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Titolo:
Adenoviral gene transfer is inhibited by soluble factors in malignant pleural effusions
Autore:
Batra, RK; Dubinett, SM; Henkle, BW; Sharma, S; Gardner, BK;
Indirizzi:
Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med, Vet Adm GreaterLos Angeles Hlth Care Syst, Los Angeles, CA 90073 USA Univ Calif Los Angeles Los Angeles CA USA 90073 Los Angeles, CA 90073 USA Univ Calif Los Angeles, Wadsworth Pulm Immunol Lab, Los Angeles, CA USA Univ Calif Los Angeles Los Angeles CA USA munol Lab, Los Angeles, CA USA Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA Univ Calif LosAngeles Los Angeles CA USA 90024 Los Angeles, CA 90024 USA
Titolo Testata:
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
fascicolo: 5, volume: 22, anno: 2000,
pagine: 613 - 619
SICI:
1044-1549(200005)22:5<613:AGTIIB>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
FIBROSIS AIRWAY EPITHELIA; PENTON BASE PROTEIN; I CLINICAL-TRIAL; IMMUNE-RESPONSES; LUNG-CANCER; ADENOASSOCIATED VIRUS; MOLECULAR MEDICINE; HELPER VIRUS; MOUSE-LIVER; DELIVERY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Batra, RK Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med, Vet Adm GreaterLos Angeles Hlth Care Syst, 111Q,11301 Wilshire Blvd, Los Angeles, CA 90073 USA Univ Calif Los Angeles 111Q,11301 Wilshire Blvd Los Angeles CA USA 90073
Citazione:
R.K. Batra et al., "Adenoviral gene transfer is inhibited by soluble factors in malignant pleural effusions", AM J RESP C, 22(5), 2000, pp. 613-619

Abstract

Direct in vivo gene delivery is a prerequisite for many gene therapy strategies; however, efficacy has been limited by a lack of therapeutic gene transfer. in studying intrapleural malignancy as a model for the gene therapy of non-small cell lung cancer, we previously identified soluble chondroitinsulfate-proteoglycans/glycosaminoglycans (CS-PG/GAGs) in malignant pleuraleffusions (MPE) as factors that inhibit retroviral vector (RV) transduction. Similarly, we have observed inhibition to gene transfer in the fluid component of MPE using adenoviral (Ad) vectors. Analyses indicate that the factors responsible for the block are filterable, soluble, titrable, and heat stable (56 degrees C). Passage through microporous membranes fractionates the inhibitory factors into large (> 100 kD) components of the effusions. Incontrast to RV transduction, hyaluronic acid or CS-PG/GAGs are not the inhibitors because the block is not reversed by pretreatment of the effusions with mammalian hyaluronidase, and exogenous addition of GAGs into the transduction media does not diminish Ad transduction. In considering the mechanism of action of the inhibitory factors, we observe that Ad entry, and specifically the binding of radiolabeled Ad to its target cell, is inhibited in the presence of MPE. Ad internalization may also be impaired; however, these studies exclude soluble fibronectin in MPE as a competitive inhibitor of Ad transduction. Lastly, sepharose A-mediated immunoglobulin depletion of MPE only partially reverses the block, and significant inhibition to Ad genetransfer persists at lower adenovirus:target cell ratios. Identifying the structural and functional basis for inhibition to Ad gene transfer may yield specific strategies to enable better in vivo translation of gene therapy approaches.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 10:45:03