Enhanced transgene expression in urothelial cancer gene therapy with histone deacetylase inhibitor. Okegawa T, Nutahara K, Pong RC, Higashihara E, Hsieh JT. Department of Urology, University of Kyorin, Tokyo, Japan

Research output: Contribution to journalArticle

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 beta-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.

Original languageEnglish (US)
Pages (from-to)565-566
Number of pages2
JournalUrologic Oncology: Seminars and Original Investigations
Volume24
Issue number6
DOIs
StatePublished - Nov 2006

Fingerprint

Histone Deacetylase Inhibitors
Tokyo
Neoplasm Genes
Urology
Transgenes
Genetic Therapy
Japan
Enterovirus
Urinary Bladder Neoplasms
Nude Mice
Infection
RNA
Neoplasms
beta-Galactosidase
romidepsin
fosfestrol
Reverse Transcriptase Polymerase Chain Reaction
Adenoviridae
Intravenous Administration
Histones

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

@article{1c243c26b86f4455852f7f90927e61bc,
title = "Enhanced transgene expression in urothelial cancer gene therapy with histone deacetylase inhibitor. Okegawa T, Nutahara K, Pong RC, Higashihara E, Hsieh JT. Department of Urology, University of Kyorin, Tokyo, Japan",
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 beta-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.",
author = "Hsieh, {Jer Tsong}",
year = "2006",
month = "11",
doi = "10.1016/j.urolonc.2006.09.003",
language = "English (US)",
volume = "24",
pages = "565--566",
journal = "Urologic Oncology: Seminars and Original Investigations",
issn = "1078-1439",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Enhanced transgene expression in urothelial cancer gene therapy with histone deacetylase inhibitor. Okegawa T, Nutahara K, Pong RC, Higashihara E, Hsieh JT. Department of Urology, University of Kyorin, Tokyo, Japan

AU - Hsieh, Jer Tsong

PY - 2006/11

Y1 - 2006/11

N2 - 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 beta-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.

AB - 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 beta-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.

UR - http://www.scopus.com/inward/record.url?scp=33751337540&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33751337540&partnerID=8YFLogxK

U2 - 10.1016/j.urolonc.2006.09.003

DO - 10.1016/j.urolonc.2006.09.003

M3 - Article

AN - SCOPUS:33751337540

VL - 24

SP - 565

EP - 566

JO - Urologic Oncology: Seminars and Original Investigations

JF - Urologic Oncology: Seminars and Original Investigations

SN - 1078-1439

IS - 6

ER -