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Titolo:
Interference with the urokinase plasminogen activator system: a promising therapy concept for solid tumours
Autore:
Muehlenweg, B; Sperl, S; Magdolen, V; Schmitt, M; Harbeck, N;
Indirizzi:
Tech Univ Munich, Klinikum Rechts Isar, Frauenklin & Poliklin, D-81675 Munich, Germany Tech Univ Munich Munich Germany D-81675 oliklin, D-81675 Munich, Germany Wilex AG, D-81675 Munich, Germany Wilex AG Munich Germany D-81675Wilex AG, D-81675 Munich, Germany
Titolo Testata:
EXPERT OPINION ON BIOLOGICAL THERAPY
fascicolo: 4, volume: 1, anno: 2001,
pagine: 683 - 691
SICI:
1471-2598(200107)1:4<683:IWTUPA>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADENOVIRUS-MEDIATED DELIVERY; RECEPTOR-BINDING REGION; PRIMARY BREAST-CANCER; TERM FOLLOW-UP; SYNTHETIC INHIBITORS; DEFICIENT MICE; GENE-TRANSFER; DRUG DESIGN; CATHEPSIN-L; IN-VIVO;
Keywords:
gene therapy; invasion; metastasis; PAI-1; plasminogen activator system; synthetic inhibitors; tumour therapy; uPA; uPA-R (CD87);
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Harbeck, N Tech Univ Munich, Klinikum Rechts Isar, Frauenklin & Poliklin, Ismaninger Str 22, D-81675 Munich, Germany Tech Univ Munich Ismaninger Str 22 Munich Germany D-81675 many
Citazione:
B. Muehlenweg et al., "Interference with the urokinase plasminogen activator system: a promising therapy concept for solid tumours", EXPERT OP B, 1(4), 2001, pp. 683-691

Abstract

There is abundant evidence that the plasminogen activator (PA) system withits key components uPA (urokinase-type plasminogen activator), its cell surface receptor uPA-R (CD87) and its inhibitor PAI-1 plays a key role in tumour invasion and metastasis. Elevated levels of these factors in tumour tissue are associated with tumour aggressiveness and poor patient outcome. Animal models suggest that the PA system is not essential for fertility or survival under physiological conditions. Thus, it seems well suited as a therapeutic target for patients with solid malignant tumours. Novel therapy concepts targeting the uPA system are currently being explored. A variety of different synthetic uPA inhibitor classes have been developed over the last decades. First generation inhibitors displayed a low uPA inhibitory potency combined with broad specificity. More recently, structure based design, x-ray crystallographic screening or NMR based screening have revealed a large number of new, potent and selective uPA-inhibitors. A few modern compounds have shown promising results in preclinical testing and are now ready for Phase I clinical studies. Other therapeutic strategies such as antagonists of uPA/uPA-R interaction or gene therapeutic approaches to suppress the uPA-system are still being evaluated in in vitro and in vivo models. For clinical application, a combination therapy targeting more than one of the interacting proteolytic pathways may be required for effective antiproteolytic therapy. in addition, antiproteolytic agents may provide additive or synergistic treatment benefits if used in combination together with conventional therapeutics, in particular in those solid tumours for which potent conventional regimens already exist.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/01/20 alle ore 06:55:17