PURPOSE: Because TRAIL (tumor necrosis factor related apoptosis inducing ligand) selectively kills cancer cells without damaging normal cells, a gene therapy approach using TRAIL is feasible for treating patients with cancer. However, recent publications suggest that significant portions of human tumors appear to be TRAIL resistant. Furthermore, there is some controversy about whether TRAIL receptor composition influences TRAIL sensitivity in cancer cells. Our recent studies suggest that TRAIL receptor composition is the major modulator of TRAIL sensitivity, as demonstrated using prostate, breast and lung cancer cells. We investigated TRAIL and TRAIL receptor expression profiles during prostate carcinogenesis to evaluate their potential as biomarkers and predict the feasibility of a related gene therapy approach. MATERIALS AND METHODS: Paraffin embedded prostate tissues of 44 patients with benign prostatic hyperplasia, 28 with organ confined prostate carcinoma and 26 with advanced prostate carcinoma were analyzed using immunohistochemical staining procedures. RESULTS: Significant levels of TRAIL-R4 decoy receptor expression were detected in patients with benign prostatic hyperplasia, and organ confined and advanced prostate carcinoma. All TRAIL markers tested appear to be valuable markers for separating patients with benign prostatic hyperplasia from patients with organ confined prostate carcinoma or advanced prostate carcinoma. CONCLUSIONS: Due to high TRAIL-R4 expression in all patient groups complementary gene therapy modalities might be needed to bypass potential TRAIL-R4 induced resistance.
PURPOSE: Because TRAIL (tumor necrosis factor related apoptosis inducing ligand) selectively kills cancer cells without damaging normal cells, a gene therapy approach using TRAIL is feasible for treating patients with cancer. However, recent publications suggest that significant portions of humantumors appear to be TRAIL resistant. Furthermore, there is some controversy about whether TRAIL receptor composition influences TRAIL sensitivity in cancer cells. Our recent studies suggest that TRAIL receptor composition is the major modulator of TRAIL sensitivity, as demonstrated using prostate, breast and lung cancer cells. We investigated TRAIL and TRAIL receptor expression profiles during prostate carcinogenesis to evaluate their potential as biomarkers and predict the feasibility of a related gene therapy approach. MATERIALS AND METHODS:Paraffin embedded prostate tissues of 44 patients with benign prostatic hyperplasia, 28 with organ confined prostate carcinoma and 26 with advanced prostate carcinoma were analyzed using immunohistochemical staining procedures. RESULTS: Significant levels of TRAIL-R4 decoy receptor expression were detected in patients with benign prostatic hyperplasia, and organ confined and advanced prostate carcinoma. All TRAIL markers tested appear to be valuable markers for separating patients with benign prostatic hyperplasia from patients with organ confined prostate carcinoma or advanced prostate carcinoma. CONCLUSIONS: Due to high TRAIL-R4 expression in all patient groups complementary gene therapy modalities might be needed to bypass potential TRAIL-R4 induced resistance.
Authors: David W McIlwain; Marloes Zoetemelk; Jason D Myers; Marshé T Edwards; Brandy M Snider; Travis J Jerde Journal: Prostate Date: 2016-02-24 Impact factor: 4.104
Authors: Silvia von Karstedt; Annalisa Conti; Max Nobis; Antonella Montinaro; Torsten Hartwig; Johannes Lemke; Karen Legler; Franka Annewanter; Andrew D Campbell; Lucia Taraborrelli; Anne Grosse-Wilde; Johannes F Coy; Mona A El-Bahrawy; Frank Bergmann; Ronald Koschny; Jens Werner; Tom M Ganten; Thomas Schweiger; Konrad Hoetzenecker; Istvan Kenessey; Balazs Hegedüs; Michael Bergmann; Charlotte Hauser; Jan-Hendrik Egberts; Thomas Becker; Christoph Röcken; Holger Kalthoff; Anna Trauzold; Kurt I Anderson; Owen J Sansom; Henning Walczak Journal: Cancer Cell Date: 2015-04-02 Impact factor: 31.743
Authors: Adam Bilski; Grażyna Pasz-Walczak; Robert Kubiak; Piotr Sek; Justyna Chalubinska; Wojciech Fendler; Konrad Wronski; Anna Piekarska; Piotr Pluta; Piotr Potemski; Arkadiusz Jeziorski; Janusz Piekarski Journal: Arch Med Sci Date: 2010-09-07 Impact factor: 3.318