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Publications (7)9.15 Total impact

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    ABSTRACT: Belinostat is a hydroxamate-type histone deactylase inhibitor (HDACi), which has recently entered phase I and II clinical trials. Microarray-based analysis of belinostat-treated cell lines showed an impact on genes associated with the G2/M phase of the cell cycle and downregulation of the aurora kinase pathway. Expression of 25 dysregulated genes was measured in eight differentially sensitive cell lines using a novel high-throughput assay that combines multiplex reverse transcriptase-PCR and fluorescence capillary electrophoresis. Sensitivity to belinostat and the magnitude of changes in overall gene modulation were significantly correlated. A belinostat-gene profile was specific for HDACi in three cell lines when compared with equipotent concentrations of four mechanistically different chemotherapeutic agents: 5-fluorouracil, cisplatin, paclitaxel, and thiotepa. Belinostat- and trichostatin A (HDACi)-induced gene responses were highly correlated with each other, but not with the limited changes in response to the other non-HDACi agents. Moreover, belinostat treatment of mice bearing human xenografts showed that the preponderance of selected genes were also modulated in vivo, more extensively in a drug-sensitive tumor than a more resistant model. We have demonstrated a gene signature that is selectively regulated by HDACi when compared with other clinical agents allowing us to distinguish HDACi responses from those related to other mechanisms.
    No preview · Article · Oct 2009 · Anti-cancer drugs
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    ABSTRACT: Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists of the thiazolidinedione family are used for the treatment of type 2 diabetes mellitus due to their ability to reduce glucose and lipid levels in patients with this disease. Three thiazolidinediones that were approved for treatment are Rezulin (troglitazone), Avandia (rosiglitazone), and Actos (pioglitazone). Troglitazone was withdrawn from the market due to idiosyncratic drug toxicity. Rosiglitazone and pioglitazone are still on the market for the treatment of type 2 diabetes. The authors present data from a gene expression screen that compares the impact these three compounds have in rats, in rat hepatocytes, and in the clone 9 rat liver cell line. The authors monitored the changes in expression in multiple genes, including those related to xenobiotic metabolism, proliferation, DNA damage, oxidative stress, apoptosis, and inflammation. Compared to the other two compounds, troglitazone had a significant impact on many of the pathways monitored in vitro although no major perturbation was detected in vivo. The changes detected predict not only general toxicity but potential mechanisms of toxicity. Based on gene expression analysis, the authors propose there is not just one but multiple ways troglitazone could be toxic, depending on a patient's environment and genetic makeup, including immune response-related toxicity.
    Preview · Article · Apr 2006 · International Journal of Toxicology
  • V Boyer · P Pezzoli · G Audoly · C Desgranges · F Jensen · F Ferre
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    ABSTRACT: A number of strategies, such as subtractive cDNA libraries and high through-put sequencing, have been devised to assess differential gene expression. Most of these approaches, however, are cumbersome and/or require tremendous technological power. In this paper, we describe a method, RNA fingerprinting using arbitrarily primed polymerase chain reaction (RAP-PCR), that is rapid, less cumbersome and can differentiate low levels of mRNA expression. To identify genes that are differentially expressed following human immunodeficiency virus type 1 (HIV-1) infection in different cell types by RAP-PCR. RNA was extracted from both HIV-1-infected and uninfected HUT78 cells and peripheral blood mononuclear cells (PBMCs), reverse transcribed, and RAP-PCR amplified using numerous primer sets. Three genes, gamma-actin, the HIV-1 nef and an unknown sequence, were identified as being differentially expressed in HUT78 cells. The level of gamma-actin mRNA expression is increased after HIV infection and, as expected, the nef gene was solely expressed in HIV-infected cells. In contrast, the unknown mRNA is down-regulated by HIV. Northern blot analysis and/or specific PCR confirmed the differential expression of these three genes. RNA fingerprinting using phytohemagglutinin (PHA)-activated PBMCs infected by HIV in vitro, revealed that gamma-actin is still up-regulated by HIV, whereas the unknown product no longer shows down-regulation. These results illustrate the usefulness of the RAP-PCR method for isolating and identifying differentially expressed genes during HIV-1 infection of primary lymphocytes.
    No preview · Article · Nov 1996 · Clinical and Diagnostic Virology

  • No preview · Article · Jan 1995
  • F. Ferré · A. Marchese · P. Pezzoli · S. Griffin · E. Buxton · V. Boyer
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    ABSTRACT: John Maddox recently wrote (Maddox, 1992) that “molecular biology seems well on the way to becoming a largely qualitative science…. It would be a worthwhile precaution against the quantitative days that lie ahead that people should make sure that published data are capable of quantitative interpretation by those who have the zeal for that.” Well, with the current outburst of publications on quantitative PCR (Q-PCR) methods and their applications, it looks like the “quantitative days” are already on us and here to stay. Quantitation of nucleic acids by PCR has been used in an array of situations in both basic and clinical research (for review see, Bej et al., 1991; Volkenandt et al. 1992; Ferré, 1992; Clementi et al., 1993)
    No preview · Chapter · Jan 1994
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    ABSTRACT: The gradual decline of CD4+ T lymphocytes in HIV-infected individuals culminates in the lethal immunosuppression of AIDS. The mechanism of CD4+ T cell loss is currently unknown, but has recently been suggested to occur as a result of an HIV-encoded superantigen which facilitates a selective deletion of T cells expressing specific V beta genes. To verify and extend such observations, peripheral blood leucocytes (PBL) from 15 HIV+ individuals, 10 of which had very low CD4 T cell counts (< 200/mm3), were analysed for T cell receptor (TCR) V beta gene expression. In contrast to a recent study, the results presented here fail to provide evidence that selective loss of V beta-bearing T cells occurs in HIV+ individuals. Furthermore, when PBL from HIV+ individuals were stimulated with Staphylococcal enterotoxin B (SEB), T cells expressing V beta subfamilies known to engage this superantigen were expanded, indicating that such cells were not deleted and were responsive to stimulation by a bacterial superantigen. Collectively, these data suggest that CD4 loss in HIV patients does not occur in a V beta-selective, superantigen-mediated fashion.
    Preview · Article · Jun 1993 · Clinical & Experimental Immunology
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    ABSTRACT: The gradual decline of CD4+ T lymphocytes in HIV-infected individuals culminates in the lethal immunosuppression of AIDS. The mechanism of CD4+ T cell loss is currently unknown, but has recently been suggested to occur as a result of an HIV-encoded superantigen which facilitates a selective deletion of T cells expressing specific Vβ genes. To verify and extend such observations, peripheral blood leucocytes (PBL) from 15 CD4+ individuals, 10 of which had very low CD4 T cell counts (< 200/mm3), were analysed for T cell receptor (TCR) V/β gene expression. In contrast to a recent study, the results presented here fail to provide evidence that selective loss of Vβ-bearing T cells occurs in HIV+ individuals. Furthermore, when PBL from HIV+ individuals were stimulated with Staphylococcal enterotoxin B (SEB), T cells expressing Vβ subfamilies known to engage this superantigen were expanded, indicating that such cells were not deleted and were responsive to stimulation by a bacterial superantigen. Collectively, these data suggest that CD4 loss in HIV patients docs not occur in a Vβ-seleetive, superantigen-mediated fashion.
    Preview · Article · May 1993 · Clinical & Experimental Immunology