@article{GrafLiHerrmannetal.2014,
  author    = {Graf, Nicolas and Li, Zhoulei and Herrmann, Ken and Weh, Daniel and Aichler, Michaela and Slawska, Jolanta and Walch, Axel and Peschel, Christian and Schwaiger, Markus and Buck, Andreas K. and Dechow, Tobias and Keller, Ulrich},
  title     = {Positron emission tomographic monitoring of dual phosphatidylinositol-3-kinase and mTOR inhibition in anaplastic large cell lymphoma},
  series = {Oncotargets and Therapy},
  volume    = {7},
  journal   = {Oncotargets and Therapy},
  doi       = {10.2147/OTT.S59314},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117915},
  pages     = {789-798},
  year      = {2014},
  abstract  = {Background: Dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibition offers an attractive therapeutic strategy in anaplastic large cell lymphoma depending on oncogenic nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) signaling. We tested the efficacy of a novel dual PI3K/mTOR inhibitor, NVP-BGT226 (BGT226), in two anaplastic large cell lymphoma cell lines in vitro and in vivo and performed an early response evaluation with positron emission tomography (PET) imaging using the standard tracer, 2-deoxy-2-[F-18] fluoro-D-glucose (FDG) and the thymidine analog, 3'-deoxy-3'-[F-18] fluorothymidine (FLT). Methods: The biological effects of BGT226 were determined in vitro in the NPM-ALK positive cell lines SU-DHL-1 and Karpas299 by 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, propidium iodide staining, and biochemical analysis of PI3K and mTOR downstream signaling. FDG-PET and FLT-PET were performed in immunodeficient mice bearing either SU-DHL-1 or Karpas299 xenografts at baseline and 7 days after initiation of treatment with BGT226. Lymphomas were removed for immunohistochemical analysis of proliferation and apoptosis to correlate PET findings with in vivo treatment effects. Results: SU-DHL-1 cells showed sensitivity to BGT226 in vitro, with cell cycle arrest in G0/G1 phase and an IC50 in the low nanomolar range, in contrast with Karpas299 cells, which were mainly resistant to BGT226. In vivo, both FDG-PET and FLT-PET discriminated sensitive from resistant lymphoma, as indicated by a significant reduction of tumor-to-background ratios on day 7 in treated SU-DHL-1 lymphoma-bearing animals compared with the control group, but not in animals with Karpas299 xenografts. Imaging results correlated with a marked decrease in the proliferation marker Ki67, and a slight increase in the apoptotic marker, cleaved caspase 3, as revealed by immunostaining of explanted lymphoma tissue. Conclusion: Dual PI3K/mTOR inhibition using BGT226 is effective in ALK-positive anaplastic large cell lymphoma and can be monitored with both FDG-PET and FLT-PET early on in the course of therapy.},
  language  = {en}
}
@article{ZukherNovikovaTikhonovetal.2014,
  author    = {Zukher, Inna and Novikova, Maria and Tikhonov, Anton and Nesterchuk, Mikhail V. and Osterman, Ilya A. and Djordjevic, Marko and Sergiev, Petr V. and Sharma, Cynthia M. and Severinov, Konstantin},
  title     = {Ribosome-controlled transcription termination is essential for the production of antibiotic microcin C},
  series = {Nucleic Acids Research},
  volume    = {42},
  journal   = {Nucleic Acids Research},
  number    = {19},
  issn      = {0305-1048},
  doi       = {10.1093/nar/gku880},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114839},
  pages     = {11891-11902},
  year      = {2014},
  abstract  = {Microcin C (McC) is a peptide-nucleotide antibiotic produced by Escherichia coli cells harboring a plasmid-borne operon mccABCDE. The heptapeptide MccA is converted into McC by adenylation catalyzed by the MccB enzyme. Since MccA is a substrate for MccB, a mechanism that regulates the MccA/MccB ratio likely exists. Here, we show that transcription from a promoter located upstream of mccA directs the synthesis of two transcripts: a short highly abundant transcript containing the mccA ORF and a longer minor transcript containing mccA and downstream ORFs. The short transcript is generated when RNA polymerase terminates transcription at an intrinsic terminator located in the intergenic region between the mccA and mccB genes. The function of this terminator is strongly attenuated by upstream mcc sequences. Attenuation is relieved and transcription termination is induced when ribosome binds to the mccA ORF. Ribosome binding also makes the mccA RNA exceptionally stable. Together, these two effects-ribosome induced transcription termination and stabilization of the message-account for very high abundance of the mccA transcript that is essential for McC production. The general scheme appears to be evolutionary conserved as ribosome-induced transcription termination also occurs in a homologous operon from Helicobacter pylori.},
  language  = {en}
}