✦ LIBER ✦

Gene therapy for prostate cancer using the cytosine deaminase/uracil phosphoribosyltransferase suicide system

✍ Scribed by Tohru Miyagi; Dr. Kiyoshi Koshida; Osamu Hori; Hiroyuki Konaka; Hiroaki Katoh; Yasuhide Kitagawa; Atsushi Mizokami; Masayuki Egawa; Satoshi Ogawa; Hirohumi Hamada; Mikio Namiki

Publisher: John Wiley and Sons
Year: 2003
Tongue: English
Weight: 204 KB
Volume: 5
Category: Article
ISSN: 1099-498X
DOI: 10.1002/jgm.317

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

Background

Cytosine deaminase (CD) activates prodrug 5‐FC to 5‐FU and is used for suicide gene therapy (the CD/5‐FC system). E. coli uracil phosphoribosyltransferase (UPRT) is a pyrimidine salvage enzyme that directly converts 5‐FU into 5‐fluorouridine monophosphate and improves the antitumoral effect of 5‐FU. This study demonstrates the effectiveness of transduction of the UPRT gene in addition to CD/5‐FC cancer suicide gene therapy.

Methods

We investigated a combined suicide gene transduction therapy for human hormone independent prostate cancer cell line DU145 using two separate adenovirus vectors expressing the E. coli CD and E. coli UPRT genes and systemic 5‐FC administration (the CD+UPRT/5‐FC system).

Results

Cells transfected with AdCA‐UPRT showed approximately 57 times lower IC50 to 5‐FU compared with those transfected with AdCA‐LacZ. Furthermore, cells transfected with AdCA‐CD and AdCA‐UPRT proved to be more sensitive to 5‐FC compared with those transfected with AdCA‐CD. Intratumoral injection of AdCA‐CD and AdCA‐UPRT drastically suppressed the growth of tumors which had generated from DU145 cells inoculated into athymic (nude) mice compared with those injected with AdCA‐LacZ or AdCA‐LacZ and AdCA‐CD.

Conclusions

📜 SIMILAR VOLUMES

Cytosine deaminase gene as a potential t

Cytosine deaminase gene as a potential tool for the genetic therapy of colorectal cancer

✍ Rowley, Simon; Lindauer, Marcus; Gebert, Johannes F.; Haberkorn, Uwe; Oberdorfer 📂 Article 📅 1996 🏛 John Wiley and Sons 🌐 English ⚖ 632 KB

The bacterial enzyme cytosine deaminase (CD) catalyzes the conversion of 5-fluorocytosine (5-FC) to the lethal 5-fluorouracil (5-Fu) and so provides a useful system for selective killing of gene-modified mammalian tumor cells. Cloning of the CD gene from Escherichiu coli and expression in human tumo

Suicide gene therapy for prostate cancer

Suicide gene therapy for prostate cancer using a replication-deficient adenovirus containing the herpesvirus thymidine kinase gene

✍ Moshe Shalev; Brian J. Miles; Timothy C. Thompson; Gustavo Ayala; Edward B. Butl 📂 Article 📅 2000 🏛 Springer-Verlag 🌐 English ⚖ 79 KB

Hypoxia response element-driven cytosine

Hypoxia response element-driven cytosine deaminase/5-fluorocytosine gene therapy system: a highly effective approach to overcome the dynamics of tumour hypoxia and enhance the radiosensitivity of prostate cancer cells in vitro

✍ Laure Marignol; Ruth Foley; Thomas D. Southgate; Mary Coffey; Donal Hollywood; M 📂 Article 📅 2009 🏛 John Wiley and Sons 🌐 English ⚖ 289 KB

## Abstract ## Background We proposed to exploit hypoxia‐inducible factor (HIF)‐1α overexpression in prostate tumours and use this transcriptional machinery to control the expression of the suicide gene cytosine deaminase (CD) through binding of HIF‐1α to arrangements of hypoxia response elements.