title: A comparison analysis of anti-tumor efficacy of adenoviral gene replacement therapy (p14ARF and p16INK4A) in human mesothelioma cells.
abstract: BACKGROUND
  Tumor suppressor genes encode critical cell cycle regulatory proteins that are frequently mutated or deleted in cancer and, therefore, are important candidates for cancer treatment based on gene replacement strategies.
  
  
  METHODS
  We evaluated and compared the relative potential therapeutic efficacy of p14ARF and p16INK4A expressed in adenoviral vectors (Adp14ARF and Adp16INK4A, respectively) in three human mesothelioma cell lines.
  
  
  RESULTS
  The cytotoxic effects of expressed p16INK4A were significantly greater than that of p14ARF in both H28 and H2052 cells. Cell cycle G1 arrest occurred earlier with Adp16INK4A treatment than Adp14ARF (24 hours vs. 48 hours, respectively). Although both Adp14ARF and Adp16INK4A inhibited cell proliferation significantly and were potentiated by chemotherapy, Adp16INK4A appeared more potent.
  
  
  CONCLUSIONS
  Our results suggest that adenoviral gene-based therapy, especially using Adp16INK4A-based strategy, may be effective in the treatment of human mesothelioma.
authors.affiliation: Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Yang
authors.forename: Liang
authors.initials: L
authors.lastname: You
authors.forename: Yu-Chin
authors.initials: YC
authors.lastname: Lin
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Lin
authors.forename: Frank
authors.initials: F
authors.lastname: Mccormick
authors.forename: David M
authors.initials: DM
authors.lastname: Jablons
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D003131:Combined Modality Therapy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D017239:Paclitaxel / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D025803:Tumor Suppressor Protein p14ARF / Q000096:biosynthesis / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D017239:Paclitaxel; D002945:Cisplatin