title: Dianthin-EGF is an effective tumor targeted toxin in combination with saponins in a xenograft model for colon carcinoma.
abstract: OBJECTIVE
  The intention of this work was to lift saponin supported tumor targeted therapies onto the next level by using targeted toxins in nude mice xenotransplant models.
  
  
  METHODS
  Combined application of dianthin coupled to EGF and saponin SO-1861 was tested in a xenograft model of colon carcinoma. In vitro cytotoxicity was tested in real-time in NIH3T3 cells (no human EGF receptor expression), HER14 and human colon carcinoma HCT116 (both EGF receptor overexpressing) cells. A xenograft model was established using HCT116 cells and tumor-bearing animals were treated with SO-1861 (30 µg/treatment) and dianthin coupled to EGF (0.35 µg/treatment). Tumor progression was monitored, using (18)F-2-fluor-2-desoxy-d-glucose, by small animal PET and by x-ray computed tomography.
  
  
  RESULTS
  In vitro results demonstrated a high-receptor specificity and the in vivo experiment showed a progressive reduction of the tumor volume and glycolytic activity in the treated group (>95% reduction; p < 0.05).
  
  
  CONCLUSIONS
  This therapy has great advantage because of high specificity, low side effects and great effectiveness for future development in the treatment of colon cancer.
authors.affiliation: Institute for Laboratory Medicine, Clinical Chemistry & Pathobiochemistry, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Benedicta
authors.initials: B
authors.lastname: von Mallinckrodt
authors.forename: Mayank
authors.initials: M
authors.lastname: Thakur
authors.forename: Alexander
authors.initials: A
authors.lastname: Weng
authors.forename: Roger
authors.initials: R
authors.lastname: Gilabert-Oriol
authors.forename: Horst
authors.initials: H
authors.lastname: Dürkop
authors.forename: Winfried
authors.initials: W
authors.lastname: Brenner
authors.forename: Mathias
authors.initials: M
authors.lastname: Lukas
authors.forename: Nicola
authors.initials: N
authors.lastname: Beindorff
authors.forename: Matthias F
authors.initials: MF
authors.lastname: Melzig
authors.forename: Hendrik
authors.initials: H
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology*; D029749:Dianthus / Q000737:chemistry; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004815:Epidermal Growth Factor; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography; D054789:Ribosome Inactivating Proteins, Type 1; D012503:Saponins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D012503:Saponins; D004815:Epidermal Growth Factor
keywords: colon cancer; dianthin-EGF; saponin SO-1861; targeted toxins; targeted tumor therapy; xenograft model