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@ARTICLE{Adwan:119413,
      author       = {H. Adwan$^*$ and A. Murtaja$^*$ and K. Kadhim Al-Taee$^*$
                      and A. Pervaiz$^*$ and T. Hielscher$^*$ and M. Berger$^*$},
      title        = {{R}iproximin's activity depends on gene expression and
                      sensitizes {PDAC} cells to {TRAIL}.{G}401},
      journal      = {Cancer biology $\&$ therapy},
      volume       = {15},
      number       = {9},
      issn         = {1555-8576},
      address      = {Georgetown, Tex.},
      publisher    = {Landes Bioscience},
      reportid     = {DKFZ-2017-00155},
      pages        = {1185 - 1197},
      year         = {2014},
      abstract     = {Riproximin (Rpx) is a type II ribosome inactivating
                      protein, which was investigated for its activity in
                      pancreatic ductal adenocarcinoma (PDAC) in a panel of 17
                      human and rat PDAC cell lines and in rat pancreatic cancer
                      liver metastasis. Cytotoxicity in response to Rpx was
                      determined by MTT assay, apoptosis by flow cytometry and
                      qRT-PCR for apoptosis related genes, and the modulation of
                      the transcriptome was monitored by micro array analysis. The
                      combination effect of Rpx and TRAIL was assessed by MTT
                      assay. Rpx showed high but varying cytotoxicity in PDAC
                      cells. Based on overall gene expression, the sensitivity of
                      these cells was linked to genes involved in apoptosis.
                      Furthermore, based on the affinity of Rpx for CEA, the
                      expression of carcinoembryonic antigen-related cell adhesion
                      molecule (CEACAM) genes was significantly related to Rpx's
                      cytotoxicity in cells with CEACAM gene expression. Exposure
                      of Suit2-007 cells to Rpx induced the mRNA expression of
                      members of signaling pathways initiating from most death
                      receptors, and down modulation of TRAIL. Apoptosis was
                      increased as shown by FACS analysis. Combination of Rpx with
                      TRAIL resulted in a synergistic cytotoxic effect in human
                      Suit2-007 and rat ASML cells, as evidenced by a 6-fold lower
                      tumor cell survival than expected from an additive
                      combination effect. Treatment of BDX rats bearing
                      intra-portally implanted Suit2-007 cells showed a highly
                      significant anticancer effect and indicated an application
                      of Rpx against pancreatic cancer metastasis to the liver.
                      These data favor further evaluation of Rpx as anticancer
                      agent in PDAC.},
      keywords     = {Antineoplastic Agents (NLM Chemicals) / Apoptosis
                      Regulatory Proteins (NLM Chemicals) / Plant Proteins (NLM
                      Chemicals) / TNF-Related Apoptosis-Inducing Ligand (NLM
                      Chemicals) / riproximin protein, Ximenia americana (NLM
                      Chemicals)},
      cin          = {G401 / C060},
      ddc          = {570},
      cid          = {I:(DE-He78)G401-20160331 / I:(DE-He78)C060-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:24918923},
      pmc          = {pmc:PMC4128861},
      doi          = {10.4161/cbt.29503},
      url          = {https://inrepo02.dkfz.de/record/119413},
}