unresponsive to IFN-γ. • Lung cancer cells with PTEN deficiency show unresponsive to IFN-γ signaling. • PTEN decrease inhibits IFN-γ-induced CD54, cell proliferation inhibition, and cytotoxicity. • ROS-mediated SHP2 activation makes PTEN-deficient cells unresponsive to IFN-γ.

  17. In Vitro and In Vivo Effects of Tumor Suppressor Gene PTEN on Endometriosis: An Experimental Study

    Science.gov (United States)

    Lv, Juan; Zhu, Qiaoying; Jia, Xuemei; Yu, Ningzhu; Li, Qian

    2016-01-01

    Background Endometriosis can cause dysmenorrhea and infertility. Its pathogenesis has not yet been clarified and its treatment continues to pose enormous challenges. The protein tyrosine phosphatase (PTEN) gene is a tumor suppressor gene. The aim of this study was to investigate the role and significance of PTEN protein in the occurrence, development, and treatment of endometriosis through changes in apoptosis rate, cell cycle, and angiogenesis. Material/Methods PTEN was overexpressed and silenced in lentiviral vectors and inserted into primary endometrial cells. The changes in cell cycle and apoptosis in the different PTEN expression groups were evaluated using flow cytometry. Vessel growth mimicry was observed using 3-dimensional culture. A human-mouse chimeric endometriosis model was constructed using SCID mice. Hematoxylin and eosin staining and immunohistochemistry were used to detect pathological changes in ectopic endometrial tissues and the expression of VEGF protein in a human-mouse chimeric endometriosis mouse model. Results PTEN overexpression significantly increased apoptosis and inhibited the cell cycle compared with the silenced and control groups. Furthermore, cells expressing low PTEN levels were better able to undergo vasculogenic mimicry, and exhibited significantly increased angiogenesis compared to cells overexpressing PTEN. We found that ectopic foci were more easily formed in the endometrial tissue of SCID mice with low PTEN expression, and the VEGF expression in this group was relatively high. Conclusions PTEN inhibits the occurrence and development of endometriosis by regulating angiogenesis and the apoptosis and cell cycle of endometrial cells; therefore, we propose that the PTEN gene can be used to treat endometriosis. PMID:27744455

  18. Mice lacking pten in osteoblasts have improved intramembranous and late endochondral fracture healing.

    Directory of Open Access Journals (Sweden)

    Travis A Burgers

    Full Text Available The failure of an osseous fracture to heal (development of a non-union is a common and debilitating clinical problem. Mice lacking the tumor suppressor Pten in osteoblasts have dramatic and progressive increases in bone volume and density throughout life. Since fracture healing is a recapitulation of bone development, we investigated the process of fracture healing in mice lacking Pten in osteoblasts (Ocn-cre(tg/+;Pten(flox/flox . Mid-diaphyseal femoral fractures induced in wild-type and Ocn-cre(tg/+;Pten(flox/flox mice were studied via micro-computed tomography (µCT scans, biomechanical testing, histological and histomorphometric analysis, and protein expression analysis. Ocn-cre(tg/+;Pten(flox/flox mice had significantly stiffer and stronger intact bones relative to controls in all cohorts. They also had significantly stiffer healing bones at day 28 post-fracture (PF and significantly stronger healing bones at days 14, 21, and 28 PF. At day 7 PF, the proximal and distal ends of the Pten mutant calluses were more ossified. By day 28 PF, Pten mutants had larger and more mineralized calluses. Pten mutants had improved intramembranous bone formation during healing originating from the periosteum. They also had improved endochondral bone formation later in the healing process, after mature osteoblasts are present in the callus. Our results indicate that the inhibition of Pten can improve fracture healing and that the local or short-term use of commercially available Pten-inhibiting agents may have clinical application for enhancing fracture healing.

  19. Detecting PTEN and PI3K signaling in brain

    Science.gov (United States)

    Zhu, Guo; Baker, Suzanne J.

    2016-01-01

    Summary The central nervous system is comprised of multiple cell types including neurons, glia and other supporting cells that may differ dramatically in levels of signaling pathway activation. Immunohistochemistry in conjunction with drug interference are powerful tools that allow evaluation of signaling pathways in different cell types of the mouse central nervous system in vivo. Here we provide detailed protocols for immunohistochemistry to evaluate three essential components in the PI3K pathway in mouse brain: Pten, p-Akt and p-4ebp1, and for rapamycin treatment to modulate mTOR signaling in vivo. PMID:27033070

  20. A defined, feeder-free, serum-free system to generate in vitro hematopoietic progenitors and differentiated blood cells from hESCs and hiPSCs.

    Directory of Open Access Journals (Sweden)

    Giorgia Salvagiotto

    Full Text Available Human ESC and iPSC are an attractive source of cells of high quantity and purity to be used to elucidate early human development processes, for drug discovery, and in clinical cell therapy applications. To efficiently differentiate pluripotent cells into a pure population of hematopoietic progenitors we have developed a new 2-dimensional, defined and highly efficient protocol that avoids the use of feeder cells, serum or embryoid body formation. Here we showed that a single matrix protein in combination with growth factors and a hypoxic environment is sufficient to generate from pluripotent cells hematopoietic progenitors capable of differentiating further in mature cell types of different lineages of the blood system. We tested the differentiation method using hESCs and 9 iPSC lines generated from different tissues. These data indicate the robustness of the protocol providing a valuable tool for the generation of clinical-grade hematopoietic cells from pluripotent cells.

  1. 人体胚胎肝细胞蛋白质组学的研究进展%Research Progress of human embryonic stem cells hESC Proteomics

    Institute of Scientific and Technical Information of China (English)

    眭维国; 谭秋培; 薛雯; 陈洁晶

    2012-01-01

    人体胚胎干细胞是一类具有自我更新能力的多潜能细胞,在一定条件下,可分化成超过200种人体细胞类型,它在发育生物学和再生医学中具有重要的研究价值.其多潜能性使得一系列疾病,包括癌症、阿尔茨海默病和帕金森病的治疗看到了希望.而胚胎干细胞蛋白质组学的研究对揭示胚胎干细胞增殖和分化的机制以及其多潜能的维持具有重大意义.在此,总结在过去几年中已报道的部分关于人体胚胎干细胞蛋白质组学研究取得的进步及其对人体胚胎干细胞研究的促进作用.%Human embryonic stem cell (hESC) is a group of pluripotent cells with self-renewal capacity, which can differentiate into more than 200 kinds of human cell types under certain conditions, and has important research value in developmental biology and regenerative medicine. Pluripotency makes cure of a range of diseases such as cancer, Alzheimer disease and Parkinson disease possible. Embryonic stem cell proteomics research plays an important role in revealing embryonic stem cell proliferation and differentiation mechanisms as well as the maintenance of the pluripotent. Here is to make a summary of some research achievements of human embryonic stem cells proteomics and their role in promoting research in hESC reported in the past few years.

  2. 变系数KdV-Burgers方程的精确解%Exact Solutions of KdV-Burgers Equations with Variable Coefficients

    Institute of Scientific and Technical Information of China (English)

    王岗伟; 张颖元

    2011-01-01

    Using the improved direct reduction method,we find the equivalence transformation of KdV-Burgers equations with variable eoeffidents,and obtain the correspondi.4g the relationshipbetween the solutions of KdV-Burgets equation and ones of the corresponding%利用修正的CK直接约化方法,把变系数KdV-Burgers方程约化为等价的常系数方程,得到了常系数和变系数KdV-Burgers方程的解之间的关系.另外,我们运用李群方法求得了常系数KdV-Burgers方程的解,从而获得了变系数KdV-Burgers方程的精确解.

  3. Residual Symmetry and Explicit Soliton-Cnoidal Wave Interaction Solutions of the (2+1)-Dimensional KdV-mKdV Equation

    Science.gov (United States)

    Cheng, Wenguang; Li, Biao

    2016-04-01

    The truncated Painlevé method is developed to obtain the nonlocal residual symmetry and the Bäcklund transformation for the (2+1)-dimensional KdV-mKdV equation. The residual symmetry is localised after embedding the (2+1)-dimensional KdV-mKdV equation to an enlarged one. The symmetry group transformation of the enlarged system is computed. Furthermore, the (2+1)-dimensional KdV-mKdV equation is proved to be consistent Riccati expansion (CRE) solvable. The soliton-cnoidal wave interaction solution in terms of the Jacobi elliptic functions and the third type of incomplete elliptic integral is obtained by using the consistent tanh expansion (CTE) method, which is a special form of CRE.

  4. NEW EXPLICIT AND EXACT TRAVELLING WAVE SOLUTIONS FOR A COMPOUND KdV-BURGERS EQUATION

    Institute of Scientific and Technical Information of China (English)

    XIA TIE-CHENG; ZHANG HONG-QING; YAN ZHEN-YA

    2001-01-01

    In this paper, new explicit and exact travelling wave solutions for a compound KdV-Burgers equation are obtained by using the hyperbola function method and the Wu elimination method, which include new solitary wave solutions and periodic solutions. Particularly important cases of the equation, such as the compound KdV, mKdV-Burgers and mKdV equations can be solved by this method. The method can also solve other nonlinear partial differential equations.

  5. New travelling wave solutions for combined KdV-mKdV equation and (2+1)-dimensional Broer-Kaup-Kupershmidt system

    Institute of Scientific and Technical Information of China (English)

    Yang Xian-Lin; Tang Jia-Shi

    2007-01-01

    Some new exact solutions of an auxiliary ordinary differential equation are obtained, which were neglected by Sirendaoreji et al in their auxiliary equation method. By using this method and these new solutions the combined Korteweg-de Vries (KdV) and modified KdV (mKdV) equation and (2+1)-dimensional Broer Kaup-Kupershmidt system are investigated and abundant exact travelling wave solutions are obtained that include new solitary wave solutions and triangular periodic wave solutions.

  6. A Darboux transformation of the sl(2|1) super KdV hierarchy and a super lattice potential KdV equation

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Ruguang, E-mail: zhouruguang@jsnu.edu.cn

    2014-05-01

    A hierarchy of super KdV equations is derived from sl(2|1) supermatrix-valued spectral problem. Each equation in the hierarchy is shown to be bi-super-Hamiltonian. Moreover, a Darboux transformation of the hierarchy is constructed. As the compatibility condition of a pair of the Darboux transformations, we obtain a super lattice potential KdV (lpKdV) equation with two discrete variables.

  7. Symmetries and Solitary Solutions of the KdV-Burgers Equation%KdV-Burgers方程的对称与孤子解

    Institute of Scientific and Technical Information of China (English)

    杜海清

    2008-01-01

    考虑KdV-Burgers方程的一些简单对称及其构成的李代数,并利用对称约化方法将KdV-Burgers方程化为常微分方程,从而得到该方程的群不变解.此外,利用多项式展开式的方法去获得KdV-Burgers方程的新的孤子波解.

  8. Travelling Wave Solutions for Time-delayed KdV-Burgers Equation%时滞KdV-Burgers方程的行波解

    Institute of Scientific and Technical Information of China (English)

    李二强; 李灵晓

    2012-01-01

    The time-delayed KdV-Burgers equation was derived by using the flux relaxation method. The travelling wave solutions of the time-delayed KdV-Burgers equation and the KdV-Burgers equation were obtained by the ( 1/G) -expansion method. According to these solutions, the qualitative analysis of the nonlinear ODEs reduced by using traveling wave variable of the time-delayed KdV-Burgers equation was given. When the delayed constant timed by the square of the traveling speed c equals the dissipative coefficient,there exist bell solitary wave and cnoidal wave solutions in the time-delayed KdV-Burgers equation, while the KdV-Burgers equation has no the two types solutions. The existence of time delaying affects the amplitude and the wave width of the solitary waves.%利用流量松弛方法导出了时滞KdV-Burgers方程,并利用(1/G)-展开法,求得时滞KdV-Burgers及KdV-Burgers方程的行波解.结合所求得的解,对时滞KdV-Burgers方程行波约化后所得的常微分方程组(ODEs)进行了定性分析.研究表明:当时间特征常数(r)与行波波速c的平方之积等于耗散系数α(即(r)c2=α)时,时滞KdV-Burgers方程出现了椭圆余弦波解和钟状孤波解,而KdV-Burgers方程没有此类解.另外,时滞的存在还影响到孤立波的振幅和波宽.

  9. KdV方程的相似变换和自相似解%Similarity Transformation and Self-Similar Solutions to Cylindrical KdV Equation

    Institute of Scientific and Technical Information of China (English)

    蔡冠

    2007-01-01

    KdV方程是一个重要的非线性模型.文章用相似变换方法对柱KdV方程进行变换,将其化为具有Painleve性质的非线性常微分方程,并且进一步讨论了柱KdV方程在两种情况下的渐近自相似解.

  10. A Limit Symmetry of Modified KdV Equation and Its Applications

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jian-Bing; JI Jie; SHEN Qing; ZHANG Da-Jun

    2011-01-01

    In this letter we consider a limit symmetry of the modified KdV equation and its application. The similarity reduction leads to limit solutions of the modified KdV equation. Besides, a modified KdV equation with new self-consistent sources is obtained and its solutions are derived.PACS numbers: 02.30.Ik, 05.45.Yv

  11. A Hidden Connection between Lax Descriptions and Superextensions of KdV Hierarchy

    OpenAIRE

    Huang, Wen-Jui

    1996-01-01

    A previously unnoticed connection between the Lax descriptions and the superextensions of the KdV hierarchy is presented. It is shown that the two different Lax descriptions of the KdV hierarchy come out naturally from two different bihamiltonian superextensions of the KdV hierarchy. Some implications of this observation are briefly mentioned.

  12. Direct Connection between the RII Chain and the Nonautonomous Discrete Modified KdV Lattice

    Directory of Open Access Journals (Sweden)

    Kazuki Maeda

    2013-11-01

    Full Text Available The spectral transformation technique for symmetric RII polynomials is developed. Use of this technique reveals that the nonautonomous discrete modified KdV (nd-mKdV lattice is directly connected with the RII chain. Hankel determinant solutions to the semi-infinite nd-mKdV lattice are also presented.

  13. Immunohistochemical expression of PTEN in normal, hyperplastic and endometrial carcinoma of endometrium

    Directory of Open Access Journals (Sweden)

    IzadiMood

    2008-08-01

    Full Text Available "nBackground: Endometrial carcinoma is the most common malignancy of the female genital tract. Different molecular alterations have been described in endometrioid endometrial carcinoma that, the most frequently altered gene is mutations of PTEN. Up to 50-83% of endometrioid carcinoma reveal altered PTEN characterized by loss of expression. In endometrial hyperplasia, which are precursors of endometrioid carcinoma, loss of PTEN expression is 30-63%."n"nMethods: Immunohistochemical staining was performed on 90 cases of endometrial curettage including: 30 proliferative endometrium, 30 hyperplastic endometrium and 30 endometroid carcinoma."n"nImmunohistochemical specimens were graded semiquatitatively by considering the percentage of staining with two cut-point 10% & 50% on the whole section for each specimen."n"nResults: loss of PTEN expression was observed 0%, 0%, 30% of 51.7% in proliferative, simple hyperplasia, complex hyperplasia and endometrioid carcinoma respectively with cut-point 10% and 0%, 5.3%, 30%, 52.2% in endometrioid carcinoma respectively with cut-point 50%. Also there was no difference in PTEN expression between atypical complex hyperplasia and endometrioid carcinoma but there was significant difference between simple hyperplasia and proliferative with endometrioid carcinoma & atypical complex hyperplasia."n"nConclusion: These results show loss of PTEN expression in endmetrioid carcinoma and no differences between endometrioid carcinoma and atypical complex hyperplasia. Therefore, assessment of PTEN expression by negative immunostaining and matched with routine hematoxylin and eosin stained can be a new tool for diagnosis of endometrioid carcinoma.

  14. Breast cancer risk and clinical implications for germline PTEN mutation carriers.

    Science.gov (United States)

    Ngeow, Joanne; Sesock, Kaitlin; Eng, Charis

    2017-08-01

    PTEN Hamartoma Tumor syndrome (PHTS) encompasses a clinical spectrum of heritable disorders including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, and Proteus and Proteus-like syndrome that are associated with germline mutations in the PTEN tumor suppressor gene. Breast cancer risk estimates (67-85 %) for women with germline PTEN mutations are similar to those quoted for patients with germline mutations in the BRCA1/2 genes. With PTEN on several germline gene testing panels, finding PTEN mutations and variants have increased exponentially. PHTS can be differentiated from other hereditary cancer syndromes including Hereditary Breast Ovarian Cancer syndrome, Lynch syndrome, and hamartomatous polyposis syndromes based on personal as well as family history. However, many of the benign features of CS are common in the general population, making the diagnosis of CS challenging. Breast cancer patients with an identified germline PTEN mutation are at increased risk of endometrial, thyroid, renal, and colorectal cancers as well as a second breast cancer. Increased screening for the various component cancers as well as predictive testing in first-degree relatives is recommended. Prophylactic mastectomy may be considered especially if breast tissue is dense or if repeated breast biopsies have been necessary. Management of women with breast cancer suspected of CS who test negative for germline PTEN mutations should be managed as per a mutation carrier if she meets CS diagnostic criteria, and should be offered enrollment in research to identify other predisposition genes.

  15. PTEN alterations of the stromal cells characterise an aggressive subpopulation of pancreatic cancer with enhanced metastatic potential.

    Science.gov (United States)

    Wartenberg, Martin; Centeno, Irene; Haemmig, Stefan; Vassella, Erik; Zlobec, Inti; Galván, José A; Neuenschwander, Maja; Schlup, Cornelia; Gloor, Beat; Lugli, Alessandro; Perren, Aurel; Karamitopoulou, Eva

    2016-09-01

    Neoplastic stroma is believed to influence tumour progression. Here, we examine phosphatase and tensin homolog deleted on chromosome ten (PTEN) status in the tumour microenvironment of pancreatic ductal adenocarcinoma (PDAC) focussing especially at the stromal cells. We asses PTEN at protein, messenger RNA and DNA level using a well-characterised PDAC cohort (n = 117). miR-21, known to target PTEN, is assessed after RNA extraction from different laser-capture-microdissected cell populations, including cancer cells and juxta-tumoural and tumour-remote stroma. PTEN deletion was the most frequent cause of PTEN protein loss in PDAC cells (71%) and correlated with vascular invasion (p = 0.0176) and decreased overall survival (p = 0.0127). Concomitant PTEN protein loss in tumour and juxta-tumoural stroma, found in 21.4% of PDACs, correlated with increased distant metastasis (p = 0.0045). Stromal cells with PTEN protein loss frequently showed PTEN genetic aberrations, including hemizygous PTEN deletion (46.6%) or chromosome 10 monosomy (40%). No alterations were found in the tumour-remote stroma. miR-21 was overexpressed by cancer- and juxta-tumoural stromal cells, in some cases without simultaneous PTEN gene alterations. No PTEN mutations or promoter methylation were detected. We find various mechanisms of PTEN protein loss in the different tumour cell populations, including allelic PTEN deletions, gross chromosomal 10 aberrations and altered miR-21 expression. PTEN deletion is a major cause of PTEN protein loss in PDAC and correlates with aggressive characteristics and worse outcome. PTEN protein loss in juxta-tumoural stromal cells is mostly due to PTEN haplo-insufficiency and characterises a subgroup of PDACs with enhanced metastatic potential. In the tumour microenvironment of the invasive front, PTEN silencing by miR-21 in cancer and surrounding stromal cells acts not only cooperatively but also independently of the genetic aberrations to precipitate PTEN

  16. Posttranslational regulation of phosphatase and tensin homolog (PTEN and its functional impact on cancer behaviors

    Directory of Open Access Journals (Sweden)

    Xu WT

    2014-10-01

    Full Text Available Wenting Xu,1 Zhen Yang,1 Shu-Feng Zhou,2 Nonghua Lu1 1Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA Abstract: The incidence of cancer is increasing worldwide, but the biochemical mechanisms for the occurrence of cancer is not fully understood, and there is no cure for advanced tumors. Defects of posttranslational modifications of proteins are linked to a number of important diseases, such as cancer. This review will update our knowledge on the critical role of posttranscriptional regulation of phosphatase and tensin homolog (PTEN and its activities and the functional impact on cancer behaviors. PTEN is a tumor suppressor gene that occupies a key position in regulating cell growth, proliferation, apoptosis, mobility, signal transduction, and other crucial cellular processes. The activity and function of PTEN are regulated by coordinated epigenetic, transcriptional, posttranscriptional, and posttranslational modifications. In particular, PTEN is subject to phosphorylation, ubiquitylation, somoylation, acetylation, and active site oxidation. Posttranslational modifications of PTEN can dynamically change its activity and function. Deficiency in the posttranslational regulation of PTEN leads to abnormal cell proliferation, apoptosis, migration, and adhesion, which are associated with cancer initiation, progression, and metastasis. With increasing information on how PTEN is regulated by multiple mechanisms and networked proteins, its exact role in cancer initiation, growth, and metastasis will be revealed. PTEN and its functionally related proteins may represent useful targets for the discovery of new anticancer drugs, and gene therapy and the therapeutic potentials should be fully explored. Keywords: phosphorylation, ubiquitination, acetylation, oxidation

  17. Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Kazuki; Okuda, Kosaku; Uehara, Takashi, E-mail: uehara@pharm.okayama-u.ac.jp

    2015-01-02

    Highlights: • PTEN is S-sulfhydrated endogenously in SH-SY5Y human neuroblastoma cells. • Preventing this modification by knocking down CBS renders PTEN sensitive to NO. • pAkt levels are increased significantly in CBS siRNA-transfected cells. • H{sub 2}S functions as an endogenous regulator of PTEN in neuronal cells. - Abstract: Hydrogen sulfide (H{sub 2}S) is a gaseous regulatory factor produced by several enzymes, and plays a pivotal role in processes such as proliferation or vasodilation. Recent reports demonstrated the physiological and pathophysiological functions of H{sub 2}S in neurons. PTEN is a target of nitric oxide (NO) or hydrogen peroxide, and the oxidative modification of cysteine (Cys) residue(s) attenuates its enzymatic activity. In the present study, we assessed the effect of H{sub 2}S on the direct modification of PTEN and the resulting downstream signaling. A modified biotin switch assay in SH-SY5Y human neuroblastoma cells revealed that PTEN is S-sulfhydrated endogenously. Subsequently, site-directed mutagenesis demonstrated that both Cys71 and Cys124 in PTEN are targets for S-sulfhydration. Further, the knockdown of cystathionine β-synthetase (CBS) using siRNA decreased this modification in a manner that was correlated to amount of H{sub 2}S. PTEN was more sensitive to NO under these conditions. These results suggest that the endogenous S-sulfhydration of PTEN via CBS/H{sub 2}S plays a role in preventing the S-nitrosylation that would inhibition its enzymatic activity under physiological conditions.

  18. The significance of PTEN and AKT aberrations in pediatric T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    Zuurbier, Linda; Petricoin, Emanuel F.; Vuerhard, Maartje J.; Calvert, Valerie; Kooi, Clarissa; Buijs-Gladdines, Jessica G.C.A.M.; Smits, Willem K.; Sonneveld, Edwin; Veerman, Anjo J.P.; Kamps, Willem A.; Horstmann, Martin; Pieters, Rob; Meijerink, Jules P.P.

    2012-01-01

    Background PI3K/AKT pathway mutations are found in T-cell acute lymphoblastic leukemia, but their overall impact and associations with other genetic aberrations is unknown. PTEN mutations have been proposed as secondary mutations that follow NOTCH1-activating mutations and cause cellular resistance to γ-secretase inhibitors. Design and Methods The impact of PTEN, PI3K and AKT aberrations was studied in a genetically well-characterized pediatric T-cell leukemia patient cohort (n=146) treated on DCOG or COALL protocols. Results PTEN and AKT E17K aberrations were detected in 13% and 2% of patients, respectively. Defective PTEN-splicing was identified in incidental cases. Patients without PTEN protein but lacking exon-, splice-, promoter mutations or promoter hypermethylation were present. PTEN/AKT mutations were especially abundant in TAL- or LMO-rearranged leukemia but nearly absent in TLX3-rearranged patients (P=0.03), the opposite to that observed for NOTCH1-activating mutations. Most PTEN/AKT mutant patients either lacked NOTCH1-activating mutations (P=0.006) or had weak NOTCH1-activating mutations (P=0.011), and consequently expressed low intracellular NOTCH1, cMYC and MUSASHI levels. T-cell leukemia patients without PTEN/AKT and NOTCH1-activating mutations fared well, with a cumulative incidence of relapse of only 8% versus 35% for PTEN/AKT and/or NOTCH1-activated patients (P=0.005). Conclusions PI3K/AKT pathway aberrations are present in 18% of pediatric T-cell acute lymphoblastic leukemia patients. Absence of strong NOTCH1-activating mutations in these cases may explain cellular insensitivity to γ-secretase inhibitors. PMID:22491738

  19. Interaction of IGF2 and PTEN in ( M alignant Breast T issues

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    Preetha J Shetty

    2012-07-01

    Full Text Available Background: Breast Cancer (BC is one of the leading malignancies affecting women worldwide. Epigenetic mechanisms regulate gene expression playing an important role in the pathophysiology of cancer. In the present study IGF2 and PTEN genes in AKT pathway were selected for evaluation. Objective: To investigate the role of methylation and interaction of IGF2 and PTEN and in the pathoetiology of BC. Methods: Paraffin embedded archival breast tumor and adjacent normal tissue samples were used for carrying out PCR based methylation assay, genomic PCR, immunohistochemistry and qRT PCR. Results: In-Silico study indicated the absence of hormone responsive elements in the promoters of the selected genes. Methylation results indicated significant loss of methylation in IGF2 exon 9 CpG cluster and significant gain of PTEN promoter methylation in tumors. Immunohistochemistry revealed enhanced cytoplasmic expression o f IGF2 protein (p< 0.0001 and decreased nuclear localization of PTEN protein (p=0.0069 in the breast tumors. RT-PCR results indicated an increased IGF2 (p=0.024 and decreased PTEN transcripts (p<0.0001 in the tumors. Conclusion: Increased IGF2 in normal tissues increases PTEN which acts as a negative regulator of AKT pathway in the cytoplasm controlling excessive proliferation while in tumors this regulation is lost. PTEN acts as a negative regulator of MAPK pathway in the nucleus, plays an important role in cell cycle arrest in normal breast tissue. Reduction of PTEN in tumor tissue affects this pathway leading to cell survival. IGF2 and PTEN have a role in breast cancer and these molecular factors can be used for targeting therapy in future.

  20. Correlation between PTEN Expression and PI3K/Akt Signal Pathway in Endometrial Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Qinglei GAO; Fei YE; Xi XIA; Hui XING; Yunping LU; Jianfeng ZHOU; Ding MA

    2009-01-01

    In order to investigate the role of the PTEN expression in carcinogenesis and develop-ment of endometrial carcinoma and clarify whether and how PTEN and PI3K/Akt pathway relate to endometrial carcinoma,the expression of PTEN and phospho-Akt was detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) methods and Western-blot from 24 cases of endomctrial carcinoma,10 cases of endometrial atypical hyperplasia,10 cases of endometrial hy-perplasia,and 10 cases of normal endometrium.SP immunohistochemical methods were used to measure levels of PTEN protein expression in following 5 study groups:31 cases of endometrium in proliferative phase,30 cases of endometrium in secretory phase,71 cases of endometrial hyperplasia,25 cases of atypical hyperplasia and 73 cases of endometrial carcinoma.Immunostaining score of PTEN was 3.39±0.15 in proliferative phase,1.90±0.21 in secretory phase,3.34~0.29 in endometrial hyperplasia,0.624±0.11 in atypical hyperplasia,and 0.74±0.19 in endometrial carcinoma,respectively.PTEN mRNA relative value in normal endometrium,endometrial hyperplasia,endometrial atypical hyperplasia,and endometrial carcinoma was 2.45±0.51,2.32±0.32,0.46±0.11,and 0.35±0.13 respec-tively.The expression levels of PTEN mRNA and protein in patients with endometrial carcinoma and atypical hyperplasia were significantly lower than in those of proliferative phase and with endo-metrial hyperplasia.The level of PTEN expression in patients with endometrial carcinoma was sig-nificantly related to tissue type (P0.05).Western blot analysis revealed that Phospho-Akt level in PTEN negative cases was significantly higher,and there was a negative correlation between PTEN and phospho-Akt (r=- 0.8973,P<0.0001).It was suggested that loss of PTEN expression was an early event in endometrial tumorigenesis.The phosphorylation of Akt induced by the loss of PTEN took part in the tumorigenesis and development of endometrial carcinoma.

  1. Metformin inhibits inflammatory response via AMPK-PTEN pathway in vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Ae [Department of Pharmacology, Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer PTEN was induced by metformin and inhibited by compound C and AMPK siRNA. Black-Right-Pointing-Pointer Metformin suppressed TNF-{alpha}-induced COX-2 and iNOS mRNA expression. Black-Right-Pointing-Pointer Compound C and bpv (pic) increased iNOS and COX-2 protein expression. Black-Right-Pointing-Pointer NF-{kappa}B activation was restored by inhibiting AMPK and PTEN. Black-Right-Pointing-Pointer AMPK and PTEN regulated TNF-{alpha}-induced ROS production in VSMCs. -- Abstract: Atherosclerosis is a chronic inflammation of the coronary arteries. Vascular smooth muscle cells (VSMCs) stimulated by cytokines and chemokines accelerate the inflammatory response and migrate to the injured endothelium during the progression of atherosclerosis. Activation of AMP activated protein kinase (AMPK), a key sensor maintaining metabolic homeostasis, suppresses the inflammatory response. However, how AMPK regulates the inflammatory response is poorly understood. To identify the mechanism of this response, we focused on phosphatase and tensin homolog (PTEN), which is a negative regulator of inflammation. We investigated that activation of AMPK-induced PTEN expression and suppression of the inflammatory response through the AMPK-PTEN pathway in VSMCs. We treated with the well-known AMPK activator metformin to induce PTEN expression. PTEN was induced by metformin (2 mM) and inhibited by compound C (10 {mu}M) and AMPK siRNA. Tumor necrosis factor-alpha (TNF-{alpha}) was used to induce inflammation. The inflammatory response was confirmed by cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expression, and activation of nuclear factor (NF)-{kappa}B. Metformin suppressed COX-2 and iNOS mRNA and protein expression dose dependently. Treatment with compound C and bpv (pic) in the presence of metformin, iNOS and COX-2 protein expression increased. NF-{kappa}B activation decreased in response to metformin and was restored by inhibiting AMPK

  2. Pten Regulates Retinal Amacrine Cell Number by Modulating Akt, Tgfβ, and Erk Signaling.

    Science.gov (United States)

    Tachibana, Nobuhiko; Cantrup, Robert; Dixit, Rajiv; Touahri, Yacine; Kaushik, Gaurav; Zinyk, Dawn; Daftarian, Narsis; Biernaskie, Jeff; McFarlane, Sarah; Schuurmans, Carol

    2016-09-07

    All tissues are genetically programmed to acquire an optimal size that is defined by total cell number and individual cellular dimensions. The retina contains stereotyped proportions of one glial and six neuronal cell types that are generated in overlapping waves. How multipotent retinal progenitors know when to switch from making one cell type to the next so that appropriate numbers of each cell type are generated is poorly understood. Pten is a phosphatase that controls progenitor cell proliferation and differentiation in several lineages. Here, using a conditional loss-of-function strategy, we found that Pten regulates retinal cell division and is required to produce the full complement of rod photoreceptors and amacrine cells in mouse. We focused on amacrine cell number control, identifying three downstream Pten effector pathways. First, phosphoinositide 3-kinase/Akt signaling is hyperactivated in Pten conditional knock-out (cKO) retinas, and misexpression of constitutively active Akt (Akt-CA) in retinal explants phenocopies the reduction in amacrine cell production observed in Pten cKOs. Second, Akt-CA activates Tgfβ signaling in retinal explants, which is a negative feedback pathway for amacrine cell production. Accordingly, Tgfβ signaling is elevated in Pten cKO retinas, and epistatic analyses placed Pten downstream of TgfβRII in amacrine cell number control. Finally, Pten regulates Raf/Mek/Erk signaling levels to promote the differentiation of all amacrine cell subtypes, which are each reduced in number in Pten cKOs. Pten is thus a positive regulator of amacrine cell production, acting via multiple downstream pathways, highlighting its diverse actions as a mediator of cell number control. Despite the importance of size for optimal organ function, how individual cell types are generated in correct proportions is poorly understood. There are several ways to control cell number, including readouts of organ function (e.g., secreted hormones reach functional

  3. Higher Spin Lifshitz Theories and the KdV-Hierarchy

    CERN Document Server

    Beccaria, Matteo; Li, Yi; Macorini, Guido

    2015-01-01

    In this paper three dimensional higher spin theories in the Chern-Simons formulation with gauge algebra $sl(N,R)$ are investigated which have Lifshitz symmetry with scaling exponent $z$. We show that an explicit map exists for all $z$ and $N$ relating the Lifshitz Chern-Simons theory to the $(n,m)$ element of the KdV hierarchy. Furthermore we show that the map and hence the conserved charges are independent of $z$. We derive these result from the Drinfeld-Sokolov formalism of integrable systems.

  4. The Linear KdV Equation with an Interface

    Science.gov (United States)

    Deconinck, Bernard; Sheils, Natalie E.; Smith, David A.

    2016-10-01

    The interface problem for the linear Korteweg-de Vries (KdV) equation in one-dimensional piecewise homogeneous domains is examined by constructing an explicit solution in each domain. The location of the interface is known and a number of compatibility conditions at the boundary are imposed. We provide an explicit characterization of sufficient interface conditions for the construction of a solution using Fokas's Unified Transform Method. The problem and the method considered here extend that of earlier papers to problems with more than two spatial derivatives.

  5. Bifurcation control in the Burgers-KdV equation

    Energy Technology Data Exchange (ETDEWEB)

    Maccari, Attilio [Technical Institute ' G. Cardano' , Piazza della Resistenza 1, 00015 Monterotondo (Rome) (Italy)], E-mail: solitone@yahoo.it

    2008-03-15

    We consider the bifurcation control for the forced Burgers-KdV equation by means of delay feedback linear terms. We use a perturbation method in order to find amplitude and phase modulation equations as well as external force-response and frequency-response curves. We observe in the resonance response a saddle-node bifurcation that leads to jump and hysteresis phenomena. We compare the uncontrolled and controlled systems and demonstrate that control terms can delay or remove the occurrence of the saddle-node bifurcation and reduce the amplitude peak of the resonant response.

  6. Numerical Complexiton Solutions of Complex KdV Equation

    Institute of Scientific and Technical Information of China (English)

    AN Hong-Li; LI Yong-Zhi; CHEN Yong

    2008-01-01

    In this paper,we directly extend the applications of the Adomian decomposition method to investigate the complex KdV equation.By choosing different forms of wave functions as the initial values,three new types of realistic numerical solutions:numerical positon,negaton solution,and paxticulaxly the numerical analytical complexiton solution are obtained,which can rapidly converge to the exact ones obtained by Lou et al.Numerical simulation figures are used to illustrate the efficiency and accuracy of the proposed method.

  7. Finite element method for extended KdV equations

    CERN Document Server

    Karczewska, Anna; Szczeciński, Maciej; Boguniewicz, Bartosz

    2016-01-01

    The finite element method (FEM) is applied to obtain numerical solutions to a recently derived nonlinear equation for the shallow water wave problem. A weak formulation and the Petrov-Galerkin method are used. It is shown that the FEM gives a reasonable description of the wave dynamics of soliton waves governed by extended KdV equations. Some new results for several cases of bottom shapes are presented. The numerical scheme presented here is suitable for taking into account stochastic effects, which will be discussed in a subsequent paper.

  8. Approximate solutions of general perturbed KdV-Burgers equations

    Directory of Open Access Journals (Sweden)

    Baojian Hong

    2014-09-01

    Full Text Available In this article, we present some approximate analytical solutions to the general perturbed KdV-Burgers equation with nonlinear terms of any order by applying the homotopy analysis method (HAM. While compared with the Adomain decomposition method (ADM and the homotopy perturbation method (HPM, the HAM contains the auxiliary convergence-control parameter $\\hbar$ and the control function $H(x,t$, which provides a useful way to adjust and control the convergence region of solution series. The numerical results reveal that HAM is accurate and effective when it is applied to the perturbed PDEs.

  9. Conditional Stability of Solitary-Wave Solutions for Generalized Compound KdV Equation and Generalized Compound KdV-Burgers Equation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wei-Guo; DONG Chun-Yan; FAN En-Gui

    2006-01-01

    In this paper, we discuss conditional stability of solitary-wave solutions in the sense of Liapunov for the generalized compound KdV equation and the generalized compound KdV-Burgers equations. Linear stability of the exact solitary-wave solutions is proved for the above two types of equations when the small disturbance of travellingwave form satisfies some special conditions.

  10. 一般变系数KdV方程的精确解%EXACT SOLUTIONS FOR GENERAL VARIABLE-COEFFICIENT KdV EQUATION

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    By asing the nonclassical method of symmetry reductions, the exact solutions for general variable-coefficient KdV equation with dissipative loss and nonuniformity terms are obtained. When the dissipative loss and nonuniformity terms don't exist, the multisoliton solutions are found and the corresponding Painleve II type equation for the variable-coefficient KdV equation is given.

  11. The Involvement of Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN in the Regulation of Inflammation Following Coronary Microembolization

    Directory of Open Access Journals (Sweden)

    Jiangyou Wang

    2014-06-01

    Full Text Available Background/Aims: Growing evidence shows that phosphatase and tensin homolog deleted on chromosome ten (PTEN is involved in regulating inflammation in different pathological conditions. Therefore, we hypothesized that the upregulation of PTEN correlates with the impairment of cardiac function in swine following coronary microembolization (CME. Methods: To possibly disclose an anti-inflammatory effect of PTEN, we induced swine CME by injecting inertia plastic microspheres (42 μm in diameter into the left anterior descending coronary artery and analyzed the myocardial tissue by immunochemistry, qRT-PCR and western blot analyses. In addition, we downregulated PTEN using siRNA. Results: Following CME, PTEN mRNA and protein levels were elevated as early as 3 h, peaked at 12 h, and then continuously decreased at 24 h and 48 h but remained elevated. Through linear correlation analysis, the PTEN protein level positively correlated with cTnI and TNF-α but was negatively correlated with LVEF. Furthermore, PTEN siRNA reduced the microinfarct volume, improved cardiac function (LVEF, reduced the release of cTnI, and suppressed PTEN and TNF-α protein expression. Conclusion: This study demonstrated, for the first time, that PTEN is involved in CME-induced inflammatory injury. The data generated from this study provide a rationale for the development of PTEN-based anti-inflammatory strategies.

  12. The drug-resistance to gefitinib in PTEN low expression cancer cells is reversed by irradiation in vitro

    Directory of Open Access Journals (Sweden)

    Zhao Lu-Jun

    2009-09-01

    Full Text Available Abstract Background Despite of the recent success of EGFR inhibitory agents, the primary drug-resistant becomes a major challenge for EGFR inhibitor therapies. PTEN gene is an important positive regulatory factor for response to EGFR inhibitor therapy. Low-expression of PTEN is clearly one of the important reasons why tumor cells resisted to tyrosine kinase inhibitors. Methods To investigate the drug-resistance reversal to gefitinb and the mechanism in PTEN low expression cells which radiated with X-rays in vitro, We demonstrated that H-157 lung cancer cells (low-expression of PTEN but phospho-EGFR overexpressed tumor cells exposed to X-rays. The PTEN expressions and radiosensitizing effects of tyrosine kinase inhibitor before and after irradiation were observed. The cell-survival rates were evaluated by colony-forming assays. The cell apoptosis was investigated using FCM. The expressions of phospho-EGFR and PTEN were determined by Western blot analysis. Results The results showed that the PTEN expressions were significantly enhanced by X-rays. Moreover, the cell growth curve and survival curve were down-regulated in the gefitinib-treated groups after irradiation. Meanwhile, the radiation-induced apoptosis of tumor cells was increased by inhibition of the EGFR through up-regulation of PTEN. Conclusion These results suggested that PTEN gene is an important regulator on TKI inhibition, and the resistance to tyrosine kinase inhibitors might be reversed by irradiation in PTEN low expression cancer cells.

  13. Two Types of New Solutions to KdV Equation

    Institute of Scientific and Technical Information of China (English)

    GUO Fu-Kui; ZHANG Yu-Feng

    2006-01-01

    It is common knowledge that the soliton solutions u(x, t) defined by the bell-shape form is required to satisfy the following condition lim u(x,t) = u(±∞,t) = 0. However, we think that the above condition can be modified as x →∞lim u(x, t) = u(±∞, t) = c, where c is a constant, which is called as a stationary height of u(x, t) in the present paper.x →∞If u(x, t) is a bell-shape solitary solution, then the stationary height of each solitary wave is just c. Under the constraint c = 0, all the solitary waves coming from the N-bell-shape-soliton solutions of the KdV equation are the same-oriented travelling. A new type of N-soliton solution with the bell shape is obtained in the paper, whose stationary height is an arbitrary constant c. Taking c ≥ 0, the resulting solitary wave is bound to be the same-oriented travelling. Otherwise,the resulting solitary wave may travel at the same orientation, and also at the opposite orientation. In addition, another type of singular rational travelling solution to the KdV equation is worked out.

  14. PROXEMAS’ VERBALIZATION IN FICTIONAL PROSE OF K.D. VOROBYOV

    Directory of Open Access Journals (Sweden)

    Lo S.

    2015-03-01

    Full Text Available The article is concerned with proxemic communication connected with changing the relative positioning of communicants when interacting, in fictional prose of K.D. Vorobyov. This essential part of interaction is implied with the individual author’s approach to verbal representation of corresponding features and lexis’s choice preferences, its quantitative and qualitative characteristics in the writer’s fictional prose. By analogy with the term paracinema, the term paraproxema is also used for defining these kinds of language phenomena. Paraproxemas were analyzed with reference to semantic, stylistic and morphological aspects. There are two thematic groups of terms with the reference to retract and extend of the relative positioning of communicants being defined in the article. The distribution is based on semantics of verbs and function words. Changing the relative positioning of communicants changes the social zone and reports different information as exemplified with three stories of K.D. Vorobyov. The mutual influence of paracinemas and paraproxemas creates the integrated image of communicants, which gestures, facial expressions, and movements not only accompany but also complete speech

  15. A study of the dynamics of PTEN proteins in living cells using in vivo fluorescence correlation spectroscopy

    Science.gov (United States)

    Du, Zhixue; Dong, Chaoqing; Ren, Jicun

    2017-06-01

    PTEN (phosphatase and tensin homolog on chromosome 10) is one of the most important tumor-suppressor proteins, which plays a key role in negative regulation of the PI3K/AKT pathway, and governs many cellular processes including growth, proliferation, survival and migration. The dynamics of PTEN proteins in single living cells is as yet unclear owing to a shortage of suitable in vivo approaches. Here, we report a single-molecule method for in vivo study of the dynamics of PTEN proteins in living cells using fluorescence correlation spectroscopy (FCS). First, we established a monoclonal H1299 stable cell line expressing enhanced green fluorescent protein (EGFP) and PTEN (EGFP-PTEN) fusion proteins; we then developed an in vivo FCS method to study the dynamics of EGFP-PTEN both in the nucleus and the cytoplasm. We investigated the diffusion behaviors of EGFP and EGFP-PTEN in solution, nucleus and cytosol, and observed that the motion of PTEN in living cells was restricted compared with EGFP. Finally, we investigated the protein dynamics in living cells under oxidative stress stimulation and a cellular ATP depletion treatment. Under oxidative stress stimulation, the EGFP-PTEN concentration increased in the nucleus, but slightly decreased in the cytoplasm. The diffusion coefficient and alpha value of EGFP-PTEN reduced significantly both in the nucleus and cytoplasm; the significantly decreased alpha parameter indicates a more restricted Brownian diffusion behavior. Under the cellular ATP depletion treatment, the concentration of EGFP-PTEN remained unchanged in the nucleus and decreased significantly in cytosol. The diffusion coefficient of EGFP-PTEN decreased significantly in cytosol, but showed no significant change in the nucleus; the alpha value decreased significantly in both the nucleus and cytoplasm. These results suggest that the concentration and mobility of PTEN in the nucleus and cytoplasm can be regulated by stimulation methods. Our approach provides a unique

  16. Application of higher-order KdV-mKdV model with higher-degree nonlinear terms to gravity waves in atmosphere

    Institute of Scientific and Technical Information of China (English)

    Li Zi-Liang

    2009-01-01

    Higher-order Korteweg-de Vries (KdV)-modified KdV (mKdV) equations with a higher-degree of nonlinear terms are derived from a simple incompressible non-hydrostatic Boussinesq equation set in atmosphere and are used to investigate gravity waves in atmosphere. By taking advantage of the auxiliary nonlinear ordinary differential equation, periodic wave and solitary wave solutions of the fifth-order KdV-mKdV models with higher-degree nonlinear terms are obtained under some constraint conditions. The analysis shows that the propagation and the periodic structures of gravity waves depend on the properties of the slope of line of constant phase and atmospheric stability. The Jacobi elliptic function wave and solitary wave solutions with slowly varying amplitude are transformed into triangular waves with the abruptly varying amplitude and breaking gravity waves under the effect of atmospheric instability.

  17. Broccoli, PTEN deletion and prostate cancer: where is the link?

    Directory of Open Access Journals (Sweden)

    Bardelli Alberto

    2010-12-01

    Full Text Available Abstract The concept that vegetables and fruits are relevant sources of cancer-preventive substances is strongly supported by population studies. Among others, cruciferous vegetables like broccoli, cabbage, cauliflower and Brussels sprouts are thought to affect the development of various types of cancers and especially prostate tumors. Yet, the identification of the molecular mechanisms by which the 'active' compounds contained in these vegetables mediate their anticancer activity has historically lagged behind. Accordingly, direct laboratory evidence of how individual nutrients affect cancer genes and the pathways they control remains the major obstacle to progress in this research field. Here we review a recent report investigating the interaction between sulforaphane, a dietary isothiocyanate derived from broccoli, and expression of the PTEN tumor suppressor gene in pre malignant prostate tissue.

  18. The effects of antisense PTEN gene transfection on the growth and invasion of glioma cells

    Institute of Scientific and Technical Information of China (English)

    CHEN Hong-jie; ZHENG Zhao-cong; WANG Ru-mi; WANG Shou-sen; YANG Wei-zhong

    2006-01-01

    Objective:To study the effects of antisense PTEN gene on the growth and invasion of glioma cells. Methods:A pcDNA3. 1/Hygro (-) recombinant plasmid containing antisense PTEN gene fragment was constructed. Glioma cells of primary culture were transfected with antisense PTEN gene vector and stably transfected clones were selected. Then, the different growth and invasion abilities and the different MMP9 mRNA expressions of three kinds of cells were observed, including the transfected cells, untransfected cells and the cells transfected with empty vector. Results :The abilities of growth and invasion of the transfected cells and the expressions of MMP9 mRNA were obviously enhanced. Conclusion: Antisense PTEN gene could have a negative impact on the growth and invasion of primary culture glioma cells.

  19. A common variation of the PTEN gene is associated with peripheral insulin resistance

    DEFF Research Database (Denmark)

    Grinder-Hansen, L; Ribel-Madsen, R; Wojtaszewski, Jørgen

    2016-01-01

    . RESULTS: The minor G allele of PTEN rs11202614 was associated with elevated fasting plasma insulin levels and a decreased peripheral glucose disposal rate, but not with the hepatic insulin resistance index or insulin secretion measured as the first-phase insulin response and disposition index. The single...... nucleotide polymorphism was not associated with either PI3K or Akt activities. CONCLUSION: A common PTEN variation is associated with peripheral insulin resistance and subsequent risk of developing T2D. However, the association with insulin resistance is not explained by decreased proximal insulin signalling......AIM: Phosphatase and tensin homologue (PTEN) reduces insulin sensitivity by inhibiting the phosphatidylinositol 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue (Akt) pathway. This study investigated how a common single nucleotide polymorphism near PTEN, previously associated...

  20. Tnactivation of PTEN is associated with increased angiogenesis and VEGF overexpression in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ye-Jiang Zhou; Yu-Xia Xiong; Xiao-Ting Wu; De Shi; Wei Fan; Tong Zhou; Yue-Chun Li; Xiong Huang

    2004-01-01

    AIM: To investigate the expression of PTEN/MMAC1/TEP1and vascular endothelial growth factor (VEGF), their roles in biologic behavior and angiogenesis and their association in gastric cancer.METHODS: Immunohistochemical staining was used to evaluate the expression of PTEN, VEGF and microvascular density (MVD) on paraffin-embedded sections in 70 patients with primary gastric cancer and 24 patients with chronic superficial gastritis (CSG). Expression of PTEN, VEGF and MVD were compared with clinicopathological features of gastric cancer. The relationship between expression of PTEN, VEGF and MVD as well as the relationship between PTEN and VEGF expression in caner cells were investigated.RESULTS: PTEN expression significantly decreased (t= 3.98,P<0.01) whereas both VEGF expression and MVD significant increased (t = 4.29 and 4.41, respectively, both P<0.01)in gastric cancer group compared with CSG group. PTEN expression was significantly down-regulated (t = 1.95,P<0.05) whereas VEGF expression (t = 2.37, P<0.05) and MVD (t = 3.28, P<0.01) was significantly up-regulated in advanced gastric cancer compared with early-stage gastric cancer. PTEN expression in gastric cancer showed a negative association with lymph node metastasis (t= 3.91, P<0.01),invasion depth (t= 1.95, P<0.05) and age (t= 4.69, P<0.01).MVD in PTEN-negative gastric cancer was significantly higher than that in PTEN-positive gastric cancer (t = 3.69,P<0.01), and there was a negative correlation between PTEN expression and MVD (γ = -0.363, P<0.05). VEGF expression was positively associated with invasion depth (especially with serosa invasion, t = 4.69, P<0.01), lymph node metastasis (t= 2.31, P<0.05) and TNM stage (t= 3.04,P<0.01). MVD in VEGF-positive gastric cancer was significantly higher than that in VEGF-negative gastric cancer (t = 4.62,P<0.01), and there was a positive correlation between VEGF expression of and MVD (γ = 0.512, P<0.05). VEGF expression in PTEN

  1. Expression and significance of PTEN and PCNA in human laryngeal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    李长青; 文莲姬; 金春顺; 崔树勋

    2004-01-01

    Objective: To elucidate the expression and significance of PTEN and PCNA in human laryngeal squamous cell carcinoma. Methods: Immunochemical method was used to study 60 cases of laryngeal carcinoma, 20 cases of normal laryngeal tissues which were closely adjacent to carcinoma and 10 cases of normal laryngeal tissues. Results: It was showed that PTEN gene was expressed in 85 % laryngeal carcinoma tissues. The percentage of lymph node metastasis of laryngeal carcinoma which were negative or positive of PTEN protein was 77.8 % and 33.3 % respectively, and the difference was significance ( P < 0.05). Conclusion: Expression of PTEN in laryngeal carcinoma was different from that of normal laryngeal tissues. It may play a role but not important in the tumorigenesis and development of laryngeal carcinoma.

  2. Kaempferol Promotes Apoptosis in Human Bladder Cancer Cells by Inducing the Tumor Suppressor, PTEN

    Directory of Open Access Journals (Sweden)

    Liqun Zhou

    2013-10-01

    Full Text Available Kaempferol (Kae, a natural flavonoid, is widely distributed in fruits and vegetables. Previous studies have identified Kae as a possible cancer preventive and therapeutic agent. We found Kae to exhibit potent antiproliferation and anti-migration effects in human bladder cancer EJ cells. Kaempferol robustly induced apoptosis in EJ cells in a dose-dependent manner, as evidenced by increased cleavage of caspase-3. Furthermore, we found Kae-induced apoptosis in EJ cells to be associated with phosphatase and the tensin homolog deleted on the chromosome 10 (PTEN/PI3K/Akt pathway. Kae significantly increased PTEN and decreased Akt phosphorylation. Kae-induced apoptosis was partially attenuated in PTEN-knockdown cells. Our findings indicate that Kae could be an alternative medicine for bladder cancer, based on a PTEN activation mechanism.

  3. PTEN phosphatase-independent maintenance of glandular morphology in a predictive colorectal cancer model system.

    Science.gov (United States)

    Jagan, Ishaan C; Deevi, Ravi K; Fatehullah, Aliya; Topley, Rebecca; Eves, Joshua; Stevenson, Michael; Loughrey, Maurice; Arthur, Kenneth; Campbell, Frederick Charles

    2013-11-01

    Organotypic models may provide mechanistic insight into colorectal cancer (CRC) morphology. Three-dimensional (3D) colorectal gland formation is regulated by phosphatase and tensin homologue deleted on chromosome 10 (PTEN) coupling of cell division cycle 42 (cdc42) to atypical protein kinase C (aPKC). This study investigated PTEN phosphatase-dependent and phosphatase-independent morphogenic functions in 3D models and assessed translational relevance in human studies. Isogenic PTEN-expressing or PTEN-deficient 3D colorectal cultures were used. In translational studies, apical aPKC activity readout was assessed against apical membrane (AM) orientation and gland morphology in 3D models and human CRC. We found that catalytically active or inactive PTEN constructs containing an intact C2 domain enhanced cdc42 activity, whereas mutants of the C2 domain calcium binding region 3 membrane-binding loop (M-CBR3) were ineffective. The isolated PTEN C2 domain (C2) accumulated in membrane fractions, but C2 M-CBR3 remained in cytosol. Transfection of C2 but not C2 M-CBR3 rescued defective AM orientation and 3D morphogenesis of PTEN-deficient Caco-2 cultures. The signal intensity of apical phospho-aPKC correlated with that of Na(+)/H(+) exchanger regulatory factor-1 (NHERF-1) in the 3D model. Apical NHERF-1 intensity thus provided readout of apical aPKC activity and associated with glandular morphology in the model system and human colon. Low apical NHERF-1 intensity in CRC associated with disruption of glandular architecture, high cancer grade, and metastatic dissemination. We conclude that the membrane-binding function of the catalytically inert PTEN C2 domain influences cdc42/aPKC-dependent AM dynamics and gland formation in a highly relevant 3D CRC morphogenesis model system.

  4. MicroRNA-21 regulates hTERT via PTEN in hypertrophic scar fibroblasts.

    Directory of Open Access Journals (Sweden)

    Hua-Yu Zhu

    Full Text Available BACKGROUND: As an important oncogenic miRNA, microRNA-21 (miR-21 is associated with various malignant diseases. However, the precise biological function of miR-21 and its molecular mechanism in hypertrophic scar fibroblast cells has not been fully elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative Real-Time PCR (qRT-PCR analysis revealed significant upregulation of miR-21 in hypertrophic scar fibroblast cells compared with that in normal skin fibroblast cells. The effects of miR-21 were then assessed in MTT and apoptosis assays through in vitro transfection with a miR-21 mimic or inhibitor. Next, PTEN (phosphatase and tensin homologue deleted on chromosome ten was identified as a target gene of miR-21 in hypertrophic scar fibroblast cells. Furthermore, Western-blot and qRT-PCR analyses revealed that miR-21 increased the expression of human telomerase reverse transcriptase (hTERT via the PTEN/PI3K/AKT pathway. Introduction of PTEN cDNA led to a remarkable depletion of hTERT and PI3K/AKT at the protein level as well as inhibition of miR-21-induced proliferation. In addition, Western-blot and qRT-PCR analyses confirmed that hTERT was the downstream target of PTEN. Finally, miR-21 and PTEN RNA expression levels in hypertrophic scar tissue samples were examined. Immunohistochemistry assays revealed an inverse correlation between PTEN and hTERT levels in high miR-21 RNA expressing-hypertrophic scar tissues. CONCLUSIONS/SIGNIFICANCE: These data indicate that miR-21 regulates hTERT expression via the PTEN/PI3K/AKT signaling pathway by directly targeting PTEN, therefore controlling hypertrophic scar fibroblast cell growth. MiR-21 may be a potential novel molecular target for the treatment of hypertrophic scarring.

  5. DNA Mismatch Repair Deficiency Accelerates Endometrial Tumorigenesis in Pten Heterozygous Mice

    OpenAIRE

    Hong WANG; Douglas, Wayne; Lia, Marie; Edelmann, Winfried; Kucherlapati, Raju; Podsypanina, Katrina; Parsons, Ramon; Ellenson, Lora Hedrick

    2002-01-01

    PTEN mutation and microsatellite instability are two of the most common genetic alterations in uterine endometrioid carcinoma. Furthermore, previous studies have suggested an association between the two alterations, however the basis and consequence of the association is not understood. Recently it has been shown that 100% of female Pten+/− mice develop complex atypical hyperplasia by 32 weeks of age that progresses to endometrial carcinoma in ∼20 to 25% of mice at 40 weeks. In an attempt to ...

  6. PTEN Phosphatase-Independent Maintenance of Glandular Morphology in a Predictive Colorectal Cancer Model System

    Directory of Open Access Journals (Sweden)

    Ishaan C. Jagan

    2013-11-01

    Full Text Available Organotypic models may provide mechanistic insight into colorectal cancer (CRC morphology. Three-dimensional (3D colorectal gland formation is regulated by phosphatase and tensin homologue deleted on chromosome 10 (PTEN coupling of cell division cycle 42 (cdc42 to atypical protein kinase C (aPKC. This study investigated PTEN phosphatase-dependent and phosphatase-independent morphogenic functions in 3D models and assessed translational relevance in human studies. Isogenic PTEN-expressing or PTEN-deficient 3D colorectal cultures were used. In translational studies, apical aPKC activity readout was assessed against apical membrane (AM orientation and gland morphology in 3D models and human CRC. We found that catalytically active or inactive PTEN constructs containing an intact C2 domain enhanced cdc42 activity, whereas mutants of the C2 domain calcium binding region 3 membrane-binding loop (M-CBR3 were ineffective. The isolated PTEN C2 domain (C2 accumulated in membrane fractions, but C2 M-CBR3 remained in cytosol. Transfection of C2 but not C2 M-CBR3 rescued defective AM orientation and 3D morphogenesis of PTEN-deficient Caco-2 cultures. The signal intensity of apical phospho-aPKC correlated with that of Na+/H+ exchanger regulatory factor-1 (NHERF-1 in the 3D model. Apical NHERF-1 intensity thus provided readout of apical aPKC activity and associated with glandular morphology in the model system and human colon. Low apical NHERF-1 intensity in CRC associated with disruption of glandular architecture, high cancer grade, and metastatic dissemination. We conclude that the membrane-binding function of the catalytically inert PTEN C2 domain influences cdc42/aPKC-dependent AM dynamics and gland formation in a highly relevant 3D CRC morphogenesis model system.

  7. Pancreas-specific Pten deficiency causes partial resistance to diabetes and elevated hepatic AKT signaling

    Institute of Scientific and Technical Information of China (English)

    Zan Tong; Yan Fan; Weiqi Zhang; Jun Xu; Jing Cheng; Mingxiao Ding; Hongkui Deng

    2009-01-01

    PTEN, a negative regulator of the phosphatidylinositol-3-kinase/AKT pathway, is an important modulator of insu-lin signaling. To determine the metabolic function of pancreatic Pten, we generated pancreas-specific Pten knockout (PPKO) mice. PPKO mice had enlarged pancreas and elevated proliferation of acinar cells. They also exhibited hy-poglycemia, hypoinsulinemia, and altered amino metabolism. Notably, PPKO mice showed delayed onset of strepto-zotocin (STZ)-induced diabetes and sex-biased resistance to high-fat-diet (HFD)-induced diabetes. To investigate the mechanism for the resistance to HFD-induced hyperglycemia in PPKO mice, we evaluated AKT phosphorylation in major insulin-responsive tissues: the liver, muscle, and fat. We found that Pten loss in the pancreas causes the eleva-tion of AKT signaling in the liver. The phosphorylation of AKT and its downstream substrate GSK3β was increased in the liver of PPKO mice, while PTEN level was decreased without detectable excision of Pten allele in the liver of PPKO mice. Proteomics analysis revealed dramatically decreased level of 78-kDa glucose-regulated protein (GRP78) in the liver of PPKO mice, which may also contribute to the lower blood glucose level of PPKO mice fed with HFD. Together, our findings reveal a novel response in the liver to pancreatic defect in metabolic regulation, adding a new dimension to understanding diabetes resistance.

  8. Relationsip between PTEN and VEGF Expression and Clinicopathological Characteristics in HCC

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To investigate the expressions and significance of the tumor suppressor gene phosphatase and tensin homlog deleted on chromosome ten protein (PTEN) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC), and to analyze the relationship between their expressions and the tumor's invasion and their pericarcinomatous tissues, the correlation of their expressions with the tumor's clinicopathological characteristics and invasion potential were studied. Our study showed that the expression level of PTEN in HCC was remarkably lower than that in pericarcinomatous liver tissues, while the expressions of both VEGF and MVD were higher than that in pericarcinomatous liver tissues. Correlation analysis revealed that the expression of PTEN was negatively related to the progression of the pathological differentiation and invasion of tumor, whereas the expressions of VEGF and MVD were positively related. Moreover, there was a negative relationship between the expression of PTEN and the expressions of VEGF and MVD, and a positive one between VEGF and MVD. The expressions of PTEN and VEGF may reveal the degree of differentiation and the invasive potential of HCC tissues. The mechanism by which the lack of PTEN expression probably induces abnormal hyperexpression of VEGF may play an important role in the invasion and metastasis of HCC.

  9. Exogenous PTEN Gene Induces Apoptosis in Breast Carcinoma Cell Line MDA468

    Institute of Scientific and Technical Information of China (English)

    CHEN Qingyong; WANG Chunyou; JIANG Chunfang; CHEN Daoda

    2007-01-01

    The effects and mechanisms of exogenous phosphatase and tensin homolog deleted from chromosome ten (PTEN) gene on phosphatase activity-dependent apoptosis of breast cancer cell line MDA468 were investigated. PTEN gene packaged with lipofectin was transferred into breast cancer cell line MDA468 and parental MDA468 cells served as controls. RT-PCR and Western blot were done to detect the expression of target genes. The expression of phosphospecific protein kinase B (PKB/Akt) and focal adhesion kinase (FAK) protein stimulated by epidermal growth factor (EGF) was also detected. Apoptosis was determined by flow cytometry with a double-staining method using FITC-conjugated annexin V and PI. MDA468 cells transfected with PTEN gene could express PTEN mRNA and protein. PTEN decreased the phosphorylation level of AKT protein and down-regulated FAK protein expression in MDA468 stimulated by EGF. The apoptosis rate was 21.68%. PTEN induced breast cancer apoptosis phosphatase activity-dependently. The mechanism is possibly relatedwith phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB)/AKT signaling pathway. Those results may provide new clues on the gene therapy in breast cancer.

  10. Regulation of mammary stem/progenitor cells by PTEN/Akt/beta-catenin signaling.

    Directory of Open Access Journals (Sweden)

    Hasan Korkaya

    2009-06-01

    Full Text Available Recent evidence suggests that many malignancies, including breast cancer, are driven by a cellular subcomponent that displays stem cell-like properties. The protein phosphatase and tensin homolog (PTEN is inactivated in a wide range of human cancers, an alteration that is associated with a poor prognosis. Because PTEN has been reported to play a role in the maintenance of embryonic and tissue-specific stem cells, we investigated the role of the PTEN/Akt pathway in the regulation of normal and malignant mammary stem/progenitor cell populations. We demonstrate that activation of this pathway, via PTEN knockdown, enriches for normal and malignant human mammary stem/progenitor cells in vitro and in vivo. Knockdown of PTEN in normal human mammary epithelial cells enriches for the stem/progenitor cell compartment, generating atypical hyperplastic lesions in humanized NOD/SCID mice. Akt-driven stem/progenitor cell enrichment is mediated by activation of the Wnt/beta-catenin pathway through the phosphorylation of GSK3-beta. In contrast to chemotherapy, the Akt inhibitor perifosine is able to target the tumorigenic cell population in breast tumor xenografts. These studies demonstrate an important role for the PTEN/PI3-K/Akt/beta-catenin pathway in the regulation of normal and malignant stem/progenitor cell populations and suggest that agents that inhibit this pathway are able to effectively target tumorigenic breast cancer cells.

  11. Glioma cell VEGFR-2 confers resistance to chemotherapeutic and antiangiogenic treatments in PTEN-deficient glioblastoma.

    Science.gov (United States)

    Kessler, Tobias; Sahm, Felix; Blaes, Jonas; Osswald, Matthias; Rübmann, Petra; Milford, David; Urban, Severino; Jestaedt, Leonie; Heiland, Sabine; Bendszus, Martin; Hertenstein, Anne; Pfenning, Philipp-Niclas; Ruiz de Almodóvar, Carmen; Wick, Antje; Winkler, Frank; von Deimling, Andreas; Platten, Michael; Wick, Wolfgang; Weiler, Markus

    2015-10-13

    Loss of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a prerequisite for tumor cell-specific expression of vascular endothelial growth factor receptor (VEGFR)-2 in glioblastoma defining a subgroup prone to develop evasive resistance towards antiangiogenic treatments. Immunohistochemical analysis of human tumor tissues showed VEGFR-2 expression in glioma cells in 19% of specimens examined, mainly in the infiltration zone. Glioma cell VEGFR-2 positivity was restricted to PTEN-deficient tumor specimens. PTEN overexpression reduced VEGFR-2 expression in vitro, as well as knock-down of raptor or rictor. Genetic interference with VEGFR-2 revealed proproliferative, antiinvasive and chemoprotective functions for VEGFR-2 in glioma cells. VEGFR-2-dependent cellular effects were concomitant with activation of 'kappa-light-chain-enhancer' of activated B-cells, protein kinase B, and N-myc downstream regulated gene 1. Two-photon in vivo microscopy revealed that expression of VEGFR-2 in glioma cells hampers antiangiogenesis. Bevacizumab induces a proinvasive response in VEGFR-2-positive glioma cells. Patients with PTEN-negative glioblastomas had a shorter survival after initiation of bevacizumab therapy compared with PTEN-positive glioblastomas. Conclusively, expression of VEGFR-2 in glioma cells indicates an aggressive glioblastoma subgroup developing early resistance to temozolomide or bevacizumab. Loss of PTEN may serve as a biomarker identifying those tumors upfront by routine neuropathological methods.

  12. Myeloid PTEN deficiency protects livers from ischemia reperfusion injury by facilitating M2 macrophage differentiation.

    Science.gov (United States)

    Yue, Shi; Rao, Jianhua; Zhu, Jianjun; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W; Lu, Ling; Wang, Xuehao; Zhai, Yuan

    2014-06-01

    Although the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in regulating cell proliferation is well established, its function in immune responses remains to be fully appreciated. In the current study, we analyzed myeloid-specific PTEN function in regulating tissue inflammatory immune response in a murine liver partial warm ischemia model. Myeloid-specific PTEN knockout (KO) resulted in liver protection from ischemia reperfusion injury (IRI) by deviating the local innate immune response against ischemia reperfusion toward the regulatory type: expression of proinflammatory genes was selectively decreased and anti-inflammatory IL-10 was simultaneously increased in ischemia reperfusion livers of PTEN KO mice compared with those of wild-type (WT) mice. PI3K inhibitor and IL-10-neutralizing Abs, but not exogenous LPS, recreated liver IRI in these KO mice. At the cellular level, Kupffer cells and peritoneal macrophages isolated from KO mice expressed higher levels of M2 markers and produced lower TNF-α and higher IL-10 in response to TLR ligands than did their WT counterparts. They had enhanced Stat3- and Stat6-signaling pathway activation, but diminished Stat1-signaling pathway activation, in response to TLR4 stimulation. Inactivation of Kupffer cells by gadolinium chloride enhanced proinflammatory immune activation and increased IRI in livers of myeloid PTEN KO mice. Thus, myeloid PTEN deficiency protects livers from IRI by facilitating M2 macrophage differentiation.

  13. PTEN mutation analysis in two genetic subtypes of high-grade oligodendroglial tumors. PTEN is only occasionally mutated in one of the two genetic subtypes.

    Science.gov (United States)

    Jeuken, J W; Nelen, M R; Vermeer, H; van Staveren, W C; Kremer, H; van Overbeeke, J J; Boerman, R H

    2000-05-01

    We recently identified two genetic subtypes of high-grade oligodendroglial tumors (HG-OT): 1p-/19q- HG-OT are characterized by a loss of chromosome 1p32-36 (del(1)(p32-p36) and/or a del(19)(q13. 3); whereas +7/-10 HG-OT harbor a gain of chromosome 7 (+7) and/or a -10 without a loss of 1p32-36 and 19q13.3. Because a -10 and a +7 are most frequently detected in glioblastomas (GBM), the genotype of +7/-10 HG-OT suggests that these tumors are GBM with a prominent oligodendroglial phenotype rather than anaplastic oligodendrogliomas. PTEN is a tumor suppressor gene, located at 10q23.3, which is involved in tumor progression of GBM and other neoplasms. In this study, we screened for PTEN mutations in six low-grade oligodendroglial tumors (LG-OT), five 1p-/19q- HG-OT, seven +7/-10 HG-OT, and nine xenografted GBM. PTEN mutations were detected in none of the LG-OT and 1p-/19q- HG-OT, once in +7/-10 HG-OT, and frequently in GBM. As one of the +7/-10 HG-OT harbored a PTEN mutation, this demonstrates that PTEN can be involved in the oncogenesis of this genetic subtype of HG-OT. The lower frequency of PTEN mutations in +7/-10 HG-OT compared to GBM suggests that these tumors are of a distinct tumor type rather than GBM. Published by Elsevier Science Inc.

  14. A multilevel adaptive mesh generation scheme using Kd-trees

    Directory of Open Access Journals (Sweden)

    Alfonso Limon

    2009-04-01

    Full Text Available We introduce a mesh refinement strategy for PDE based simulations that benefits from a multilevel decomposition. Using Harten's MRA in terms of Schroder-Pander linear multiresolution analysis [20], we are able to bound discontinuities in $mathbb{R}$. This MRA is extended to $mathbb{R}^n$ in terms of n-orthogonal linear transforms and utilized to identify cells that contain a codimension-one discontinuity. These refinement cells become leaf nodes in a balanced Kd-tree such that a local dyadic MRA is produced in $mathbb{R}^n$, while maintaining a minimal computational footprint. The nodes in the tree form an adaptive mesh whose density increases in the vicinity of a discontinuity.

  15. Moyal Noncommutative Integrability and the Burgers-KdV Mapping

    CERN Document Server

    Sedra, M B

    2005-01-01

    The Moyal momentum algebra is, once again, used to discuss some important aspects of NC integrable models and 2d conformal field theories. Among the results presented, we setup algebraic structures and makes useful convention notations leading to extract non trivial properties of the Moyal momentum algebra. We study also the Lax pair building mechanism for particular examples namely, the noncommutative KdV and Burgers systems. We show in a crucial step that these two systems are mapped to each others through a crucial mapping. This makes a strong constraint on the NC Burgers system which corresponds to linearizing its associated differential equation. From the conformal field theory point of view, this constraint equation is nothing but the analogue of the conservation law of the conformal current. We believe that this mapping might help to bring new insights towards understanding the integrability of noncommutative 2d-systems.

  16. Long-term consequences of conditional genetic deletion of PTEN in the sensorimotor cortex of neonatal mice.

    Science.gov (United States)

    Gutilla, Erin A; Buyukozturk, Melda M; Steward, Oswald

    2016-05-01

    Targeted deletion of the phosphatase and tensin homolog on chromosome ten (PTEN) gene in the sensorimotor cortex of neonatal mice enables robust regeneration of corticospinal tract (CST) axons following spinal cord injury as adults. Here, we assess the consequences of long-term conditional genetic PTEN deletion on cortical structure and neuronal morphology and screen for neuropathology. Mice with a LoxP-flanked exon 5 of the PTEN gene (PTENf/f mice) received AAV-Cre injections into the sensorimotor cortex at postnatal day 1 (P1) and were allowed to survive for up to 18months. As adults, mice were assessed for exploratory activity (open field), and motor coordination using the Rotarod®. Some mice received injections of Fluorogold into the spinal cord to retrogradely label the cells of origin of the CST. Brains were prepared for neurohistology and immunostained for PTEN and phospho-S6, which is a downstream marker of mammalian target of rapamycin (mTOR) activation. Immunostaining revealed a focal area of PTEN deletion affecting neurons in all cortical layers, although in some cases PTEN expression was maintained in many small-medium sized neurons in layers III-IV. Neurons lacking PTEN were robustly stained for pS6. Cortical thickness was significantly increased and cortical lamination was disrupted in the area of PTEN deletion. PTEN-negative layer V neurons that give rise to the CST, identified by retrograde labeling, were larger than neurons with maintained PTEN expression, and the relative area occupied by neuropil vs. cell bodies was increased. There was no evidence of tumor formation or other neuropathology. Mice with PTEN deletion exhibited open field activity comparable to controls and there was a trend for impaired Rotarod performance (not statistically significant). Our findings indicate that early postnatal genetic deletion of PTEN that is sufficient to enable axon regeneration by adult neurons causes neuronal hypertrophy but no other detectable

  17. EFFECTS OF MUTATION AND EXPRESSION OF PTEN GENE mRNA ON TUMORIGENESIS AND PROGRESSION OF EPITHELIAL OVARIAN CANCER

    Institute of Scientific and Technical Information of China (English)

    陈颖; 郑华川; 杨雪飞; 孙丽梅; 辛彦

    2004-01-01

    Objective To investigate the mutation and expression of tumor suppressor gene-PTEN mRNA and explore their roles in tumorigenesis and progression of ovarian cancer. Methods Mutated exon 5 of PTEN gene was examined in normal ovary (n = 5), ovarian cyst (n =5), ovarian borderline tumor (n=9), epithelial ovarian cancer (n=60), and ovarian cancer cell line (n= 1)by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). mRNA expression of PTEN gene was evaluated in corresponding tissues and cell line by reverse transcription polymerase chain reaction(RT-PCR). The mutation and mRNA expression of PTEN gene were compared with clinicopathological features of ovarian cancer. Results Mutated exon 5 of PTEN gene was detected only in 5 (7.1%) cases of epithelial ovarian cancer. mRNA expression level of PTEN gene in ovarian borderline tumor or ovarian cancer was lower than that in normal ovary or ovarian cyst (P < 0.05). The level of PTEN gene mRNA expression was negatively correlated with clinicopathological staging of ovarian cancer, whereas positively correlated with histological differentiation (P < 0.05). mRNA expression level of PTEN gene in ovarian endometrioid cancer was significantly lower than that in ovarian serous or mucinous cancer (P < 0.05). Conclusions Mutation of PTEN gene occurs in ovarian cancer. Down-regulated expression of PTEN is probably an important molecular event in tumorigenesis of ovarian cancer. Abnormal expression of PTEN gene is involved in progression of ovarian cancer. Reduced expression of PTEN gene is closely associated with tumorigenesis and pathobiological behaviors of ovarian endometrioid cancer.

  18. A Direct Linearization Method of the Non-Isospectral KdV Equation

    Institute of Scientific and Technical Information of China (English)

    ZHAO Song-Lin; ZHANG Da-Jun; CHEN Deng-Yuan

    2011-01-01

    Direct linearization method is used to solve the non-isospectral KdV equation. The corresponding singular linear integral equation and the time dependence of measure in the singular linear integral equation are proposed. Furthermore, the solutions to the non-isospectral modified KdV equation are also derived by using the singular h'near integral equation of the non-isospectral KdV equation.%@@ Direct linearization method is used to solve the non-isospectral KdV equation.The corresponding singular linear integral equation and the time dependence of measure in the singular linear integral equation are proposed.Furthermore, the solutions to the non-isospectral modified KdV equation are also derived by using the singular linear integral equation of the non-isospectral KdV equation.

  19. The Exact Analytical Solutions to the Burgers-KdV Equation by the Superposition Approach%用叠加法求Burgers-KdV方程的精确解析解

    Institute of Scientific and Technical Information of China (English)

    刘辉; 谢元喜

    2005-01-01

    基于对Burgers方程、KdV方程和Burgers-KdV方程特点的分析,提出了一种由Burgers方程的解和KdV方程的解构造Burgers-KdV方程的解的叠加法,并用该法求得了Burgers-KdV方程的解,所得结果与已有结果完全吻合.

  20. A numerical simulation and explicit solutions of KdV-Burgers' and Lax's seventh-order KdV equations

    Energy Technology Data Exchange (ETDEWEB)

    Soliman, A.A. [Department of Mathematics, Faculty of Education (AL-Arish), Suez Canal University, AL-Arish 45111 (Egypt)]. E-mail: asoliman_99@yahoo.com

    2006-07-15

    By means of variational iteration method the solution of the Korteweg-de Vries Burgers (for short, KdVB) and a Lax's seventh-order KdV (for short, LsKdV) equations are exactly obtained and in compared with that found by means of Adomian decomposition method. The comparison demonstrate that the two obtained solutions are an excellent agreement. The numerical results calculated and show that this method, variational iteration method, can be readily implemented to this type of nonlinear equations and excellent accuracy can be also achieved. The results of variation iteration method confirm the correctness of those obtained by mean of Adomian decomposition method.

  1. New Travelling Wave Solutions to Compound KdV-Burgers Equation

    Institute of Scientific and Technical Information of China (English)

    YU Jun; KE Yun-Quan; ZHANG Wei-Jun

    2004-01-01

    The compound KdV-Burgers equation and combined KdV-mKdV equation are real physical models concerning many branches in physics.In this paper,applying the improved trigonometric function method to these equations,rich explicit and exact travelling wave solutions,which contain solitary-wave solutions,periodic solutions,and combined formal solitary-wave solutions,are obtained.

  2. A correction on two dimensional KdV equation with topography

    Institute of Scientific and Technical Information of China (English)

    XU Zhaoting; Efim PELINOVSKY; SHEN Guojin; Tapiana TALIPOVA

    2004-01-01

    The correction on the 2D KdV equation derived by Djordjevic and Redekopp is presented. A lapsus calami in the 2D KdV equation is removed by means of the conservation principle of the energy flux in a wave ray tube. The results show that the coefficient of the third term in the inhomogeneous term of 2D KdV equation in the paper of Djordjevic and Redekopp is 2, instead of 3.

  3. Conserved quantities and generalized solutions of the ultradiscrete KdV equation

    CERN Document Server

    Kanki, Masataka; Tokihiro, Tetsuji

    2010-01-01

    We construct generalized solutions to the ultradiscrete KdV equation, including the so-called negative solition solutions. The method is based on the ultradiscretization of soliton solutions to the discrete KdV equation with gauge transformation. The conserved quantities of the ultradiscrete KdV equation are shown to be constructed in a similar way to those for the box-ball system.

  4. Conserved quantities and generalized solutions of the ultradiscrete KdV equation

    Energy Technology Data Exchange (ETDEWEB)

    Kanki, Masataka; Tokihiro, Tetsuji [Graduate school of Mathematical Sciences, University of Tokyo, 3-8-1 Komaba, Tokyo 153-8914 (Japan); Mada, Jun, E-mail: kanki@ms.u-tokyo.ac.jp [College of Industrial Technology, Nihon University, 2-11-1 Shin-ei, Narashino, Chiba 275-8576 (Japan)

    2011-04-08

    We construct generalized solutions to the ultradiscrete KdV equation, including the so-called negative solition solutions. The method is based on the ultradiscretization of soliton solutions to the discrete KdV equation with gauge transformation. The conserved quantities of the ultradiscrete KdV equation are shown to be constructed in a similar way to those for the box-ball system.

  5. Low pH-induced conformational changes in 33 kD protein of photosystem Ⅱ

    Institute of Scientific and Technical Information of China (English)

    WENG Jun; TAN Cuiyan; YU Yong; RUAN Kangcheng; XU Chunhe

    2004-01-01

    33 kD protein, located on the lumen side of thylakoid membranes, is one of three extrinsic proteins of photosystemⅡ(PSⅡ). Previous study showed that NBS modification of W241, the only tryptophan in 33 kD protein, is helpful for understanding the function of W241 in maintaining functional conformation of 33 kD protein. In this paper, studies of both circular dichroism and fluorescence spectra showed that upon decreasing pH from 6.2 to 2.5, the conformation of soluble 33 kD protein changed significantly, with an increase or a decrease in percentage of random coil or ?-helix and turns. The changes in secondary structures of this protein are pH reversible. After NBS modification at pH 2.5, the conformational change of 33 kD protein was kept fixed. The CD ellipticity at 200 nm for NBS-modified 33 kD protein is much lower than that for control, indicating that the unfolding degree of 33 kD protein was enhanced after the NBS modification. Moreover, the conformational flexibility is lost in NBS-modified 33 kD protein, and the conformational change becomes pH irreversible, indicating that NBS modification blocked the reversibility of conformational change of 33 kD protein. The specific binding capability of NBS-modi- fied 33 kD protein is much lower than that of low pH-treated control. Furthermore, the rebinding of modified protein on PSⅡ membranes cannot restore the activity of oxygen evolution. We suggest that it is low pH but not NBS modification of W241 that leads to the conformational change of 33 kD protein from one functional to another non-functional state. The significant capability of proton transport of 33 kD protein is discussed.

  6. A Critical Role of the PTEN/PDGF Signaling Network for the Regulation of Radiosensitivity in Adenocarcinoma of the Prostate

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, Michael, E-mail: mechristense@uwalumni.com [Department of Radiation Oncology, Wayne State University School of Medicine, Barbara Ann Karmanos Cancer Center, Detroit, Michigan (United States); Najy, Abdo J. [Department of Pathology, Wayne State University School of Medicine, Barbara Ann Karmanos Cancer Center, Detroit, Michigan (United States); Snyder, Michael; Movilla, Lisa S. [Department of Radiation Oncology, Wayne State University School of Medicine, Barbara Ann Karmanos Cancer Center, Detroit, Michigan (United States); Kim, Hyeong-Reh Choi [Department of Pathology, Wayne State University School of Medicine, Barbara Ann Karmanos Cancer Center, Detroit, Michigan (United States)

    2014-01-01

    Purpose: Loss or mutation of the phosphate and tensin homologue (PTEN) is a common genetic abnormality in prostate cancer (PCa) and induces platelet-derived growth factor D (PDGF D) signaling. We examined the role of the PTEN/PDGF axis on radioresponse using a murine PTEN null prostate epithelial cell model. Methods and Materials: PTEN wild-type (PTEN{sup +/+}) and PTEN knockout (PTEN{sup −/−}) murine prostate epithelial cell lines were used to examine the relationship between the PTEN status and radiosensitivity and also to modulate the PDGF D expression levels. PTEN{sup −/−} cells were transduced with a small hairpin RNA (shRNA) lentiviral vector containing either scrambled nucleotides (SCRM) or sequences targeted to PDGF D (shPDGF D). Tumorigenesis and morphogenesis of these cell lines were evaluated in vivo via subcutaneous injection of male nude mice and in vitro using Matrigel 3-dimensional (3D) culture. Effects of irradiation on clonogenic survival, cell migration, and invasion were measured with respect to the PTEN status and the PDGF D expression level. In addition, apoptosis and cell cycle redistribution were examined as potential mechanisms for differences seen. Results: PTEN{sup −/−} cells were highly tumorigenic in animals and effectively formed foci in 3D culture. Importantly, loss of PDGF D in these cell lines drastically diminished these phenotypes. Furthermore, PTEN{sup −/−} cells demonstrated increased clonogenic survival in vitro compared to PTEN{sup +/+}, and attenuation of PDGF D significantly reversed this radioresistant phenotype. PTEN{sup −/−} cells displayed greater migratory and invasive potential at baseline as well as after irradiation. Both the basal and radiation-induced migratory and invasive phenotypes in PTEN{sup −/−} cells required PDGF D expression. Interestingly, these differences were independent of apoptosis and cell cycle redistribution, as they showed no significant difference. Conclusions: We propose

  7. Dysregulation of synaptic plasticity precedes appearance of morphological defects in a Pten conditional knockout mouse model of autism.

    Science.gov (United States)

    Takeuchi, Koichi; Gertner, Michael J; Zhou, Jing; Parada, Luis F; Bennett, Michael V L; Zukin, R Suzanne

    2013-03-19

    The phosphoinositide signaling system is a crucial regulator of neural development, cell survival, and plasticity. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) negatively regulates phosphatidylinositol 3-kinase signaling and downstream targets. Nse-Cre Pten conditional knockout mice, in which Pten is ablated in granule cells of the dentate gyrus and pyramidal neurons of the hippocampal CA3, but not CA1, recapitulate many of the symptoms of humans with inactivating PTEN mutations, including progressive hypertrophy of the dentate gyrus and deficits in hippocampus-based social and cognitive behaviors. However, the impact of Pten loss on activity-dependent synaptic plasticity in this clinically relevant mouse model of Pten inactivation remains unclear. Here, we show that two phosphatidylinositol 3-kinase- and protein synthesis-dependent forms of synaptic plasticity, theta burst-induced long-term potentiation and metabotropic glutamate receptor (mGluR)-dependent long-term depression, are dysregulated at medial perforant path-to-dentate gyrus synapses of young Nse-Cre Pten conditional knockout mice before the onset of visible morphological abnormalities. In contrast, long-term potentiation and mGluR-dependent long-term depression are normal at CA3-CA1 pyramidal cell synapses at this age. Our results reveal that deletion of Pten in dentate granule cells dysregulates synaptic plasticity, a defect that may underlie abnormal social and cognitive behaviors observed in humans with Pten inactivating mutations and potentially other autism spectrum disorders.

  8. Attenuation of PTEN increases p21 stability and cytosolic localization in kidney cancer cells: a potential mechanism of apoptosis resistance

    Directory of Open Access Journals (Sweden)

    Baksh Shairaz

    2007-02-01

    Full Text Available Abstract Background The PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten tumor suppressor gene is frequently mutated or deleted in a wide variety of solid tumors, and these cancers are generally more aggressive and difficult to treat than those possessing wild type PTEN. While PTEN lies upstream of the phosphoinositide-3 kinase signaling pathway, the mechanisms that mediate its effects on tumor survival remain incompletely understood. Renal cell carcinoma (RCC is associated with frequent treatment failures (~90% in metastatic cases, and these tumors frequently contain PTEN abnormalities. Results Using the ACHN cell line containing wild type PTEN, we generated a stable PTEN knockdown RCC cell line using RNA interference. We then used this PTEN knockdown cell line to show that PTEN attenuation increases resistance to cisplatin-induced apoptosis, a finding associated with increased levels of the cyclin kinase inhibitor p21. Elevated levels of p21 result from stabilization of the protein, and they are dependent on the activities of phosphoinositide-3 kinase and Akt. More specifically, the accumulation of p21 occurs preferentially in the cytosolic compartment, which likely contributes to both cell cycle progression and resistance to apoptosis. Conclusion Since p21 regulates a decision point between repair and apoptosis after DNA damage, our data suggest that p21 plays a key role in mechanisms used by PTEN-deficient tumors to escape chemotherapy. This in turn raises the possibility to use p21 attenuators as chemotherapy sensitizers, an area under active continuing investigation in our laboratories.

  9. Extending the field of view of KD/asterisk/P electrooptic modulators

    Science.gov (United States)

    West, E. A.

    1978-01-01

    The use of KD(asterisk)P as a polarization rotator has been limited to small field of view instruments. To investigate this limitation, the index ellipsoid is used to describe the optical properties of KD(asterisk)P and to calculate the retardance and fast axis as a function of the angle of incidence and voltage. Computed converging light patterns are then compared with observed intensity patterns formed by KD(asterisk)P. Finally, computed intensity patterns are used to demonstrate how the field of view of KD(asterisk)P can be increased when properly aligned with a positive uniaxial crystal.

  10. An application of the decomposition method for the generalized KdV and RLW equations

    Energy Technology Data Exchange (ETDEWEB)

    Kaya, Dogan E-mail: dkaya@firat.edu.tr; El-Sayed, Salah M. E-mail: ms4elsayed@yahoo.com

    2003-08-01

    We consider solitary-wave solutions of the generalized regularized long-wave (RLW) and Korteweg-de Vries (KdV) equations. We prove the convergence of Adomian decomposition method applied to the generalized RLW and KdV equations. Then we obtain the exact solitary-wave solutions and numerical solutions of the generalized RLW and KdV equations for the initial conditions. The numerical solutions are compared with the known analytical solutions. Their remarkable accuracy are finally demonstrated for the generalized RLW and KdV equations.

  11. An application of the decomposition method for the generalized KdV and RLW equations

    CERN Document Server

    Kaya, D

    2003-01-01

    We consider solitary-wave solutions of the generalized regularized long-wave (RLW) and Korteweg-de Vries (KdV) equations. We prove the convergence of Adomian decomposition method applied to the generalized RLW and KdV equations. Then we obtain the exact solitary-wave solutions and numerical solutions of the generalized RLW and KdV equations for the initial conditions. The numerical solutions are compared with the known analytical solutions. Their remarkable accuracy are finally demonstrated for the generalized RLW and KdV equations.

  12. Variable expression of PIK3R3 and PTEN in Ewing Sarcoma impacts oncogenic phenotypes.

    Directory of Open Access Journals (Sweden)

    Brian F Niemeyer

    Full Text Available Ewing Sarcoma is an aggressive malignancy of bone and soft tissue affecting children and young adults. Ewing Sarcoma is driven by EWS/Ets fusion oncoproteins, which cause widespread alterations in gene expression in the cell. Dysregulation of receptor tyrosine kinase signaling, particularly involving IGF-1R, also plays an important role in Ewing Sarcoma pathogenesis. However, the basis of this dysregulation, including the relative contribution of EWS/Ets-dependent and independent mechanisms, is not well understood. In the present study, we identify variable expression of two modifiers of PI3K signaling activity, PIK3R3 and PTEN, in Ewing Sarcoma, and examine the consequences of this on PI3K pathway regulation and oncogenic phenotypes. Our findings indicate that PIK3R3 plays a growth-promotional role in Ewing Sarcoma, but suggest that this role is not strictly dependent on regulation of PI3K pathway activity. We further show that expression of PTEN, a well-established, potent tumor suppressor, is lost in a subset of Ewing Sarcomas, and that this loss strongly correlates with high baseline PI3K pathway activity in cell lines. In support of functional importance of PTEN loss in Ewing Sarcoma, we show that re-introduction of PTEN into two different PTEN-negative Ewing Sarcoma cell lines results in downregulation of PI3K pathway activity, and sensitization to the IGF-1R small molecule inhibitor OSI-906. Our findings also suggest that PTEN levels may contribute to sensitivity of Ewing Sarcoma cells to the microtubule inhibitor vincristine, a relevant chemotherapeutic agent in this cancer. Our studies thus identify PIK3R3 and PTEN as modifiers of oncogenic phenotypes in Ewing Sarcoma, with potential clinical implications.

  13. PTEN coding product:a new marker for tumorigenesis and progession of endometrial carcinoma

    Institute of Scientific and Technical Information of China (English)

    Gao Qinglei; Li Jing; Xing Hui; Lu Yunping; Zhou Jianfeng; Ma Ding

    2008-01-01

    Objective :To investigate the expression of PTEN in carcinogenesis and development of endometrial carcinoma.Methods: The expression of PTEN was detected by reverse transcription-polymerase chain reaction(RT-PCR) methods from 24 cases with endometrial carcinoma,10 cases with endometrial atypical hyperplasia,I0 eases with endometrial hyperplasia and I0 cases with normal endometrium and by SP immunohistochemical methods from 73 cases with endometrial carcinoma,25 cases with endometrial atypical hyperplasia,71 cases with endometrial hyperplasia and 31 cases with normal endometrium.Results:PTEN expression of both RNA and protein in patients with endometrial carcinoma and endometrial atypical hyperplasia was significantly lower than that of patients with endometrial hyperplasia and normal endometriurn.mRNA relative value was 0.35±0.13,0.46±0.11,2.32±0.32,2.45±0.51,respectively.Loss of PTEN expression rates were 66.67% (38/57) ,76.00% ( 19/25 ) ,5.63% (4/71 ) ,0 (0/31 ),repeetively.The results were also compared with clinical parameters.Loss of PTEN expression in patients with endometrial carcinoma was significantly related to histological classification ( P < 0.0001 ) and differentiation ( P < 0.05 ).It was not related to depth of myometrium invasion and clinical stage( P >0.05 ).Conclusion:Loss of PTEN expression is an early event in endometrial tumorigenesis.Detection of PTEN protein may be a diagnostic biomarker for endometrial precancers and adenocareinoma.

  14. Glandular epithelial AR inactivation enhances PTEN deletion-induced uterine pathology.

    Science.gov (United States)

    Choi, Jaesung Peter; Zheng, Yu; Handelsman, David J; Simanainen, Ulla

    2016-05-01

    Phosphatase and tensin homolog (PTEN) deletion induces uterine pathology, whereas androgen actions via androgen receptor (AR) support uterine growth and therefore may modify uterine cancer risk. We hypothesized that the androgen actions mediated via uterine glandular epithelial AR could modify PTEN deletion-induced uterine pathology. To test our hypothesis, we developed uterine glandular epithelium-specific PTEN and/or AR knockout mouse models comparing the uterine pathology among wild-type (WT), glandular epithelium-specific AR inactivation (ugeARKO), PTEN deletion (ugePTENKO), and the combined PTEN and AR knockout (ugePTENARKO) female mice. The double knockout restricted to glandular epithelium showed that AR inactivation enhanced PTEN deletion-induced uterine pathology with development of intraepithelial neoplasia by 20 weeks of age. In ugePTENARKO, 6/10 (60%) developed intraepithelial neoplasia, whereas 3/10 (30%) developed only glandular hyperplasia in ugePTENKO uterus. No uterine pathology was observed in WT (n=8) and ugeARKO (n=7) uteri. Uterine weight was significantly (P=0.002) increased in ugePTENARKO (374±97 mg (mean±s.e.)) compared with WT (97±6 mg), ugeARKO (94±12 mg), and ugePTENKO (205±33 mg). Estrogen receptor alpha (ERα) and P-AKT expression was modified by uterine pathology but did not differ between ugePTENKO and ugePTENARKO, suggesting that its expressions are not directly affected by androgens. However, progesterone receptor (PR) expression was reduced in ugePTENARKO compared to ugePTENKO uterus, suggesting that PR expression could be regulated by glandular epithelial AR inactivation. In conclusion, glandular epithelial AR inactivation (with persistent stromal AR action) enhanced PTEN deletion-induced uterine pathology possibly by downregulating PR expression in the uterus.

  15. Cancer Prognosis Defined by the Combined Analysis of 8q, PTEN and ERG

    Directory of Open Access Journals (Sweden)

    Maria P. Silva

    2016-12-01

    Full Text Available Overtreatment is a major concern in men diagnosed with prostate cancer. The aim of this study was to evaluate the combined prognostic role of three frequent molecular alterations in prostate cancer, namely relative 8q gain, ERG overexpression, and loss of PTEN expression, in a series of 136 patients with prostate cancer treated with prostatectomy and with a long follow-up. Fluorescent in situ hybridization was used to detect the relative copy number of 8q and immunohistochemistry was used for quantitative assessment of ERG and PTEN expression. During a median follow-up period of 117.8 months, 66 (49% patients had disease recurrence. Relative 8q gain, ERG overexpression, and loss of PTEN expression were observed in 18%, 56%, and 33% of the cases, respectively. No association with patient recurrence-free survival was found for relative 8q gain or ERG overexpression on their own, whereas loss of PTEN expression was associated with worse recurrence-free survival (P = .006. Interestingly, in the subgroup of patients with normal PTEN expression, we found that the combined relative 8q gain/ERG overexpression is associated with high risk of recurrence (P = .008, suggesting that alternative mechanisms exist for progression into clinically aggressive disease. Additionally, in intermediate-risk patients with normal PTEN expression in their tumors, the combination of 8q gain/ERG overexpression was associated with a poor recurrence-free survival (P < .001, thus indicating independent prognostic value. This study shows that the combined analysis of 8q, ERG and PTEN contributes to an improved clinical outcome stratification of prostate cancer patients treated with radical prostatectomy.

  16. Adenovirus replication-competent vectors (KD1, KD3) complement the cytotoxicity and transgene expression from replication-defective vectors (Ad-GFP, Ad-Luc).

    Science.gov (United States)

    Habib, Nagy A; Mitry, Ragai; Seth, Prem; Kuppuswamy, Mohan; Doronin, Konstantin; Toth, Karoly; Krajcsi, Peter; Tollefson, Ann E; Wold, William S M

    2002-08-01

    The successful clinical application of adenovirus (Ad) in cancer control has been of limited success because of the current inability to infect the majority of cancer cells with a large amount of vector. In this study, we show that when human lung tumors growing in immunodeficient nude mice were coinfected with a replication-defective (RD) Ad vector expressing green fluorescent protein and a replication-competent (RC) Ad vector named KD3, KD3 enhanced the expression of green fluorescent protein throughout the tumor. Also, KD3 and another RC vector named KD1 complemented the expression of luciferase from a RD vector in a human liver tumor xenotransplant in nude mice. Altogether, these results suggest that the combination of a RD vector with a RC vector might be a more effective treatment for cancer than either vector alone due to more widespread dissemination of the virus.

  17. Circumsporozoite Protein-Specific Kd-Restricted CD8+ T Cells Mediate Protective Antimalaria Immunity in Sporozoite-Immunized MHC-I-Kd Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Jing Huang

    2014-01-01

    Full Text Available Although the roles of CD8+ T cells and a major preerythrocytic antigen, the circumsporozoite (CS protein, in contributing protective antimalaria immunity induced by radiation-attenuated sporozoites, have been shown by a number of studies, the extent to which these players contribute to antimalaria immunity is still unknown. To address this question, we have generated C57BL/6 (B6 transgenic (Tg mice, expressing Kd molecules under the MHC-I promoter, called MHC-I-Kd-Tg mice. In this study, we first determined that a single immunizing dose of IrPySpz induced a significant level of antimalaria protective immunity in MHC-I-Kd-Tg mice but not in B6 mice. Then, by depleting various T-cell subsets in vivo, we determined that CD8+ T cells are the main mediator of the protective immunity induced by IrPySpz. Furthermore, when we immunized (MHC-I-Kd-Tg × CS-Tg F1 mice with IrPySpz after crossing MHC-I-Kd-Tg mice with PyCS-transgenic mice (CS-Tg, which are unable to mount PyCS-specific immunity, we found that IrPySpz immunization failed to induce protective antimalaria immunity in (MHC-I-Kd-Tg × CS-Tg F1 mice, thus indicating the absence of PyCS antigen-dependent immunity in these mice. These results indicate that protective antimalaria immunity induced by IrPySpz in MHC-I-Kd-Tg mice is mediated by CS protein-specific, Kd-restricted CD8+ T cells.

  18. Several Kinds of Accurate Solutions on Generalized KdV-Burgers Equation%广义KdV-Burgers方程的几类精确解

    Institute of Scientific and Technical Information of China (English)

    胡建兰; 张汉林

    2000-01-01

    The general KdV-Burgers equation has been discussed in this paper. By using improved the method of HBM, we have gotten several kinds of accurate traveling wave solution.%讨论了广义KdV-Burgers方程. 通过使用改进的HBM方法,我们得到理几类精确的行波解.

  19. New solutions for conformable fractional Boussinesq and combined KdV-mKdV equations using Jacobi elliptic function expansion method

    Science.gov (United States)

    Tasbozan, Orkun; Çenesiz, Yücel; Kurt, Ali

    2016-07-01

    In this paper, the Jacobi elliptic function expansion method is proposed for the first time to construct the exact solutions of the time conformable fractional two-dimensional Boussinesq equation and the combined KdV-mKdV equation. New exact solutions are found. This method is based on Jacobi elliptic functions. The results obtained confirm that the proposed method is an efficient technique for analytic treatment of a wide variety of nonlinear conformable time-fractional partial differential equations.

  20. The Jacobi elliptic function-like exact solutions to two kinds of KdV equations with variable coefficients and KdV equation with forcible term

    Institute of Scientific and Technical Information of China (English)

    Taogetusang; Sirendaoerji

    2006-01-01

    By use of an auxiliary equation and through a function transformation, the Jacobi elliptic function wave-like solutions, the degenerated soliton-like solutions and the triangle function wave solutions to two kinds of Korteweg-de Vries (KdV) equations with variable coefficients and a KdV equation with a forcible term are constructed with the help of symbolic computation system Mathematica, where the new solutions are also constructed.

  1. Comparison of Nutech Functional Score with European Stroke Scale for Patients with Cerebrovascular Accident Treated with Human Embryonic Stem Cells: NFS for CVA Patients Treated with hESCs.

    Science.gov (United States)

    Shroff, Geeta

    2017-06-01

    Stem cell therapy is a promising modality for treatment of patients with chronic cerebrovascular accident (CVA) in whom treatment other than physiotherapy or occupational therapy does not address the repair or recovery of the lost function. In this study, the author aimed at evaluating CVA patients treated with human embryonic stem cell (hESC) therapy and comparing their study outcomes with globally accepted European Stroke Scale (ESS) to that with novel scoring system, Nutech functional score (NFS), a 21-point positional and directional scoring system for assessing patients with CVA. Patients diagnosed with CVA were assessed with NFS and ESS before and after hESC therapy. NFS assessed the patients in the direction of 1-5 (bad to good), where 5 was considered as the highest possible grade (HPG). The findings were obtained for the patients who scored HPG, and had shown improvement by at least one grade. Overall, 66.7% of patients scored HPG level on the NFS scale and about 62.5% of the patients scored HPG according to the ESS scale. Approximately, 52.2% patients showed an improvement of 100% (by at least one grade) on NFS scale. None of the patients showed 100% improvement in the alteration of the score by at least one grade when scored with ESS. NFS and ESS scores show that a large population of CVA patients was benefitted with hESC therapy. NFS was found to give more convincing results than ESS, and overcomes the shortcomings of ESS.

  2. Expression and significance of PTEN, hypoxia-inducible factor-1 alpha in colorectal adenoma and adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Ying-An Jiang; Li-Fang Fan; Chong-Qing Jiang; You-Yuan Zhang; He-Sheng Luo; Zhi-Jiao Tang; Dong Xia; Ming Wang

    2003-01-01

    AIM: To investigate the expression and significance of PTEN,hypoxia-inducible factor-1 alpha (HIF-1α), and targeting gene VEGF during colorectal carciogenesis.METHODS: Total 71 cases colorectal neoplasms (9 cases of colorectal adenoma and 62 colorectal adenocarcinoma)were formalin fixed and paraffin-embedded, and all specimens were evaluated for PTEN mRNA, HIF-1α mRNA and VEGF protein expression. PTEN mRNA, HIF-1α mRNA were detected by in situ hybridization. VEGF protein was identified by citrate-microwave SP immunohistochemical method.RESULTS: There were significant differences in PTEN, HIF1α and VEGF expression between colorectal adenomas and colorectal adenocarcinoma (P<0.05). The level of PTEN expression decreased as the pathologic stage increased.Conversely, HIF-1α and VEGF expression increased with the Dukes stage as follows: stage A (0.1029±0.0457:0.1207± 0.0436), stage B (0.1656±0.0329: 0.1572±0.0514),and stage C+D (0.2335±0.0748: 0.2219±0.0803). For PTEN expression, there was a significant difference among Dukes stage A, B, and C+D, and the level of PTEN expression was found to be significant higher in Dukes stage A or B than that of Dukes stage C or D. For HIF-1α expression,there was a significant difference between Dukes stage A and B, and the level of HIF-1α expression was found to be significantly higher in Dukes stage C+D than that of Dukes stage A or B. The VEGF expression had similar results as HIF-1α expression. In colorectal adenocarcinoma,decreased levels of PTEN were significantly associated with increased expression of HIF-1α mRNA (r=-0.36, P<0.05)and VEGF protein (r=-0.48, P<0.05) respectively. The levels of HIF-1 were positively correlated with VEGF expression (r=0.71, P<0.01).CONCLUSION: Loss of PTEN expression and increased levels of HIF-1α and VEGF may play an important role in carcinogenesis and progression of colorectal adenocarcinoma.

  3. Von Hippel-Lindau status influences phenotype of liver cancers arising from PTEN loss

    Directory of Open Access Journals (Sweden)

    Sendor AB

    2015-02-01

    Full Text Available Adam B Sendor,1 Kathryn E Hacker,1 Shufen Chen,1 Armando L Corona,1 Oishee Sen,1 Derek Y Chiang,1 Anna Snavely,1 Arlin B Rogers,2 Stephanie A Montgomery,1 W Kimryn Rathmell,1 Autumn J McRee11Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA; 2Section of Pathology, Department of Biomedical Sciences, Cummings School of Veterinary Medicine, Tufts University, Boston, MA, USABackground: PTEN loss contributes to the development of liver diseases including hepatic steatosis and both hepatocellular carcinoma (HCC and cholangiocarcinoma (CC. The factors that influence the penetrance of these conditions are unclear. We explored the influence of sustained hypoxia signaling through co-deletion of Pten and Vhl in a murine model.Methods: We used a CreER-linked Keratin 18 mouse model to conditionally delete Pten, Vhl or both in somatic cells of adult mice, evaluating the resultant tumors by histology and gene expression microarray. Existing sets of gene expression data for human HCC and CC were examined for pathways related to those observed in the murine tumors, and a cohort of human CC samples was evaluated for relationships between HIF-1α expression and clinical outcomes.Results: Both Pten deletion genotypes developed liver tumors, but with differing phenotypes. Pten deletion alone led to large hepatic tumors with widespread hepatosteatosis. Co-deletion of Pten and Vhl with the Keratin 18 promoter resulted in reduced steatosis and a reduced tumor burden that was characterized by a trabecular architecture similar to CC. Genes associated with hepatic steatosis were coordinately expressed in the human HCC dataset, while genes involved in hypoxia response were upregulated in tumors from the human CC dataset. HIF-1α expression and overall survival were examined in an independent cohort of human CC tumors with no statistical differences uncovered.Conclusion: Pten deletion in Keratin 18 expressing cells leads to

  4. Combined Phosphatase and Tensin Homolog (PTEN Loss and Fatty Acid Synthase (FAS Overexpression Worsens the Prognosis of Chinese Patients with Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Xuehua Zhu

    2012-08-01

    Full Text Available We aimed to investigate the expression pattern of phosphatase and tensin homolog (PTEN, to evaluate the relationship between PTEN expression and clinicopathological characteristics, including fatty acid synthase (FAS expression, and to determine the correlations of PTEN and FAS expression with survival in Chinese patients with hepatocellular carcinoma (HCC. The expression patterns of PTEN and FAS were determined using tissue microarrays and immunohistochemistry. The expression of PTEN was compared with the clinicopathological characteristics of HCC, including FAS expression. Receiver operator characteristic curves were used to calculate the clinical sensitivity and specificity of PTEN expression. Kaplan-Meier survival curves were constructed to evaluate the correlations of PTEN loss and FAS overexpression with overall survival. We found that the loss of PTEN expression occurred predominantly in the cytoplasm, while FAS was mainly localized to the cytoplasm. Cytoplasmic and total PTEN expression levels were significantly decreased in HCC compared with adjacent non-neoplastic tissue (both, p < 0.0001. Decreased cytoplasmic and total PTEN expression showed significant clinical sensitivity and specificity for HCC (both, p < 0.0001. Downregulation of PTEN in HCC relative to non-neoplastic tissue was significantly correlated with histological grade (p = 0.043 for histological grades I–II versus grade III. Loss of total PTEN was significantly correlated with FAS overexpression (p = 0.014. Loss of PTEN was also associated with poor prognosis of patients with poorly differentiated HCC (p = 0.049. Moreover, loss of PTEN combined with FAS overexpression was associated with significantly worse prognosis compared with other HCC cases (p = 0.011. Our data indicate that PTEN may serve as a potential diagnostic and prognostic marker of HCC. Upregulating PTEN expression and inhibiting FAS

  5. Moyal noncommutative integrability and the Burgers-KdV mapping

    Energy Technology Data Exchange (ETDEWEB)

    Sedra, M.B. [International Centre for Theoretical Physics, Trieste (Italy) and Virtual African Center for Basic Sciences and Technology, VACBT, Focal point: Lab/UFR-Physique des Haute Energies, Faculte des Sciences, Rabat (Morocco) and Groupement National de Physique de Hautes Energies, GNPHE, Rabat (Morocco) and Universite Ibn Tofail, Faculte des Sciences, Departement de Physique, Laboratoire de Physique de la Matiere et Rayonnement - LPMR, Kenitra (Morocco)]. E-mail: sedra@ictp.it

    2006-04-24

    The Moyal momentum algebra, studied in previous occasions, is once again used to discuss some important aspects of NC integrable models and 2d conformal field theories. Among the results presented, we setup algebraic structures and makes useful convention notations leading to extract nontrivial properties of the Moyal momentum algebra. We study also the Lax pair building mechanism for particular examples namely, the noncommutative KdV and Burgers systems. We show in a crucial step that these two systems are mapped to each others through the following crucial mapping -bar {sub t2}-bar -bar {sub t3}=-bar {sub t2}-bar {sub x}+{alpha}-bar {sub x}{sup 3}. This makes a strong constraint on the NC Burgers system which corresponds to linearizing its associated differential equation. From the CFT's point of view, this constraint equation is nothing but the analogue of the conservation law of the conformal current. We believe that the considered mapping might help to bring new insights towards understanding the integrability of noncommutative 2d-systems.

  6. Prognostic Significance of mTOR and PTEN in Patients with Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Jianjun Lu

    2015-01-01

    Full Text Available The prognostic value of mTOR in ESCC is much controversial; this study aimed to determine the prognostic importance of mTOR and PTEN in patients with ESCC. A total of 148 consecutive patients who underwent esophagectomy from 2010 to 2012 were included in this study, tested by western bolt and immunohistochemistry for mTOR and PTEN expression. Correlation coefficient was calculated using Pearson’s correlation test. The 3-year overall survival (OS and disease-free survival (DFS were calculated in relation to the two markers. 94 (63.5% of 148 were mTOR high expression, and PTEN high expression was detected in 46 (31.1% of the 148 patients with ESCC. The Pearson correlation coefficient revealed a significant negative correlation in two proteins (correlation coefficient = −0.189, P<0.005. The 3-year OS and DFS time in the mTOR-high group was 23.9 and 18.4 months, respectively, and the time in the mTOR-low group was 33.9 months and 31.4 months, respectively. The difference of survival rate between the two groups remained statistically significant. mTOR-low or PTEN-high patients had better 3-year rates of OS and DFS than mTOR-high or PTEN-low group (P<0.001 by the log-rank test. This study also found that mTOR was an independence prognostic factor by multivariate analysis.

  7. miR-17 inhibitor suppressed osteosarcoma tumor growth and metastasis via increasing PTEN expression

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yong, E-mail: gaoyongunion@163.com [Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Luo, Ling-hui [Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Li, Shuai; Yang, Cao [Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China)

    2014-02-07

    Highlights: • miR-17 was increased in OS tissues and cell lines. • Inhibition of miR-17 suppressed OS cell proliferation. • Inhibition of miR-17 suppressed OS cell migration and invasion. • PTEN was a target of miR-17. • miR-17 was negatively correlated with PTEN in OS tissues. - Abstract: MicroRNAs (miRNAs) play essential roles in cancer development and progression. Here, we investigated the role of miR-17 in the progression and metastasis of osteosarcoma (OS). miR-17 was frequently increased in OS tissues and cell lines. Inhibition of miR-17 in OS cell lines substantially suppressed cell proliferation, migration, and invasion. Phosphatase and tensin homolog (PTEN) was identified as a target of miR-17, and ectopic expression of miR-17 inhibited PTEN by direct binding to its 3′-untranslated region (3′-UTR). Expression of miR-17 was negatively correlated with PTEN in OS tissues. Together, these findings indicate that miR-17 acts as an oncogenic miRNA and may contribute to the progression and metastasis of OS, suggesting miR-17 as a potential novel diagnostic and therapeutic target of OS.

  8. Reciprocal positive regulation between TRPV6 and NUMB in PTEN-deficient prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung-Young; Hong, Chansik; Wie, Jinhong [Department of Physiology, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Kim, Euiyong [Department of Physiology, College of Medicine, Inje University, Busan 614-735 (Korea, Republic of); Kim, Byung Joo [Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870 (Korea, Republic of); Ha, Kotdaji [Department of Physiology, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Cho, Nam-Hyuk; Kim, In-Gyu [Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Jeon, Ju-Hong [Department of Physiology, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); So, Insuk, E-mail: insuk@snu.ac.kr [Department of Physiology, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)

    2014-04-25

    Highlights: • TRPV6 interacts with tumor suppressor proteins. • Numb has a selective effect on TRPV6, depending on the prostate cancer cell line. • PTEN is a novel regulator of TRPV6–Numb complex. - Abstract: Calcium acts as a second messenger and plays a crucial role in signaling pathways involved in cell proliferation. Recently, calcium channels related to calcium influx into the cytosol of epithelial cells have attracted attention as a cancer therapy target. Of these calcium channels, TRPV6 is overexpressed in prostate cancer and is considered an important molecule in the process of metastasis. However, its exact role and mechanism is unclear. NUMB, well-known tumor suppressor gene, is a novel interacting partner of TRPV6. We show that NUMB and TRPV6 have a reciprocal positive regulatory relationship in PC-3 cells. We repeated this experiment in two other prostate cancer cell lines, DU145 and LNCaP. Interestingly, there were no significant changes in TRPV6 expression following NUMB knockdown in DU145. We revealed that the presence or absence of PTEN was the cause of NUMB–TRPV6 function. Loss of PTEN caused a positive correlation of TRPV6–NUMB expression. Collectively, we determined that PTEN is a novel interacting partner of TRPV6 and NUMB. These results demonstrated a novel relationship of NUMB–TRPV6 in prostate cancer cells, and show that PTEN is a novel regulator of this complex.

  9. Conditional Inactivation of Pten with EGFR Overexpression in Schwann Cells Models Sporadic MPNST

    Directory of Open Access Journals (Sweden)

    Vincent W. Keng

    2012-01-01

    Full Text Available The genetic mechanisms involved in the transformation from a benign neurofibroma to a malignant sarcoma in patients with neurofibromatosis-type-1- (NF1-associated or sporadic malignant peripheral nerve sheath tumors (MPNSTs remain unclear. It is hypothesized that many genetic changes are involved in transformation. Recently, it has been shown that both phosphatase and tensin homolog (PTEN and epidermal growth factor receptor (EGFR play important roles in the initiation of peripheral nerve sheath tumors (PNSTs. In human MPNSTs, PTEN expression is often reduced, while EGFR expression is often induced. We tested if these two genes cooperate in the evolution of PNSTs. Transgenic mice were generated carrying conditional floxed alleles of Pten, and EGFR was expressed under the control of the 2′,3′-cyclic nucleotide 3′phosphodiesterase (Cnp promoter and a desert hedgehog (Dhh regulatory element driving Cre recombinase transgenic mice (Dhh-Cre. Complete loss of Pten and EGFR overexpression in Schwann cells led to the development of high-grade PNSTs. In vitro experiments using immortalized human Schwann cells demonstrated that loss of PTEN and overexpression of EGFR cooperate to increase cellular proliferation and anchorage-independent colony formation. This mouse model can rapidly recapitulate PNST onset and progression to high-grade PNSTs, as seen in sporadic MPNST patients.

  10. Complex and singular solutions of KdV and MKdV equations

    Science.gov (United States)

    Buti, B.; Rao, N. N.; Khadkikar, S. B.

    1986-01-01

    The Korteweg-de Vries (KdV) and the modified Korteweg-de Vries (MKdV) equations are shown to have, besides the regular real solutions, exact regular complex as well as singular solutions. The singular solution for the KdV is real but for the MKdV it is pure imaginary. Implications of the complex solutions are discussed.

  11. New Exact Solutions of Multi-component mKdV Equation

    Institute of Scientific and Technical Information of China (English)

    YE Cai-Er

    2006-01-01

    In this paper, new Jacobi elliptic function solutions of multi-component mKdV equation are obtained directly in a unified way. When the modulus m →1, those periodic solutions degenerate as the corresponding hyperbolic function solutions. Then, to the three-component mKdV equation, five types of effective solution are presented in detail.

  12. Solitary Solution of Discrete mKdV Equation by Homotopy Analysis Method

    Institute of Scientific and Technical Information of China (English)

    XU Xi-Xiang; WANG Zhen; YANG Hong-Xiang; ZOU Li; LU Rong-Wu; ZHANG Hong-Qing

    2008-01-01

    In this paper, we apply homotopy analysis method to solve discrete mKdV equation and successfully obtain the bell-shaped solitary solution to mKdV equation. Comparison between our solution and the exact solution shows that homotopy analysis method is effective and validity in solving hybrid nonlinear problems, including solitary solution of difference-differential equation.

  13. Multi-indexed Extensions of Soliton Potential and Extended Integer Solitons of KdV Equation

    CERN Document Server

    Ho, Choon-Lin

    2014-01-01

    We discover new infinite set of initial profiles of KdV solitons, which are both exactly solvable for the Schrodinger equation and for the Gel'fand-Levitan-Marchenko equation in the inverse scattering transform method of KdV equation. These new solutions are based on the multi-indexed extensions of the reflectionless soliton potential.

  14. Various methods for solving time fractional KdV-Zakharov-Kuznetsov equation

    Science.gov (United States)

    Guner, Ozkan; Aksoy, Esin; Bekir, Ahmet; Cevikel, Adem C.

    2016-06-01

    This paper presents the exact analytical solution of the (3+1)-dimensional time fractional KdV-Zakharov-Kuznetsov (KdV-ZK) equation with the help of the Kudryashov method, the exp-function method and the functional variable method. The fractional derivatives are described in Jumarie's sense.

  15. Miura and generalized Bäcklund transformation for KdV hierarchy

    Science.gov (United States)

    Gomes, J. F.; Retore, A. L.; Zimerman, A. H.

    2016-12-01

    Using the fact that Miura transformation can be expressed in the form of gauge transformation connecting the KdV and mKdV equations, we discuss the derivation of the Bäcklund transformation and its Miura-gauge transformation connecting both hierarchies.

  16. Miura and Generalized B\\"acklund Transformation for KdV Hierarchy

    CERN Document Server

    Gomes, J F; Zimerman, A H

    2016-01-01

    Using the fact that Miura transformation can be expressed in the form of gauge transformation connecting the KdV and mKdV equations, we discuss the derivation of the B\\"acklund transformation and its Miura-gauge transformation connecting both hierarchies.

  17. EXACT SOLUTIONS FOR GENERAL VARIABLE-COEFFICIENT KdV EQUATION

    Institute of Scientific and Technical Information of China (English)

    LiuXiqiang; JiangSong

    2001-01-01

    By asing the nonclassical method of symmetry reductions, the exact solutions for general variable-coefficient KdV equation with dissipative loss and nonuniformity terms are obtained. When the dissipative loss and nonuniformity terms don't exist, the multisoliton solutions are found and the corresponding Painleve II type equation for the variable-coefficient KdV equation is given.

  18. Kd-Jump: a path-preserving stackless traversal for faster isosurface raytracing on GPUs.

    Science.gov (United States)

    Hughes, David M; Lim, Ik Soo

    2009-01-01

    Stackless traversal techniques are often used to circumvent memory bottlenecks by avoiding a stack and replacing return traversal with extra computation. This paper addresses whether the stackless traversal approaches are useful on newer hardware and technology (such as CUDA). To this end, we present a novel stackless approach for implicit kd-trees, which exploits the benefits of index-based node traversal, without incurring extra node visitation. This approach, which we term Kd-Jump, enables the traversal to immediately return to the next valid node, like a stack, without incurring extra node visitation (kd-restart). Also, Kd-Jump does not require global memory (stack) at all and only requires a small matrix in fast constant-memory. We report that Kd-Jump outperforms a stack by 10 to 20% and kd-restart by 100%. We also present a Hybrid Kd-Jump, which utilizes a volume stepper for leaf testing and a run-time depth threshold to define where kd-tree traversal stops and volume-stepping occurs. By using both methods, we gain the benefits of empty space removal, fast texture-caching and realtime ability to determine the best threshold for current isosurface and view direction.

  19. Equivalence of two approaches to the mKdV hierarchies

    CERN Document Server

    Enriquez, B; Enriquez, Benjamin; Frenkel, Edward

    1996-01-01

    The equivalence between the approaches of Drinfeld-Sokolov and Feigin-Frenkel to the mKdV hierarchies is established. A new derivation of the mKdV equations in the zero curvature form is given. Connection with the Baker-Akhiezer function and the tau-function is also discussed.

  20. PTEN status is a crucial determinant of the functional outcome of combined MEK and mTOR inhibition in cancer

    Science.gov (United States)

    Milella, Michele; Falcone, Italia; Conciatori, Fabiana; Matteoni, Silvia; Sacconi, Andrea; De Luca, Teresa; Bazzichetto, Chiara; Corbo, Vincenzo; Simbolo, Michele; Sperduti, Isabella; Benfante, Antonina; Del Curatolo, Anais; Cesta Incani, Ursula; Malusa, Federico; Eramo, Adriana; Sette, Giovanni; Scarpa, Aldo; Konopleva, Marina; Andreeff, Michael; McCubrey, James Andrew; Blandino, Giovanni; Todaro, Matilde; Stassi, Giorgio; De Maria, Ruggero; Cognetti, Francesco; Del Bufalo, Donatella; Ciuffreda, Ludovica

    2017-01-01

    Combined MAPK/PI3K pathway inhibition represents an attractive, albeit toxic, therapeutic strategy in oncology. Since PTEN lies at the intersection of these two pathways, we investigated whether PTEN status determines the functional response to combined pathway inhibition. PTEN (gene, mRNA, and protein) status was extensively characterized in a panel of cancer cell lines and combined MEK/mTOR inhibition displayed highly synergistic pharmacologic interactions almost exclusively in PTEN-loss models. Genetic manipulation of PTEN status confirmed a mechanistic role for PTEN in determining the functional outcome of combined pathway blockade. Proteomic analysis showed greater phosphoproteomic profile modification(s) in response to combined MEK/mTOR inhibition in PTEN-loss contexts and identified JAK1/STAT3 activation as a potential mediator of synergistic interactions. Overall, our results show that PTEN-loss is a crucial determinant of synergistic interactions between MAPK and PI3K pathway inhibitors, potentially exploitable for the selection of cancer patients at the highest chance of benefit from combined therapeutic strategies. PMID:28220839

  1. PTEN, a widely known negative regulator of insulin/PI3K signaling, positively regulates neuronal insulin resistance

    Science.gov (United States)

    Gupta, Amit; Dey, Chinmoy Sankar

    2012-01-01

    Lipid and protein tyrosine phosphatase, phosphatase and tension homologue (PTEN), is a widely known negative regulator of insulin/phosphoinositide 3-kinase signaling. Down-regulation of PTEN is thus widely documented to ameliorate insulin resistance in peripheral tissues such as skeletal muscle and adipose. However, not much is known about its exact role in neuronal insulin signaling and insulin resistance. Moreover, alterations of PTEN in neuronal systems have led to discovery of several unexpected outcomes, including in the neurodegenerative disorder Alzheimer's disease (AD), which is increasingly being recognized as a brain-specific form of diabetes. In addition, contrary to expectations, its neuron-specific deletion in mice resulted in development of diet-sensitive obesity. The present study shows that PTEN, paradoxically, positively regulates neuronal insulin signaling and glucose uptake. Its down-regulation exacerbates neuronal insulin resistance. The positive role of PTEN in neuronal insulin signaling is likely due to its protein phosphatase actions, which prevents the activation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK), the kinases critically involved in neuronal energy impairment and neurodegeneration. Results suggest that PTEN acting through FAK, the direct protein substrate of PTEN, prevents ERK activation. Our findings provide an explanation for unexpected outcomes reported earlier with PTEN alterations in neuronal systems and also suggest a novel molecular pathway linking neuronal insulin resistance and AD, the two pathophysiological states demonstrated to be closely linked. PMID:22875989

  2. Interaction of E-cadherin and PTEN regulates morphogenesis and growth arrest in human mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Fournier, Marcia V.; Fata, Jimmie E.; Martin, Katherine J.; Yaswen, Paul; Bissell, Mina J.

    2009-06-03

    PTEN is a dual function phosphatase with tumor suppressor function compromised in a wide spectrum of cancers. Because tissue polarity and architecture are crucial modulators of normal and malignant behavior, we postulated that PTEN may play a role in maintenance of tissue integrity. We used two non-malignant human mammary epithelial cell lines (HMECs) that form polarized, growth-arrested structures (acini) when cultured in 3-dimensional laminin-rich extracellular matrix gels (3D lrECM). As acini begin to form, PTEN accumulates in both the cytoplasm, and at cell-cell contacts where it colocalizes with E-cadherin/{beta}-catenin complex. Reduction of PTEN levels by shRNA in lrECM prevents formation of organized breast acini and disrupts growth arrest. Importantly, disruption of acinar polarity and cell-cell contact by E-cadherin function-blocking antibodies reduces endogenous PTEN protein levels and inhibits its accumulation at cell-cell contacts. Conversely, in SKBR3 breast cancer cells lacking endogenous E-cadherin expression, exogenous introduction of E-cadherin gene causes induction of PTEN expression and its accumulation at sites of cell interactions. These studies provide evidence that E-cadherin regulates both the PTEN protein levels and its recruitment to cell-cell junctions in 3D lrECM indicating a dynamic reciprocity between architectural integrity and the levels and localization of PTEN. This interaction thus appears to be a critical integrator of proliferative and morphogenetic signaling in breast epithelial cells.

  3. Loss of PTEN is not associated with poor survival in newly diagnosed glioblastoma patients of the temozolomide era.

    Directory of Open Access Journals (Sweden)

    Christine Carico

    Full Text Available INTRODUCTION: Pre-temozolomide studies demonstrated that loss of the tumor suppressor gene PTEN held independent prognostic significance in GBM patients. We investigated whether loss of PTEN predicted shorter survival in the temozolomide era. The role of PTEN in the PI3K/Akt pathway is also reviewed. METHODS: Patients with histologically proven newly diagnosed GBM were identified from a retrospective database between 2007 and 2010. Cox proportional hazards analysis was used to calculate the independent effects of PTEN expression, age, extent of resection, Karnofsky performance scale (KPS, and treatment on overall survival. RESULTS: Sixty-five percent of patients were men with median age of 63 years, and 70% had KPS≥80. Most patients (81% received standard treatment (temozolomide with concurrent radiation. A total of 72 (47% patients had retained PTEN expression. Median overall survival (OS was 19.1 months (95% CI: 15.0-22.5. Median survival of 20.0 months (95% CI: 15.0-25.5 and 18.2 months (95% CI: 13.0-25.7 was observed in PTEN retained and PTEN loss patients, respectively (p = .71. PTEN loss patients were also found to have amplifications of EGFR gene more frequently than patients with retained PTEN (70.8% vs. 47.8%, p = .01. Multivariate analysis showed that older age (HR 1.64, CI: 1.02-2.63, p = .04, low KPS (HR 3.57, CI: 2.20-5.79, p<.0001, and lack of standard treatment (HR 3.98, CI: 2.38-6.65, p<.0001 yielded worse survival. PTEN loss was not prognostic of overall survival (HR 1.31, CI: 0.85-2.03, p = .22. CONCLUSIONS: Loss of expression of PTEN does not confer poor overall survival in the temozolomide era. These findings imply a complex and non-linear molecular relationship between PTEN, its regulators and effectors in the tumorigenesis of glioblastoma. Additionally, there is evidence that temozolomide may be more effective in eradicating GBM cancer cells with PTEN loss and hence, level the outcomes between the PTEN

  4. The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium.

    Science.gov (United States)

    Grego-Bessa, Joaquim; Bloomekatz, Joshua; Castel, Pau; Omelchenko, Tatiana; Baselga, José; Anderson, Kathryn V

    2016-01-26

    Epithelial morphogenesis and stability are essential for normal development and organ homeostasis. The mouse neural plate is a cuboidal epithelium that remodels into a columnar pseudostratified epithelium over the course of 24 hr. Here we show that the transition to a columnar epithelium fails in mutant embryos that lack the tumor suppressor PTEN, although proliferation, patterning and apical-basal polarity markers are normal in the mutants. The Pten phenotype is mimicked by constitutive activation of PI3 kinase and is rescued by the removal of PDK1 (PDPK1), but does not depend on the downstream kinases AKT and mTORC1. High resolution imaging shows that PTEN is required for stabilization of planar cell packing in the neural plate and for the formation of stable apical-basal microtubule arrays. The data suggest that appropriate levels of membrane-associated PDPK1 are required for stabilization of apical junctions, which promotes cell elongation, during epithelial morphogenesis.

  5. Redox regulation of tumor suppressor PTEN in cancer and aging (Review).

    Science.gov (United States)

    Kitagishi, Yasuko; Matsuda, Satoru

    2013-03-01

    Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has been shown to act as a tumor suppressor whose function includes important roles in regulating oxidative stress, indicating a potential role in oxidative damage-associated cancer. Accumulating evidence has revealed that PTEN also acts as a pivotal determinant of cell fate, regarding senescence and apoptosis, which is mediated by intracellular reactive oxygen species (ROS) generation. Cells are continuously exposed to ROS, which represent mutagens and are thought to be a major contributor to cancer and the aging process. Therefore, cellular ROS sensing and metabolism are firmly regulated by a variety of proteins involved in the redox mechanism. In this review, PTEN and the roles of oxidative stress in phosphoinositide-3 kinase/AKT signaling are summarized with a focus on the links between the pathways and ROS in cancer and aging.

  6. Preclinical Remodeling of Human Prostate Cancer through the PTEN/AKT Pathway

    Directory of Open Access Journals (Sweden)

    Marco A. De Velasco

    2012-01-01

    Full Text Available Knowledge gained from the identification of genetic and epigenetic alterations that contribute to the progression of prostate cancer in humans is now being implemented in the development of functionally relevant translational models. GEM (genetically modified mouse models are being developed to incorporate the same molecular defects associated with human prostate cancer. Haploinsufficiency is common in prostate cancer and homozygous loss of PTEN is strongly correlated with advanced disease. In this paper, we discuss the evolution of the PTEN knockout mouse and the cooperation between PTEN and other genetic alterations in tumor development and progression. Additionally, we will outline key points that make these models key players in the development of personalized medicine, as potential tools for target and biomarker development and validation as well as models for drug discovery.

  7. Loss of PTEN Is Associated with Aggressive Behavior in ERG-Positive Prostate Cancer

    Science.gov (United States)

    Leinonen, Katri A.; Saramäki, Outi R.; Furusato, Bungo; Kimura, Takahiro; Takahashi, Hiroyuki; Egawa, Shin; Suzuki, Hiroyoshi; Keiger, Kerri; Hahm, Sung Ho; Isaacs, William B.; Tolonen, Teemu T.; Stenman, Ulf-Håkan; Tammela, Teuvo L.J.; Nykter, Matti; Bova, G. Steven; Visakorpi, Tapio

    2014-01-01

    Background The associations of ERG overexpression with clinical behavior and molecular pathways of prostate cancer are incompletely known. We assessed the association of ERG expression with AR, PTEN, SPINK1, Ki-67, and EZH2 expression levels, deletion, and mutations of chromosomal region 3p14 and TP53, and clinicopathologic variables. Methods The material consisted of 326 prostatectomies, 166 needle biopsies from men treated primarily with endocrine therapy, 177 transurethral resections of castration-resistant prostate cancers (CRPC), and 114 CRPC metastases obtained from 32 men. Immunohistochemistry, FISH, and sequencing was used for the measurements. Results ERG expression was found in about 45% of all patient cohorts. In a multivariate analysis, ERG expression showed independent value of favorable prognosis (P = 0.019). ERG positivity was significantly associated with loss of PTEN expression in prostatectomy (P = 0.0348), and locally recurrent CRPCs (P = 0.0042). Loss of PTEN expression was associated (P = 0.0085) with shorter progression-free survival in ERG-positive, but not in negative cases. When metastases in each subject were compared, consistent ERG, PTEN, and AR expression as well as TP53 mutations were found in a majority of subjects. Conclusions A similar frequency of ERG positivity from early to late stage of the disease suggests lack of selection of ERG expression during disease progression. The prognostic significance of PTEN loss solely in ERG-positive cases indicates interaction of these pathways. The finding of consistent genetic alterations in different metastases suggests that the major genetic alterations take place in the primary tumor. Impact Interaction of PTEN and ERG pathways warrants further studies. PMID:24083995

  8. Oncogenic microRNA-4534 regulates PTEN pathway in prostate cancer.

    Science.gov (United States)

    Nip, Hannah; Dar, Altaf A; Saini, Sharanjot; Colden, Melissa; Varahram, Shahryari; Chowdhary, Harshika; Yamamura, Soichiro; Mitsui, Yozo; Tanaka, Yuichiro; Kato, Taku; Hashimoto, Yutaka; Shiina, Marisa; Kulkarni, Priyanka; Dasgupta, Pritha; Imai-Sumida, Mitsuho; Tabatabai, Z Laura; Greene, Kirsten; Deng, Guoren; Dahiya, Rajvir; Majid, Shahana

    2016-10-18

    Prostate carcinogenesis involves alterations in several signaling pathways, the most prominent being the PI3K/AKT pathway. This pathway is constitutively active and drives prostate cancer (PCa) progression to advanced metastatic disease. PTEN, a critical tumor and metastasis suppressor gene negatively regulates cell survival, proliferation, migration and angiogenesis via the PI3K/Akt pathway. PTEN is mutated, downregulated/dysfunctional in many cancers and its dysregulation correlates with poor prognosis in PCa. Here, we demonstrate that microRNA-4534 (miR-4534) is overexpressed in PCa and show that miR-4534 is hypermethylated in normal tissues and cell lines compared to PCa tissues/cells. miR-4534 exerts its oncogenic effects partly by downregulating the tumor suppressor PTEN gene. Knockdown of miR-4534 impaired cell proliferation, migration/invasion and induced G0/G1 cell cycle arrest and apoptosis in PCa. Suppression of miR-4534 and its effects on tumor growth was confirmed in a xenograft mouse model. We performed parallel experiments in non-cancer RWPE1 cells by overexpessing miR-4534 followed by functional assays. Overexpression of miR-4534 induced pro-cancerous characteristics in this non-cancer cell line. Statistical analyses revealed that miR-4534 has potential to independently distinguish malignant from normal tissues and positively correlated with poor overall and PSA recurrence free survival. Taken together, our results show that depletion of miR-4534 in PCa induces a tumor suppressor phenotype partly through induction of PTEN. These results have important implications for identifying and defining the role of new PTEN regulators such as microRNAs in prostate tumorigenesis. Understanding aberrantly overexpressed miR-4534 and its downregulation of PTEN will provide mechanistic insight and therapeutic targets for PCa therapy.

  9. BMP-2 up-regulates PTEN expression and induces apoptosis of pulmonary artery smooth muscle cells under hypoxia.

    Directory of Open Access Journals (Sweden)

    Weifeng Pi

    Full Text Available AIM: To investigate the role of bone morphogenetic protein 2 (BMP-2 in regulation of phosphatase and tensin homologue deleted on chromosome ten (PTEN and apoptosis of pulmonary artery smooth muscle cells (PASMCs under hypoxia. METHODS: Normal human PASMCs were cultured in growth medium (GM and treated with BMP-2 from 5-80 ng/ml under hypoxia (5% CO(2+94% N(2+1% O(2 for 72 hours. Gene expression of PTEN, AKT-1 and AKT-2 were determined by quantitative RT-PCR (QRT-PCR. Protein expression levels of PTEN, AKT and phosph-AKT (pAKT were determined. Apoptosis of PASMCs were determined by measuring activities of caspases-3, -8 and -9. siRNA-smad-4, bpV(HOpic (PTEN inhibitor and GW9662 (PPARγ antagonist were used to determine the signalling pathways. RESULTS: Proliferation of PASMCs showed dose dependence of BMP-2, the lowest proliferation rate was achieved at 60 ng/ml concentration under hypoxia (82.2±2.8%. BMP-2 increased PTEN gene expression level, while AKT-1 and AKT-2 did not change. Consistently, the PTEN protein expression also showed dose dependence of BMP-2. AKT activity significantly reduced in BMP-2 treated PASMCs. Increased activities of caspase-3, -8 and -9 of PASMCs were found after cultured with BMP-2. PTEN expression remained unchanged when Smad-4 expression was inhibited by siRNA-Smad-4. bpV(HOpic and GW9662 (PPARγ inhibitor inhibited PTEN protein expression and recovered PASMCs proliferation rate. CONCLUSION: BMP-2 increased PTEN expression under hypoxia in a dose dependent pattern. BMP-2 reduced AKT activity and increased caspase activity of PASMCs under hypoxia. The increased PTEN expression may be mediated through PPARγ signalling pathway, instead of BMP/Smad signalling pathway.

  10. PTEN enhances G2/M arrest in etoposide-treated MCF‑7 cells through activation of the ATM pathway.

    Science.gov (United States)

    Zhang, Ruopeng; Zhu, Li; Zhang, Lirong; Xu, Anli; Li, Zhengwei; Xu, Yijuan; He, Pei; Wu, Maoqing; Wei, Fengxiang; Wang, Chenhong

    2016-05-01

    As an effective tumor suppressor, phosphatase and tensin homolog (PTEN) has attracted the increased attention of scientists. Recent studies have shown that PTEN plays unique roles in the DNA damage response (DDR) and can interact with the Chk1 pathway. However, little is known about how PTEN contributes to DDR through the ATM-Chk2 pathway. It is well-known that etoposide induces G2/M arrest in a variety of cell lines, including MCF-7 cells. The DNA damage-induced G2/M arrest results from the activation of protein kinase ataxia telangiectasia mutated (ATM), followed by the activation of Chk2 that subsequently inactivates CDC25C, resulting in G2/M arrest. In the present study, we assessed the contribution of PTEN to the etoposide-induced G2/M cell cycle arrest. PTEN was knocked down in MCF-7 cells by specific shRNA, and the effects of PTEN on the ATM-Chk2 pathway were investigated through various approaches. The results showed that knockdown of PTEN strongly antagonized ATM activation in response to etoposide treatment, and thereby reduced the phosphorylation level of ATM substrates, including H2AX, P53 and Chk2. Furthermore, depletion of PTEN reduced the etoposide-induced phosphorylation of CDC25C and strikingly compromised etoposide-induced G2/M arrest in the MCF-7 cells. Altogether, we demonstrated that PTEN plays a unique role in etoposide-induced G2/M arrest by facilitating the activation of the ATM pathway, and PTEN was required for the proper activation of checkpoints in response to DNA damage in MCF-7 cells.

  11. EGFR- and AKT-mediated reduction in PTEN expression contributes to tyrphostin resistance and is reversed by mTOR inhibition in endometrial cancer cells.

    Science.gov (United States)

    Li, Tian; Yang, Yuebo; Li, Xiaomao; Xu, Chengfang; Meng, Lirong

    2012-02-01

    Loss or mutation of the PTEN (phosphatase and tensin homologue deleted on chromosome 10) gene is associated with resistance to epidermal growth factor receptor (EGFR) inhibitors. However, the mechanism underlying remains elusive. In this study, we aimed to explore whether sensitivity to the EGFR tyrosine kinase inhibitor (TKI) is affected by PTEN status in endometrial cancer cells. PTEN siRNA and the PTEN gene were transfected into HEC-1A and Ishikawa endometrial cancer cells using lentiviral vectors. Cells were treated under various concentrations of RG14620 and rapamycin, which are EGFR and mammalian target of rapamycin (mTOR) inhibitors, respectively. The IC(50) of RG16420 was determined by using the MTT method. Cell apoptosis and the cell cycle were studied, and activation of EGFR, AKT, and p70S6 were detected by Western blot analysis. Loss of PTEN promoted cell proliferation and led to significant increases in the levels of EGFR, phospho-EGFR, AKT, phospho-AKT, and phospho-mTOR proteins. Ishikawa and HEC-1A(PTENkd) cells that displayed loss and inactivation of PTEN function were resistant to RG14620. HEC-1A and Ishikawa(PTEN) cells with intact PTEN were sensitive to RG14620. The combination of two inhibitors was more effective than both monotherapies, particularly in carcinoma cells with PTEN dysfunction. Decreased phospho-EGFR protein expression was observed in all cell lines that were sensitive to RG14620. Decreased phospho-AKT and phospho-p70S6 protein expression was observed in PTEN-intact cells that were sensitive to RG14620. PTEN loss results in resistance to EGFR TKI, which was reversed by PTEN reintroduction or mTOR inhibitor treatment. The combined treatment of EGFR TKI and the mTOR inhibitor provided a synergistic effect by promoting cell death in PTEN-deficient and PTEN-intact endometrial cancer cells, particularly in PTEN-deficient carcinoma cells with up-regulated EGFR activation.

  12. mRNA EXPRESSION OF PTEN AND VEGF GENES IN EPITHELIAL OVARIAN CANCER

    Institute of Scientific and Technical Information of China (English)

    陈颖; 赵雨杰; 郑华川; 杨雪飞; 汪桂兰; 辛彦

    2003-01-01

    Objective: To investigate the mRNA expression of PTEN and vascular endothelial growth factor (VEGF) genes in ovarian cancer. Methods:We examined mRNA expression of PTEN and VEGF165 in normal ovary (n=5), ovarian cyst (n=5), ovarian borderline tumor (n=9), epithelial ovarian cancer (n=60) and ovarian cancer cell line (CAOV-3) by RT-PCR. Their expressions were compared with clinicopathological features of ovarian cancer. The relationship between their expressions was concerned in all ovarian samples as well. Results:mRNA expression level of PTEN gene was significantly lower in ovarian borderline tumor or ovarian cancer than that in normal ovary or ovarian cyst(P<0.05). It was negatively correlated with clinicopathological staging(P<0.05),whereas positively with histological differentiation (P<0.05). mRNA expression level of PTEN gene was significantly lower in ovarian endometrioid cancer than ovarian serous or mucinous cancer(P<0.05). mRNA expression level of VEGF165 gene was significantly higher in ovarian cancer than that in normal ovary or ovarian cyst(P<0.05). It was positively correlated with clinicopathological staging(P<0.05), whereas negatively with histological differentiation (P<0.05). mRNA expression level of VEGF165 gene was significantly higher in ovarian serous cancer than in other ovarian epithelial cancers (P<0.05). mRNA expression of VEGF165 gene was inversely correlated with mRNA expression level of PTEN gene. Conclusion:Down-regulated expression of PTEN and up-regulated expression of VEGF were considered as two important events in tumorigenesis of ovarian cancer and could be used as molecular markers to indicate the pathobiological behaviors of ovarian cancer. Decreased PTEN expression and increased VEGF expression were closely associated with tumorigenesis and pathobiological behaviors of ovarian endometrioid and serous cancer respectively. Reduced expression of PTEN gene might be involved in carcinogenesis and progression of ovarian cancer by

  13. KdV方程带修正函数的格子Boltzmann模拟%Lattice Boltzmann model with amending function for KdV equation

    Institute of Scientific and Technical Information of China (English)

    何郁波; 董晓亮; 林晓艳

    2012-01-01

    A new lattice Boltzmann model with amending-function for KdV equation is presented. Monotonicity and stability of the scheme are analyzed. The conditions of monotonicity are obtained, under which the stability of the scheme is proved in the L1 norm. Applied the proposed scheme, the solutions of KdV equation are simulated, and numerical results agree with the analytical solutions quite well.%采用一种带修正函数的新格子Boltzmann模型模拟了KdV方程,分析了由此得出的迭代格式的单调性和稳定性,得到了格式的单调性条件.在单调性条件下,迭代格式是L1稳定的.数值模拟结果表明该格式是可行的.

  14. Division algebras and extended N = 2, 4, 8 super KdVs

    CERN Document Server

    Carrion, H L; Toppan, F

    2003-01-01

    The first example of an N = 8 supersymmetric extension of the KdV equation is here explicitly constructed. It involves 8 bosonic and 8 fermionic fields. It corresponds to the unique N = 8 solution based a generalized hamiltonian dynamics with (generalized) Poisson brackets given by the Non-associate N = 8 Superconformal Algebra. The complete list of inequivalent classes of parametric-dependent N = 3 and N = 4 superKdVs obtained from the 'Non-associative N= 8 SCA' is also furnished. Furthermore, a fundamental domain characterizing the class of inequivalent N = 4 superKdVs based on the 'minimal N = 4 SCA' is given.

  15. Quasi-Modular instanton partition function and elliptic solution of KdV equations

    CERN Document Server

    He, Wei

    2014-01-01

    Four dimensional N=2 supersymmetric gauge theories are related to some solvable quantum mechanics models. For SU(2) theory with an adjoint matter, or with 4 fundamental matters, if the mass of matter takes special value then the potential of quantum model is the elliptic solution of KdV equations. We show that the prepotential of the gauge theory can be obtained from the average densities of the conserved charges of classical KdV solution, the UV gauge coupling dependence is assembled into Eisenstein series. The Eisenstein series come from integration of elliptic functions in KdV Hamiltonians. The gauge theory with adjoint mass is taken as the example.

  16. Darboux transformation of generalized coupled KdV soliton equation and its odd-soliton solutions

    Institute of Scientific and Technical Information of China (English)

    LIU Ping

    2008-01-01

    Based on the resulting Lax pairs of the generalized coupled KdV soliton equation,a new Darboux transformation with multi-parameters for the generalized coupled KdV soliton equation is derived with the help of a gauge transformation of the spectral problem.By using Darboux transformation,the generalized odd-soliton solutions of the generalized coupled KdV soliton equation are given and presented in determinant form.As an application,the first two cases are given.

  17. A New Homotopy Analysis Method for Approximating the Analytic Solution of KdV Equation

    Directory of Open Access Journals (Sweden)

    Vahid Barati

    2014-01-01

    Full Text Available In this study a new technique of the Homotopy Analysis Method (nHAM is applied to obtain an approximate analytic solution of the well-known Korteweg-de Vries (KdV equation. This method removes the extra terms and decreases the time taken in the original HAM by converting the KdV equation to a system of first order differential equations. The resulted nHAM solution at third order approximation is then compared with that of the exact soliton solution of the KdV equation and found to be in excellent agreement.

  18. KdV Equation with Self-consistent Sources in Non-uniform Media

    Institute of Scientific and Technical Information of China (English)

    HAO Hong-Hai; WANG Guang-Sheng; ZHANG Da-Jun

    2009-01-01

    Two non-isospectral KdV equations with self-consistent sources are derived. Gauge transformation between the first non-isospectral KdV equation with self-consistent sources (corresponding to λt=-2aλ) and its isospectral counterpart is given, from which exact solutions for the first non-isospectral KdV equation with self-consistent sources is easily listed. Besides, the soliton solutions for the two equations are obtained by means of Hirota's method and Wronskian technique, respectively. Meanwhile, the dynamical properties for these solutions are investigated.

  19. Two Types of Coupling Integrable Couplings of the S-mKdV Hierarchy

    Institute of Scientific and Technical Information of China (English)

    WEI Yuan; ZHANG Yu-Feng

    2011-01-01

    Firstly 4 Lie algebras are constructed. Then applications of the loop algebra are presented to obtain two types of coupling integrable couplings of the S-mKdV hierarchy by using Tu scheme. The coupling integrable couplings of the S-mKdV hierarchy obtained in the paper reduce to the coupling integrable couplings of the mKdV equation and the coupling integrable couplings of the nonlinear schr(o)dinger equation respectively. The method given in the paper can be used to other hierarchies generally.

  20. 基于KD-Tree的KNN文本分类算法%KNN Algorithm for Text Classification Based on KD-Tree

    Institute of Scientific and Technical Information of China (English)

    刘忠; 刘洋; 建晓

    2012-01-01

    This paper apply KD-Tree to KNN text classification algorithm,firstly put a training text set into a KD-Tree,then search KD-Tree for the all parents nodes of the tested text node,the set including these parents text nodes is the most nearest text set,the type of the tested text is the same as the type of the most nearest text which has the most similarity with the test text,this algorithm decreases the number of the compared texts,and the time complexity is o(log2N).Experiments show that the improved KNN text classification algorithm is better than the traditional KNN text classification in classification efficiency.%本文将KD-Tree应用到KNN文本分类算法中,先对训练文本集建立一个KD-Tree,然后在KD-Tree中搜索测试文本的所有祖先节点文本,这些祖先节点文本集合就是待测文本的最邻近文本集合,与测试文本有最大相似度的祖先的文本类型就是待测试文本的类型,这种算法大大减少了参与比较的向量文本数目,时间复杂度仅为O(log2N)。实验表明,改进后的KNN文本分类算法具有比传统KNN文本分类法更高的分类效率。

  1. Hodograph solutions of the dispersionless coupled KdV hierarchies, critical points and the Euler-Poisson-Darboux equation

    Energy Technology Data Exchange (ETDEWEB)

    Konopelchenko, B [Dipartimento di Fisica, Universita di Lecce and Sezione INFN, 73100 Lecce (Italy); Alonso, L MartInez [Departamento de Fisica Teorica II, Universidad Complutense, E28040 Madrid (Spain); Medina, E [Departamento de Matematicas, Universidad de Cadiz, E11510 Puerto Real, Cadiz (Spain)

    2010-10-29

    It is shown that the hodograph solutions of the dispersionless coupled KdV (dcKdV) hierarchies describe critical and degenerate critical points of a scalar function which obeys the Euler-Poisson-Darboux equation. Singular sectors of each dcKdV hierarchy are found to be described by solutions of higher genus dcKdV hierarchies. Concrete solutions exhibiting shock-type singularities are presented.

  2. General projective Riccati equation method and exact solutions for generalized KdV-type and KdV-Burgers-type equations with nonlinear terms of any order

    Energy Technology Data Exchange (ETDEWEB)

    Chen Yong E-mail: chenyong@dlut.edu.cn; Li Biao E-mail: libiao@dlut.edu.cn

    2004-03-01

    Applying the improved generalized method, which is a direct and unified algebraic method for constructing multiple travelling wave solutions of nonlinear partial differential equations and implemented in a computer algebraic system, we consider the KdV-type equations and KdV-Burgers-type equations with nonlinear terms of any order. As a result, we can not only successfully recover the previously known travelling wave solutions found by existing various tanh methods and other sophisticated methods, but also obtain some new formal solutions. The solutions obtained include kink-shaped solitons, bell-shaped solitons, singular solitons and periodic solutions.

  3. PTEN loss is associated with worse outcome in HER2-amplified breast cancer patients but is not associated with trastuzumab resistance

    Science.gov (United States)

    Stern, Howard M.; Gardner, Humphrey; Burzykowski, Tomasz; Elatre, Wafaa; O’Brien, Carol; Lackner, Mark R.; Pestano, Gary A.; Santiago, Angela; Villalobos, Ivonne; Eiermann, Wolfgang; Pienkowski, Tadeusz; Martin, Miguel; Robert, Nicholas; Crown, John; Nuciforo, Paolo; Bee, Valerie; Mackey, John; Slamon, Dennis J.; Press, Michael F.

    2015-01-01

    Purpose To investigate the clinical relevance of PTEN in HER2-amplified and HER2-non-amplified disease. Experimental Design We assessed PTEN status in two large adjuvant breast cancer trials (BCIRG-006 and BCIRG-005) using a PTEN IHC assay that was previously validated in a panel of 33 breast cancer cell lines and prostate cancer tissues with known PTEN gene deletion. Results In the HER2-positive patient population, absence of tumor cell PTEN staining occurred at a rate of 5.4% and was independent of ER/PR status. In contrast, 15.9% of HER2-negative patients exhibited absence of PTEN staining with the highest frequency seen in triple negative breast cancer (TNBC) subgroup versus ER/PR-positive patients (35.1% vs. 10.9%). Complete absence of PTEN staining in tumor cells was associated with poor clinical outcome in HER2-positive disease. Those patients whose cancers demonstrated absent PTEN staining had a significant decrease in disease-free survival (DFS) and overall survival (OS) compared to patients with tumors exhibiting any PTEN staining patterns (low, moderate or high). Trastuzumab appeared to provide clinical benefit even for patients lacking PTEN staining. In the HER2-negative population there were no statistically significant differences in clinical outcome based on PTEN status. Conclusions This study is the largest to date examining PTEN status in breast cancer and the data suggest that the rate and significance of PTEN status differ between HER2-positive and HER2-negative disease. Furthermore, the data clearly suggest that HER2-positive patients with PTEN loss still benefit from trastuzumab. PMID:25649019

  4. Alterations in PTEN and PIK3CA in colorectal cancers in the EPIC Norfolk study: associations with clinicopathological and dietary factors

    Directory of Open Access Journals (Sweden)

    Mitrou Panagiota N

    2011-04-01

    Full Text Available Abstract Background The PTEN tumour suppressor gene and PIK3CA proto-oncogene encode proteins which contribute to regulation and propagation of signal transduction through the PI3K/AKT signalling pathway. This study investigates the prevalence of loss of PTEN expression and mutations in both PTEN and PIK3CA in colorectal cancers (CRC and their associations with tumour clinicopathological features, lifestyle factors and dietary consumptions. Methods 186 adenocarcinomas and 16 adenomas from the EPIC Norfolk study were tested for PTEN and PIK3CA mutations by DNA sequencing and PTEN expression changes by immunohistochemistry. Dietary and lifestyle data were collected prospectively using seven day food diaries and lifestyle questionnaires. Results Mutations in exons 7 and 8 of PTEN were observed in 2.2% of CRC and PTEN loss of expression was identified in 34.9% CRC. Negative PTEN expression was associated with lower blood low-density lipoprotein concentrations (p = 0.05. PIK3CA mutations were observed in 7% of cancers and were more frequent in CRCs in females (p = 0.04. Analysis of dietary intakes demonstrated no link between PTEN expression status and any specific dietary factor. PTEN expression negative, proximal CRC were of more advanced Dukes' stage (p = 0.02 and poor differentiation (p PIK3CA mutations and loss of PTEN expression demonstrated that these two events were independent (p = 0.55. Conclusion These data demonstrated the frequent occurrence (34.9% of PTEN loss of expression in colorectal cancers, for which gene mutations do not appear to be the main cause. Furthermore, dietary factors are not associated with loss of PTEN expression. PTEN expression negative CRC were not homogenous, as proximal cancers were associated with a more advanced Dukes' stage and poor differentiation, whereas distal cancers were associated with earlier Dukes' stage.

  5. Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence

    Science.gov (United States)

    Revandkar, Ajinkya; Perciato, Maria Luna; Toso, Alberto; Alajati, Abdullah; Chen, Jingjing; Gerber, Hermeto; Dimitrov, Mitko; Rinaldi, Andrea; Delaleu, Nicolas; Pasquini, Emiliano; D'Antuono, Rocco; Pinton, Sandra; Losa, Marco; Gnetti, Letizia; Arribas, Alberto; Fraering, Patrick; Bertoni, Francesco; Nepveu, Alain; Alimonti, Andrea

    2016-01-01

    Activation of NOTCH signalling is associated with advanced prostate cancer and treatment resistance in prostate cancer patients. However, the mechanism that drives NOTCH activation in prostate cancer remains still elusive. Moreover, preclinical evidence of the therapeutic efficacy of NOTCH inhibitors in prostate cancer is lacking. Here, we provide evidence that PTEN loss in prostate tumours upregulates the expression of ADAM17, thereby activating NOTCH signalling. Using prostate conditional inactivation of both Pten and Notch1 along with preclinical trials carried out in Pten-null prostate conditional mouse models, we demonstrate that Pten-deficient prostate tumours are addicted to the NOTCH signalling. Importantly, we find that pharmacological inhibition of γ-secretase promotes growth arrest in both Pten-null and Pten/Trp53-null prostate tumours by triggering cellular senescence. Altogether, our findings describe a novel pro-tumorigenic network that links PTEN loss to ADAM17 and NOTCH signalling, thus providing the rational for the use of γ-secretase inhibitors in advanced prostate cancer patients. PMID:27941799

  6. Mechanistic Rationale to Target PTEN-Deficient Tumor Cells with Inhibitors of the DNA Damage Response Kinase ATM.

    Science.gov (United States)

    McCabe, Nuala; Hanna, Conor; Walker, Steven M; Gonda, David; Li, Jie; Wikstrom, Katarina; Savage, Kienan I; Butterworth, Karl T; Chen, Clark; Harkin, D Paul; Prise, Kevin M; Kennedy, Richard D

    2015-06-01

    Ataxia telangiectasia mutated (ATM) is an important signaling molecule in the DNA damage response (DDR). ATM loss of function can produce a synthetic lethal phenotype in combination with tumor-associated mutations in FA/BRCA pathway components. In this study, we took an siRNA screening strategy to identify other tumor suppressors that, when inhibited, similarly sensitized cells to ATM inhibition. In this manner, we determined that PTEN and ATM were synthetically lethal when jointly inhibited. PTEN-deficient cells exhibited elevated levels of reactive oxygen species, increased endogenous DNA damage, and constitutive ATM activation. ATM inhibition caused catastrophic DNA damage, mitotic cell cycle arrest, and apoptosis specifically in PTEN-deficient cells in comparison with wild-type cells. Antioxidants abrogated the increase in DNA damage and ATM activation in PTEN-deficient cells, suggesting a requirement for oxidative DNA damage in the mechanism of cell death. Lastly, the ATM inhibitor KU-60019 was specifically toxic to PTEN mutant cancer cells in tumor xenografts and reversible by reintroduction of wild-type PTEN. Together, our results offer a mechanistic rationale for clinical evaluation of ATM inhibitors in PTEN-deficient tumors.

  7. Overexpression of LRIG1 regulates PTEN via MAPK/MEK signaling pathway in esophageal squamous cell carcinoma

    Science.gov (United States)

    Jiang, Xiaofang; Li, Huiwu

    2016-01-01

    The present study aimed to evaluate the role of leucine-rich repeats and immunoglobulin-like domain protein 1 (LRIG1) in the regulation of phosphatase and tensin homolog (PTEN) expression in esophageal carcinogenesis. LRIG1 was overexpressed in esophageal squamous cell carcinoma (ESCC) cell lines, and the effect of LRIG1 overexpression on the mRNA and protein expression levels of PTEN was evaluated by reverse transcription-quantitative polymerase chain reaction and western blotting. Furthermore, the effects of LRIG1 overexpression on the cell cycle distribution and apoptosis of ESCC cells were examined by flow cytometry. Various cell signaling pathway inhibitors were used to assess the effects of LRIG1 on downstream signaling in ESCC cell lines. In addition, the association between LRIG1 and PTEN expression was examined in 48 samples from patients with ESCC. LRIG1 overexpression was demonstrated to downregulate PTEN expression in ESCC cell lines, and promote their proliferation and inhibit apoptosis. In addition, LRIG1-mediated suppression of PTEN expression was inhibited by the U0126 inhibitor, which suggests that LRIG1 may inhibit the activation of PTEN signaling molecules by triggering the mitogen-activated protein kinase (MAPK)/MAPK kinase 1 (MEK) signaling pathway. In conclusion, the present study demonstrated that overexpression of LRIG1 significantly and adversely affected the survival of ESCC cells, and that the MAPK/MEK signaling pathway may be responsible for the repression of PTEN expression and function. PMID:27698691

  8. PTEN sequence analysis in endometrial hyperplasia and endometrial carcinoma in Slovak women.

    Science.gov (United States)

    Gbelcová, H; Bakeš, P; Priščáková, P; Šišovský, V; Hojsíková, I; Straka, Ľ; Konečný, M; Markus, J; D'Acunto, C W; Ruml, T; Böhmer, D; Danihel, Ľ; Repiská, V

    2015-01-01

    Phosphatase and tensin homolog (PTEN) is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function has been implicated in the pathogenesis of a number of different tumors, particularly endometrial carcinoma (ECa). ECa is the most common neoplasia of the female genital tract. Our study evaluates an association between the morphological appearance of endometrial hyperplasia and endometrial carcinoma and the degree of PTEN alterations. A total of 45 endometrial biopsies from Slovak women were included in present study. Formalin-fixed and paraffin-embedded tissue samples with simple hyperplasia (3), complex hyperplasia (5), atypical complex hyperplasia (7), endometrioid carcinomas G1 (20) and G3 (5), and serous carcinoma (5) were evaluated for the presence of mutations in coding regions of PTEN gene, the most frequently mutated tumor suppressor gene in endometrial carcinoma. 75% of the detected mutations were clustered in exons 5 and 8. Out of the 39 mutations detected in 24 cases, 20 were frameshifts and 19 were nonsense, missense, or silent mutations. Some specimens harboured more than one mutation. The results of current study on Slovak women were compared to a previous study performed on Polish population. The two sets of results were similar.

  9. Variable phenotypes associated with 10q23 microdeletions involving the PTEN and BMPR1A genes.

    NARCIS (Netherlands)

    Menko, F.H.; Kneepkens, C.M.; Leeuw, N. de; Peeters, E.A.; Maldergem, L Van; Kamsteeg, E.J.; Davidson, R.; Rozendaal, L.; Lasham, C.A.; Peeters-Scholte, C.M.; Jansweijer, M.C.E.; Hilhorst-Hofstee, Y.; Gille, J.J.P.; Heins, Y.M.; Nieuwint, A.W.; Sistermans, E.A.

    2008-01-01

    Infantile juvenile polyposis is a rare disease with severe gastrointestinal symptoms and a grave clinical course. Recently, 10q23 microdeletions involving the PTEN and BMPR1A genes were found in four patients with infantile juvenile polyposis. It was hypothesized that a combined and synergistic effe

  10. PTEN Gene and Prostate Cancer%PTEN基因与前列腺癌

    Institute of Scientific and Technical Information of China (English)

    孙健玮(综述); 王剑松(审校)

    2013-01-01

    The deletion of tumor suppressor gene PTEN's expression was familiar in many tumors, including prostate cancer. The guide would be given in the diagnosis, therapy and prognosis of prostate cancer by studying about PTEN's tumor suppression mechanism and relation with expression deletion. This review makes an overview focusing on the recent progress of PTEN's structure, function, expression deletion, and the correlation between PTEN and prostate cancer.%抑癌基因PTEN的表达缺失多见于包括前列腺癌在内的多种散发性肿瘤,对其抑癌机制以及表达缺失所导致的肿瘤发生发展机理的研究,将为前列腺癌的诊断、治疗以及预后判断提供指导。就PTEN基因的结构、作用机制、表达缺失及其与前列腺癌发病相关的研究进展作一综述。

  11. PTEN Mediates the Antioxidant Effect of Resveratrol at Nutritionally Relevant Concentrations

    Directory of Open Access Journals (Sweden)

    Marta Inglés

    2014-01-01

    Full Text Available Introduction. Antioxidant properties of resveratrol have been intensively studied for the last years, both in vivo and in vitro. Its bioavailability after an oral dose is very low and therefore it is very important to make sure that plasma concentrations of free resveratrol are sufficient enough to be active as antioxidant. Aims. In the present study, using nutritionally relevant concentrations of resveratrol, we aim to confirm its antioxidant capacity on reducing peroxide levels and look for the molecular pathway involved in this antioxidant effect. Methods. We used mammary gland tumor cells (MCF-7, which were pretreated with different concentrations of resveratrol for 48 h, and/or a PTEN inhibitor (bpV: bipy. Hydrogen peroxide levels were determined by fluorimetry, PTEN levels and Akt phosphorylation by Western Blotting, and mRNA expression of antioxidant genes by real-time reverse transcriptase-polymerase chain reaction (RT-PCR. Results. Resveratrol treatment for 48 h lowered peroxide levels in MCF-7, even at low nutritional concentrations (1 nM. This effect was mediated by the activation of PTEN/Akt pathway, which resulted in an upregulation of catalase and MnSOD mRNA levels. Conclusion. Resveratrol acts as an antioxidant at nutritionally relevant concentrations by inducing the expression of antioxidant enzymes, through a mechanism involving PTEN/Akt signaling pathway.

  12. Propylthiouracil, independent of its antithyroid effect, promotes vascular smooth muscle cells differentiation via PTEN induction.

    Science.gov (United States)

    Chen, Wei-Jan; Pang, Jong-Hwei S; Lin, Kwang-Huei; Lee, Dany-Young; Hsu, Lung-An; Kuo, Chi-Tai

    2010-01-01

    Propylthiouracil (PTU), independent of its antithyroid effect, is recently found to have an antiatherosclerotic effect. The aim of this study is to determine the impact of PTU on phenotypic modulation of vascular smooth muscle cells (VSMCs), as phenotypic modulation may contribute to the growth of atherosclerotic lesions and neointimal formation after arterial injury. Propylthiouracil reduced neointimal formation in balloon-injured rat carotid arteries. In vitro, PTU may convert VSMCs from a serum-induced dedifferentiation state to a differentiated state, as indicated by a spindle-shaped morphology and an increase in the expression of SMC differentiation marker contractile proteins, including calponin and smooth muscle (SM)-myosin heavy chain (SM-MHC). Transient transfection studies in VSMCs demonstrated that PTU induced the activity of SMC marker genes (calponin and SM-MHC) promoters, indicating that PTU up-regulates these genes expression predominantly at the transcriptional level. Furthermore, PTU enhanced the expression of PTEN and inhibition of PTEN by siRNA knockdown blocked PTU-induced activation of contractile proteins expression and promoter activity. In the rat carotid injury model, PTU reversed the down-regulation of contractile proteins and up-regulated PTEN in the neointima induced by balloon injury. Propylthiouracil promotes VSMC differentiation, at lest in part, via induction of the PTEN-mediated pathway. These findings suggest a possible mechanism by which PTU may contribute to its beneficial effects on atherogenesis and neointimal formation after arterial injury.

  13. Deletion of PTEN Produces Deficits in Conditioned Fear and Increases Fragile X Mental Retardation Protein

    Science.gov (United States)

    Lugo, Joaquin N.; Smith, Gregory D.; Morrison, Jessica B.; White, Jessika

    2013-01-01

    The phosphatase and tensin homolog detected on chromosome 10 (PTEN) gene product modulates activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. The PI3K pathway has been found to be involved in the regulation of the fragile X mental retardation protein, which is important for long-term depression and in the formation of new…

  14. Methodological aspects of the molecular and histological study of prostate cancer: focus on PTEN.

    Science.gov (United States)

    Ugalde-Olano, Aitziber; Egia, Ainara; Fernández-Ruiz, Sonia; Loizaga-Iriarte, Ana; Zuñiga-García, Patricia; Garcia, Stephane; Royo, Félix; Lacasa-Viscasillas, Isabel; Castro, Erika; Cortazar, Ana R; Zabala-Letona, Amaia; Martín-Martín, Natalia; Arruabarrena-Aristorena, Amaia; Torrano-Moya, Verónica; Valcárcel-Jiménez, Lorea; Sánchez-Mosquera, Pilar; Caro-Maldonado, Alfredo; González-Tampan, Jorge; Cachi-Fuentes, Guido; Bilbao, Elena; Montero, Rocío; Fernández, Sara; Arrieta, Edurne; Zorroza, Kerman; Castillo-Martín, Mireia; Serra, Violeta; Salazar, Eider; Macías-Cámara, Nuria; Tabernero, Jose; Baselga, Jose; Cordón-Cardo, Carlos; Aransay, Ana M; Villar, Amaia Del; Iovanna, Juan L; Falcón-Pérez, Juan M; Unda, Miguel; Bilbao, Roberto; Carracedo, Arkaitz

    2015-05-01

    Prostate cancer is among the most frequent cancers in men, and despite its high rate of cure, the high number of cases results in an elevated mortality worldwide. Importantly, prostate cancer incidence is dramatically increasing in western societies in the past decades, suggesting that this type of tumor is exquisitely sensitive to lifestyle changes. Prostate cancer frequently exhibits alterations in the PTEN gene (inactivating mutations or gene deletions) or at the protein level (reduced protein expression or altered sub-cellular compartmentalization). The relevance of PTEN in this type of cancer is further supported by the fact that the sole deletion of PTEN in the murine prostate epithelium recapitulates many of the features of the human disease. In order to study the molecular alterations in prostate cancer, we need to overcome the methodological challenges that this tissue imposes. In this review we present protocols and methods, using PTEN as proof of concept, to study different molecular characteristics of prostate cancer. Copyright © 2015. Published by Elsevier Inc.

  15. PTEN Sequence Analysis in Endometrial Hyperplasia and Endometrial Carcinoma in Slovak Women

    Directory of Open Access Journals (Sweden)

    H. Gbelcová

    2015-01-01

    Full Text Available Phosphatase and tensin homolog (PTEN is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function has been implicated in the pathogenesis of a number of different tumors, particularly endometrial carcinoma (ECa. ECa is the most common neoplasia of the female genital tract. Our study evaluates an association between the morphological appearance of endometrial hyperplasia and endometrial carcinoma and the degree of PTEN alterations. A total of 45 endometrial biopsies from Slovak women were included in present study. Formalin-fixed and paraffin-embedded tissue samples with simple hyperplasia (3, complex hyperplasia (5, atypical complex hyperplasia (7, endometrioid carcinomas G1 (20 and G3 (5, and serous carcinoma (5 were evaluated for the presence of mutations in coding regions of PTEN gene, the most frequently mutated tumor suppressor gene in endometrial carcinoma. 75% of the detected mutations were clustered in exons 5 and 8. Out of the 39 mutations detected in 24 cases, 20 were frameshifts and 19 were nonsense, missense, or silent mutations. Some specimens harboured more than one mutation. The results of current study on Slovak women were compared to a previous study performed on Polish population. The two sets of results were similar.

  16. High-calorie diet exacerbates prostate neoplasia in mice with haploinsufficiency of Pten tumor suppressor gene

    Directory of Open Access Journals (Sweden)

    Jehnan Liu

    2015-03-01

    Conclusion: High-calorie diet promotes prostate cancer progression in the genetically susceptible Pten haploinsufficient mouse while preserving insulin sensitivity. This appears to be partly due to increased inflammatory response to high-caloric intake in addition to increased ability of insulin to promote lipogenesis.

  17. Welcoming Treat: Astrocyte-Derived Exosomes Induce PTEN Suppression to Foster Brain Metastasis.

    Science.gov (United States)

    Alečković, Maša; Kang, Yibin

    2015-11-09

    Metastasis to distant organs depends on pathological crosstalk between tumor cells and various tissue-specific stromal components. Zhang and colleagues recently demonstrated that astrocyte-derived exosomal miR-19a reversibly downregulated PTEN expression in cancer cells, thereby increasing their CCL2 secretion and recruitment of myeloid cell to promote brain metastasis.

  18. PTEN and p16 genes as epigenetic biomarkers in oral squamous cell carcinoma (OSCC): a study on south Indian population.

    Science.gov (United States)

    Sushma, P S; Jamil, Kaiser; Kumar, P Uday; Satyanarayana, U; Ramakrishna, M; Triveni, B

    2016-06-01

    Phosphatase and tensin homolog (PTEN) and p16INK4a (p16) genes are tumor suppressor genes, associated with epigenetic alterations. PTEN and p16 promoter hypermethylation is a major epigenetic silencing mechanism leading to cancer. The cooperation between PTEN and p16 in pathogenesis of cancers suggest that their combination might be considered as potential molecular marker for specific subgroups of patients. Hence, the present study aimed to investigate whether PTEN and p16 promoter methylations were involved in oral squamous cell carcinoma (OSCC) in south Indian subjects. DNA methylation quantitative analyses of the two candidate tumor suppressor genes PTEN and p16 were performed by methylation-specific polymerase chain reaction (MSP). Fifty OSCC biopsy samples and their corresponding non-malignant portions as controls were studied comparatively. The methylation status was correlated with the clinical manifestations. Twelve out of 50 patients (24 %) were found to be methylated for PTEN gene, whereas methylation of the p16 gene occurred in 19 out of 50 cases (38 %). A statistically significant result was obtained (P = p16 genes. PTEN and p16 promoter methylation may be the main mechanism leading to the low expression of PTEN and p16 genes indicating the progress of tumor development. Our data suggest that a low PTEN and p16 expression due to methylation may contribute to the cancer progression and could be useful for prognosis of OSCC. Therefore, analysis of promoter methylation in such genes may provide a biomarker valuable for early detection of oral cancer.

  19. Correlation between Protein Expression of PTEN in Human Pancreatic Cancer and the Proliferation, Infiltration, Metastasis and Prognosis

    Institute of Scientific and Technical Information of China (English)

    TAO Jing; XIONG Jiongxin; LI Tao; YANG Zhiyong; LI Xiaohui; LI Kai; WU Heshui; WANG Chunyou

    2006-01-01

    In order to investigate the correlation between protein expression of PTEN and the proliferation, infiltration, metastasis and prognosis in pancreatic cancer, immunohistochemical SP method was used to examine the protein expression of PTEN, PCNA, MVD, MMP-2, MMP-9 and TUNEL method to detect the levels of apoptosis of pancreatic cells in 41 pancreatic head cancers from regional pancreatectomy (RP) and 10 normal pancreatic tissues. The results showed that among 41 cases of pancreatic cancers, the positive staining of PTNE (39.02 %) was significantly weaker than that in normal pancreatic tissues (P<0.05). The levels of PCNA labeling index (LI), apoptotic index(AI), microvessel density (MVD), MMP-2 LI and MMP-9 LI were decreased gradually with the increase of the expression intensity of PTEN, and there was a significant difference in the above parameters among the patients having different expression levels of PTEN (P<0.01 or P<0.05). There was a negative correlation between the expression of PTEN and PCNA LI, MVD, MMP-2 LI,MMP-9 LI, and a positive correlation between AI and the expression of PTEN. The expression intensity of PTEN was correlated with the postoperative survival of the patients with pancreatic cancer(x2=22.3400, P<0.0001, RR=2.030). It was suggested that the expression levels of PTEN protein were closely related with proliferation, infiltration and metastasis in human pancreatic cancer, and the expression of PTEN protein was one of the prognostic factors for pancreatic cancer following RP.

  20. Adomian Decomposition Method and Exact Solutions of the Perturbed KdV Equation

    Institute of Scientific and Technical Information of China (English)

    WU Bin; LOU Sen-Yue

    2002-01-01

    The Adomian decomposition method is used to solve the Cauchy problem of the perturbed KdV equation.Three types of exact solitary wave solutions are reobtained via the A domian's approach by selecting the initial conditionsappropriately.

  1. Division algebras and extended N = 2, 4, 8 superKdVs

    Energy Technology Data Exchange (ETDEWEB)

    Carrion, H L; Rojas, M; Toppan, F [CBPF - CCP, Rua Dr Xavier Sigaud 150, cep 22290-180 Rio de Janeiro (RJ) (Brazil)

    2003-04-04

    A no-go result for integrable minimal N = 8 supersymmetric extensions of KdV is found. However, allowing for non-associative realizations of the extended supersymmetries, the first example of an N = 8 supersymmetric KdV equation is explicitly constructed. It involves eight bosonic and eight fermionic fields and corresponds to the unique N = 8 solution based on a generalized Hamiltonian dynamics with (generalized) Poisson brackets given by the non-associative N = 8 superconformal algebra. The complete list of inequivalent classes of parametric-dependent N = 3 and N = 4 superKdVs obtained from the 'non-associative N = 8 SCA' is also furnished. Furthermore, a fundamental domain characterizing the class of inequivalent N = 4 superKdVs based on the 'minimal N = 4 SCA' is given.

  2. Adomian Decomposition Method and Exact Solutions of the Perturbed KdV Equation

    Institute of Scientific and Technical Information of China (English)

    WuBin; LOUSen-Yue

    2002-01-01

    The Adomian decomposition method is used to solve the Cauchy problem of the perturbed KdV equation.Three types of exact solitary wave solutions are reobtained via the Adomian's approach by selcting the initial conditions appropriately.

  3. The novel multi-solitary wave solution to the fifth-order KdV equation

    Institute of Scientific and Technical Information of China (English)

    Zhang Yi; Chen Deng-Yuan

    2004-01-01

    By using Hirota's method, the novel multi-solitary wave solutions to the fifth-order KdV equation are obtained.Furthermore, various new solitary wave solutions are also derived by a reconstructed bilinear Backlund transformation.

  4. PARAMETER REGION FOR EXISTENCE OF SOLITONS IN GENERALIZED KdV EQUATION

    Institute of Scientific and Technical Information of China (English)

    ShengPingxing

    2003-01-01

    This paper considers the generalized KdV equation with or without natural boundary conditions and provides a parameter region for solitons and solitary waves,and also modifies a result of Zabusky's.The solitary bifurcation has been discussed.

  5. Stability of solitonic solutions of Super KdV equations under Susy breaking conditions

    CERN Document Server

    Restuccia, A

    2012-01-01

    A supersymmetric breaking procedure for N=1 Super KdV, preserving the positivity of the hamiltonian as well as the existence of solitonic solutions, is implemented. The resulting integrable system is shown to have nice stability properties.

  6. (2+1-Dimensional mKdV Hierarchy and Chirp Effect of Rossby Solitary Waves

    Directory of Open Access Journals (Sweden)

    Chunlei Wang

    2015-01-01

    Full Text Available By constructing a kind of generalized Lie algebra, based on generalized Tu scheme, a new (2+1-dimensional mKdV hierarchy is derived which popularizes the results of (1+1-dimensional integrable system. Furthermore, the (2+1-dimensional mKdV equation can be applied to describe the propagation of the Rossby solitary waves in the plane of ocean and atmosphere, which is different from the (1+1-dimensional mKdV equation. By virtue of Riccati equation, some solutions of (2+1-dimensional mKdV equation are obtained. With the help of solitary wave solutions, similar to the fiber soliton communication, the chirp effect of Rossby solitary waves is discussed and some conclusions are given.

  7. Recommended Partition Coefficient (Kd) Values for Nuclide Partitioning in the Presence of Cellulose Degradation Products

    Energy Technology Data Exchange (ETDEWEB)

    Serkiz, S.M.

    2001-02-23

    This report documents the data analysis of the results of the described laboratory studies in order to recommend Kd values for use in Performance Assessment modeling of nuclide transport in the presence of CDP.

  8. PTEN gene mutations correlate to poor prognosis in glioma patients: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Han F

    2016-06-01

    Full Text Available Feng Han,1,* Rong Hu,2,* Hua Yang,1 Jian Liu,1 Jianmei Sui,1 Xin Xiang,1 Fan Wang,1 Liangzhao Chu,1 Shibin Song1 1Department of Neurosurgery, Affiliated Hospital of Guizhou Medical University, 2Department of Histology and Embryology, College of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China *These authors contributed equally to this work Background: We conducted this meta-analysis based on eligible trials to investigate the relationship between phosphatase and tensin homolog (PTEN genetic mutation and glioma patients’ survival. Methods: PubMed, Web of Science, and EMBASE were searched for eligible studies regarding the relationship between PTEN genetic mutation and glioma patients’ survival. The primary outcome was the overall survival of glioma patient with or without PTEN genetic mutation, and second outcome was prognostic factors for the survival of glioma patient. A fixed-effects or random-effects model was used to pool the estimates according to the heterogeneity among the included studies. Results: Nine cohort studies, involving 1,173 patients, were included in this meta-analysis. Pooled results suggested that glioma patients with PTEN genetic mutation had a significant shorter overall survival than those without PTEN genetic mutation (hazard ratio [HR] =2.23, 95% confidence interval [CI]: 1.35, 3.67; P=0.002. Furthermore, subgroup analysis indicated that this association was only observed in American patients (HR =2.19, 95% CI: 1.23, 3.89; P=0.008, but not in Chinese patients (HR =1.44, 95% CI: 0.29, 7.26; P=0.657. Histopathological grade (HR =1.42, 95% CI: 0.07, 28.41; P=0.818, age (HR =0.94, 95% CI: 0.43, 2.04; P=0.877, and sex (HR =1.28, 95% CI: 0.55, 2.98; P=0.564 were not significant prognostic factors for the survival of patients with glioma. Conclusion: Current evidence indicates that PTEN genetic mutation is associated with poor prognosis in glioma patients. However, this

  9. Nonvanishing boundary condition for the mKdV hierarchy and the Gardner equation

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, J F; Franca, Guilherme S; Zimerman, A H, E-mail: jfg@ift.unesp.br, E-mail: guisf@ift.unesp.br, E-mail: zimerman@ift.unesp.br [Instituto de Fisica Teorica - IFT/UNESP, Rua Dr. Bento Teobaldo Ferraz, 271, Bloco II, 01140-070, Sao Paulo, SP (Brazil)

    2012-01-13

    A Kac-Moody algebra construction for the integrable hierarchy containing the Gardner equation is proposed. Solutions are systematically constructed by employing the dressing method and deformed vertex operators, which take into account the nonvanishing boundary value problem for the modified Korteweg-de Vries (mKdV) hierarchy. Explicit examples are given and besides the usual KdV-like solitons, our solutions contemplate the large amplitude table-top solitons, kinks, dark solitons, breathers and wobbles. (paper)

  10. Exact Traveling Wave Solutions for Wick-Type Stochastic Schamel KdV Equation

    Directory of Open Access Journals (Sweden)

    Hossam A. Ghany

    2014-01-01

    Full Text Available F-expansion method is proposed to seek exact solutions of nonlinear partial differential equations. By means of Hermite transform, inverse Hermite transform, and white noise analysis, the variable coefficients and Wick-type stochastic Schamel KdV equations are completely described. Abundant exact traveling wave solutions for variable coefficients Schamel KdV equations are given. These solutions include exact stochastic Jacobi elliptic functions, trigonometric functions, and hyperbolic functions solutions.

  11. Solitary and compacton solutions of fractional KdV-like equations

    Directory of Open Access Journals (Sweden)

    Tang Bo

    2016-01-01

    Full Text Available In this paper, based on Jumarie’s modified Riemann-Liouville derivative, we apply the fractional variational iteration method using He’s polynomials to obtain solitary and compacton solutions of fractional KdV-like equations. The results show that the proposed method provides a very effective and reliable tool for solving fractional KdV-like equations, and the method can also be extended to many other fractional partial differential equations.

  12. Well and ill-posed problems for the KdV and Kawahara equations

    Directory of Open Access Journals (Sweden)

    Nikolai A. Larkin

    2008-11-01

    Full Text Available Well and ill-posedness of initial-boundary value problems for the KdV and Kawahara equations posed on a finite interval are discussed. Non-existence of solutions to ill-posed problem for the KdV equation is proved as well as solvability, uniqueness, exponential decay and asymptotics of regular solutions to the Kawahara equation subject to reasonable boundary conditions.

  13. Darboux Transformation for a Four-Component KdV Equation

    Science.gov (United States)

    Li, Nian-Hua; Wu, Li-Hua

    2016-10-01

    With the aid of a gauge transformation, we propose a Darboux transformation for a four-component KdV equation. As an application, we obtain some explicit solutions for the four-component KdV equation. Supported by the National Natural Science Foundation of China under Grant Nos. 11401572, 11401230, and 11505064 and Promotion Program for Young and Middle-aged Teacher in Science and Technology Research of Huaqiao University under Grant No. ZQN-PY301

  14. Existence Analysis of Traveling Wave Solutions for a Generalization of KdV Equation

    Directory of Open Access Journals (Sweden)

    Yao Long

    2013-01-01

    Full Text Available By using the bifurcation theory of dynamic system, a generalization of KdV equation was studied. According to the analysis of the phase portraits, the existence of solitary wave, cusp wave, periodic wave, periodic cusp wave, and compactons were discussed. In some parametric conditions, exact traveling wave solutions of this generalization of the KdV equation, which are different from those exact solutions in existing references, were given.

  15. Global Well-Posedness for a Coupled Modified KdV System

    CERN Document Server

    Panthee, Adan J Corcho And Mahendra

    2011-01-01

    We prove the sharp global well-posedness results for the initial value problems (IVPs) associated to the modified Korteweg-de Vries (mKdV) equation and a system modeled by the coupled modified Korteweg-de Vries equations (mKdV-system). To obtain our results we use the second generation of the modified energy and almost conserved quantities, more precisely, the refined I-method introduced by Colliander, Keel, Staffilani, Takaoka and Tao.

  16. Significance Of 30 KD Protein As A Diagnostic Marker In CSF Of tuberculour Meningits

    Directory of Open Access Journals (Sweden)

    Kashyap R.S

    2001-01-01

    Full Text Available Tuberculous meningitis (TBM is a sub acute or chronic inflammation of the cerebral meninges caused by tubercule bacilli, the diagnosis for which is still very intricate. To establish a rapid diagnosis, we used Sodium dodecyl suplhate polyacrylamide gel electrophoresis (SDS-PAGE for the detection of marker protein in CSF specific to TBM patients. CSF was collected by standard lumbar puncture technique. Polyclonal antibody was raised against sonicated M.tuberculosis of H37RV in rabbit. 145 CSF samples were collected for this study over a period of two and half years which included 44 suspected and one proven case of TBM. In this communication we have investigated for a possible presence of a marker protein(s in cerebrospinal fluid (CSF of TBM patients. Two bands, a 30kd and a 14kd were detected. The 30kd band was observed in 92% cases of TBM patients. The 14kd band was not much of diagnostic importance since it was found in only about 45%. None of the control group patients had these protein bands. The 30 kd protein band either disappeared or became faint on anti-TB medication. To evaluate whether the eluted 30 kd protein was a mycobacterium tuberculosis product, gel retardation assay was also performed. The 30kd protein did not react with the polyclonal antisera. The CSF biochemical picture correlated well with the presence of this protein band. This study suggests that 30kd protein band observed in CSF is not a Mycobacterium product and is not only an important diagnostic marker for early diagnosis of TBM but may also be useful for monitoring the post treatment phase.

  17. A Lattice Boltzmann Model and Simulation of KdV-Burgers Equation

    Institute of Scientific and Technical Information of China (English)

    ZHANGChao-Ying; TANHui-Li; LIUMu-Ren; KONGLing-Jiang

    2004-01-01

    A lattice Boltzmann model of KdV-Burgers equation is derived by using the single-relaxation form of the lattice Boltzmann equation. With the present model, we simulate the traveling-wave solutions, the solitary-wave solutions, and the sock-wave solutions of KdV-Burgers equation, and calculate the decay factor and the wavelength of the sock-wave solution, which has exponential decay. The numerical results agree with the analytical solutions quite well.

  18. A New Lattice Boltzmann Model for KdV-Burgers Equation

    Institute of Scientific and Technical Information of China (English)

    MA Chang-Feng

    2005-01-01

    @@ A new lattice Boltzmann model with amending-function for KdV-Burgers equation, ut +uux - αuxx +βuxxx = 0,is presented by using the single-relaxation form of the lattice Boltzmann equation. Applying the proposed model,we simulate the solutions ofa kind of KdV-Burgers equations, and the numerical results agree with the analytical solutions quite well.

  19. On the solution of the coupled Schroedinger-KdV equation by the decomposition method

    Energy Technology Data Exchange (ETDEWEB)

    Kaya, Dogan; El-Sayed, Salah M

    2003-06-23

    In this Letter, we consider a coupled Schroedinger-Korteweg-de Vries equation (or Sch-KdV) equation with appropriate initial values using the Adomian's decomposition method (or ADM). In this method, the solution is calculated in the form of a convergent power series with easily computable components. The method does not need linearization, weak nonlinearity assumptions or perturbation theory. The convergence of the method as applied to Sch-KdV is illustrated numerically.

  20. Traveling wave solution of fractional KdV-Burger-Kuramoto equation describing nonlinear physical phenomena

    Science.gov (United States)

    Gupta, A. K.; Ray, S. Saha

    2014-09-01

    In this paper, KdV-Burger-Kuramoto equation involving instability, dissipation, and dispersion parameters is solved numerically. The numerical solution for the fractional order KdV-Burger-Kuramoto (KBK) equation has been presented using two-dimensional Legendre wavelet method. The approximate solutions of nonlinear fractional KBK equation thus obtained by Legendre wavelet method are compared with the exact solutions. The present scheme is very simple, effective and convenient for obtaining numerical solution of the KBK equation.

  1. Traveling wave solution of fractional KdV-Burger-Kuramoto equation describing nonlinear physical phenomena

    Directory of Open Access Journals (Sweden)

    A. K. Gupta

    2014-09-01

    Full Text Available In this paper, KdV-Burger-Kuramoto equation involving instability, dissipation, and dispersion parameters is solved numerically. The numerical solution for the fractional order KdV-Burger-Kuramoto (KBK equation has been presented using two-dimensional Legendre wavelet method. The approximate solutions of nonlinear fractional KBK equation thus obtained by Legendre wavelet method are compared with the exact solutions. The present scheme is very simple, effective and convenient for obtaining numerical solution of the KBK equation.

  2. New exact solutions to the generalized KdV equation with generalized evolution

    Indian Academy of Sciences (India)

    Yongan Xie; Shengqiang Tang; Dahe Feng

    2012-04-01

    In this paper, by using a transformation and an application of Fan subequation, we study a class of generalized Korteweg–de Vries (KdV) equation with generalized evolution. As a result, more types of exact solutions to the generalized KdV equation with generalized evolution are obtained, which include more general single-hump solitons, multihump solitons, kink solutions and Jacobian elliptic function solutions with double periods.

  3. Compressive and rarefactive DIA solitons beyond the KdV limit

    Energy Technology Data Exchange (ETDEWEB)

    Mamun, A. A. [Abdus Salam International Centre for Theoretical Physics (Italy); Deeba, F., E-mail: farah.ju35@gmail.com [Jahangirnagar University, Department of Physics (Bangladesh)

    2012-04-15

    The modified Gardner equation (MGE), showing the existence of compressive and rarefactive dust-ion-acoustic (DIA) solitons in a nonplanar dusty plasma (containing inertial ions, Boltzmann electrons, and negatively charged stationary dust) beyond the KdV Korteweg-de Vries (KdV) limit, is derived and numerically solved. The basic features of the compressive and rarefactive cylindrical and spherical DIA solitons, which are found to exist beyond the KdV limit, i.e., exist for {mu} {approx} 2/3 (where {mu} = Z{sub n}n{sub d0}/n{sub i0}, z{sub d} is the number of electrons residing onto the dust grain surface, n{sub d0}(n{sub i0}) is the dust (ion) number density at equilibrium, and {mu} {approx} 2/3 means that {mu} is not equal to 2/3, but it is around 2/3) are identified. These solitons (which can be referred to as DIA Gardner solitons (DIA-GSs)) are completely different from the KdV solitons because {mu} = 2/3 corresponds to the vanishing of the nonlinear coefficient of the KdV equation, and {mu} {approx} 2/3 corresponds to extremely large amplitude KdV solitons for which the validity of the reductive perturbation method breaks down. It is also shown that the properties of the nonplanar (cylindrical and spherical) DIA-GSs are significantly different from those of the one dimensional planar ones.

  4. KdV and kink antikink solitons in car-following models

    Science.gov (United States)

    Ge, H. X.; Cheng, R. J.; Dai, S. Q.

    2005-11-01

    The jams in the congested traffic are related with various density waves, which might be governed by the nonlinear wave equations, such as the Korteweg-de-Vries (KdV) equation, the Burgers equation and the modified Korteweg-de-Vries (mKdV) equation. Three different versions of optimal velocity models are examined. The stability conditions of the models are obtained by using the linear stability theory. The KdV equation near the neutral stability line and the mKdV equation around the critical point are derived by applying the reductive perturbation method, respectively. The traffic jams could be thus described by the KdV and kink-antikink soliton solutions for the two kinds of equations. The general solutions are given for, which can lead to specific solutions in previous work. Moreover, they are applied to solve a new model-the full velocity difference model and the corresponding KdV and kink-antikink soliton solutions could be quickly obtained, which demonstrates the general solutions presented herein are useful.

  5. Hamiltonian Structures and Integrability for a Discrete Coupled KdV-Type Equation Hierarchy

    Institute of Scientific and Technical Information of China (English)

    ZHAO Hai-Qiong; ZHU Zuo-Nong; ZHANG Jing-Li

    2011-01-01

    @@ Coupled Korteweg-de Vries(KdV) systems have many important physical applications.By considering a 4 × 4spectral problem,we derive a discrete coupled KdV-type equation hierarchy.Our hierarchy includes the coupled Volterra system proposed by Lou et al.(e-print arXiv:0711.0420) as the first member which is a discrete version of the coupled KdV equation.We also investigate the integrability in the Liouville sense and the multi-Hamiltonian structures for the obtained hierarchy.%Coupled Korteweg-de Vries (KdV) systems have many important physical applications.By considering a 4 × 4 spectral problem, we derive a discrete coupled KdV-type equation hierarchy.Our hierarchy includes the coupled Volterra system proposed by Lou et al.(e-print arXiv: 0711.0420) as the first member which is a discrete version of the coupled KdV equation.We also investigate the integrability in the Liouville sense and the multi-Hamiltonian structures for the obtained hierarchy.

  6. On the orbital stability of Gaussian solitary waves in the log-KdV equation

    Science.gov (United States)

    Carles, Rémi; Pelinovsky, Dmitry

    2014-12-01

    We consider the logarithmic Korteweg-de Vries (log-KdV) equation, which models solitary waves in anharmonic chains with Hertzian interaction forces. By using an approximating sequence of global solutions of the regularized generalized KdV equation in H^1({R}) with conserved L2 norm and energy, we construct a weak global solution of the log-KdV equation in a subset of H^1({R}) . This construction yields conditional orbital stability of Gaussian solitary waves of the log-KdV equation, provided that uniqueness and continuous dependence of the constructed solution holds. Furthermore, we study the linearized log-KdV equation at the Gaussian solitary wave and prove that the associated linearized operator has a purely discrete spectrum consisting of simple purely imaginary eigenvalues in addition to the double zero eigenvalue. The eigenfunctions, however, do not decay like Gaussian functions but have algebraic decay. Using numerical approximations, we show that the Gaussian initial data do not spread out but produce visible radiation at the left slope of the Gaussian-like pulse in the time evolution of the linearized log-KdV equation.

  7. Time-Fractional KdV Equation for the plasma in auroral zone using Variational Methods

    CERN Document Server

    El-Wakil, El-Said A; Elshewy, Emad K; Mahmoud, Aber A

    2010-01-01

    The reductive perturbation method has been employed to derive the Korteweg-de Vries (KdV) equation for small but finite amplitude electrostatic waves. The Lagrangian of the time fractional KdV equation is used in similar form to the Lagrangian of the regular KdV equation. The variation of the functional of this Lagrangian leads to the Euler-Lagrange equation that leads to the time fractional KdV equation. The Riemann-Liouvulle definition of the fractional derivative is used to describe the time fractional operator in the fractional KdV equation. The variational-iteration method given by He is used to solve the derived time fractional KdV equation. The calculations of the solution with initial condition A0*sech(cx)^2 are carried out. Numerical studies have been made using plasma parameters close to those values corresponding to the dayside auroral zone. The effects of the time fractional parameter on the electrostatic solitary structures are presented.

  8. 高阶广义微扰KdV方程的弱解%Weak Solution of Generalized KdV Equation with High Order Perturbation Terms

    Institute of Scientific and Technical Information of China (English)

    成军祥; 王艳红

    2011-01-01

    By using the theory of compensated compactness, we prove that there exists a sequence {uεδ}converges nearly everywhere to the solution of the initial-value problem of generalized KdV equation with high order perturbation terms, namely we prove the existence of the weak solution.

  9. The role of phosphoinositide-3 kinase and PTEN in cardiovascular physiology and disease.

    Science.gov (United States)

    Oudit, Gavin Y; Sun, Hui; Kerfant, Benoit-Gilles; Crackower, Michael A; Penninger, Josef M; Backx, Peter H

    2004-08-01

    Phosphoinositide-3 kinases (PI3Ks) are a family of evolutionary conserved lipid kinases that mediate many cellular responses in both physiologic and pathophysiologic states. Class I PI3K can be activated by either receptor tyrosine kinase (RTK)/cytokine receptor activation (class I(A)) or G-protein-coupled receptors (GPCR) (class I(B)). Once activated PI3Ks generate phosphatidylinositols (PtdIns) (3,4,5)P(3) leading to the recruitment and activation of Akt/protein kinase B (PKB), PDK1 and monomeric G-proteins (e.g. Rac-GTPases), which then activate a range of downstream targets including glycogen synthase kinase-3beta (GSK-3beta), mammalian target of rapamycin (mTOR), p70S6 kinase, endothelial nitric oxide synthase (eNOS) and several anti-apoptotic effectors. Class I(A) (PI3Kalpha, beta and delta) and class I(B) (PI3Kgamma) PI3Ks mediate distinct phenotypes in the heart and under negative control by the 3'-lipid phosphatase, phosphatase and tensin homolog on chromosome ten (PTEN) which dephosphorylate PtdIns(3,4,5)P(3) into PtdIns(4,5)P(2). PI3Kalpha, gamma and PTEN are expressed in cardiomyocytes, fibroblasts, endothelial cells and vascular smooth muscle cells where they modulate cell survival/apoptosis, hypertrophy, contractility, metabolism and mechanotransduction. Several transgenic and knockout models support a fundamental role of PI3K/PTEN signaling in the regulation of myocardial contractility and hypertrophy. Consequently the PI3K/PTEN signaling pathways are involved in a wide variety of diseases including cardiac hypertrophy, heart failure, preconditioning and hypertension. In this review, we discuss the biochemistry and molecular biology of PI3K (class I isoforms) and PTEN and their critical role in cardiovascular physiology and diseases.

  10. PTEN loss represses glioblastoma tumor initiating cell differentiation via inactivation of Lgl1.

    Science.gov (United States)

    Gont, Alexander; Hanson, Jennifer E L; Lavictoire, Sylvie J; Parolin, Doris A; Daneshmand, Manijeh; Restall, Ian J; Soucie, Mathieu; Nicholas, Garth; Woulfe, John; Kassam, Amin; Da Silva, Vasco F; Lorimer, Ian A J

    2013-08-01

    Glioblastoma multiforme is an aggressive and incurable type of brain tumor. A subset of undifferentiated glioblastoma cells, known as glioblastoma tumor initiating cells (GTICs), has an essential role in the malignancy of this disease and also appears to mediate resistance to radiation therapy and chemotherapy. GTICs retain the ability to differentiate into cells with reduced malignant potential, but the signaling pathways controlling differentiation are not fully understood at this time. PTEN loss is a very common in glioblastoma multiforme and leads to aberrant activation of the phosphoinositide 3-kinase pathway. Increased signalling through this pathway leads to activation of multiple protein kinases, including atypical protein kinase C. In Drosophila, active atypical protein kinase C has been shown to promote the self-renewal of neuroblasts, inhibiting their differentiation along a neuronal lineage. This effect is mediated by atypical protein kinase c-mediated phosphorylation and inactivation of Lgl, a protein that was first characterized as a tumour suppressor in Drosophila. The effects of the atypical protein kinase C/Lgl pathway on the differentiation status of GTICs, and its potential link to PTEN loss, have not been assessed previously. Here we show that PTEN loss leads to the phosphorylation and inactivation of Lgl by atypical protein kinase C in glioblastoma cells. Re-expression of PTEN in GTICs promoted their differentiation along a neuronal lineage. This effect was also seen when atypical protein kinase C was knocked down using RNA interference, and when a non-phosphorylatable, constitutively active form of Lgl was expressed in GTICs. Thus PTEN loss, acting via atypical protein kinase C activation and Lgl inactivation, helps to maintain GTICs in an undifferentiated state.

  11. Second Malignant Neoplasms in Patients With Cowden Syndrome With Underlying Germline PTEN Mutations

    Science.gov (United States)

    Ngeow, Joanne; Stanuch, Kim; Mester, Jessica L.; Barnholtz-Sloan, Jill S.; Eng, Charis

    2014-01-01

    Purpose Patients with Cowden syndrome (CS) with underlying germline PTEN mutations are at increased risk of breast, thyroid, endometrial, and renal cancers. To our knowledge, risk of subsequent cancers in these patients has not been previously explored or quantified. Patients and Methods We conducted a 7-year multicenter prospective study (2005 to 2012) of patients with CS or CS-like disease, all of whom underwent comprehensive PTEN mutational analysis. Second malignant neoplasms (SMNs) were ascertained by medical records and confirmed by pathology reports. Standardized incidence ratios (SIRs) for all SMNs combined and for breast, thyroid, endometrial, and renal cancers were calculated. Results Of the 2,912 adult patients included in our analysis, 2,024 had an invasive cancer history. Germline pathogenic PTEN mutations (PTEN mutation positive) were identified in 114 patients (5.6%). Of these 114 patients, 46 (40%) had an SMN. Median age of SMN diagnosis was 50 years (range, 21 to 71 years). Median interval between primary cancer and SMN was 5 years (range, breast cancer, 11 (22%) had a subsequent new primary breast cancer and 10-year second breast cancer cumulative risk of 29% (95% CI, 15.3 to 43.7). Risk of SMNs compared with that of the general population was significantly elevated for all cancers (SIR, 7.74; 95% CI, 5.84 to 10.07), specifically for breast (SIR, 8.92; 95% CI, 5.85 to 13.07), thyroid (SIR, 5.83; 95% CI, 3.01 to 10.18), and endometrial SMNs (SIR, 14.08.07; 95% CI, 7.10 to 27.21). Conclusion Patients with CS with germline PTEN mutations are at higher risk for SMNs compared with the general population. Prophylactic mastectomy should be considered on an individual basis given the significant risk of subsequent breast cancer. PMID:24778394

  12. The genetic basis of Cowden's syndrome: three novel mutations in PTEN/MMAC1/TEP1.

    Science.gov (United States)

    Tsou, H C; Ping, X L; Xie, X X; Gruener, A C; Zhang, H; Nini, R; Swisshelm, K; Sybert, V; Diamond, T M; Sutphen, R; Peacocke, M

    1998-04-01

    Cowden's syndrome (CS) is an autosomal dominant disorder associated with an increased risk of developing benign and malignant tumors in a variety of tissues, including the skin, thyroid, breast and brain. Women with CS are felt to have an increased risk of developing breast cancer, and virtually all women with CS develop bilateral fibrocystic disease of the breast. Recently, a series of germline mutations have been identified from CS families in a gene known as PTEN/MMAC1/TEP1. In this study, we used heteroduplex analysis and direct sequencing analysis and identified three novel germline mutations in the PTEN/MMAC1/TEP1 coding sequence from unrelated individuals with CS. We report a de novo transition (T-->C) at nucleotide 335 in exon 5. This missense mutation resulted in a leucine to proline (CTA to CCA) change at codon 112. We also describe a novel splice site mutation (801+2T-->G) in intron 7 that caused exon skipping in PTEN/MMAC1/TEP1 mRNA. The third mutation we report is a missense mutation, consisting of a transition (T-->C) at nucleotide 202 in exon 3, resulting in a tyrosine to histidine (TAC to CAC) change at codon 68. Finally, we also detected a rare polymorphism in exon 7 of the PTEN/MMAC1/TEP1 coding sequence. These data confirm the observation that mutations of the PTEN/MMAC1/TEP1 coding sequence are responsible for at least some cases of CS, and further define the spectrum of mutations in this autosomal dominant disorder.

  13. PTEN and p53 cross-regulation induced by soy isoflavone genistein promotes mammary epithelial cell cycle arrest and lobuloalveolar differentiation.

    Science.gov (United States)

    Rahal, Omar M; Simmen, Rosalia C M

    2010-08-01

    The tumor suppressors phosphatase and tensin homologue deleted on chromosome ten (PTEN) and p53 are closely related to the pathogenesis of breast cancer, yet pathway-specific mechanisms underlying their participation in mediating the protective actions of dietary bioactive components on breast cancer risk are poorly understood. We recently showed that dietary exposure to the soy isoflavone genistein (GEN) induced PTEN expression in mammary epithelial cells in vivo and in vitro, consistent with the breast cancer preventive effects of soy food consumption. Here, we evaluated PTEN and p53 functional interactions in the nuclear compartment of mammary epithelial cells as a mechanism for mammary tumor protection by GEN. Using the non-tumorigenic human mammary epithelial cells MCF10-A, we demonstrate that GEN increased PTEN expression and nuclear localization. We show that increased nuclear PTEN levels initiated an autoregulatory loop involving PTEN-dependent increases in p53 nuclear localization, PTEN-p53 physical association, PTEN-p53 co-recruitment to the PTEN promoter region and p53 transactivation of PTEN promoter activity. The PTEN-p53 cross talk induced by GEN resulted in increased cell cycle arrest; decreased pro-proliferative cyclin D1 and pleiotrophin gene expression and the early formation of mammary acini, indicative of GEN promotion of lobuloalveolar differentiation. Our findings provide support to GEN-induced PTEN as both a target and regulator of p53 action and offer a mechanistic basis for PTEN pathway activation to underlie the antitumor properties of dietary factors, with important implications for reducing breast cancer risk.

  14. Coordinate activation of Shh and PI3K signaling in PTEN-deficient glioblastoma: new therapeutic opportunities.

    Science.gov (United States)

    Filbin, Mariella Gruber; Dabral, Sukriti K; Pazyra-Murphy, Maria F; Ramkissoon, Shakti; Kung, Andrew L; Pak, Ekaterina; Chung, Jarom; Theisen, Matthew A; Sun, Yanping; Franchetti, Yoko; Sun, Yu; Shulman, David S; Redjal, Navid; Tabak, Barbara; Beroukhim, Rameen; Wang, Qi; Zhao, Jean; Dorsch, Marion; Buonamici, Silvia; Ligon, Keith L; Kelleher, Joseph F; Segal, Rosalind A

    2013-11-01

    In glioblastoma, phosphatidylinositol 3-kinase (PI3K) signaling is frequently activated by loss of the tumor suppressor phosphatase and tensin homolog (PTEN). However, it is not known whether inhibiting PI3K represents a selective and effective approach for treatment. We interrogated large databases and found that sonic hedgehog (SHH) signaling is activated in PTEN-deficient glioblastoma. We demonstrate that the SHH and PI3K pathways synergize to promote tumor growth and viability in human PTEN-deficient glioblastomas. A combination of PI3K and SHH signaling inhibitors not only suppressed the activation of both pathways but also abrogated S6 kinase (S6K) signaling. Accordingly, targeting both pathways simultaneously resulted in mitotic catastrophe and tumor apoptosis and markedly reduced the growth of PTEN-deficient glioblastomas in vitro and in vivo. The drugs tested here appear to be safe in humans; therefore, this combination may provide a new targeted treatment for glioblastoma.

  15. Detection of 65 kD heat shock protein in cerebrospinal fluid of tuberculous meningitis patients

    Directory of Open Access Journals (Sweden)

    Taori Girdhar M

    2006-09-01

    Full Text Available Abstract Background Diagnosis of tuberculous meningitis (TBM is difficult. Rapid confirmatory diagnosis is essential to initiate required therapy. There are very few published reports about the diagnostic significance of 65 kD heat shock protein (hsp in TBM patients, which is present in a wide range of Mycobacterium tuberculosis species and elicits a cellular and humoral immune response. In the present study we have conducted a prospective evaluation for the demonstration of 65 kD hsp antigen in cerebrospinal fluid (CSF of TBM patients, by indirect ELISA method using monoclonal antibodies (mAb against the 65 kD hsp antigen, for the diagnosis of TBM. Methods A total of 160 CSF samples of different groups of patients (confirmed TBM {n = 18}, clinically suspected TBM {n = 62}, non TBM infectious meningitis {n = 35} and non-infectious neurological diseases {n = 45} were analyzed by indirect ELISA method using mAb to 65 kD hsp antigen. The Kruskal Wallis test (Non-Parametric ANOVA with the Dunnett post test was used for statistical analysis. Results The indirect ELISA method yielded 84% sensitivity and 90% specificity for the diagnosis of TBM using mAb to 65 kD hsp antigen. The mean absorbance value of 65 kD hsp antigen in TBM patients was [0.70 ± 0.23 (0.23–1.29], significantly higher than the non-TBM infectious meningitis group [0.32 ± 0.14 (0.12–0.78, P P P Conclusion The presence of 65 kD hsp antigen in the CSF of confirmed and suspected cases of TBM would indicate that the selected protein is specific to M. tuberculosis and could be considered as a diagnostic marker for TBM.

  16. PTEN and PI-3 kinase inhibitors control LPS signaling and the lymphoproliferative response in the CD19+ B cell compartment

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Alok R. [UCSD Department of Pediatrics, Moores UCSD Cancer Center, University of California School of Medicine, San Diego, CA 92093 (United States); Peirce, Susan K. [Department of Pediatrics, Emory University School of Medicine, Atlanta, GA (United States); Joshi, Shweta [UCSD Department of Pediatrics, Moores UCSD Cancer Center, University of California School of Medicine, San Diego, CA 92093 (United States); Durden, Donald L., E-mail: ddurden@ucsd.edu [UCSD Department of Pediatrics, Moores UCSD Cancer Center, University of California School of Medicine, San Diego, CA 92093 (United States); Division of Pediatric Hematology-Oncology, UCSD Rady Children' s Hospital, La Jolla, CA (United States)

    2014-09-10

    Pattern recognition receptors (PRRs), e.g. toll receptors (TLRs) that bind ligands within the microbiome have been implicated in the pathogenesis of cancer. LPS is a ligand for two TLR family members, TLR4 and RP105 which mediate LPS signaling in B cell proliferation and migration. Although LPS/TLR/RP105 signaling is well-studied; our understanding of the underlying molecular mechanisms controlling these PRR signaling pathways remains incomplete. Previous studies have demonstrated a role for PTEN/PI-3K signaling in B cell selection and survival, however a role for PTEN/PI-3K in TLR4/RP105/LPS signaling in the B cell compartment has not been reported. Herein, we crossed a CD19cre and PTEN{sup fl/fl} mouse to generate a conditional PTEN knockout mouse in the CD19+ B cell compartment. These mice were further crossed with an IL-14α transgenic mouse to study the combined effect of PTEN deletion, PI-3K inhibition and expression of IL-14α (a cytokine originally identified as a B cell growth factor) in CD19+ B cell lymphoproliferation and response to LPS stimulation. Targeted deletion of PTEN and directed expression of IL-14α in the CD19+ B cell compartment (IL-14+PTEN-/-) lead to marked splenomegaly and altered spleen morphology at baseline due to expansion of marginal zone B cells, a phenotype that was exaggerated by treatment with the B cell mitogen and TLR4/RP105 ligand, LPS. Moreover, LPS stimulation of CD19+ cells isolated from these mice display increased proliferation, augmented AKT and NFκB activation as well as increased expression of c-myc and cyclinD1. Interestingly, treatment of LPS treated IL-14+PTEN-/- mice with a pan PI-3K inhibitor, SF1126, reduced splenomegaly, cell proliferation, c-myc and cyclin D1 expression in the CD19+ B cell compartment and normalized the splenic histopathologic architecture. These findings provide the direct evidence that PTEN and PI-3K inhibitors control TLR4/RP105/LPS signaling in the CD19+ B cell compartment and that pan PI

  17. Poor prognostic clinicopathologic features correlate with VEGF expression but not with PTEN expression in squamous cell carcinoma of the larynx

    Directory of Open Access Journals (Sweden)

    Karagoz Filiz

    2010-06-01

    Full Text Available Abstract Background The aim of this study was to assess the relationship between expression of vascular endothelial growth factor (VEGF and phosphatase and tensin homolog deleted in chromosome ten (PTEN, angiogenesis and clinicopathological parameters of squamous cell carcinoma of the larynx. Methods We examined immunohistochemical expression of VEGF and PTEN and CD34 for microvessel density (MVD in sections of formalin-fixed, paraffin embedded tissue blocks of 140 patients with squamous cell carcinoma of the larynx. The intensity of VEGF and PTEN staining and the proportion of cells staining were scored. Results The tumor grade was not significantly related to PTEN expression, but it was to VEGF expression (p = 0.400; p = 0.015, respectively. While there was no significant relationship between PTEN expression and tumor size and cartilage invasion (p = 0.311, p = 0.128, there was a significant relationship between the severity of VEGF expression and tumor size (p = 0.006 and lymph node metastasis (p = 0.048 but not cartilage invasion (p = 0.129. MVD was significantly higher in high-grade tumors (p = 0.003 but had no significant relationship between MVD, lymph node metastasis, and cartilage invasion (p = 0.815, p = 0.204. There was also no significant relationship between PTEN and VEGF expression (p = 0.161 and between PTEN and VEGF expression and the MVD (p = 0.120 and p = 0.175, respectively. Conclusions Increased VEGF expression may play an important role in the outcome of squamous cell carcinoma of the larynx. PTEN expression was not related to VEGF expression and clinicopathological features of squamous cell carcinoma of the larynx.

  18. Role of phosphatase PTEN in the activation of extracellular signal-regulated kinases induced by estradiol in endometrial carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    张育军; 魏丽惠; 王建六; 孙铁铮

    2003-01-01

    Objectives To study extracellular signal-regulated kinase (ERK) activation in the endometrial carcinoma cell line Ishikawa with stimulation by 17-β-estradiol, and to elucidate the role of phosphatase and tensin homologue (PTEN) and estrogen receptor (ER) subtype on the activation of ERKs.Methods Western blot was used to examine the expression of PTEN and PTEN (G129E) in Ishikawa cells after stable transfection as well as ERK activation in Ishikawa-EGFP, Ishikawa- PTEN and Ishikawa- PTEN (G129E) stimulated with various doses of 17-β-estradiol for different lengths of time. Western blot was also used for examining the expression of ERα and ERβ in NIH3T3 fibroblasts after transient transfection of pCXN2hERα and pCXN2hERβ. Then, ERK activation was examined after stimulation with 17-β-estradiol. Results 17-β-estradiol activated ERK cascades (mainly ERK2) in Ishikawa cells. The activation of ERK increased gradually as concentration of 17-β-estradiol also increased. The maximal activation of ERK2 took place 5 min after stimulation with 17-β-estradiol. The activation of ERK2 was inhibited markedly by PTEN, but not by PTEN (G129E). 17-β-estradiol activated ERK cascades in NIH3T3 fibroblasts after transient transfection of pCXN2hERα.Conclusions 17-β-estradiol activate ERK cascades in Ishikawa cells by integrating with ERα. Lipid phosphatase PTEN has an inhibitory role on the activation of ERK stimulated by 17-β-estradiol in Ishikawa cells.

  19. PTEN dephosphorylates AKT to prevent the expression of GLUT1 on plasmamembrane and to limit glucose consumption in cancer cells.

    Science.gov (United States)

    Phadngam, Suratchanee; Castiglioni, Andrea; Ferraresi, Alessandra; Morani, Federica; Follo, Carlo; Isidoro, Ciro

    2016-12-20

    GLUT1 is the facilitative transporter playing the major role in the internalization of glucose. Basally, GLUT1 resides on vesicles located in a para-golgian area, and is translocated onto the plasmamembrane upon activation of the PI3KC1-AKT pathway. In proliferating cancer cells, which demand a high quantity of glucose for their metabolism, GLUT1 is permanently expressed on the plasmamembrane. This is associated with the abnormal activation of the PI3KC1-AKT pathway, consequent to the mutational activation of PI3KC1 and/or the loss of PTEN. The latter, in fact, could antagonize the phosphorylation of AKT by limiting the availability of Phosphatidylinositol (3,4,5)-trisphosphate. Here, we asked whether PTEN could control the plasmamembrane expression of GLUT1 also through its protein-phosphatase activity on AKT. Experiments of co-immunoprecipitation and in vitro de-phosphorylation assay with homogenates of cells transgenically expressing the wild type or knocked-down mutants (lipid-phosphatase, protein-phosphatase, or both) isoforms demonstrated that indeed PTEN physically interacts with AKT and drives its dephosphorylation, and so limiting the expression of GLUT1 at the plasmamembrane. We also show that growth factors limit the ability of PTEN to dephosphorylate AKT. Our data emphasize the fact that PTEN acts in two distinct steps of the PI3k/AKT pathway to control the expression of GLUT1 at the plasmamembrane and, further, add AKT to the list of the protein substrates of PTEN.

  20. Connexin43 recruits PTEN and Csk to inhibit c-Src activity in glioma cells and astrocytes

    Science.gov (United States)

    González-Sánchez, Ana; Jaraíz-Rodríguez, Myriam; Domínguez-Prieto, Marta; Herrero-González, Sandra; Medina, José M.; Tabernero, Arantxa

    2016-01-01

    Connexin43 (Cx43), the major protein forming gap junctions in astrocytes, is reduced in high-grade gliomas, where its ectopic expression exerts important effects, including the inhibition of the proto-oncogene tyrosine-protein kinase Src (c-Src). In this work we aimed to investigate the mechanism responsible for this effect. The inhibition of c-Src requires phosphorylation at tyrosine 527 mediated by C-terminal Src kinase (Csk) and dephosphorylation at tyrosine 416 mediated by phosphatases, such as phosphatase and tensin homolog (PTEN). Our results showed that the antiproliferative effect of Cx43 is reduced when Csk and PTEN are silenced in glioma cells, suggesting the involvement of both enzymes. Confocal microscopy and immunoprecipitation assays confirmed that Cx43, in addition to c-Src, binds to PTEN and Csk in glioma cells transfected with Cx43 and in astrocytes. Pull-down assays showed that region 266–283 in Cx43 is sufficient to recruit c-Src, PTEN and Csk and to inhibit the oncogenic activity of c-Src. As a result of c-Src inhibition, PTEN was increased with subsequent inactivation of Akt and reduction of proliferation of human glioblastoma stem cells. We conclude that the recruitment of Csk and PTEN to the region between residues 266 and 283 within the C-terminus of Cx43 leads to c-Src inhibition. PMID:27391443

  1. BCR-mediated apoptosis associated with negative selection of immature B cells is selectively dependent on Pten

    Institute of Scientific and Technical Information of China (English)

    Shuhua Cheng; Constance Yu Hsia; Biao Feng; Me-Ling Liou; Xiaoying Fang; Pier Paolo Pandolfi; Hsiou-Chi Liou

    2009-01-01

    The molecular basis of B cell receptor (BCR)-induced apoptosis during the negative selection of immature B cells is largely unknown. We use transitional immature B cells that are highly susceptible to BCR-induced apoptosis to show that Pten is selectively required for BCR-mediated initiation of the mitochondrial death pathway. Specifically,deleting Pten, but not other pro-apoptotic molecules, abrogates BCR-elicited apoptosis and improves viability in wild-type immature B cells. We further identify a physiologically and significantly higher intracellular Pten level in immature B cells, as compared to mature B cells, which is responsible for low AKT activity and the propensity towards death in immature B cells. Restoration of AKT activity using a constitutive form of AKT or reduction of Pten to a level comparable with that seen in mature B cells rescues immature B cells from BCR-induced apoptosis. Thus,we provide evidence that Pten is an essential mediator of BCR-induced cell death, and that differential regulation of intracellular Pten levels determines whether BCR ligation promotes cell death or survival. Our findings provide a valuable insight into the mechanisms underlying negative selection and clonal deletion of immature B cells.

  2. Phosphorylation of the actin binding protein Drebrin at S647 is regulated by neuronal activity and PTEN.

    Directory of Open Access Journals (Sweden)

    Patricia Kreis

    Full Text Available Defects in actin dynamics affect activity-dependent modulation of synaptic transmission and neuronal plasticity, and can cause cognitive impairment. A salient candidate actin-binding protein linking synaptic dysfunction to cognitive deficits is Drebrin (DBN. However, the specific mode of how DBN is regulated at the central synapse is largely unknown. In this study we identify and characterize the interaction of the PTEN tumor suppressor with DBN. Our results demonstrate that PTEN binds DBN and that this interaction results in the dephosphorylation of a site present in the DBN C-terminus--serine 647. PTEN and pS647-DBN segregate into distinct and complimentary compartments in neurons, supporting the idea that PTEN negatively regulates DBN phosphorylation at this site. We further demonstrate that neuronal activity increases phosphorylation of DBN at S647 in hippocampal neurons in vitro and in ex vivo hippocampus slices exhibiting seizure activity, potentially by inducing rapid dissociation of the PTEN:DBN complex. Our results identify a novel mechanism by which PTEN is required to maintain DBN phosphorylation at dynamic range and signifies an unusual regulation of an actin-binding protein linked to cognitive decline and degenerative conditions at the CNS synapse.

  3. Phosphorylation of PTEN increase in pathological right ventricular hypertrophy in rats with chronic hypoxia induced pulmonary hypertension

    Institute of Scientific and Technical Information of China (English)

    Nie Xin; Shi Yiwei; Yu Wenyan; Xu Jianying; Hu Xiaoyun; Du Yongcheng

    2014-01-01

    Background Phosphatase and tensin homologue on chromosome ten (PTEN) acts as a convergent nodal signalling point for cardiomyocyte hypertrophy,growth and survival.However,the role of PTEN in cardiac conditions such as right ventricular hypertrophy caused by chronic hypoxic pulmonary,hypertension remains unclear.This study preliminarily discussed the role of PTEN in the cardiac response to increased pulmonary vascular resistance using the hypoxia-induced PH rats.Methods Male Sprague Dawley rats were exposed to 10% oxygen for 1,3,7,14 or 21 days to induce hypertension and right ventricular hypertrophy.Right ventricular systolic pressure was measured via catheterization.Hypertrophy index was calculated as the ratio of right ventricular mass to left ventricle plus septum mass.Tissue morphology and fibrosis were measured using hematoxylin,eosin and picrosirius red staining.The expression and phosphorylation levels of PTEN in ventricles were determined by real time PCR and Western blotting.Results Hypoxic exposure of rats resulted in pathological hypertrophy,interstitial fibrosis and remodelling of the right ventricle.The phosphorylation of PTEN increased significantly in the hypertrophic right ventricle compared to the normoxic control group.There were no changes in protein expression in either ventricle.Conclusion Hypoxia induced pulmonary hypertension developed pathological right ventricular hypertrophy and remodelling probablv related to an increased phosohorvlation of PTEN.

  4. PTEN microdeletions in T-cell acute lymphoblastic leukemia are caused by illegitimate RAG-mediated recombination events.

    Science.gov (United States)

    Mendes, Rui D; Sarmento, Leonor M; Canté-Barrett, Kirsten; Zuurbier, Linda; Buijs-Gladdines, Jessica G C A M; Póvoa, Vanda; Smits, Willem K; Abecasis, Miguel; Yunes, J Andres; Sonneveld, Edwin; Horstmann, Martin A; Pieters, Rob; Barata, João T; Meijerink, Jules P P

    2014-07-24

    Phosphatase and tensin homolog (PTEN)-inactivating mutations and/or deletions are an independent risk factor for relapse of T-cell acute lymphoblastic leukemia (T-ALL) patients treated on Dutch Childhood Oncology Group or German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia protocols. Some monoallelic mutated or PTEN wild-type patients lack PTEN protein, implying that additional PTEN inactivation mechanisms exist. We show that PTEN is inactivated by small deletions affecting a few exons in 8% of pediatric T-ALL patients. These microdeletions were clonal in 3% and subclonal in 5% of patients. Conserved deletion breakpoints are flanked by cryptic recombination signal sequences (cRSSs) and frequently have non-template-derived nucleotides inserted in between breakpoints, pointing to an illegitimate RAG recombination-driven activity. Identified cRSSs drive RAG-dependent recombination in a reporter system as efficiently as bona fide RSSs that flank gene segments of the T-cell receptor locus. Remarkably, equivalent microdeletions were detected in thymocytes of healthy individuals. Microdeletions strongly associate with the TALLMO subtype characterized by TAL1 or LMO2 rearrangements. Primary and secondary xenotransplantation of TAL1-rearranged leukemia allowed development of leukemic subclones with newly acquired PTEN microdeletions. Ongoing RAG activity may therefore actively contribute to the acquisition of preleukemic hits, clonal diversification, and disease progression. © 2014 by The American Society of Hematology.

  5. New analytical exact solutions of time fractional KdV-KZK equation by Kudryashov methods

    Science.gov (United States)

    S Saha, Ray

    2016-04-01

    In this paper, new exact solutions of the time fractional KdV-Khokhlov-Zabolotskaya-Kuznetsov (KdV-KZK) equation are obtained by the classical Kudryashov method and modified Kudryashov method respectively. For this purpose, the modified Riemann-Liouville derivative is used to convert the nonlinear time fractional KdV-KZK equation into the nonlinear ordinary differential equation. In the present analysis, the classical Kudryashov method and modified Kudryashov method are both used successively to compute the analytical solutions of the time fractional KdV-KZK equation. As a result, new exact solutions involving the symmetrical Fibonacci function, hyperbolic function and exponential function are obtained for the first time. The methods under consideration are reliable and efficient, and can be used as an alternative to establish new exact solutions of different types of fractional differential equations arising from mathematical physics. The obtained results are exhibited graphically in order to demonstrate the efficiencies and applicabilities of these proposed methods of solving the nonlinear time fractional KdV-KZK equation.

  6. A gamma dose distribution evaluation technique using the k-d tree for nearest neighbor searching.

    Science.gov (United States)

    Yuan, Jiankui; Chen, Weimin

    2010-09-01

    The authors propose an algorithm based on the k-d tree for nearest neighbor searching to improve the gamma calculation time for 2D and 3D dose distributions. The gamma calculation method has been widely used for comparisons of dose distributions in clinical treatment plans and quality assurances. By specifying the acceptable dose and distance-to-agreement criteria, the method provides quantitative measurement of the agreement between the reference and evaluation dose distributions. The gamma value indicates the acceptability. In regions where gamma nearest neighbor can be an O (log N) operation with a k-d tree, where N is the total number of the dose points, the authors propose an algorithm based on the k-d tree for the gamma evaluation in this work. In the experiment, the authors found that the average k-d tree construction time per reference point is O (log N), while the nearest neighbor searching time per evaluation point is proportional to O (N(1/k), where k is between 2 and 3 for two-dimensional and three-dimensional dose distributions, respectively. Comparing with other algorithms such as exhaustive search and sorted list O (N), the k-d tree algorithm for gamma evaluation is much more efficient.

  7. Antiidiotypic antibody related to the 84 kD human sperm membrane protein

    Institute of Scientific and Technical Information of China (English)

    YUJUN; WANGLINFANG; 等

    1990-01-01

    Wistar rats were inoculated with purified YWK-I antibody.The anti-idiotypic antibodies were isolated from rat sera by successive passage over affinity chromatography columns of YWK-I mAb and normal mouse Igs.Specificity of anti-Id antibody was established by ELISA.The 84kD protein inhibited the binding of anti-Id to YWK-I mAb,but failed to repress antibody against normal mouse Ig binding to YWK-I mAb.In competitive inhibition assay,84kD protein had shown the ability to compete with anti-Id binding to YWK-I mAb in a dose-dependent manner.Crude sperm extract showed a lower competitive ability.No effect was found with the irrelevant 36kD sperm protein.The antisera from the Balb/C micr immunized with AId contained Ab3 that reacted with 84kD sperm protein.The binding of anti-Id to YWK-I mAb was inhibited by Ab3 in a dose-dependent fashion and Ab3 was shown to be able to induce human sperm agglutination.These results indicate that anti-Id which may mimic an epitope of the 84kD protein could be exploited as an antigen to raise antibodies against sperm protein.

  8. $D_{s0}^{\\ast\\pm}(2317)$ and $KD$ scattering from $B^0_s$ decay

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    Albaladejo, Miguel; Oset, Eulogio

    2015-01-01

    We study the $\\bar{B}_s^0\\to D_s^-(DK)^+$ weak decay, and look at the $DK$ invariant mass distribution with the aim of obtaining relevant information on the nature of the $D_{s0}^{\\ast+}(2317)$ resonance. We make a simulation of the experiment using the actual mass of the $D_{s0}^{\\ast+}(2317)$ resonance and recent lattice QCD relevant parameters of the $KD$ scattering amplitude. We then solve the inverse problem of obtaining the $KD$ amplitude from these synthetic data, to which we have added a 5\\% or 10\\% error. We prove that one can obtain from these "data" the existence of a bound $KD$ state, the $KD$ scattering length and effective range, and most importantly, the $KD$ probability in the wave function of the bound state obtained, which was found to be largely dominant from the lattice QCD results. This means that one can obtain information on the nature of the $D_{s0}^{\\ast+}(2317)$ resonance from the implementation of this experiment, in the line of finding the structure of resonances, which is one of t...

  9. General, Label-Free Method for Determining K(d) and Ligand Concentration Simultaneously.

    Science.gov (United States)

    Jalali-Yazdi, Farzad; Takahashi, Terry T; Roberts, Richard W

    2015-12-01

    Some of the most commonly used affinity reagents (e.g., antibodies) are often developed and used in conditions where their input concentrations ([L]0) and affinities (K(d)) are not known. Here, we have developed a general approach to determine both [L]0 and K(d) values simultaneously for affinity reagents (small molecules, proteins, and antibodies). To do this, we perform quantitative equilibrium exclusion immunoassays with two different concentrations of target and fit the data simultaneously to determine K(d) and [L]0. The results give accurate and reproducible measures of both values compared to established methods. By performing detailed error analysis, we demonstrate that our fitting gives unique solutions and indicates where K(d) and [L]0 measures are reliable. Furthermore, we found that a divalent model of antibody binding gives accurate K(d) and [L]0 values in both the forward (antibody immobilized) and the reverse (target immobilized) assays-addressing the long-term problem of obtaining quantitative data from reverse assays.

  10. 广义Hirota-Satsuma耦合KdV方程的精确解%The Exact Solutions of a Generalized Hirota- Satsuma Coupled KdV Equation

    Institute of Scientific and Technical Information of China (English)

    刘倩; 周钰谦; 刘合春

    2011-01-01

    In recent years, (G'/G)-expansion method is widely used in solving nonlinear evolution equations.In this paper, by using (G'/G)-expansion method, with the help of mathematics software Maple, the new exact solutions of a generalized Hirota-Satsuma coupled KdV equation are obtained, including the solitary wave solutions, trigonometrie function periodic solutions and rational solutions.For better understanding their numerical simulations are also given.%利用(G'/G)-展开法结合数学软件Maple求得了广义Hirota-Satsuma耦合KdV方程的新精确解,包括孤波解、三角函数周期解和有理解.为了更直观地理解这些解,给出了它们的数值模拟图.

  11. New explicit exact solutions to a type of generalized Burgers-KdV equations with variant coefficients%具有变系数的广义Burgers-KdV方程新精确解

    Institute of Scientific and Technical Information of China (English)

    赵熙强; 张玉峰; 闫庆友; 龚新波

    2003-01-01

    Truncation expansion method is used to obtain new explicit exact solutions to a type of generalized Burgers-KdV equations with variant coefficients. As special reduction cases, the exact solutions for the generalized KdV equation and the generalized cylinder KdV equation with variant coefficients are presented respectively; and thereafter a new explicit exact solitary solution for the well-known Burgers equation is shown, which was not found before.%利用截断展开法求得了具有变系数的一类广义Burgers-KdV方程的新的精确解. 作为特例, 分别获得了具有变系数的广义KdV方程和广义柱KdV方程的精确解. 由此发现了Burgers方程的一类新的孤子解.

  12. The Numerical Solution and Simulation for KdV Equation%KdV方程的数值解及数值模拟

    Institute of Scientific and Technical Information of China (English)

    郝树艳; 刘波; 李广兴

    2009-01-01

    文章在已构造的一种分片光滑的Lagrange型插值多项式空间中利用Galerkin法对非线性KdV方程进行求解.分析了数值格式的线性稳定性并进行了数值模拟,结果表明格式精确有效.

  13. mKdV和mBBM方程的新型孤子解%New type soliton solutions to mKdV and mBBM equations

    Institute of Scientific and Technical Information of China (English)

    刘煜; 刘伟庆; 吕卫东

    2012-01-01

    Peakon solution and compacton solution are new type soliton solutions to nonlinear wave equations. In this paper, we researched two nonlinear wave equations- modified Korteweg-de Vries (mKdV) equation and modified Benjamin-Bona-Mahbny( mBBM) equation, respectively, and obtained three kinds of new type soliton solutions; peakon solutions, double-peak soliton solutions and peaked compacton solution. These results further enriched the patterns of explicit and exact solutions to mKdV and mBBM equations. The graphs of these solutions were given through numerical simulation, one of which was a double-peak solitary wave. One of three ansatz solutions proposed could also be used in many other nonlinear wave equations such as Klein-Gordon equation, φ4equation, Sine-Gordon equation and Landau-Ginzburg-Higgs equation.%尖峰孤子解和紧孤子解是非线性方程的新型孤子解.利用相关文献提出的方法分别研究修正的KdV方程(mKdV)和修正的BBM方程(mBBM),得到3种形式的孤子解:尖峰孤子解、双峰孤子解和尖峰紧孤子解.通过数值模拟得到解的图像,其中之一为双峰形的孤立波.这些结果进一步丰富了这2个非线性波方程的精确解的形式和内容.该文提出的3个拟解之一还可以用于其他多个非线性波方程,如:Klein-Gordon方程、φ4方程、Sine-Gordon方程和Landau -Ginzburg- Higgs方程.

  14. A functional network of the tumor suppressors APC, hDlg, and PTEN, that relies on recognition of specific PDZ-domains.

    Science.gov (United States)

    Sotelo, Natalia S; Valiente, Miguel; Gil, Anabel; Pulido, Rafael

    2012-08-01

    APC and PTEN are tumor suppressor proteins that bind through their C-termini to the PDZ domain containing-hDlg scaffolding protein. We have found that co-expression of PTEN and hDlg enhanced the negative regulation of the PI3K/Akt pathway by PTEN, indicating the physiologic importance of these interactions. APC and PTEN share other PDZ domain containing-interacting partners, including the MAGI scaffolding proteins and the MAST family of protein kinases. Mutational analysis revealed that the C-terminal PDZ-binding motifs from APC and PTEN were differentially recognized by distinct PDZ domains. APC bound to the three PDZ domains from hDlg, whereas PTEN mainly bound to PDZ-2/hDlg. This indicates the existence of overlapping, but distinct PDZ-domain recognition patterns by APC and PTEN. Furthermore, a ternary complex formed by APC, PTEN, and hDlg was detected, suggesting that hDlg may serve as a platform to bring in proximity APC and PTEN tumor suppressor activities. In line with this, tumor-related mutations targeting the PDZ-2/hDlg domain diminished its interaction with APC and PTEN. Our results expand the PDZ-domain counterparts for the tumor suppressor APC, show that APC and PTEN share PDZ-domain partners but have individual molecular determinants for specific recognition of PDZ domains, and suggest the participation of the tumor suppressors APC, PTEN, and hDlg in PDZ-domain interaction networks which may be relevant in oncogenesis.

  15. MTDH mediates trastuzumab resistance in HER2 positive breast cancer by decreasing PTEN expression through an NFκB-dependent pathway

    OpenAIRE

    Du, Cheng; Yi, Xiaomin; Liu, Wenchao; Han, Tao; Liu,Zhaozhe; Ding, Zhenyu; Zheng, Zhendong; PIAO, YING; Yuan, Jianlin; Han, Yaling; Xie, Manjiang; Xie, Xiaodong

    2014-01-01

    Background Trastuzumab resistance is almost inevitable in the management of human epidermal growth factor receptor (HER) 2 positive breast cancer, in which phosphatase and tensin homolog deleted from chromosome 10 (PTEN) loss is implicated. Since metadherin (MTDH) promotes malignant phenotype of breast cancer, we sought to define whether MTDH promotes trastuzumab resistance by decreasing PTEN expression through an NFκB-dependent pathway. Methods The correlations between MTDH and PTEN expressi...

  16. 含修正项的KdV方程是否一定存在孤子尾%Is There the Shelf behind the Soliton of the KdV Equation with Corrections

    Institute of Scientific and Technical Information of China (English)

    陈昌永

    2003-01-01

    含修正项的KdV方程是否一定存在孤子尾是最近孤子理论中争论的中心问题之一.给出几类含修正项的KdV方程的精确解,证明含修正项的KdV方程不一定存在孤子尾.

  17. Division algebras and extended N = 2, 4, 8 super KdVs

    Energy Technology Data Exchange (ETDEWEB)

    Carrion, H.L.; Rojas, M.; Toppan, F. [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil). Coordenacao de Teoria de Campos e Particulas]. E-mail: lenyj@cbpf.br; mrojas@cbpf.br; toppan@cbpf.br

    2001-09-01

    The first example of an N = 8 supersymmetric extension of the KdV equation is here explicitly constructed. It involves 8 bosonic and 8 fermionic fields. It corresponds to the unique N = 8 solution based a generalized hamiltonian dynamics with (generalized) Poisson brackets given by the Non-associate N = 8 Superconformal Algebra. The complete list of inequivalent classes of parametric-dependent N = 3 and N = 4 superKdVs obtained from the 'Non-associative N= 8 SCA' is also furnished. Furthermore, a fundamental domain characterizing the class of inequivalent N = 4 superKdVs based on the 'minimal N = 4 SCA' is given. (author)

  18. Approximate K-Nearest Neighbour Based Spatial Clustering Using K-D Tree

    Directory of Open Access Journals (Sweden)

    Mohammed Otair

    2013-03-01

    Full Text Available Different spatial objects that vary in their characteristics, such as molecular biology and geography, arepresented in spatial areas. Methods to organize, manage, and maintain those objects in a structuredmanner are required. Data mining raised different techniques to overcome these requirements. There aremany major tasks of data mining, but the mostly used task is clustering. Data set within the same clustershare common features that give each cluster its characteristics. In this paper, an implementation ofApproximate kNN-based spatial clustering algorithm using the K-d tree is proposed. The majorcontribution achieved by this research is the use of the k-d tree data structure for spatial clustering, andcomparing its performance to the brute-force approach. The results of the work performed in this paperrevealed better performance using the k-d tree, compared to the traditional brute-force approach.

  19. Estimation of Kd of lead and (210)Po in 11 soils from India.

    Science.gov (United States)

    Maity, Sukanta; Pandit, G G

    2014-12-01

    The fate of contaminant transport is often estimated using the distribution (partition) coefficient, Kd. It is a measure of sorption of contaminants to soil. As Kd is element, soil type and ground water dependent, chemical characterization of soil and ground water of the particular site is essential. In this study, soil and ground water samples from different locations around India were collected. The soil samples were physically characterized and pH, CaCO3, cation exchange capacity (CEC), organic matter and organic carbon were determined. Equilibration time for lead and (210)Po were estimated with respect to contact time and were found to be 28 and 72 h respectively. The Kd of lead varied from 6700 to 31,000 L/kg with a geometric mean of 15,200 L/kg, and for (210)Po from 1400 to 8700 L/kg with a geometric mean of 3700 L/kg.

  20. Analytical and numerical solution of coupled KdV-MKdV system

    CERN Document Server

    Halim, A; Leble, S B

    2002-01-01

    The matrix 2x2 spectral differential equation of the second order is considered on x in ($-\\infty,+\\infty$). We establish elementary Darboux transformations covariance of the problem and analyze its combinations. We select a second covariant equation to form Lax pair of a coupled KdV-MKdV system. The sequence of the elementary Darboux transformations of the zero-potential seed produce two-parameter solution for the coupled KdV-MKdV system with reductions. We show effects of parameters on the resulting solutions (reality, singularity). A numerical method for general coupled KdV-MKdV system is introduced. The method is based on a difference scheme for Cauchy problems for arbitrary number of equations with constants coefficients. We analyze stability and prove the convergence of the scheme which is also tested by numerical simulation of the explicit solutions.

  1. Cooperativity Between Oncogenic PKC Epsilon and Pten Loss in Prostate Cancer Progression

    Science.gov (United States)

    2015-10-01

    initiated studies to dissect the signaling mechanisms that mediate CXCL13 induction. We took advantage of a cellular model that we generated in our...metastatic loop that is mediated by CXCL13. We also hypothesize that PKCε is a CXCL13:CXCR5 effector that contributes to positively amplify this oncogenic...shown). Therefore, it is possible that an autocrine CXCL13:CXCR5 loop mediates effects driven by PKCε overexpression and Pten loss. * * R el at iv

  2. MicroRNA-22 promotes cell survival upon UV radiation by repressing PTEN

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Guangyun [Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN (United States); Center for Adult Cancer Research, University of Tennessee Health Science Center, Memphis, TN (United States); Jilin Province Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun (China); Shi, Yuling [Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN (United States); Center for Adult Cancer Research, University of Tennessee Health Science Center, Memphis, TN (United States); Wu, Zhao-Hui, E-mail: zwu6@uthsc.edu [Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN (United States); Center for Adult Cancer Research, University of Tennessee Health Science Center, Memphis, TN (United States)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer miR-22 is induced in cells treated with UV radiation. Black-Right-Pointing-Pointer ATM is required for miR-22 induction in response to UV. Black-Right-Pointing-Pointer miR-22 targets 3 Prime -UTR of PTEN to repress its expression in UV-treated cells. Black-Right-Pointing-Pointer Upregulated miR-22 inhibits apoptosis in cells exposed to UV. -- Abstract: DNA damage response upon UV radiation involves a complex network of cellular events required for maintaining the homeostasis and restoring genomic stability of the cells. As a new class of players involved in DNA damage response, the regulation and function of microRNAs in response to UV remain poorly understood. Here we show that UV radiation induces a significant increase of miR-22 expression, which appears to be dependent on the activation of DNA damage responding kinase ATM (ataxia telangiectasia mutated). Increased miR-22 expression may result from enhanced miR-22 maturation in cells exposed to UV. We further found that tumor suppressor gene phosphatase and tensin homolog (PTEN) expression was inversely correlated with miR-22 induction and UV-induced PTEN repression was attenuated by overexpression of a miR-22 inhibitor. Moreover, increased miR-22 expression significantly inhibited the activation of caspase signaling cascade, leading to enhanced cell survival upon UV radiation. Collectively, these results indicate that miR-22 is an important player in the cellular stress response upon UV radiation, which may promote cell survival via the repression of PTEN expression.

  3. Exploring the Hypersensitivity of PTEN Deleted Prostate Cancer Stem Cells to WEE1 Tyrosine Kinase Inhibitors

    Science.gov (United States)

    2015-12-01

    deletion Inhibitors/drugs ABL1 4% SAC, 2% AML Stomach adenocarcinoma (SAC), Acute myeloid leukemias (AML) Amplifications and missense mutations, Gene fusion...Rassool,F.V. (2013) Targeting abnormal DNA double-strand break repair in tyrosine kinase inhibitor-resistant chronic myeloid leukemias . Oncogene, 32, 1784...with the WEE1 inhibitor, MK1775. In contrast to LNCaP, MK1775 induces a differentiation like phenotype in the PTEN wildtype prostate cancer derived

  4. Promoting Axon Regeneration in the Adult CNS by Modulation of the PTEN/mTOR Pathway

    OpenAIRE

    2008-01-01

    The failure of axons to regenerate is a major obstacle for functional recovery after central nervous system (CNS) injury. Removing extracellular inhibitory molecules results in limited axon regeneration in vivo. To test for the role of intrinsic impediments to axon regrowth, we analyzed cell growth control genes using a virus-assisted in vivo conditional knockout approach. Deletion of PTEN (phosphatase and tensin homolog), a negative regulator of the mammalian target of rapamycin (mTOR) pathw...

  5. Loss of heterozygosity on 10q23.3 and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions

    Institute of Scientific and Technical Information of China (English)

    Yi-Ling Li; Zhong Tian; Dong-Ying Wu; Bao-Yu Fu; Yan Xin

    2005-01-01

    AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions.METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gastric cancer, intestinal metaplasia, atrophic gastritis, and atypical hyperplasia were analyzed for PTEN LOH and mutations within the entire coding region of PTEN gene by PCR-SSCP denaturing PAGE gel electrophoresis,and PTEN mutation was detected by PCR-SSCP sequencing followed by silver staining.RESULTS: LOH rate found in respectively atrophic gastritis was 10% (3/30), intestinal metaplasia 10% (3/30), atypical hyperpiasia 13.3% (4/30), early stage gastric cancer 20%(6/30), and advanced stage gastric cancer 33.3% (9/30),None of the precancerous lesions and early stage gastric cancer showed PTEN mutations, but 10% (3/30) of the advanced stage gastric cancers, which were all positive for LOH, showed PTEN mutation.CONCLUSION: LOH of PTEN gene appears in precancerous lesions, and PTEN mutations are restricted to advanced gastric cancer, LOH and mutation of PTEN gene are closely related to the infiltration and metastasis of gastric cancer.

  6. Tumor Suppressor Pten Inhibits Nuclear Accumulation of β-Catenin and T Cell/Lymphoid Enhancer Factor 1–Mediated Transcriptional Activation

    Science.gov (United States)

    Persad, Sujata; A.Troussard, Armelle; McPhee, Timothy R.; Mulholland, David J.; Dedhar, Shoukat

    2001-01-01

    β-Catenin is a protein that plays a role in intercellular adhesion as well as in the regulation of gene expression. The latter role of β-catenin is associated with its oncogenic properties due to the loss of expression or inactivation of the tumor suppressor adenomatous polyposis coli (APC) or mutations in β-catenin itself. We now demonstrate that another tumor suppressor, PTEN, is also involved in the regulation of nuclear β-catenin accumulation and T cell factor (TCF) transcriptional activation in an APC-independent manner. We show that nuclear β-catenin expression is constitutively elevated in PTEN null cells and this elevated expression is reduced upon reexpression of PTEN. TCF promoter/luciferase reporter assays and gel mobility shift analysis demonstrate that PTEN also suppresses TCF transcriptional activity. Furthermore, the constitutively elevated expression of cyclin D1, a β-catenin/TCF–regulated gene, is also suppressed upon reexpression of PTEN. Mechanistically, PTEN increases the phosphorylation of β-catenin and enhances its rate of degradation. We define a pathway that involves mainly integrin-linked kinase and glycogen synthase kinase 3 in the PTEN-dependent regulation of β-catenin stability, nuclear β-catenin expression, and transcriptional activity. Our data indicate that β-catenin/TCF–mediated gene transcription is regulated by PTEN, and this may represent a key mechanism by which PTEN suppresses tumor progression. PMID:11402061

  7. PTEN insufficiency modulates ER+ breast cancer cell cycle progression and increases cell growth in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Chiang KC

    2015-08-01

    Full Text Available Kun-Chun Chiang,1,4 Huang-Yang Chen,1 Shu-Yuan Hsu,2 Jong-Hwei S Pang,3 Shang-Yu Wang,4 Jun-Te Hsu,4 Ta-Sen Yeh,4 Li-Wei Chen,5 Sheng-Fong Kuo,6 Chi-Chin Sun,7 Jim-Ming Lee,1 Chun-Nan Yeh,4 Horng-Heng Juang21Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University, Keelung, 2Department of Anatomy, 3Graduate Institute of Clinical Medical Sciences, 4Department of General Surgery, 5Department of Gastroenterology, 6Department of Endocrinology and Metabolism, 7Department of Ophthalmology, Chang Gung Memorial Hospital, Chang Gung University, Keelung, Taiwan, Republic of China Abstract: Phosphatase and tensin homolog (PTEN, a well-known tumor suppressor gene and frequently mutated or lost in breast cancer, possesses the negative regulation function over the PI3K/Akt/mTOR pathway. PTEN insufficiency has been associated with advanced breast cancer and poor prognosis of breast cancer patients. Recently, target therapies aimed at PI3K/Akt/mTOR pathway to treat breast cancer have got popularity. However, the exact effect of PTEN on breast cancer cells is still not well understood. This study demonstrated that PTEN knockdown in MCF-7 cells strengthened the downstream gene expressions, including p-Akt, p-ERK1/2, p-mTOR, p-p70s6k, and p-GSK3ß. PTEN knockdown MCF-7 cells had increased cell growth and Ki-67 expression. Further Western blot demonstrated that p27 was repressed obviously with p21 slightly inhibited and CDK1, 2, 4, 6, cyclin A, and Cdc25C were upregulated in MCF-7 PTEN knockdown cells, leading to the higher growth rate. More importantly, PTEN knockdown MCF-7 cells had higher tumorigenesis and tumor growth in vivo. From our current work, we provided more detailed PTEN-mediated mechanisms to stimulate ER+ breast cancer cell growth. Our result may pave the way for further target therapy development used alone or in combination with other drugs for ER+ breast cancer with PTEN insufficiency.Keywords: PTEN, breast cancer, MCF-7

  8. A New Multi-Symplectic Scheme for the KdV Equation

    Institute of Scientific and Technical Information of China (English)

    LV Zhong-Quan; XUE Mei; WANG Yu-Shun

    2011-01-01

    We propose a new multi-symplectic integrating scheme for the Korteweg-de Vries (KdV) equation. The new scheme is derived by concatenating spatial discretization of the multi-symplectic Fourier pseudospectral method with temporal discretization of the symplectic Euler scheme. The new scheme is explicit in the sense that it does not need to solve nonlinear algebraic equations. It is verified that the multi-symplectic semi-discretization of the KdV equation under periodic boundary conditions has N semi-discrete multi-symplectic conservation laws. We also prove that the full-discrete scheme has N full-discrete multi-symplectic conservation laws. Numerical experiments of the new scheme on the KdV equation are made to demonstrate the stability and other merits for long-time integration.%@@ We propose a new multi-symplectic integrating scheme for the Korteweg-de Vries (KdV) equation.The new scheme is derived by concatenating spatial discretization of the multi-symplectic Fourier pseudospectral method with temporal discretization of the symplectic Euler scheme.The new scheme is explicit in the sense that it does not need to solve nonlinear algebraic equations.It is verified that the multi-symplectic semi-discretization of the KdV equation under periodic boundary conditions has N semi-discrete multi-symplectic conservation laws.We also prove that the full-discrete scheme has N full-discrete multi-symplectic conservation laws.Numerical experiments of the new scheme on the KdV equation are made to demonstrate the stability and other merits for long-time integration.

  9. Integral—Type Darboux Transformations for the mKdV Hierarchy with Self—COnsistent Sources

    Institute of Scientific and Technical Information of China (English)

    ZENGYun-Bo; MAWen-Xiu; 等

    2002-01-01

    We present integral-type Darboux transformation for the mKdV hierarchy and for the mKdV hierarchy with self-consistent sources,In contrast tiwh the nomal Darboux transformation,the integral-type Darboux transformations can offer non-auto-Baecklund transformation between two(2n+1)-th mKdV equations with self-consistent sources with different degrees.This kind of Darboux transformation enables us to construct the N-soliton solution for the mKdV hierarchy with self-consistent sources.We also propose the formulas for the m times repeated integral-type Darboux transformations for both mKdV hierarchy and mKdV hierarchy with self-consistent sources.

  10. Integral-Type Darboux Transformations for the mKdV Hierarchy with Self-Consistent Sources

    Institute of Scientific and Technical Information of China (English)

    ZENG Yun-Bo; SHAO Yi-Jun; MA Wen-Xiu

    2002-01-01

    We present integral-type Darboux transformation for the mKdV hierarchy and for the mKdV hierarchy withself-consistent sources. In contrast with the normal Darboux transformation, the integral-type Darboux transformationscan offer non-auto-Backlund transformation between two (2n + 1)-th mKdV equations with self-consistent sources withdifferent degrees. This kind of Darboux transformation enables us to construct the N-soliton solution for the mKdVhierarchy with self-consistent sources. We also propose the formulas for the m times repeated integral-type Darbouxtransformations for both mKdV hierarchy and mKdV hierarchy with self-consistent sources.

  11. Superoxide anion radicals induce IGF-1 resistance through concomitant activation of PTP1B and PTEN.

    Science.gov (United States)

    Singh, Karmveer; Maity, Pallab; Krug, Linda; Meyer, Patrick; Treiber, Nicolai; Lucas, Tanja; Basu, Abhijit; Kochanek, Stefan; Wlaschek, Meinhard; Geiger, Hartmut; Scharffetter-Kochanek, Karin

    2015-01-01

    The evolutionarily conserved IGF-1 signalling pathway is associated with longevity, metabolism, tissue homeostasis, and cancer progression. Its regulation relies on the delicate balance between activating kinases and suppressing phosphatases and is still not very well understood. We report here that IGF-1 signalling in vitro and in a murine ageing model in vivo is suppressed in response to accumulation of superoxide anions (O2∙-) in mitochondria, either by chemical inhibition of complex I or by genetic silencing of O2∙--dismutating mitochondrial Sod2. The O2∙--dependent suppression of IGF-1 signalling resulted in decreased proliferation of murine dermal fibroblasts, affected translation initiation factors and suppressed the expression of α1(I), α1(III), and α2(I) collagen, the hallmarks of skin ageing. Enhanced O2∙- led to activation of the phosphatases PTP1B and PTEN, which via dephosphorylation of the IGF-1 receptor and phosphatidylinositol 3,4,5-triphosphate dampened IGF-1 signalling. Genetic and pharmacologic inhibition of PTP1B and PTEN abrogated O2∙--induced IGF-1 resistance and rescued the ageing skin phenotype. We thus identify previously unreported signature events with O2∙-, PTP1B, and PTEN as promising targets for drug development to prevent IGF-1 resistance-related pathologies.

  12. Matrine Activates PTEN to Induce Growth Inhibition and Apoptosis in V600EBRAF Harboring Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Shuiying Wang

    2013-07-01

    Full Text Available Here, we report a natural chemical Matrine, which exhibits anti-melanoma potential with its PTEN activation mechanism. Matrine effectively inhibited proliferation of several carcinoma cell lines, including melanoma V600EBRAF harboring M21 cells. Flow cytometry analysis showed Matrine induced G0/G1 cell cycle arrest in M21 cells dose-dependently. Apoptosis in M21 cells induced by Matrine was identified by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL analysis and Annexin-V/FITC staining. Molecular mechanistic study suggested that Matrine upregulated both mRNA level and protein expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN, leading to inhibition of the PI3K/Akt pathway. Downregulation of phosphor-Aktser473 by Matrine activated p21 and Bax, which contributed to G0/G1 cell cycle and apoptosis. Besides, Matrine enhanced the PI3K/Akt inhibition effects to inhibit the cell proliferation with PI3K inhibitor, LY2940002. In summary, our findings suggest Matrine is a promising antitumor drug candidate with its possible PTEN activation mechanisms for treating cancer diseases, such as melanomas.

  13. Depletion of DNMT3A Suppressed Cell Proliferation and Restored PTEN in Hepatocellular Carcinoma Cell

    Directory of Open Access Journals (Sweden)

    Zhujiang Zhao

    2010-01-01

    Full Text Available Promoter hypermethylation mediated by DNA methyltransferases (DNMTs is the main reason for epigenetic inactivation of tumor suppressor genes (TSGs. Previous studies showed that DNMT1 and DNMT3B play an important role in CpG island methylation in tumorigenesis. Little is known about the role of DNMT3A in this process, especially in hepatocellular carcinoma (HCC. In the present study, increased DNMT3A expression in 3 out of 6 HCC cell lines and 16/25 (64% HCC tissues implied that DNMT3A is involved in hepatocellular carcinogenesis. Depletion of DNMT3A in HCC cell line SMMC-7721 inhibited cell proliferation and decreased the colony formation (about 65%. Microarray data revealed that 153 genes were upregulated in DNMT3A knockdown cells and that almost 71% (109/153 of them contain CpG islands in their 5′ region. 13 of them including PTEN, a crucial tumor suppressor gene in HCC, are genes involved in cell cycle and cell proliferation. Demethylation of PTEN promoter was observed in DNMT3A-depleted cells implying that DNMT3A silenced PTEN via DNA methylation. These results provide insights into the mechanisms of DNMT3A to regulate TSGs by an epigenetic approach in HCC.

  14. Analysis of Phosphatidylinositol 3,4,5-Trisphosphates of PTEN Expression on Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Nusrat Jahan

    2013-09-01

    Full Text Available The goal of this study is to find an experimental condition which enables us to perform enzymatic studies on the cellular behavior of PTEN (phosphatase and tensine homolog through identification of molecular species of phosphatidylinositol 3,4,5- trisphosphates and their quantitative analysis in a mammalian cell line using mass spectrometry. We initially exployed a two-step extraction process using HCl for extraction of phosphatidylinositol 3,4,5-trisphosphates from two mammalian cell lines and further analyzed the extracted phosphatidylinositol 3,4,5-trisphosphates using tandem mass spectrometry for the identification of them. We finally quantified the concentration of phosphatidylinositol 3,4,5-trisphosphates using internal standard calibration. From these observation, we found that HEK 293-T cells is a good model to examine the enzymatic behavior of PTEN in a cell, and the minimum amount of phosphatidylinositol 3,4,5-trisphosphates is more than 50 pmol for quantification in a mass spectrometer. These results suggest that the well-optimized experimental conditions are required for the investigation of the cellular PTEN in terms of the catalytic mechanism and further for the detailed identification of cellular substrates

  15. PTEN基因与皮肤肿瘤%PTEN gene and skin cancer

    Institute of Scientific and Technical Information of China (English)

    郭泽; 周炳荣; 李巍; 骆丹

    2011-01-01

    皮肤肿瘤是一类最常见的肿瘤,在引起皮肤肿瘤发生的诸多原因中,紫外线照射是主要影响因素之一。PTEN是近年来研究较多的一个肿瘤抑制基因,位于染色体10q23,3。目前研究证实,PTEN在多种皮肤肿瘤,如基底细胞癌、鳞状细胞癌、恶性黑素瘤中都起着抑制基因的作用,发现在皮肤肿瘤形成过程中,紫外线照射可引起PTEN失活,对肿瘤的形成可能起着促进的作用。%Skin cancer is one of the most common cancers. Ultraviolet irradiation is the predominant environmental factor causing skin cancer. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene located on chromosome 10 q23,3, which has been frequently studied in recent years. There is evidence that PTEN acts as a tumor suppressor in many skin cancers, such as basal cell carcinoma, squamous cell carcinoma, and melanoma. Ultraviolet irradiation can result in the inactivation of PTEN and in turn promote the development of cancer.

  16. Multisoliton Solutions of the (2+1)-Dimensional KdV Equation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jie-Fang; HUANG Wen-Hua

    2001-01-01

    Using the extension homogeneous balance method,we have obtained some new special types of soliton solutions of the (2+1)-dimensional KdV equation.Starting from the homogeneous balance method,one can obtain a nonlinear transformation to simple (2+1)-dimensional KdV equation into a linear partial differential equation and two bilinear partial differential equations.Usually,one can obtain only a kind of soliton-like solutions.In this letter,we find further some special types of the multisoliton solutions from the linear and bilinear partial differential equations.``

  17. Lie symmetry analysis and reduction of a new integrable coupled KdV system

    Institute of Scientific and Technical Information of China (English)

    Qian Su-Ping; Tian Li-Xin

    2007-01-01

    In this paper, Lie symmetry is investigated for a new integrable coupled Korteweg-de Vries (KdV) equation system. Using some symmetry subalgebra of the equation system, we obtain five types of the significant similarity reductions. Abundant solutions of the coupled KdV equation system, such as the solitary wave solution, exponential solution, rational solution and polynomial solution, etc. are obtained from the reduced equations. Especially, one type of group-invariant solution of reduced equations can be acquired by means of the Painlev?I transcendent function.

  18. Travelling wave solutions for the Painleve-integrable coupled KdV equations

    Directory of Open Access Journals (Sweden)

    Xiao-Biao Lin

    2008-06-01

    Full Text Available We study the travelling wave solutions for a system of coupled KdV equations derived by Lou et al [11]. In that paper, they found 5 types of Painleve integrable systems for the coupled KdV system. We show that each of them can be reduced to a partially or completely uncoupled system, through which the dynamical behavior of travelling wave solutions can be determined. In some parameter regions, exact formulas for periodic and solitary waves can be obtained while in other cases, bounded travelling wave solution are discussed.

  19. On a Schwarzian PDE associated with the KdV Hierarchy

    CERN Document Server

    Nijhoff, F W; Joshi, N; Nijhoff, Frank; Hone, Andrew; Joshi, Nalini

    1999-01-01

    We present a novel integrable non-autonomous partial differential equation of the Schwarzian type, i.e. invariant under Möbius transformations, that is related to the Korteweg-de Vries hierarchy. In fact, this PDE can be considered as the generating equation for the entire hierarchy of Schwarzian KdV equations. We present its Lax pair, establish its connection with the SKdV hierarchy, its Miura relations to similar generating PDEs for the modified and regular KdV hierarchies and its Lagrangian structure. Finally we demonstrate that its similarity reductions lead to the {\\it full} Painlevé VI equation, i.e. with four arbitary parameters.

  20. Integrable KdV Hierarchies on $T^2=S^1\\times S^1$

    CERN Document Server

    Sedra, M B

    2007-01-01

    Following our previous works on extended higher spin symmetries on the torus we focus in the present contribution to make a setup of the integrable KdV hierarchies on $T^{2} = S^{1} \\times S^{1}$. Actually two particular systems are considered, namely the KdV and the Burgers non linear integrable model associated to currents of conformal weights (2, 2) and (1, 1) respectively. One key steps towards proving the integrability of these systems is to find their Lax pair operators. This is explicitly done and a mapping between the two systems is discussed.

  1. New Jacobian Elliptic Function Solutions of Modified KdV Equation: Ⅱ

    Institute of Scientific and Technical Information of China (English)

    YAN Zhen-Ya

    2002-01-01

    Recently, we obtained thirteen families of Jacobian elliptic function solutions of mKdV equation by usingour extended Jacobian elliptic function expansion method. In this note, the mKdV equation is investigated and anotherthree families of new doubly periodic solutions (Jacobian elliptic function solutions) are fbund again by using a newtransformation, which and our extended Jacobian elliptic function expansion method form a new method still called theextended Jacobian elliptic function expansion method. The new method can be more powertul to be applied to othernonlinear differential equations.

  2. New Jacobian Elliptic Function Solutions of Modified KdV Equation: Ⅲ

    Institute of Scientific and Technical Information of China (English)

    YAN Zhen-Ya

    2003-01-01

    More recently, sixteen families of Jacobian elliptic function solutions of mKdV equation have been foundby using our extended Jacobian elliptic function expansion method. In this paper, we continue to improve our methodby using another eight pairs of the closed Jacobian elliptic functions. The mKdV equation is chosen to illustrate theimproved method such that another eight families of new Jacobian elliptic function solutions are obtained again. Thenew method can be more powerful to be applied to other nonlinear differential equations.

  3. Using KD(asterisk)P modulators for polarization measurements of the sun

    Science.gov (United States)

    West, E. A.

    1990-01-01

    Longitudinal KD(asterisk)Ps are used in ground-based solar magnetographs to eliminate seeing effects by rapidly changing their retardation characteristics. Although one of the main applications for longitudinal KD(asteriak)Ps has been their use as a variable retarder for 'imaging' applications, an understanding of their limitations is important when developing scientific instruments that make very accurate polarization measurements. This paper discusses some of the problems associated with the use of these devices in the Marshall Space Flight Center (MSFC) vector magnetograph, including temperature, field of view errors, and electrical characteristics.

  4. Multi-symplectic method for generalized fifth-order KdV equation

    Institute of Scientific and Technical Information of China (English)

    Hu Wei-Peng; Deng Zi-Chen

    2008-01-01

    This paper considers the multi-symplectic formulations of the generalized fifth-order KdV equation in Hamiltonian space.Recurring to the midpoint rule,it presents an implicit multi-symplectic scheme with discrete multi-symplectic conservation law to solve the partial differential equations which are derived from the generalized fifth-order KdV equation numerically.The results of the numerical experiments show that this multi-symplectie algorithm is good in accuracy and its long-time numerical behaviour is also perfect.

  5. Lie symmetry analysis and explicit solutions of the time fractional fifth-order KdV equation.

    Directory of Open Access Journals (Sweden)

    Gang Wei Wang

    Full Text Available In this paper, using the Lie group analysis method, we study the invariance properties of the time fractional fifth-order KdV equation. A systematic research to derive Lie point symmetries to time fractional fifth-order KdV equation is performed. In the sense of point symmetry, all of the vector fields and the symmetry reductions of the fractional fifth-order KdV equation are obtained. At last, by virtue of the sub-equation method, some exact solutions to the fractional fifth-order KdV equation are provided.

  6. Lie symmetry analysis and explicit solutions of the time fractional fifth-order KdV equation.

    Science.gov (United States)

    Wang, Gang Wei; Xu, Tian Zhou; Feng, Tao

    2014-01-01

    In this paper, using the Lie group analysis method, we study the invariance properties of the time fractional fifth-order KdV equation. A systematic research to derive Lie point symmetries to time fractional fifth-order KdV equation is performed. In the sense of point symmetry, all of the vector fields and the symmetry reductions of the fractional fifth-order KdV equation are obtained. At last, by virtue of the sub-equation method, some exact solutions to the fractional fifth-order KdV equation are provided.

  7. Method of Multiple Scales and Travelling Wave Solutions for (2+1)-Dimensional KdV Type Nonlinear Evolution Equations

    Science.gov (United States)

    Ayhan, Burcu; Özer, M. Naci; Bekir, Ahmet

    2016-08-01

    In this article, we applied the method of multiple scales for Korteweg-de Vries (KdV) type equations and we derived nonlinear Schrödinger (NLS) type equations. So we get a relation between KdV type equations and NLS type equations. In addition, exact solutions were found for KdV type equations. The ( G'} over G )-expansion methods and the ( {G'} over G, {1 over G}} )-expansion methods were proposed to establish new exact solutions for KdV type differential equations. We obtained periodic and hyperbolic function solutions for these equations. These methods are very effective for getting travelling wave solutions of nonlinear evolution equations (NEEs).

  8. Loss of PTEN expression is associated with increased risk of recurrence after prostatectomy for clinically localized prostate cancer.

    Science.gov (United States)

    Chaux, Alcides; Peskoe, Sarah B; Gonzalez-Roibon, Nilda; Schultz, Luciana; Albadine, Roula; Hicks, Jessica; De Marzo, Angelo M; Platz, Elizabeth A; Netto, George J

    2012-11-01

    PTEN (phosphatase and tensin homolog on chromosome 10) is one of the most frequently lost tumor suppressor genes in human cancers and it has been described in more than two-thirds of patients with advanced/aggressive prostate cancer. Previous studies suggest that, in prostate cancer, genomic PTEN loss is associated with tumor progression and poor prognosis. Thus, we evaluated whether immunohistochemical PTEN expression in prostate cancer glands was associated with higher risk of recurrence, using a nested case-control study that included 451 men who recurred and 451 men who did not recur with clinically localized prostate cancer treated by radical prostatectomy. Recurrence was defined as biochemical recurrence (serum prostate-specific antigen >0.2 ng/ml) or clinical recurrence (local recurrence, systemic metastases, or prostate cancer-related death). Cases and controls were matched on pathological T stage, Gleason score, race/ethnicity, and age at surgery. Odds ratios of recurrence and 95% confidence intervals were estimated using conditional logistic regression to account for the matching factors and to adjust for year of surgery, preoperative prostate-specific antigen concentrations, and status of surgical margins. Men who recurred had a higher proportion of PTEN negative expression (16 vs 11%, P=0.05) and PTEN loss (40 vs 31%, P=0.02) than controls. Men with markedly decreased PTEN staining had a higher risk of recurrence (odds ratio=1.67; 95% confidence intervals 1.09, 2.57; P=0.02) when compared with all other men. In summary, in patients with clinically localized prostate cancer treated by prostatectomy, decreased PTEN expression was associated with an increased risk of recurrence, independent of known clinicopathological factors.

  9. An integrative genomic and proteomic analysis of PIK3CA, PTEN and AKT mutations in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Stemke-Hale, Katherine; Gonzalez-Angulo, Ana Maria; Lluch, Ana; Neve, Richard M.; Kuo, Wen-Lin; Davies, Michael; Carey, Mark; Hu, Zhi; Guan, Yinghui; Sahin, Aysegul; Symmans, W. Fraser; Pusztai, Lajos; Nolden, Laura K.; Horlings, Hugo; Berns, Katrien; Hung, Mien-Chie; van de Vijver, Marc J.; Valero, Vicente; Gray, Joe W.; Bernards, Rene; Mills, Gordon B.; Hennessy, Bryan T.

    2008-05-06

    Phosphatidylinositol-3-kinase (PI3K)/AKT pathway aberrations are common in cancer. By applying mass spectroscopy-based sequencing and reverse phase protein arrays to 547 human breast cancers and 41 cell lines, we determined the subtype specificity and signaling effects of PIK3CA, AKT and PTEN mutations, and the effects of PIK3CA mutations on responsiveness to PI3K inhibition in-vitro and on outcome after adjuvant tamoxifen. PIK3CA mutations were more common in hormone receptor positive (33.8%) and HER2-positive (24.6%) than in basal-like tumors (8.3%). AKT1 (1.4%) and PTEN (2.3%) mutations were restricted to hormone receptor-positive cancers with PTEN protein levels also being significantly lower in hormone receptor-positive cancers. Unlike AKT1 mutations, PIK3CA (39%) and PTEN (20%) mutations were more common in cell lines than tumors, suggesting a selection for these but not AKT1 mutations during adaptation to culture. PIK3CA mutations did not have a significant impact on outcome in 166 hormone receptor-positive breast cancer patients after adjuvant tamoxifen. PIK3CA mutations, in comparison with PTEN loss and AKT1 mutations, were associated with significantly less and indeed inconsistent activation of AKT and of downstream PI3K/AKT signaling in tumors and cell lines, and PTEN loss and PIK3CA mutation were frequently concordant, suggesting different contributions to pathophysiology. PTEN loss but not PIK3CA mutations rendered cells sensitive to growth inhibition by the PI3K inhibitor LY294002. Thus, PI3K pathway aberrations likely play a distinct role in the pathogenesis of different breast cancer subtypes. The specific aberration may have implications for the selection of PI3K-targeted therapies in hormone receptor-positive breast cancer.

  10. Inhibitory Effect of Isoflavones on Prostate Cancer Cells and PTEN Gene

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To explore the mechanisms by which genistein and daidzein inhibit the growth of prostate cancer cells. Methods LNCaP and PC-3 cells were exposed to genistein and daidzein and cell viability was determined by MTT assay and cytotoxicity of the drugs by LDH test. Flow cytometry (FCM) was used to assess the cell cycle in LNCaP and PC-3 cells.Reverse transcription-polymerase chain reaction (RT-PCR) was applied to examine the expression of PTEN gene (a tumor suppressor gene), estrogen receptor alpha gene (Erα), estrogen receptor beta gene (Erβ), androgen receptor gene (AR) and vascular endothelial growth factor gene (VEGF). Results The viability of PC-3 and LNCaP cells decreased with increasing concentrations and exposure time of genistein and daidzein. Genistein increased G2/M phase cells in PC-3 cells while decreased S phase cells in LNCaP cells in a dose-dependent manner. Daidzein exerted no influence on the cell cycle of LNCaP and PC-3 cells, but the apoptosis percentage of LNCaP cells was elevated significantly by daidzein. Genistein induced the expression of PTEN gene in PC-3 and LNCaP cells. Daidzein induced the expression of PTEN gene in LNCaP but not in PC-3 cells. The expression of VEGF, Erα and Erβ genes decreased and AR gene was not expressed after incubation with genistein and daidzein in PC-3 cells. In LNCaP cells, the expression of VEGF and AR gene decreased but there was no change in the expression of Erα and Erβ gene after incubation with genistein and daidzein. Conclusion Genistein and daidzein exert a time- and dose-dependent inhibitory effect on PC-3 and LNCaP cells. The down-regulation of ER gene by daidzein influences the growth of PC-3 cells directly. The inhibition of PC-3 cells by genistein and that of LNCaP cells by genistein and daidzein may be via Akt pathway that is repressed by PTEN gene, which subsequently down-regulates the expression of AR and VEGF genes. Our results suggest that the expression of PTEN gene plays a key

  11. Deletion of PTEN produces autism-like behavioral deficits and alterations in synaptic proteins.

    Science.gov (United States)

    Lugo, Joaquin N; Smith, Gregory D; Arbuckle, Erin P; White, Jessika; Holley, Andrew J; Floruta, Crina M; Ahmed, Nowrin; Gomez, Maribel C; Okonkwo, Obi

    2014-01-01

    Many genes have been implicated in the underlying cause of autism but each gene accounts for only a small fraction of those diagnosed with autism. There is increasing evidence that activity-dependent changes in neuronal signaling could act as a convergent mechanism for many of the changes in synaptic proteins. One candidate signaling pathway that may have a critical role in autism is the PI3K/AKT/mTOR pathway. A major regulator of this pathway is the negative repressor phosphatase and tensin homolog (PTEN). In the current study we examined the behavioral and molecular consequences in mice with neuron subset-specific deletion of PTEN. The knockout (KO) mice showed deficits in social chamber and social partition test. KO mice demonstrated alterations in repetitive behavior, as measured in the marble burying test and hole-board test. They showed no changes in ultrasonic vocalizations emitted on postnatal day 10 or 12 compared to wildtype (WT) mice. They exhibited less anxiety in the elevated-plus maze test and were more active in the open field test compared to WT mice. In addition to the behavioral alterations, KO mice had elevation of phosphorylated AKT, phosphorylated S6, and an increase in S6K. KO mice had a decrease in mGluR but an increase in total and phosphorylated fragile X mental retardation protein. The disruptions in intracellular signaling may be why the KO mice had a decrease in the dendritic potassium channel Kv4.2 and a decrease in the synaptic scaffolding proteins PSD-95 and SAP102. These findings demonstrate that deletion of PTEN results in long-term alterations in social behavior, repetitive behavior, activity, and anxiety. In addition, deletion of PTEN significantly alters mGluR signaling and many synaptic proteins in the hippocampus. Our data demonstrates that deletion of PTEN can result in many of the behavioral features of autism and may provide insights into the regulation of intracellular signaling on synaptic proteins.

  12. Construction and identification of the PTEN expression plasmid GFP-PTEN%PTEN基因真核表达载体的构建及在MG63中表达

    Institute of Scientific and Technical Information of China (English)

    徐生林; 胡勇; 金问森; 王明明; 王京; 王娟

    2012-01-01

    目的 构建PTEN基因真核表达载体,为PTEN基因功能研究提供工具.方法 从人淋巴细胞中提取总RNA,采用反转录-聚合酶链反应扩增PTEN基因编码区,将其克隆入pEGFP-N1载体中.通过聚合酶链反应、酶切和DNA测序鉴定所构建的载体.脂质体包裹重组载体转染骨肉瘤MG63细胞,RT-PCR和Western blot检测转染后的骨肉瘤MG63细胞中PTEN基因mRNA和蛋白质表达情况.结果 经过限制性酶切和测序鉴定得到重组子GFP-PTEN大小符合,序列与GenBank中人DNA的PTEN基因(NM_000314)完全一致.转染GFP-PTEN基因的骨肉瘤MG63细胞中PTEN基因mRNA和蛋白高水平表达.结论 成功地构建了PTEN基因真核表达载体.%Objective To construct an eukaryotic expression vector for phosphatase and tensin homology deletedon chromosome ten( PTEN ) gene lymphocytes and provide a tool for studying of PTEN gene function. Methods The total RNAs were isolated from human lymphocytes. The cDNA of PTEN gene was amplified by reverse transcription polymerase chain reaction( RT-PCR ). After purification, the gene was cloned into pEGFP-Nl vector. The recombi-nant plasmid was identified by enzyme digestion and DNA sequencing. Then GFP and GFP-PTEN were respectively transfected into the osteosaocoma cell line( MG63 )with Lipofectamine 2000. The mRNA and protein expression level of PTEN gene in each cell group was detected by fluorescent quantitative RT-PCR and Western blot. Results Re-combinant vector of GFP-PTEN was constructed successfully. After transfection with GFP-PTEN, the mRNA and protein expression level of PTEN rose in MG63 cells. There were significant differences between transfected group and control group. Conclusion The eukaryotic expression vector of PTEN gene has been successfully constructed, which may provide a basis for further researches.

  13. Honey bee PTEN--description, developmental knockdown, and tissue-specific expression of splice-variants correlated with alternative social phenotypes.

    Directory of Open Access Journals (Sweden)

    Navdeep S Mutti

    Full Text Available BACKGROUND: Phosphatase and TENsin (PTEN homolog is a negative regulator that takes part in IIS (insulin/insulin-like signaling and Egfr (epidermal growth factor receptor activation in Drosophila melanogaster. IIS and Egfr signaling events are also involved in the developmental process of queen and worker differentiation in honey bees (Apis mellifera. Here, we characterized the bee PTEN gene homologue for the first time and begin to explore its potential function during bee development and adult life. RESULTS: Honey bee PTEN is alternatively spliced, resulting in three splice variants. Next, we show that the expression of PTEN can be down-regulated by RNA interference (RNAi in the larval stage, when female caste fate is determined. Relative to controls, we observed that RNAi efficacy is dependent on the amount of PTEN dsRNA that is delivered to larvae. For larvae fed queen or worker diets containing a high amount of PTEN dsRNA, PTEN knockdown was significant at a whole-body level but lethal. A lower dosage did not result in a significant gene down-regulation. Finally, we compared same-aged adult workers with different behavior: nursing vs. foraging. We show that between nurses and foragers, PTEN isoforms were differentially expressed within brain, ovary and fat body tissues. All isoforms were expressed at higher levels in the brain and ovaries of the foragers. In fat body, isoform B was expressed at higher level in the nurse bees. CONCLUSION: Our results suggest that PTEN plays a central role during growth and development in queen- and worker-destined honey bees. In adult workers, moreover, tissue-specific patterns of PTEN isoform expression are correlated with differences in complex division of labor between same-aged individuals. Therefore, we propose that knowledge on the roles of IIS and Egfr activity in developmental and behavioral control may increase through studies of how PTEN functions can impact bee social phenotypes.

  14. Travelling wave solutions for a singularly perturbed Burgers–KdV equation

    Indian Academy of Sciences (India)

    M B A Mansour

    2009-11-01

    This paper concerns with the existence problem of travelling wave solutions to a singularly perturbed Burgers–KdV equation. For this, we use the dynamical systems approach, specifically, the geometric singular perturbation theory and centre manifold theory. We also numerically show approximations, in particular, for kink-type waves.

  15. NEW EXACT SOLUTIONS TO KdV EQUATIONS WITH VARIABLE COEFFICIENTS OR FORCING

    Institute of Scientific and Technical Information of China (English)

    付遵涛; 刘式达; 刘式适; 赵强

    2004-01-01

    Jacobi elliptic function expansion method is extended to construct the exact solutions to another kind of KdV equations, which have variable coefficients or forcing terms. And new periodic solutions obtained by this method can be reduced to the solitontyped solutions under the limited condition.

  16. A Note on the Painlevé Property of Coupled KdV Equations

    Directory of Open Access Journals (Sweden)

    Sergei Sakovich

    2014-01-01

    Full Text Available We prove that one system of coupled KdV equations, claimed by Hirota et al. to pass the Painlevé test for integrability, actually fails the test at the highest resonance of the generic branch and therefore must be nonintegrable.

  17. The Pentagram map in higher dimensions and KdV flows

    CERN Document Server

    Khesin, Boris

    2012-01-01

    We extend the definition of the pentagram map from 2D to higher dimensions and describe its integrability properties for both closed and twisted polygons by presenting its Lax form. The corresponding continuous limit of the pentagram map in dimension $d$ is shown to be the $(2,d+1)$-flow of the KdV hierarchy, generalizing the Boussinesq equation in 2D.

  18. General mixed problems for the KdV equations on bounded intervals

    Directory of Open Access Journals (Sweden)

    Nikolai A. Larkin

    2010-11-01

    Full Text Available This article is concerned with initial-boundary value problems for the Korteweg-de Vries (KdV equation on bounded intervals. For general linear boundary conditions and small initial data, we prove the existence and uniqueness of global regular solutions and its exponential decay, as $toinfty$.

  19. Deformation and recursion for the $N = 2 \\; \\alpha = 1$ supersymmetric KdV hierarchy

    NARCIS (Netherlands)

    Sorin, A.S.; Kersten, P.H.M.

    2002-01-01

    A detailed description is given for the construction of the deformation of the $N=2$ supersymmetric $\\alpha=1$ KdV-equation, leading to the recursion operator for symmetries and the zero-th Hamiltonian structure; the solution to a longstanding problem.

  20. Bi-Hamiltonian structure of the $N=2$ supersymmetric $\\alpha = 1$ KdV hierarchy

    NARCIS (Netherlands)

    Kersten, P.H.M.; Sorin, A.S.

    2002-01-01

    The $N=2$ supersymmetric ${\\alpha}=1$ KdV hierarchy in $N=2$ superspace is considered and its rich symmetry structure is uncovered. New nonpolynomial and nonlocal, bosonic and fermionic symmetries and Hamiltonians, bi-Hamiltonian structure as well as a recursion operator connecting all symmetries an

  1. Deformation and Recursion for the N=2 α=1 Supersymmetric KdV Hierarchy

    NARCIS (Netherlands)

    Sorin, Alexander S.; Kersten, Paul H.M.

    2004-01-01

    A detailed description is given for the construction of the deformation of the N=2 supersymmetric α=1 KdV equation, leading to the recursion operator for symmetries and the zero-order Hamiltonian structure; the solution to a longstanding problem.

  2. The Integrability of New Two-Component KdV Equation

    Directory of Open Access Journals (Sweden)

    Ziemowit Popowicz

    2010-02-01

    Full Text Available We consider the bi-Hamiltonian representation of the two-component coupled KdV equations discovered by Drinfel'd and Sokolov and rediscovered by Sakovich and Foursov. Connection of this equation with the supersymmetric Kadomtsev-Petviashvilli-Radul-Manin hierarchy is presented. For this new supersymmetric equation the Lax representation and odd Hamiltonian structure is given.

  3. Bi-Hamiltonian structure of the N=2 supersymmetric α=1 KdV hierarchy

    NARCIS (Netherlands)

    Kersten, P.H.M.; Sorin, A.S.

    2002-01-01

    The N=2 supersymmetric α=1 KdV hierarchy in N=2 superspace is considered and its rich symmetry structure is uncovered. New nonpolynomial and nonlocal, bosonic and fermionic symmetries and Hamiltonians, bi-Hamiltonian structure as well as a recursion operator connecting all symmetries and Hamiltonian

  4. Exact Solutions for a Nonisospectral and Variable-Coefficient KdV Equation

    Institute of Scientific and Technical Information of China (English)

    DENG Shu-Fang

    2005-01-01

    The bilinear form for a nonisospectral and variable-coefficient KdV equation is obtained and some exact soliton solutions are derived through Hirota method and Wronskian technique. We also derive the bilinear transformation from its Lax pairs and find solutions with the help of the obtained bilinear transformation.

  5. EXPLICIT SOLUTIONS TO THE COUPLED KdV EQUATIONS WITH VARIABLE COEFFICIENTS

    Institute of Scientific and Technical Information of China (English)

    徐桂琼; 李志斌

    2005-01-01

    By means of sn-function expansion method and cn-function expansion method,several kinds of explicit solutions to the coupled KdV equations with variable coefficients are obtained, which include three sets of periodic wave-like solutions. These solutions degenerate to solitary wave-like solutions at a certain limit. Some new solutions are presented.

  6. Alice-Bob Physics: Coherent Solutions of Nonlocal KdV Systems

    CERN Document Server

    Lou, S Y

    2016-01-01

    In natural and social science, many events happened at different space-times may be closely entangled or correlated. Two events, $A$ (Alice) and $B$ (Bob) are defined as correlated if one event is determined by another, say, $B=\\hat{f}A$ for suitable $\\hat{f}$ operators. Can we find these kinds of correlated solutions from the known physically significant models? Alternatively, can we establish/derive some significant physical models to describe these kinds of correlated phenomena? Taking KdV and coupled KdV systems as examples, we can find some types of models (defined as Alice-Bob KdV systems) to exhibit the existence on the correlated solutions linked with two events, event $A=A(x,\\ t)$ and event $B=B(x',\\ t')=\\hat{f}A$ happened at $\\{x,\\ t\\}$ and $\\{x',\\ t'\\}$ respectively. The idea of this letter is valid not only for the physical problems related to the KdV systems but also for all physical problems which can be described by arbitrary continuous or discrete mathematical models.

  7. 海外KD出口项目分析%Analysis on Overseas KD Export Project

    Institute of Scientific and Technical Information of China (English)

    张伟亮

    2012-01-01

    With increasingly fierce compelition of automolive enterprises inm domestic, overseas KD exporl will play more imporlanl role as ecmumic growlh of enlerprises. From destination market exploration, export parmer choosing, producl cerlification, producllon preparation, KD packing, trial producllon and inilial batch production,lhls arlicle systematically describes dlflerenl slages of KD exporl projecl. It provides reDrence lbr overseas KD export projecl of enterprises in the future.%随着国内汽车企业竞争日益激烈,海外KD(k,reekeddown)出口作为企业经济增长点变得尤为重要.文章系统地从海外KD出口项目市场的考察、出口合作方的选择、产品认证、生产准备、KD出口包装以及试生产和量产初期阶段进行了比较全面的描述,为今后企业海外KD项目出口提供指导。

  8. Kelley Direct (KD) Toolkit: Toward the Development of Innovative Pedagogical Tools for Business Education

    Science.gov (United States)

    Magjuka, Richard J.; Liu, Xiaojing; Lee, Seung-Hee

    2006-01-01

    KD Toolkit shows a representative synthesis of the best practices learned by world-renowned instructors in a top ranked online MBA program in the United States. This article will share and discuss the pedagogical implications of this learning technology and the leadership and innovative effort of the program that afforded the development of KD…

  9. Modified KdV equation for solitary Rossby waves with β effect in barotropic fluids

    Institute of Scientific and Technical Information of China (English)

    Song Jian; Yang Lian-Gui

    2009-01-01

    This paper uses the weakly nonlinear method and perturbation method to deal with the quasi-geostrophic vorticity equation, and the modified Korteweg-de Vries(mKdV) equations describing the evolution of the amplitude of solitary Rossby waves as the change of Rossby parameter β(y) with latitude y is obtained.

  10. A KdV-like advection-dispersion equation with some remarkable properties

    CERN Document Server

    Sen, Abhijit; Thyagaraja, Anantanarayanan; Krishnaswami, Govind S

    2011-01-01

    We discuss a new non-linear advection-dispersion equation u_t + (2 u_{xx}/u) u_x = epsilon u_{xxx}, invariant under scaling of dependent variable and referred to here as SIdV. This PDE (with dispersion coefficient unity) was discovered in a genetic programming search for equations sharing the Korteweg-de Vries (KdV) solitary wave solution. Indeed, there is a one-parameter family of first order advection equations with cubic dispersion sharing the KdV solitary wave, that interpolate between SIdV and KdV. SIdV is one of the two simplest such translation and space-time reflection-symmetric equations invariant under rescaling of wave amplitude u. The scale-invariant advection in SIdV is reminiscent of the (E x B)/B^2 velocity of plasma physics. We identify two conservation laws, though initial investigations indicate that SIdV does not follow from a polynomial Lagrangian of the KdV sort. Nevertheless, SIdV possesses solitary and periodic travelling waves and recurrence properties usually associated with integrabl...

  11. Capillary Gravity Waves over an Obstruction - Forced Generalized KdV equation

    Science.gov (United States)

    Choi, Jeongwhan; Whang, S. I.; Sun, Shu-Ming

    2013-11-01

    Capillary gravity surface waves of an ideal fluid flow over an obstruction is considered. When the Bond number is near the critical value 1/3, a forced generalized KdV equation of fifth order is derived. We study the equation analytically and numerically. Existence and stability of solutions are studied and new types of numerical solutions are found.

  12. Dynamics of KdV solitons in the presence of a slowly varying potential

    CERN Document Server

    Holmer, Justin

    2010-01-01

    We study the dynamics of solitons as solutions to the perturbed KdV (pKdV) equation $\\partial_t u = -\\partial_x (\\partial_x^2 u + 3u^2-bu)$, where $b(x,t) = b_0(hx,ht)$, $h\\ll 1$ is a slowly varying, but not small, potential. We option an explicit description of the trajectory of the soliton parameters of scale and position on the dynamically relevant time scale $\\delta h^{-1}\\log h^{-1}$, together with an estimate on the error of size $h^{1/2}$. In addition to the Lyapunov analysis commonly applied to these problems, we use a local virial estimate due to Martel-Merle (2005). The results are supported by numerics. The proof does not rely on the inverse scattering machinery and is expected to carry through for the $L^2$ subcritical gKdV-$p$ equation, $1KdV) equation, is structurally simpler and more precise results can be obtained by the method of Holmer-Zworski (2007).

  13. New modification of Laplace decomposition method for seventh order KdV equation

    Science.gov (United States)

    Kashkari, B. S.; Bakodah, H. O.

    2013-10-01

    In this paper, we develop a new modification of Laplace decomposition method for solving the seventh order KdV equations. The numerical results show that the method converges rapidly and compared with the Adomian decomposition method. The conservation properties of solution are examined by calculating the first three invariants.

  14. Analytical and numerical solution of a coupled KdV-MKdV system

    Energy Technology Data Exchange (ETDEWEB)

    Halim, A.A.; Leble, S.B. E-mail: leble@mif.pg.gda.pl

    2004-01-01

    In this work a two-fold compound elementary Darboux transformations (DTs) are newly used to produce two-parameters explicit solutions for a coupled KdV-MKdV system. We consider a second order differential equation as a spectral problem with 2 x 2 matrix coefficients. A second covariant (with respect to DTs) equation is selected to form a Lax pair of a coupled KdV-MKdV system, under correspondent reduction constraint. This reduction gives an automorphism that relates two pairs of solutions of the spectral equation corresponding to different values of the spectral parameters. We use this result in the compound elementary DTs to produce explicit solutions to the coupled KdV-MKdV system being the compatibility condition of Lax pair under this reduction. Effects of parameters on the solution (reality, singularity) are analyzed. A numerical method of solution (difference scheme) of a Cauchy problem for the coupled KdV-MKdV system is also introduced. We analyze stability and prove the convergence of the scheme which gives the conditions and the appropriate choice of the grid sizes. The scheme is tested by numerical simulation of the explicit solutions evaluation.

  15. Application of homotopy analysis method to fractional KdV-Burgers-Kuramoto equation

    Energy Technology Data Exchange (ETDEWEB)

    Song, Lina [Department of Applied Mathematics, Dalian University of Technology, Dalian 116024 (China)]. E-mail: songlina1981@yahoo.com.cn; Zhang, Hongqing [Department of Applied Mathematics, Dalian University of Technology, Dalian 116024 (China)

    2007-07-16

    In the Letter, homotopy analysis method that developed for integer-order differential equation is directly extended to derive explicit and numerical solutions of nonlinear fractional differential equation for the first time. The fractional derivatives are described in the Caputo sense. To our knowledge, the Letter represents the first available numerical solutions of the fractional KdV-Burgers-Kuramoto equation.

  16. A Difference Scheme for the Coupled KdV Equation 14

    Institute of Scientific and Technical Information of China (English)

    ShaohongZHU

    1999-01-01

    In this paper,a difference scheme for the periodic initial-boundary problem of the coupled KdV equation is given.The scheme keeps the first two conserved quantities which the differential equation possesses.The catch-ran iterative method is used to solve the difference equations.The numerical simulation exhibits the existence of two-soliton solutions.

  17. 1-Soliton solutions of complex modified KdV equation with time-dependent coefficients

    Science.gov (United States)

    Kumar, H.; Chand, F.

    2013-09-01

    In this paper, we have obtained exact 1-soliton solutions of complex modified KdV equation with variable—coefficients using solitary wave ansatz. Restrictions on parameters of the soliton have been observed in course of the derivation of soliton solutions. Finally, a few numerical simulations of dark and bright solitons have been given.

  18. Implementasi KD-Tree K-Means Clustering untuk Klasterisasi Dokumen

    Directory of Open Access Journals (Sweden)

    Eric Budiman Gosno

    2013-09-01

    Full Text Available Klasterisasi dokumen adalah suatu proses pengelompokan dokumen secara otomatis dan unsupervised. Klasterisasi dokumen merupakan permasalahan yang sering ditemui dalam berbagai bidang seperti text mining dan sistem temu kembali informasi. Metode klasterisasi dokumen yang memiliki akurasi dan efisiensi waktu yang tinggi sangat diperlukan untuk meningkatkan hasil pada mesin pencari web,  dan untuk proses filtering. Salah satu metode klasterisasi yang telah dikenal dan diaplikasikan dalam klasterisasi dokumen adalah K-Means Clustering. Tetapi K-Means Clustering sensitif terhadap pemilihan posisi awal dari titik tengah klaster sehingga pemilihan posisi awal dari titik tengah klaster yang buruk akan mengakibatkan K-Means Clustering terjebak dalam local optimum. KD-Tree K-Means Clustering merupakan perbaikan dari K-Means Clustering. KD-Tree K-Means Clustering menggunakan struktur data K-Dimensional Tree dan nilai kerapatan pada proses inisialisasi titik tengah klaster. Pada makalah ini diimplementasikan algoritma KD-Tree K-Means Clustering untuk permasalahan klasterisasi dokumen. Performa klasterisasi dokumen yang dihasilkan oleh metode KD-Tree K-Means Clustering pada data set 20 newsgroup memiliki nilai distorsi 3×105 lebih rendah dibandingkan dengan nilai rerata distorsi K-Means Clustering dan nilai NIG 0,09 lebih baik dibandingkan dengan nilai NIG K-Means Clustering.

  19. The fractional coupled KdV equations: Exact solutions and white noise functional approach

    Institute of Scientific and Technical Information of China (English)

    Hossam A.Ghany; A.S.Okb El Bab; A.M.Zabel; Abd-Allah Hyder

    2013-01-01

    Variable coefficients and Wick-type stochastic fractional coupled KdV equations are investigated.By using the modified fractional sub-equation method,Hermite transform,and white noise theory the exact travelling wave solutions and white noise functional solutions are obtained,including the generalized exponential,hyperbolic,and trigonometric types.

  20. Solid/liquid partition coefficients (Kd) for selected soils and sediments at Forsmark and Laxemar-Simpevarp

    Energy Technology Data Exchange (ETDEWEB)

    Sheppard, Steve; Long, Jeff; Sanipelli, Barb (ECOMatters Inc., Pinawa (Canada)); Sohlenius, Gustav (Geological Survey of Sweden (SGU), Uppsala (Sweden))

    2009-03-15

    Soil and sediment solid/liquid partition coefficients (Kd) are used to indicate the relative mobility of radionuclides and elements of concern from nuclear fuel waste, as well as from other sources. The Kd data are inherently extremely variable, but also vary systematically with key environmental attributes. For soil Kd, the key variables are pH, clay content and organic carbon content. For sediment Kd, water type (freshwater versus marine) and sediment type (benthic versus suspended) are important. This report summarized Kd data for soils and sediments computed from indigenous stable element concentrations measured at the Forsmark and Laxemar-Simpevarp sites. These were then compared to several literature sources of Kd data for Ce, Cl, Co, Cr, Cs, Fe, Ho, I, La, Mn, Mo, Nb, Nd, Ni, Np, Pa, Pb, Pu, Ra, Sb, Se, Sm, Sn, Sr, Tc, Th, Tm, U and Yb. The Kd data computed from indigenous stable element concentrations may be especially relevant for assessment of long-lived radionuclides from deep disposal of waste, because the long time frame for the potential releases is more consistent with the steady state measured using indigenous stable elements. For almost every one of these elements in soils, a statistically meaningful regression equation was developed to allow estimation of Kd for any soil given a modest amount of information about the soil. Nonetheless, the median residual geometric standard deviation (GSD) was 4.3-fold, implying confidence bounds of about 18-fold above and below the best estimate Kd. For sediment, the values are categorised simply by water type and sediment type. The median GSD for sediment Kd as measured at the Forsmark and Laxemar-Simpevarp sites was 2.5-fold, but the median GSD among literature values was as high as 8.6-fold. Clearly, there remains considerable uncertainty in Kd values, and it is important to account for this in assessment applications

  1. Electric field-induced suppression of PTEN drives epithelial-to-mesenchymal transition via mTORC1 activation.

    Science.gov (United States)

    Yan, Tiantian; Jiang, Xupin; Guo, Xiaowei; Chen, Wen; Tang, Di; Zhang, Junhui; Zhang, Xingyue; Zhang, Dongxia; Zhang, Qiong; Jia, Jiezhi; Huang, Yuesheng

    2017-02-01

    Naturally occurring electric fields (EFs) are an intrinsic property of wounds. Endogenous EFs in skin wounds play critical roles in the dynamic and well-ordered biological process of wound healing. The epithelial-to-mesenchymal transition (EMT) allows keratinocytes to transition from sedentary cells to motile cells, facilitating wound healing. However, EMT-related studies have been performed without considering endogenous EFs. Thus, the relationship between electrical signals and the EMT remain elusive. Phosphatase and tension homolog (PTEN) and mammalian target of rapamycin complex 1 (mTORC1) are key molecules in sensing electrical cues, and they play significant roles in cellular responses to EFs. In addition, these molecules are closely related to the occurrence of the EMT in other cells. We used primary human keratinocytes to investigate the influence of EFs on the EMT as well as the roles of PTEN and mTORC1 in this process. The effects of EFs on the EMT were investigated by analyzing the levels of specific proteins and transcription factors. The roles of mTORC1 and PTEN and their relationship with each other were studied via pharmacological inhibition or genetic knockdown. A Zeiss imaging system and scratch assays were used to study single-cell motility and monolayer cell migration. EFs induced a range of both biochemical changes (e.g., increased Snail, Slug, vimentin, and N-cadherin expression, decreased E-cadherin expression) and functional changes (e.g., enhanced migratory capacity) that are characteristic of the EMT. EF-stimulated cells exhibited suppressed PTEN expression, and further PTEN downregulation led to the acquisition of more mesenchymal features and the loss of epithelial characteristics, which was accompanied by increased migratory capacity. PTEN overexpression reversed the EF-induced EMT and inhibited the migratory capacity of keratinocytes. EF-induced mTORC1 activation was a required component of the causal relationship between PTEN

  2. 修正cKdV方程组的孤立波结构及其稳定性%Solitary Wave Solutions of Modified Coupled KdV Equation and Their Stability

    Institute of Scientific and Technical Information of China (English)

    石玉仁; 周志刚; 张娟; 杨红娟; 段文山

    2012-01-01

    利用函数展开法求解修正耦合KdV( Coupled KdV,cKdV)方程组,得到几类孤立波解,包括扭结型一钟型、双扭结型、双钟型以及双扭结一双钟型结构的单孤子解.在不同的极限情况下,这些解分别退化为修正cKdV方程的扭结状或钟状孤波解.对孤立波的稳定性进行了数值研究,结果表明:修正cKdV方程既存在稳定的孤立波解,也存在不稳定的孤立波解.%With function expansion method, we obtain several types of solitary wave solutions of modified coupled KdV ( cKdV) equations ,including kink-bell-like soliton,double kinks soliton,double bells soliton and double kinks-double bells soliton. These solitary wave solutions are reduced to kink or bell-like solitons solution under different limitations. We also investigate numerically stability of solitary wave solutions. It indicates that the system of modified cKdV equations has both stable solitary wave solutions and unstable solitary wave solutions.

  3. A γ dose distribution evaluation technique using the k-d tree for nearest neighbor searching.

    Science.gov (United States)

    Yuan, Jiankui; Chen, Weimin

    2010-09-01

    The authors propose an algorithm based on the k-d tree for nearest neighbor searching to improve theγ calculation time for 2D and 3D dose distributions. Theγ calculation method has been widely used for comparisons of dose distributions in clinical treatment plans and quality assurances. By specifying the acceptable dose and distance-to-agreement criteria, the method provides quantitative measurement of the agreement between the reference and evaluation dose distributions. The γ value indicates the acceptability. In regions where γ≤1, the predefined criterion is satisfied and thus the agreement is acceptable; otherwise, the agreement fails. Although the concept of the method is not complicated and a quick naïve implementation is straightforward, an efficient and robust implementation is not trivial. Recent algorithms based on exhaustive searching within a maximum radius, the geometric Euclidean distance, and the table lookup method have been proposed to improve the computational time for multidimensional dose distributions. Motivated by the fact that the least searching time for finding a nearest neighbor can be an O(logN) operation with a k-d tree, where N is the total number of the dose points, the authors propose an algorithm based on the k-d tree for the γ evaluation in this work. In the experiment, the authors found that the average k-d tree construction time per reference point isO(logN), while the nearest neighbor searching time per evaluation point is proportional to O(N1/k), where k is between 2 and 3 for two-dimensional and three-dimensional dose distributions, respectively. Comparing with other algorithms such as exhaustive search and sorted listO(N), the k-d tree algorithm for γ evaluation is much more efficient. © 2010 American Association of Physicists in Medicine.

  4. A single-copy Sleeping Beauty transposon mutagenesis screen identifies new PTEN-cooperating tumor suppressor genes.

    Science.gov (United States)

    de la Rosa, Jorge; Weber, Julia; Friedrich, Mathias Josef; Li, Yilong; Rad, Lena; Ponstingl, Hannes; Liang, Qi; de Quirós, Sandra Bernaldo; Noorani, Imran; Metzakopian, Emmanouil; Strong, Alexander; Li, Meng Amy; Astudillo, Aurora; Fernández-García, María Teresa; Fernández-García, María Soledad; Hoffman, Gary J; Fuente, Rocío; Vassiliou, George S; Rad, Roland; López-Otín, Carlos; Bradley, Allan; Cadiñanos, Juan

    2017-03-20

    The overwhelming number of genetic alterations identified through cancer genome sequencing requires complementary approaches to interpret their significance and interactions. Here we developed a novel whole-body insertional mutagenesis screen in mice, which was designed for the discovery of Pten-cooperating tumor suppressors. Toward this aim, we coupled mobilization of a single-copy inactivating Sleeping Beauty transposon to Pten disruption within the same genome. The analysis of 278 transposition-induced prostate, breast and skin tumors detected tissue-specific and shared data sets of known and candidate genes involved in cancer. We validated ZBTB20, CELF2, PARD3, AKAP13 and WAC, which were identified by our screens in multiple cancer types, as new tumor suppressor genes in prostate cancer. We demonstrated their synergy with PTEN in preventing invasion in vitro and confirmed their clinical relevance. Further characterization of Wac in vivo showed obligate haploinsufficiency for this gene (which encodes an autophagy-regulating factor) in a Pten-deficient context. Our study identified complex PTEN-cooperating tumor suppressor networks in different cancer types, with potential clinical implications.

  5. C-reactive protein inhibits survivin expression via Akt/mTOR pathway downregulation by PTEN expression in cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Beom Seob Lee

    Full Text Available C-reactive protein (CRP is one of the most important biomarkers for arteriosclerosis and cardiovascular disease. Recent studies have shown that CRP affects cell cycle and inflammatory process in cardiac myocytes. Survivin is also involved in cardiac myocytes replication and apoptosis. Reduction of survivin expression is associated with less favorable cardiac remodeling in animal models. However, the effect of CRP on survivin expression and its cellular mechanism has not yet been studied. We demonstrated that treatment of CRP resulted in a significant decrease of survivin protein expression in a concentration-dependent manner in cardiac myocytes. The upstream signaling proteins of survivin, such as Akt, mTOR and p70S6K, were also downregulated by CRP treatment. In addition, CRP increased the protein and mRNA levels of PTEN. The siRNA transfection or specific inhibitor treatment for PTEN restored the CRP-induced downregulation of Akt/mTOR/p70S6K pathway and survivin protein expression. Moreover, pretreatment with a specific p53 inhibitor decreased the CRP-induced PTEN expression. ERK-specific inhibitor also blocked the p53 phosphorylation and PTEN expression induced by CRP. Our study provides a novel insight into CRP-induced downregulation of survivin protein expression in cardiac myocytes through mechanisms that involved in downregulation of Akt/mTOR/p70S6K pathway by expression of PTEN.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-08

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

  7. Gene Expression and Correlation of Pten and Fabp4 in Liver, Muscle, and Adipose Tissues of Type 2 Diabetes Rats.

    Science.gov (United States)

    Su, Di; Zhang, Chuan-Ling; Gao, Ying-Chun; Liu, Xiao-Ying; Li, Cai-Ping; Huangfu, Jian; Xiao, Rui

    2015-11-22

    The aim of this work was to study the Fabp4 and Pten gene expression and correlation in the liver, muscle, and adipose tissues of type 2 diabetes mellitus (T2DM) rats. Male Wistar rats (8 weeks old) were randomly divided into 2 groups (n=12/group): a control group fed a normal diet for 8 weeks and an experimental group fed a high-fat, high-sugar diet for 8 weeks and that received 25 mg/kg streptozotocin by intraperitoneal injection to induce T2DM. The random blood glucose, fasting blood glucose, and fasting insulin levels were measured. The expression of Pten and Fabp4 in the liver, muscle, and epididymal adipose tissues was estimated by real-time quantitative PCR. Pearson correlation coefficient analysis was used to investigate the expression correlation between Pten and Fabp4 in T2DM rats. The gene expressions of Pten and Fabp4 in the liver, muscle, and adipose tissues of T2DM rats were all significantly higher than those in the control group (Pmuscles and Fabp4 was highly expressed in muscle and adipose tissues. Furthermore, expressions of Fabp4 and Pten in the muscle and adipose tissues of T2DM rats were positively correlated (Pmuscles of T2DM rats may play an important role in the insulin resistance of T2DM. However, the mechanism by which these 2 genes function in T2DM needs further study.

  8. Systems biology reveals new strategies for personalizing cancer medicine and confirms the role of PTEN in resistance to trastuzumab.

    Science.gov (United States)

    Faratian, Dana; Goltsov, Alexey; Lebedeva, Galina; Sorokin, Anatoly; Moodie, Stuart; Mullen, Peter; Kay, Charlene; Um, In Hwa; Langdon, Simon; Goryanin, Igor; Harrison, David J

    2009-08-15

    Resistance to targeted cancer therapies such as trastuzumab is a frequent clinical problem not solely because of insufficient expression of HER2 receptor but also because of the overriding activation states of cell signaling pathways. Systems biology approaches lend themselves to rapid in silico testing of factors, which may confer resistance to targeted therapies. Inthis study, we aimed to develop a new kinetic model that could be interrogated to predict resistance to receptor tyrosine kinase (RTK) inhibitor therapies and directly test predictions in vitro and in clinical samples. The new mathematical model included RTK inhibitor antibody binding, HER2/HER3 dimerization and inhibition, AKT/mitogen-activated protein kinase cross-talk, and the regulatory properties of PTEN. The model was parameterized using quantitative phosphoprotein expression data from cancer cell lines using reverse-phase protein microarrays. Quantitative PTEN protein expression was found to be the key determinant of resistance to anti-HER2 therapy in silico, which was predictive of unseen experiments in vitro using the PTEN inhibitor bp(V). When measured in cancer cell lines, PTEN expression predicts sensitivity to anti-HER2 therapy; furthermore, this quantitative measurement is more predictive of response (relative risk, 3.0; 95% confidence interval, 1.6-5.5; P biology approach has successfully been used to stratify patients for personalized therapy in cancer and is further compelling evidence that PTEN, appropriately measured in the clinical setting, refines clinical decision making in patients treated with anti-HER2 therapies.

  9. Effect of aging and dietary salt and potassium intake on endothelial PTEN (Phosphatase and tensin homolog on chromosome 10 function.

    Directory of Open Access Journals (Sweden)

    Wei-Zhong Ying

    Full Text Available Aging promotes endothelial dysfunction, defined as a reduction in bioavailable nitric oxide (NO produced by the endothelial isoform of nitric oxide synthase (NOS3. This enzyme is critically regulated by phosphorylation by protein kinase B (Akt, which in turn is regulated by the lipid phosphatase, PTEN. The present series of studies demonstrated a reduction in bioavailable NO as the age of rats increased from 1 to 12 months. At 12 months of age, rats no longer demonstrated increases in phosphorylated NOS3 in response to high dietary salt intake. Endothelial cell levels of PTEN increased with age and became refractory to change with increased salt intake. In contrast to the reduction in NO production, endothelial cell production of transforming growth factor-ß (TGF-ß relative to NO increased progressively with age. In macrovascular endothelial cells, PTEN was regulated in a dose-dependent fashion by TGF-ß, which was further regulated by extracellular [KCl]. When combined with prior studies, the present series of experiments suggested an integral role for PTEN in endothelial cell pathobiology of aging and an important mitigating function of TGF-ß in endothelial PTEN regulation. The findings further supported a role for diet in affecting vascular function through the production of TGF-ß and NO.

  10. 广义变系数KdV-Burgers方程的微分不变量及群分类%Differential invariants and group classification of KdV-Burgers equation

    Institute of Scientific and Technical Information of China (English)

    郭美玉; 刘希强; 高洁

    2009-01-01

    应用李无穷小不变规则,得到了广义变系数KdV-Burgers方程的连续等价变换.从等价代数开始,构造了一阶微分不变量并依据微分不变量对方程作了群分类.最后,通过等价变换将一般的变系数KdV-Burgers方程映射为常系数Burgers方程、KdV方程、KdV-Burgers方程.同时,也得到了变系数KdV-Burgers方程的一些精确解.

  11. Scattering Amplitudes for Multi-indexed Extensions of Soliton Potential and Extended KdV Integer Solitons

    CERN Document Server

    Lee, Jen-Chi

    2014-01-01

    We calculate quantum mechanical scattering problems for multi-indexed extensions of soliton potential by Darboux transformations in terms of pseudo virtual wavefunctions. As an application, we calculate infinite set of higher integer KdV solitons by the inverse scattering transform method of KdV equation.

  12. Gene Expression Analysis of an EGFR Indirectly Related Pathway Identified PTEN and MMP9 as Reliable Diagnostic Markers for Human Glial Tumor Specimens

    Directory of Open Access Journals (Sweden)

    Sergio Comincini

    2009-01-01

    Full Text Available In this study the mRNA levels of five EGFR indirectly related genes, EGFR, HB-EGF, ADAM17, PTEN, and MMP9, have been assessed by Real-time PCR in a panel of 37 glioblastoma multiforme specimens and in 5 normal brain samples; as a result, in glioblastoma, ADAM17 and PTEN expression was significantly lower than in normal brain samples, and, in particular, a statistically significant inverse correlation was found between PTEN and MMP9 mRNA levels. To verify if this correlation was conserved in gliomas, PTEN and MMP9 expression was further investigated in an additional panel of 16 anaplastic astrocytoma specimens and, in parallel, in different human normal and astrocytic tumor cell lines. In anaplastic astrocytomas PTEN expression was significantly higher than in glioblastoma multiforme, but no significant correlation was found between PTEN and MMP9 expression. PTEN and MMP9 mRNA levels were also employed to identify subgroups of specimens within the different glioma malignancy grades and to define a gene expression-based diagnostic classification scheme. In conclusion, this gene expression survey highlighted that the combined measurement of PTEN and MMP9 transcripts might represent a novel reliable tool for the differential diagnosis of high-grade gliomas, and it also suggested a functional link involving these genes in glial tumors.

  13. The dietary isothiocyanate sulforaphane modulates gene expression and alternative gene splicing in a PTEN null preclinical murine model of prostate cancer

    Directory of Open Access Journals (Sweden)

    Ball Richard Y

    2010-07-01

    Full Text Available Abstract Background Dietary or therapeutic interventions to counteract the loss of PTEN expression could contribute to the prevention of prostate carcinogenesis or reduce the rate of cancer progression. In this study, we investigate the interaction between sulforaphane, a dietary isothiocyanate derived from broccoli, PTEN expression and gene expression in pre malignant prostate tissue. Results We initially describe heterogeneity in expression of PTEN in non-malignant prostate tissue of men deemed to be at risk of prostate cancer. We subsequently use the mouse prostate-specific PTEN deletion model, to show that sulforaphane suppresses transcriptional changes induced by PTEN deletion and induces additional changes in gene expression associated with cell cycle arrest and apoptosis in PTEN null tissue, but has no effect on transcription in wild type tissue. Comparative analyses of changes in gene expression in mouse and human prostate tissue indicate that similar changes can be induced in humans with a broccoli-rich diet. Global analyses of exon expression demonstrated that sulforaphane interacts with PTEN deletion to modulate alternative gene splicing, illustrated through a more detailed analysis of DMBT1 splicing. Conclusion To our knowledge, this is the first report of how diet may perturb changes in transcription induced by PTEN deletion, and the effects of diet on global patterns of alternative gene splicing. The study exemplifies the complex interaction between diet, genotype and gene expression, and the multiple modes of action of small bioactive dietary components.

  14. Combined deletion of Pten and p53 in mammary epithelium accelerates triple-negative breast cancer with dependency on eEF2K.

    Science.gov (United States)

    Liu, Jeff C; Voisin, Veronique; Wang, Sharon; Wang, Dong-Yu; Jones, Robert A; Datti, Alessandro; Uehling, David; Al-awar, Rima; Egan, Sean E; Bader, Gary D; Tsao, Ming; Mak, Tak W; Zacksenhaus, Eldad

    2014-12-01

    The tumor suppressors Pten and p53 are frequently lost in breast cancer, yet the consequences of their combined inactivation are poorly understood. Here, we show that mammary-specific deletion of Pten via WAP-Cre, which targets alveolar progenitors, induced tumors with shortened latency compared to those induced by MMTV-Cre, which targets basal/luminal progenitors. Combined Pten-p53 mutations accelerated formation of claudin-low, triple-negative-like breast cancer (TNBC) that exhibited hyper-activated AKT signaling and more mesenchymal features relative to Pten or p53 single-mutant tumors. Twenty-four genes that were significantly and differentially expressed between WAP-Cre:Pten/p53 and MMTV-Cre:Pten/p53 tumors predicted poor survival for claudin-low patients. Kinome screens identified eukaryotic elongation factor-2 kinase (eEF2K) inhibitors as more potent than PI3K/AKT/mTOR inhibitors on both mouse and human Pten/p53-deficient TNBC cells. Sensitivity to eEF2K inhibition correlated with AKT pathway activity. eEF2K monotherapy suppressed growth of Pten/p53-deficient TNBC xenografts in vivo and cooperated with doxorubicin to efficiently kill tumor cells in vitro. Our results identify a prognostic signature for claudin-low patients and provide a rationale for using eEF2K inhibitors for treatment of TNBC with elevated AKT signaling.

  15. Reduction of 13 kD prolamins increases recombinant protein yield and recovery rate in rice endosperm.

    Science.gov (United States)

    Kawakatsu, Taiji; Takaiwa, Fumio

    2012-11-01

    RNA silencing inducible sequence (RSIS) causes post-transcriptional gene silencing (PTGS) of 5' or 3' flanking sequence-containing genes by inhibiting proper transcriptional termination. Exploiting this nature, 13 kD Pro-less, in which major seed storage protein (SSP) 13 kD prolamins are reduced, has been generated. In 13 kD Pro-less, other SSPs, such as glutelins, are increased as a compensation effect to maintain amino acid pool. 7Crp is the seven-linked epitope peptide derived from major cedar pollen allergens Cry j 1 and Cry j 2. When 7Crp is expressed in 13 kD Pro-less endosperm, accumulation level of 7Crp increased. Furthermore, recovery rate of 7Crp without reducing reagent increased. These findings indicate that 13 kD Pro-less endosperm provides a good production platform for recombinant proteins.

  16. Cloning and sequence analysis of the gene encoding 19-kD subunit of Complex I from Dunaliella salina.

    Science.gov (United States)

    Liu, Yi; Qiao, Dai Rong; Zheng, Hong Bo; Dai, Xu Lan; Bai, Lin Han; Zeng, Jing; Cao, Yi

    2008-09-01

    NADH:ubiquinone oxidoreductase (complex I ) of the mitochondrial respiratory chain catalyzes the transfer of electrons from NADH to ubiquinone coupled to proton translocation across the membrane. The cDNA sequence of Dunaliella salina mitochondrial NADH: ubiquinone oxidoreductase 19-kD subunit contains a 682-bp ORF encoding a protein with an apparent molecular mass of 19 kD. The sequence has been submitted to the GenBank database under Accession No. EF566890 (cDNA sequences) and EF566891 (genomic sequence). The deduced amino-acid sequence is 74% identical to Chlamydomonas reinhardtii mitochondrial NADH:ubiquinone oxidoreductase 18-kD subunit. The 19-kD subunit mRNA expression was observed in oxygen deficiency, salt treatment, and rotenone treatment with lower levels. It demonstrate that the 19-kD subunit of Complex I from Dunaliella salina is regulated by these stresses.

  17. Solution of the KdV Equation Based on COMSOL Multiphysics%基于COMSOL Multiphysics求解KdV方程

    Institute of Scientific and Technical Information of China (English)

    糜凯华

    2014-01-01

    In order to obtain numerical solutions of the KdV equation,COMSOL Multiphysics software based on finite element method established a finite element model and solved the distribution of solitary waves at various points in time. The results can study the propagation of solitary waves. Simulation results indicate that the soli-tary wave does not occur in isolation. Solitary waves can be found within a certain space where collisions occur as well as reproduced by representing as a three dimensional map distribution. Two different speed and ampli-tude solitons collided and did not affect each other.%为了得到KdV方程的数值解,基于有限单元法的COMSOL Multiphysics软件建立有限元模型并求解孤立波在各个时间点的分布情况,以研究孤立波的传播特性。数值模拟结果表明:孤立波不会发生消散,以三维图的分布形式表示,可以发现孤立子在一定的空间内会发生碰撞以及发生重现,也即两个不同速度和振幅的孤子相互碰撞、相互穿过,互相之间没有影响。

  18. Expression of PIK3CA, PTEN mRNA and PIK3CA mutations in primary breast cancer

    DEFF Research Database (Denmark)

    Palimaru, Irina; Brügmann, Anja; Wium-Andersen, Marie Kim;

    2013-01-01

    tissue samples of breast carcinoma and normal breast tissue were obtained from 175 breast cancer patients at the time of primary surgery, of these 105 patients were lymph node positive. Expression of PIK3CA and PTEN mRNA was quantified with Quantitative Real Time PCR. Somatic mutations in exon 9 and exon......PURPOSE: High activity of the intracellular phosphatidylinositol-3 kinase (PI3K) pathway is common in breast cancer. Here, we explore differences in expression of important PI3K pathway regulators: the activator, phosphatidylinositol-3-kinase catalytic subunit alpha (PIK3CA), and the tumour...... suppressor, phosphatase and tensin homolog (PTEN), in breast carcinoma tissue and normal breast tissue. Furthermore, we examine whether expression of PIK3CA and PTEN mRNA and occurrence of PIK3CA mutations are associated with lymph node metastases in patients with primary breast cancer. METHODS: Paired...

  19. Feedback regulation on PTEN/AKT pathway by the ER stress kinase PERK mediated by interaction with the Vault complex

    DEFF Research Database (Denmark)

    Zhang, Wei; Neo, Suat Peng; Gunaratne, Jayantha

    2015-01-01

    The high proliferation rate of cancer cells, together with environmental factors such as hypoxia and nutrient deprivation can cause Endoplasmic Reticulum (ER) stress. The protein kinase PERK is an essential mediator in one of the three ER stress response pathways. Genetic and pharmacological...... inhibition of PERK has been reported to limit tumor growth in xenograft models. Here we provide evidence that inactive PERK interacts with the nuclear pore-associated Vault complex protein and that this compromises Vault-mediated nuclear transport of PTEN. Pharmacological inhibition of PERK under ER stress...... results is abnormal sequestration of the Vault complex, leading to increased cytoplasmic PTEN activity and lower AKT activation. As the PI3K/PTEN/AKT pathway is crucial for many aspects of cell growth and survival, this unexpected effect of PERK inhibitors on AKT activity may have implications...

  20. Characterization of apple 18 and 31 kd allergens by microsequencing and evaluation of their content during storage and ripening.

    Science.gov (United States)

    Hsieh, L S; Moos, M; Lin, Y

    1995-12-01

    Patients with tree pollinosis frequently report allergic reactions after ingestion of apples. The severity of apple allergy has been related to the variety of apples and their degree of maturity. To generate a serum pool that is representative of various IgE-binding patterns of apple-allergic sera, serum samples from 34 patients allergic to tree pollens were screened. Only 24 serum samples reacted to the apple extract. Pooled serum was used to identify allergens in apples. An efficient and consistent extraction method for apple fruits was used to compare the immunoreactivities of extracts of different varieties (McIntosh, Red Delicious, Granny Smith, and Golden Delicious) of freshly picked and store-purchased apples. We found that Golden Delicious apples had the greatest amount of the 18 kd allergen, which has been reported to be a potent IgE-binding apple allergen. Store-purchased apples contained higher concentrations of the 18 kd allergen than freshly picked apples. In our study only 37.5% of sera reacted to the 18 kd protein, whereas 75% of the sera reacted to a 31 kd allergen. Other immunoreactive bands in apple extracts included proteins of 50, 38, 16, 14, and 13 kd. The amino-terminal amino acid sequences of the two major allergens, 18 kd and 31 kd, were determined. These sequences shared approximately 50% identity with disease resistance proteins of various plants or Bet v 1 in birch tree pollens. The appearance of various allergens was also investigated in mature apples during storage. The amount of 18 kd allergen increased significantly when apples were stored at 4 degrees C. However, under controlled atmospheric conditions in which oxygen- and carbon dioxide-induced ripening were regulated, the amount of 18 kd allergen remained unaffected. Because ripening and maturation were not associated with increases in 18 kd allergen content, the observed changes might be induced by factors related to disease resistance.