Inhibition of metastasis of intraocular melanomas by adenovirus-mediated gene transfer of plasminogen activator inhibitor type I (PAI-1) in an athymic mouse model

Ding Ma, Robert D. Gerard, Xiao Yan Li, Hassan Alizadeh, Jerry Y. Niederkorn

Research output: Contribution to journalArticle

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Abstract

Uveal melanoma is the most common intraocular malignancy in adults and results in the death of 50% of the patients. Plasminogen activators (PA) are believed to facilitate tumor metastasis by promoting invasion of tissue barriers. The present study explored the possibility of preventing the metastasis of intraocular melanomas by disrupting plasminogen activator function through gene transfer. A replication-deficient adenovirus vector was used for the in vivo transfer of plasminogen activator inhibitor type 1 (PAI- 1) cDNA. Intraocular injection of an adenovirus vector (AdCMV-PAI-1) expressing plasminogen activator inhibitor-1 resulted in: (1) the transduction of more than 95% of human and murine uveal melanoma cells in the eyes of nude mice; (2) a 50% reduction in the number of animals developing liver metastases; and (3) a 78% reduction in the metastatic tumor burden in animals that eventually developed metastases. In other experiments intravenous injections of AdCMV-PAI-1 resulted in transduction of normal liver cells and culminated in a sharp reduction in the incidence of metastases and a significant prolongation of host survival. The results support the feasibility of disruption of PA function through gene transfer as a therapeutic strategy for preventing metastases and prolonging host survival.

Original languageEnglish (US)
Pages (from-to)2738-2746
Number of pages9
JournalBlood
Volume90
Issue number7
StatePublished - Oct 1 1997

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Gene transfer
Plasminogen Inactivators
Plasminogen Activator Inhibitor 1
Adenoviridae
Nude Mice
Plasminogen Activators
Melanoma
Neoplasm Metastasis
Liver
Genes
Tumors
Animals
Intraocular Injections
Survival
Complementary DNA
Tissue
Tumor Burden
Intravenous Injections
Neoplasms
Experiments

ASJC Scopus subject areas

  • Hematology

Cite this

Inhibition of metastasis of intraocular melanomas by adenovirus-mediated gene transfer of plasminogen activator inhibitor type I (PAI-1) in an athymic mouse model. / Ma, Ding; Gerard, Robert D.; Li, Xiao Yan; Alizadeh, Hassan; Niederkorn, Jerry Y.

In: Blood, Vol. 90, No. 7, 01.10.1997, p. 2738-2746.

Research output: Contribution to journalArticle

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abstract = "Uveal melanoma is the most common intraocular malignancy in adults and results in the death of 50{\%} of the patients. Plasminogen activators (PA) are believed to facilitate tumor metastasis by promoting invasion of tissue barriers. The present study explored the possibility of preventing the metastasis of intraocular melanomas by disrupting plasminogen activator function through gene transfer. A replication-deficient adenovirus vector was used for the in vivo transfer of plasminogen activator inhibitor type 1 (PAI- 1) cDNA. Intraocular injection of an adenovirus vector (AdCMV-PAI-1) expressing plasminogen activator inhibitor-1 resulted in: (1) the transduction of more than 95{\%} of human and murine uveal melanoma cells in the eyes of nude mice; (2) a 50{\%} reduction in the number of animals developing liver metastases; and (3) a 78{\%} reduction in the metastatic tumor burden in animals that eventually developed metastases. In other experiments intravenous injections of AdCMV-PAI-1 resulted in transduction of normal liver cells and culminated in a sharp reduction in the incidence of metastases and a significant prolongation of host survival. The results support the feasibility of disruption of PA function through gene transfer as a therapeutic strategy for preventing metastases and prolonging host survival.",
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AB - Uveal melanoma is the most common intraocular malignancy in adults and results in the death of 50% of the patients. Plasminogen activators (PA) are believed to facilitate tumor metastasis by promoting invasion of tissue barriers. The present study explored the possibility of preventing the metastasis of intraocular melanomas by disrupting plasminogen activator function through gene transfer. A replication-deficient adenovirus vector was used for the in vivo transfer of plasminogen activator inhibitor type 1 (PAI- 1) cDNA. Intraocular injection of an adenovirus vector (AdCMV-PAI-1) expressing plasminogen activator inhibitor-1 resulted in: (1) the transduction of more than 95% of human and murine uveal melanoma cells in the eyes of nude mice; (2) a 50% reduction in the number of animals developing liver metastases; and (3) a 78% reduction in the metastatic tumor burden in animals that eventually developed metastases. In other experiments intravenous injections of AdCMV-PAI-1 resulted in transduction of normal liver cells and culminated in a sharp reduction in the incidence of metastases and a significant prolongation of host survival. The results support the feasibility of disruption of PA function through gene transfer as a therapeutic strategy for preventing metastases and prolonging host survival.

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