Application of targeted radiotherapy/gene therapy to bladder cancer cell lines.
Eur Urol
; 47(2): 250-6, 2005 Feb.
Article
em En
| MEDLINE
| ID: mdl-15661422
ABSTRACT
OBJECTIVES:
A targeted radiotherapy/gene therapy strategy for transitional cell carcinoma of bladder is described, using [131I]meta-iodobenzylguanidine ([131I]MIBG), a radionuclide combined with a tumour-seeking drug. The aim is to decrease side effects from radiation toxicity, while increasing radiation dose to tumour. This tumour cell kill approach is augmented by radiological bystander effects.METHODS:
The bladder cancer cell line EJ138 was transfected with a gene encoding the noradrenaline transporter (NAT) under the control of tumour-specific telomerase promoters. Resulting uptake of [131I]MIBG was assessed by gamma-counting of cell lysates, and NAT transgene expression by real-time RT-PCR. Cell kill of monolayers and disaggregated spheroids, dosed with [131I]MIBG, was assessed by clonogenic assay.RESULTS:
NAT gene transfected cells exhibited a significantly increased active uptake of [131I]MIBG, leading to dose-dependent cell kill. Clonogenic assay of disaggregated spheroids, a three-dimensional model, suggested cell kill via bystander effects.CONCLUSIONS:
Expression of a functional NAT after in vitro transfection of bladder cancer cells with the NAT gene under the control of telomerase promoters leads to active uptake of [131I]MIBG and dose-dependent cell kill. This strategy could produce a promising new treatment option for bladder cancer.
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Base de dados:
MEDLINE
Assunto principal:
Radioterapia
/
Neoplasias da Bexiga Urinária
/
Carcinoma de Células de Transição
/
Terapia Genética
Limite:
Humans
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article