title: Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma.
abstract: BACKGROUND
  Malignant mesothelioma (MM) is a rare, highly aggressive tumor, associated to asbestos exposure. To date no chemotherapy regimen for MM has proven to be definitively curative, and new therapies for MM treatment need to be developed. We have previously shown in vivo that piroxicam/cisplatin combined treatment in MM, specifically acts on cell cycle regulation triggering apoptosis, with survival increase.
  
  
  RESULTS
  We analyzed, at molecular level, the apoptotic increase caused by piroxicam/cisplatin treatment in MM cell lines. By means of genome wide analyses, we analyzed transcriptional gene deregulation both after the single piroxicam or cisplatin and the combined treatment. Here we show that apoptotic increase following combined treatment is mediated by p21, since apoptotic increase in piroxicam/cisplatin combined treatment is abolished upon p21 silencing.
  
  
  CONCLUSIONS
  Piroxicam/cisplatin combined treatment determines an apoptosis increase in MM cells, which is dependent on the p21 expression. The results provided suggest that piroxicam/cisplatin combination might be tested in clinical settings in tumor specimens that express p21.
authors.affiliation: Department of Biochemistry, Section of Pathology, Second University of Naples, Naples, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Baldi
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Piccolo
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Boccellino
authors.forename: Aldo
authors.initials: A
authors.lastname: Donizetti
authors.forename: Irene
authors.initials: I
authors.lastname: Cardillo
authors.forename: Raffaele
authors.initials: R
authors.lastname: La Porta
authors.forename: Lucio
authors.initials: L
authors.lastname: Quagliuolo
authors.forename: Enrico P
authors.initials: EP
authors.lastname: Spugnini
authors.forename: Francesca
authors.initials: F
authors.lastname: Cordero
authors.forename: Gennaro
authors.initials: G
authors.lastname: Citro
authors.forename: Massimo
authors.initials: M
authors.lastname: Menegozzo
authors.forename: Raffaele A
authors.initials: RA
authors.lastname: Calogero
authors.forename: Stefania
authors.initials: S
authors.lastname: Crispi
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010894:Piroxicam / Q000008:administration & dosage / Q000494:pharmacology*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016861:Cyclooxygenase Inhibitors; D010894:Piroxicam; C084429:CDKN3 protein, human; D054637:Dual-Specificity Phosphatases; D002945:Cisplatin