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ENHANCED TRANSGENE EXPRESSION IN UROTHELIAL CANCER GENE THERAPY WITH HISTONE DEACETYLASE INHIBITOR

2005; Lippincott Williams & Wilkins; Volume: 174; Issue: 2 Linguagem: Inglês

10.1097/01.ju.0000164723.20555.e6

1527-3792

Takatsugu Okegawa, Kikuo Nutahara, Rey-Chen Pong, Eiji Higashihara, Jer‐Tsong Hsieh,

CAR-T cell therapy research

No AccessJournal of UrologyInvestigative Urology1 Aug 2005ENHANCED TRANSGENE EXPRESSION IN UROTHELIAL CANCER GENE THERAPY WITH HISTONE DEACETYLASE INHIBITOR TAKATSUGU OKEGAWA, KIKUO NUTAHARA, REY-CHEN PONG, EIJI HIGASHIHARA, and JER-TSONG HSIEH TAKATSUGU OKEGAWATAKATSUGU OKEGAWA , KIKUO NUTAHARAKIKUO NUTAHARA , REY-CHEN PONGREY-CHEN PONG , EIJI HIGASHIHARAEIJI HIGASHIHARA , and JER-TSONG HSIEHJER-TSONG HSIEH View All Author Informationhttps://doi.org/10.1097/01.ju.0000164723.20555.e6AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Efficient adenoviral infection requires the presence of the coxsackievirus and adenovirus receptor (CAR). We determined whether the histone deacetylase inhibitor FR901228 (Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan) increases the efficiency of adenoviral gene therapy in bladder cancer in vivo and in vitro. Materials and Methods: Cytotoxicity studies were performed to determine a minimally cytotoxic FR901228 concentration for bladder cancer cells. The level of CAR expression was determined by fluorescence activated cell scanning and/or reverse transcriptase-polymerase chain reaction analysis in FR901228 treated bladder cell lines. The in vivo effect on adenoviral gene expression was investigated in athymic mice. Results: The concentration of FR901228 showing no or minimal cytotoxicity that was selected for these studies was 0.5 ng/ml for bladder cancer cells. Treatment of cancer cells with 0.5 ng/ml histone deacetylase inhibitor increased CAR RNA levels and acetylated histone H3. This increase was associated with a 5 to 10-fold increase in adenoviral infection, as evidenced by increased transgene expression from a β-galactosidase containing adenoviral vector. Intravenous administration of FR901228 enhanced CAR expression in athymic mice. The combination of p53 adenovirus and histone deacetylase inhibitor resulted in significant tumor inhibition in vitro and in vivo. Conclusions: Nontoxic doses of the histone deacetylase inhibitor FR901228 increased CAR RNA levels and resulted in the marked enhancement of transgene expression after adenoviral infections. FR901228 pretreatment may increase the sensitivity of tumor cells to adenoviral gene therapy vectors. References 1 : The growth inhibitory effect of p21 adenovirus on human bladder cancer cells. J Urol2000; 163: 1033. Abstract, Google Scholar 2 : Progress in pathology of tumors of the urinary tract. Prog Clin Biol Res1988; 277: 1. Google Scholar 3 : Bladder cancer. I. Molecular and genetic basis of carcinogenesis. Eur Urol2001; 39: 491. Google Scholar 4 : Loss of adenoviral receptor expression in human bladder cancer cells: a potential impact on the efficacy of gene therapy. Cancer Res1999; 59: 325. Google Scholar 5 : Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science1997; 275: 1320. Google Scholar 6 : Efficient oncolysis by a replicating adenovirus (ad) in vivo is critically dependent on tumor expression of primary Ad receptors. Cancer Res2001; 61: 813. Google Scholar 7 : Integrin alpha(v) and coxsackie adenovirus receptor expression in clinical bladder cancer. Urology2002; 60: 531. Google Scholar 8 : Expression of the coxsackie adenovirus receptor in normal prostate and in primary and metastatic prostate carcinoma: potential relevance to gene therapy. Cancer Res2002; 62: 3812. Google Scholar 9 : The mechanism of growth-inhibitory effect of coxsackie and adenovirus receptor (CAR) on human bladder cancer: a functional analysis of CAR protein structure. Cancer Res2001; 61: 6592. Google Scholar 10 : Enhanced adenovirus transgene in malignant cells treated with the histone deacetylase inhibitor FR901228. Cancer Res2001; 61: 6328. Google Scholar 11 : Histone deacetylase inhibitor FR901228 enhances adenovirus infection of hematopoietic cells. Blood2002; 99: 2248. Google Scholar 12 : Differential effects of adenovirus-p16 on bladder cancer cell lines can be overcome by the addition of butyrate. Clin Cancer Res2001; 7: 210. Google Scholar 13 : Modulation of coxsackie-adenovirus receptor expression for increased adenoviral transgene expression. Cancer Res2003; 63: 847. Google Scholar 14 : The histone deacetylase inhibitor FK228 preferentially enhances adenovirus transgene expression in malignant cells. Clin Cancer Res2003; 9: 5394. Google Scholar 15 : Impact of novel histone deacetylase inhibitors, CHAP31 and FR901228 (FK228), on adenovirus-mediated transgene expression. J Gene Med2004; 6: 526. Google Scholar 16 : Histone deacetylase inhibitors upregulate expression of the coxsackie adenovirus receptor (CAR) preferentially in bladder cancer cells. Cancer Gene Ther2004; 11: 477. Google Scholar 17 : The dual impact of coxsackie and adenovirus receptor expression on human prostate cancer gene therapy. Cancer Res2000; 60: 5031. Google Scholar 18 : Fibroblast-mediated acceleration of human epithelial tumor growth in vivo. Proc Natl Acad Sci USA1990; 87: 75. Google Scholar 19 : Histone-deacetylase inhibitors: novel drugs for the treatment of cancer. Nat Rev Drug Discov2002; 1: 287. Google Scholar 20 : Epigenetic regulation of coxsackie and adenovirus receptor (CAR) gene promoter in urogenital cancer cells. Cancer Res2003; 63: 8680. Google Scholar Departments of Urology, University of Kyorin, Tokyo, Japan, and University of Texas Southwestern Medical Center, Dallas, Texas© 2005 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited ByOkegawa T, Sayne J, Nutahara K, Pong R, Saboorian H, Kabbani W, Higashihara E and Hsieh J (2018) A Histone Deacetylase Inhibitor Enhances Adenoviral Infection of Renal Cancer CellsJournal of Urology, VOL. 177, NO. 3, (1148-1156), Online publication date: 1-Mar-2007. Volume 174Issue 2August 2005Page: 747-752 Advertisement Copyright & Permissions© 2005 by American Urological Association, Inc.Keywordsbladderhistone deacetylasesbladder neoplasmsadenovirus receptorMetricsAuthor Information TAKATSUGU OKEGAWA More articles by this author KIKUO NUTAHARA More articles by this author REY-CHEN PONG More articles by this author EIJI HIGASHIHARA More articles by this author JER-TSONG HSIEH More articles by this author Expand All Advertisement PDF DownloadLoading ...