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  1. AU="Arun Seth"
  2. AU="Woitok, Mira"
  3. AU="Amparo MoraguesauthorDpto. Ingeniera Civil: Construccin, E.T.S.I. de Caminos, Canales y Puertos, Universidad Politcnica de Madrid, C/ Profesor Aranguren 3, 28040 Madrid, Spain"
  4. AU="Guidry, Jessie"
  5. AU=Mitry Maria A.
  6. AU="Rhodes, Rosamond"
  7. AU="Gromova, Alexandra S"
  8. AU=Ockene Ira
  9. AU=Hirsch Daniela
  10. AU=Navaratnam Annalan MD
  11. AU="Johnson, Matthew Thomas"
  12. AU=Wagstaff Peter GK
  13. AU="Almahboub, Sarah A"
  14. AU="Tuana Aksu"
  15. AU="Bozin, Tonci"
  16. AU="Rachel Marie Towle"
  17. AU="Soriano-Ursúa, Marvin A"
  18. AU="Cagnin, A"
  19. AU="Ivens, Al C"
  20. AU="Juan Mucci"
  21. AU="Alejandro Hlavnika"
  22. AU="Makarenko V."

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Treffer 1 - 10 von insgesamt 12

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  1. Artikel ; Online: Multisite verification of the accuracy of a multi-gene next generation sequencing panel for detection of mutations and copy number alterations in solid tumours.

    John Bartlett / Yutaka Amemiya / Heleen Arts / Jane Bayani / Barry Eng / Daria Grafodatskaya / Suzanne Kamel Reid / Mathieu Lariviere / Bryan Lo / Rebecca McClure / Vinay Mittal / Bekim Sadikovic / Seth Sadis / Arun Seth / Jeff Smith / Xiao Zhang / Harriet Feilotter

    PLoS ONE, Vol 16, Iss 10, p e

    2021  Band 0258188

    Abstract: Molecular variants including single nucleotide variants (SNVs), copy number variants (CNVs) and fusions can be detected in the clinical setting using deep targeted sequencing. These assays support low limits of detection using little genomic input ... ...

    Abstract Molecular variants including single nucleotide variants (SNVs), copy number variants (CNVs) and fusions can be detected in the clinical setting using deep targeted sequencing. These assays support low limits of detection using little genomic input material. They are gaining in popularity in clinical laboratories, where sample volumes are limited, and low variant allele fractions may be present. However, data on reproducibility between laboratories is limited. Using a ring study, we evaluated the performance of 7 Ontario laboratories using targeted sequencing panels. All laboratories analysed a series of control and clinical samples for SNVs/CNVs and gene fusions. High concordance was observed across laboratories for measured CNVs and SNVs. Over 97% of SNV calls in clinical samples were detected by all laboratories. Whilst only a single CNV was detected in the clinical samples tested, all laboratories were able to reproducibly report both the variant and copy number. Concordance for information derived from RNA was lower than observed for DNA, due largely to decreased quality metrics associated with the RNA components of the assay, suggesting that the RNA portions of comprehensive NGS assays may be more vulnerable to variations in approach and workflow. Overall the results of this study support the use of the OFA for targeted sequencing for testing of clinical samples and suggest specific internal quality metrics that can be reliable indicators of assay failure. While we believe this evidence can be interpreted to support deep targeted sequencing in general, additional studies should be performed to confirm this.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 616
    Sprache Englisch
    Erscheinungsdatum 2021-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Loss of Igfbp7 causes precocious involution in lactating mouse mammary gland.

    Sumanta Chatterjee / Stephanie Bacopulos / Wenyi Yang / Yutaka Amemiya / Demetri Spyropoulos / Afshin Raouf / Arun Seth

    PLoS ONE, Vol 9, Iss 2, p e

    2014  Band 87858

    Abstract: BACKGROUND: Insulin like growth factors (IGFs) and their binding proteins (IGFBPs) are secreted peptides that play major roles in regulating the normal development and maturation of mammary gland. While Igfbp7 has been shown to decrease breast tumor ... ...

    Abstract BACKGROUND: Insulin like growth factors (IGFs) and their binding proteins (IGFBPs) are secreted peptides that play major roles in regulating the normal development and maturation of mammary gland. While Igfbp7 has been shown to decrease breast tumor growth, its role in regulating the normal mammary gland development has not been studied. To this end, we generated Igfbp7-null mice and examined the development and maturation of mammary glands in the virgin, pregnant and lactating animals. RESULTS: We report here that loss of Igfbp7 significantly retards mammary gland development in the virgin animals. More significantly, the pregnant Igfpb7-null glands contained fewer alveolar structures and that during lactation these glands exhibit the morphological changes that are associated with involution. The transcriptome profile of the Igfbp7-null glands on the lactation day 3 revealed a distinct involution-related gene signature compared to the lactating WT glands. Interestingly, we found that the lactating Igfbp7-null glands exhibit increased expression of Stat3 and enhanced activation of (phosphorylated) Stat3, combined with decreased expression of Stat5 suggesting that the absence of Igfbp7 accelerates the onset of involution. We also found that in absence of Igfpb7, the lactating glands contain increased Igfbp5 protein along with decreased expression of IGF-1 Receptor and Akt activation. Finally, we show that during the normal course of involution, Igfbp7 expression is significantly decreased in the mammary gland. CONCLUSION: Our data suggest that loss of Igfbp7 induces precocious involution possibly through diminished cell survival signals. Our findings identify Igfbp7 as major regulator of involution in the mammary gland.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 590
    Sprache Englisch
    Erscheinungsdatum 2014-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: From Melanocyte to Metastatic Malignant Melanoma

    Bizhan Bandarchi / Linglei Ma / Roya Navab / Arun Seth / Golnar Rasty

    Dermatology Research and Practice, Vol

    2010  Band 2010

    Abstract: Malignant melanoma is one of the most aggressive malignancies in human and is responsible for almost 60% of lethal skin tumors. Its incidence has been increasing in white population in the past two decades. There is a complex interaction of environmental ...

    Abstract Malignant melanoma is one of the most aggressive malignancies in human and is responsible for almost 60% of lethal skin tumors. Its incidence has been increasing in white population in the past two decades. There is a complex interaction of environmental (exogenous) and endogenous, including genetic, risk factors in developing malignant melanoma. 8–12% of familial melanomas occur in a familial setting related to mutation of the CDKN2A gene that encodes p16. The aim of this is to briefly review the microanatomy and physiology of the melanocytes, epidemiology, risk factors, clinical presentation, historical classification and histopathology and, more in details, the most recent discoveries in biology and genetics of malignant melanoma. At the end, the final version of 2009 AJCC malignant melanoma staging and classification is presented.
    Schlagwörter Dermatology ; RL1-803 ; Medicine ; R ; DOAJ:Dermatology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Sprache Englisch
    Erscheinungsdatum 2010-01-01T00:00:00Z
    Verlag Hindawi Publishing Corporation
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: pGlcNAc Nanofiber Treatment of Cutaneous Wounds Stimulate Increased Tensile Strength and Reduced Scarring via Activation of Akt1.

    Haley Buff Lindner / Lloyd McPherson Felmly / Marina Demcheva / Arun Seth / Russell Norris / Amy D Bradshaw / John Vournakis / Robin C Muise-Helmericks

    PLoS ONE, Vol 10, Iss 5, p e

    2015  Band 0127876

    Abstract: Treatment of cutaneous wounds with poly-N-acetyl-glucosamine containing nanofibers (pGlcNAc), a novel polysaccharide material derived from a marine diatom, results in increased wound closure, antibacterial activities and innate immune responses. We have ... ...

    Abstract Treatment of cutaneous wounds with poly-N-acetyl-glucosamine containing nanofibers (pGlcNAc), a novel polysaccharide material derived from a marine diatom, results in increased wound closure, antibacterial activities and innate immune responses. We have shown that Akt1 plays a central role in the regulation of these activities. Here, we show that pGlcNAc treatment of cutaneous wounds results in a smaller scar that has increased tensile strength and elasticity. pGlcNAc treated wounds exhibit decreased collagen content, increased collagen organization and decreased myofibroblast content. A fibrin gel assay was used to assess the regulation of fibroblast alignment in vitro. In this assay, fibrin lattice is formed with two pins that provide focal points upon which the gel can exert force as the cells align from pole to pole. pGlcNAc stimulation of embedded fibroblasts results in cellular alignment as compared to untreated controls, by a process that is Akt1 dependent. We show that Akt1 is required in vivo for the pGlcNAc-induced increased tensile strength and elasticity. Taken together, our findings suggest that pGlcNAc nanofibers stimulate an Akt1 dependent pathway that results in the proper alignment of fibroblasts, decreased scarring, and increased tensile strength during cutaneous wound healing.
    Schlagwörter Medicine ; R ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2015-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Anti-bacterial effects of poly-N-acetyl-glucosamine nanofibers in cutaneous wound healing

    Haley Buff Lindner / Aiguo Zhang / Juanita Eldridge / Marina Demcheva / Philip Tsichlis / Arun Seth / John Vournakis / Robin C Muise-Helmericks

    PLoS ONE, Vol 6, Iss 4, p e

    requirement for Akt1.

    2011  Band 18996

    Abstract: Treatment of cutaneous wounds with poly-N-acetyl-glucosamine nanofibers (sNAG) results in increased kinetics of wound closure in diabetic animal models, which is due in part to increased expression of several cytokines, growth factors, and innate immune ... ...

    Abstract Treatment of cutaneous wounds with poly-N-acetyl-glucosamine nanofibers (sNAG) results in increased kinetics of wound closure in diabetic animal models, which is due in part to increased expression of several cytokines, growth factors, and innate immune activation. Defensins are also important for wound healing and anti-microbial activities. Therefore, we tested whether sNAG nanofibers induce defensin expression resulting in bacterial clearance.The role of sNAG in defensin expression was examined using immunofluoresence microscopy, pharmacological inhibition, and shRNA knockdown in vitro. The ability of sNAG treatment to induce defensin expression and bacterial clearance in WT and AKT1-/- mice was carried out using immunofluoresent microscopy and tissue gram staining. Neutralization, using an antibody directed against β-defensin 3, was utilized to determine if the antimicrobial properties of sNAG are dependent on the induction of defensin expression.sNAG treatment causes increased expression of both α- and β-type defensins in endothelial cells and β-type defensins in keratinocytes. Pharmacological inhibition and shRNA knockdown implicates Akt1 in sNAG-dependent defensin expression in vitro, an activity also shown in an in vivo wound healing model. Importantly, sNAG treatment results in increased kinetics of wound closure in wild type animals. sNAG treatment decreases bacterial infection of cutaneous wounds infected with Staphylococcus aureus in wild type control animals but not in similarly treated Akt1 null animals. Furthermore, sNAG treatment of S. aureus infected wounds show an increased expression of β-defensin 3 which is required for sNAG-dependent bacterial clearance. Our findings suggest that Akt1 is involved in the regulation of defensin expression and the innate immune response important for bacterial clearance. Moreover, these findings support the use of sNAG nanofibers as a novel method for enhancing wound closure while simultaneously decreasing wound infection.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2011-04-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: Correction

    Haley Buff Lindner / Aiguo Zhang / Juanita Eldridge / Marina Demcheva / Philip Tsichilis / Arun Seth / John Vournakis / Robin C. Muise-Helmericks

    PLoS ONE, Vol 6, Iss

    Anti-Bacterial Effects of Poly-N-Acetyl-Glucosamine Nanofibers in Cutaneous Wound Healing: Requirement for Akt1.

    2011  Band 7

    Schlagwörter Medicine ; R ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2011-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: Correction

    Haley Buff Lindner / Aiguo Zhang / Juanita Eldridge / Marina Demcheva / Philip Tsichilis / Arun Seth / John Vournakis / Robin C. Muise-Helmericks

    PLoS ONE, Vol 6, Iss

    Anti-Bacterial Effects of Poly-N-Acetyl-Glucosamine Nanofibers in Cutaneous Wound Healing: Requirement for Akt1

    2011  Band 7

    Schlagwörter Medicine ; R ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2011-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: Novel KRAS gene mutations in sporadic colorectal cancer.

    Walid M Naser / Mohamed A Shawarby / Dalal M Al-Tamimi / Arun Seth / Abdulaziz Al-Quorain / Areej M Al Nemer / Omar M E Albagha

    PLoS ONE, Vol 9, Iss 11, p e

    2014  Band 113350

    Abstract: In this article, we report 7 novel KRAS gene mutations discovered while retrospectively studying the prevalence and pattern of KRAS mutations in cancerous tissue obtained from 56 Saudi sporadic colorectal cancer patients from the Eastern Province.Genomic ...

    Abstract In this article, we report 7 novel KRAS gene mutations discovered while retrospectively studying the prevalence and pattern of KRAS mutations in cancerous tissue obtained from 56 Saudi sporadic colorectal cancer patients from the Eastern Province.Genomic DNA was extracted from formalin-fixed, paraffin-embedded cancerous and noncancerous colorectal tissues. Successful and specific PCR products were then bi-directionally sequenced to detect exon 4 mutations while Mutector II Detection Kits were used for identifying mutations in codons 12, 13 and 61. The functional impact of the novel mutations was assessed using bioinformatics tools and molecular modeling.KRAS gene mutations were detected in the cancer tissue of 24 cases (42.85%). Of these, 11 had exon 4 mutations (19.64%). They harbored 8 different mutations all of which except two altered the KRAS protein amino acid sequence and all except one were novel as revealed by COSMIC database. The detected novel mutations were found to be somatic. One mutation is predicted to be benign. The remaining mutations are predicted to cause substantial changes in the protein structure. Of these, the Q150X nonsense mutation is the second truncating mutation to be reported in colorectal cancer in the literature.Our discovery of novel exon 4 KRAS mutations that are, so far, unique to Saudi colorectal cancer patients may be attributed to environmental factors and/or racial/ethnic variations due to genetic differences. Alternatively, it may be related to paucity of clinical studies on mutations other than those in codons 12, 13, 61 and 146. Further KRAS testing on a large number of patients of various ethnicities, particularly beyond the most common hotspot alleles in exons 2 and 3 is needed to assess the prevalence and explore the exact prognostic and predictive significance of the discovered novel mutations as well as their possible role in colorectal carcinogenesis.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 616
    Sprache Englisch
    Erscheinungsdatum 2014-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  9. Artikel ; Online: Correction

    William Weidong Du / Burton B. Yang / Bing L. Yang / Zhaoqun Deng / Ling Fang / Sze Wan Shan / Zina Jeyapalan / Yaou Zhang / Arun Seth / Albert J. Yee

    PLoS ONE, Vol 7, Iss

    Versican G3 Domain Modulates Breast Cancer Cell Apoptosis: A Mechanism for Breast Cancer Cell Response to Chemotherapy and EGFR Therapy.

    2012  Band 1

    Schlagwörter Medicine ; R ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2012-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  10. Artikel ; Online: Versican G3 domain modulates breast cancer cell apoptosis

    William Weidong Du / Burton B Yang / Bing L Yang / Zhaoqun Deng / Ling Fang / Sze Wan Shan / Zina Jeyapalan / Yaou Zhang / Arun Seth / Albert J Yee

    PLoS ONE, Vol 6, Iss 11, p e

    a mechanism for breast cancer cell response to chemotherapy and EGFR therapy.

    2011  Band 26396

    Abstract: Overexpression of EGFR and versican has been reported in association with breast cancers. Considered oncogenic, these molecules may be attractive therapeutic targets. Possessing anti-apoptotic and drug resistant properties, overexpression of these ... ...

    Abstract Overexpression of EGFR and versican has been reported in association with breast cancers. Considered oncogenic, these molecules may be attractive therapeutic targets. Possessing anti-apoptotic and drug resistant properties, overexpression of these molecules is accompanied by selective sensitization to the process of apoptosis. In this study, we exogenously expressed a versican G3 construct in breast cancer cell lines and analyzed the effects of G3 on cell viability in fetal bovine serum free conditioned media and evaluated the effects of apoptotic agent C2-ceramide, and chemotherapeutic agents including Docetaxel, Doxorubicin, and Epirubicin. Versican G3 domain enhanced tumor cell resistance to apoptosis when cultured in serum free medium, Doxorubicin, or Epirubicin by up-regulating pERK and GSK-3β (S9P). However, it could be prevented by selective EGFR inhibitor AG 1478 and selective MEK inhibitor PD 98059. Both AG 1478 and PD 98059 enhanced expression of pSAPK/JNK, while selective JNK inhibitor SP 600125 enhanced expression of GSK-3β (S9P). Versican G3 promoted cell apoptosis induced by C2-ceramide or Docetaxel by enhancing expression of pSAPK/JNK and decreasing expression of GSK-3β (S9P), an observation blocked by AG 1478 or SP 6000125. Inhibition of endogenous versican expression by siRNA or reduction of versican G3's expression by linking G3 with 3'UTR prevented G3 modulated cell apoptosis. The dual roles of G3 in modulating breast cancer cell resistance to chemotherapeutic agents may in part explain a potential mechanism for breast cancer cell resistance to chemotherapy and EGFR therapy. The apoptotic effects of chemotherapeutics depend upon the activation and balance of down stream signals in the EGFR pathway. GSK-3β (S9P) appears to function as a key checkpoint in this balance of apoptosis and anti-apoptosis. Investigation and potential consideration of targeting GSK-3β (S9P) merits further study.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610 ; 616
    Sprache Englisch
    Erscheinungsdatum 2011-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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