Breast cancer prognosis is poor when total plasminogen activator activity is low

Abstract

Summary Plasminogen activator (PA) is a serine protease which exists in two forms: tissue-type (t-PA) and urokinase-type (u-PA). The activity (<60 unitmg-' vs >,60 unitmg-' protein) was found to be a significant prognostic factor for disease-free and overall survival of about the same import as lymph node involvement. Furthermore, the combination of total PA activity and nodal status could be even more precise in predicting survival times and probabilities in individual patients. This retrospective study demonstrates the total PA activity is a valuable prognostic factor in determining prognosis in human breast cancer.

Transgenic mouse models of human breast cancer

“…HGF and its receptor tyrosine kinase Met are involved in the development of the normal mammary gland (Niemann et al, 1998;Yang et al, 1995). Several studies have also shown overexpression of both Met and HGF in human breast cancers (Lamszus et al, 1997;Tuck et al, 1996;Yamashita et al, 1994). Two studies have generated mice which express an activated form of the Met receptor under control of the metallothionein promoter with varying results (Je ers et al, 1998;Liang et al, 1996).…”

Somatic mutations of the MET oncogene are selected during metastatic spread of human HNSC carcinomas

“…Germline missense mutations in the tyrosine kinase domain were detected in the majority of hereditary papillary renal cell carcinomas (HPRCC) Olivero et al, 1999), while somatic mutations have been found in a small proportion of sporadic papillary kidney carcinomas and in childhood hepatocellular carcinomas (Park et al, 1999). In patients with invasive breast carcinoma, tumor expression of either MET (Ghoussoub et al, 1998) or its ligand SF/HGF (Yamashita et al, 1994) was an independent predictor of decreased survival, suggesting a role for the MET receptor in tumor aggressive behavior and progression. The concept that MET drives cells to invade and to metastasize has been validated in the mouse, using either transfected cells (Rong et al, 1994;Giordano et al, 1997;Meiners et al, 1998) or transgenic animals (Liang et al, 1996;Jeers et al, 1998;Otsuka et al, 1998).…”

In vitro inhibition of human malignant brain tumour cell line proliferation by anti-urokinase-type plasminogen activator monoclonal antibodies

“…receptor-bound uPA v ill promote plasminogen actixation and thus the dissolution of the tumour matrix and the basement membrane. which is a prerequisite for invasion and metastasis.Plasminogen actix ators in tumours of the central nernous sx stem hax e not been studied extensix ely despite the intense in estigation into their possible role in cancer biologv Hoosein et al 1991: Foekens et al 1992: Hollas et al 1992: Kobaxashi et al 1992 Reith and Rucklidge et al 1992: Sumivoshi et al 1992: Hsui et al 1993: Janicke et al 1993: Pujade-Lauraine et al 1993: Yamashita et al 1993: Achbarou et al 1994: Bianchi et al 1994: Bouchet et al 1994and Young et al 1994. In this study.…”