Our previous data indicate that the expression of the PLK gene which codes for a serine/threonine kinase is restricted to proliferating cells. In Northern blot experiments PLK mRNA expression was at the limit of detection in normal lung tissue but elevated in most samples of non-small cell lung cancer (NSCLC). A very low frequency of PLK transcripts was only found in bronchiolo-alveolar carcinomas. NSCLC patients whose tumors showed moderate PLK expression survived signi®cantly longer (5 year survival rate=51.8%) than those with high levels of PLK transcripts (24.2%, P=0.001). No statistically signi®cant correlation was found between PLK mRNA expression and age, sex, TNM status, histological type or degree of dierentiation. Interestingly, the prognosis of patients in postsurgical stages I and II was correlated with PLK expression (5 year survival rates in stage I: 69.1% (moderate PLK) ± 43.5% (high PLK), P=0.03 or in stage II: 51.9% (moderate PLK) ± 9.9% (high PLK), P=0.006). These results suggest that PLK mRNA expression provides a new independent prognostic indicator for patients with NSCLC.

Summary Recent studies have shown that elevated levels of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) in breast cancer correlate with an increased risk of a reduced relapse-free survival time and shortened overall survival times. Urokinase PA and PAI-I are independent prognostic indicators for breast cancer (Goldfarb and Liotta, 1986). Among the diverse extracellular proteolytic enzymes produced by tumours, urokinase plasminogen activator (uPA) is considered to play a pivotal role in tissue invasion, vascular invasion and formation of metastases (Dano et al., 1985).Tumour cells synthesise and secrete uPA as an inactive proenzyme (pro-uPA) (Stump, 1986), which binds to specific receptors on the cell surface (Vasalli et al., 1985). After binding, pro-uPA is activated by cathepsin B or plasmin (Kobayashi et al., 1990). Receptor-bound active uPA converts plasminogen to plasmin. Subsequently, plasmin is also bound to a different receptor on the tumour cell surface (Miles and Plow, 1988). Plasmin then degrades components of the stroma (e.g. fibrin, fibronectin, proteoglycans, laminin), and may activate procollagenase type IV, which then degrades collagen type IV, a major part of the basement membrane (Dvorak, 1986). Thus uPA promotes the dissolution of the tumour matrix and the basement membrane, which is a prerequisite for invasion and metastases. This implies that the proteolytic activity of uPA also causes a degradation of vessel walls. Vessel wall dissolution is one of the first steps in neovascularisation (Mahadevan and Hart, 1990). Furthermore, some ECM molecules become angiogenic after hydrolytic degradation (West et al., 1985

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We have used two experimental models of immune complexes to study the secretion of interleukin (IL)-10, IL-6 and their connection with the immune complex-induced synthesis of prostaglandin (PG) E2 by human monocytes in vitro. Immune complexes formed of tetanus toxoid and polyclonal anti-tetanus toxoid antiserum as well as heat-aggregated human serum immunoglobulins induced the release of IL-6 and IL-10 in a dose- and antigen: antibody ratio-dependent manner. Antigen-antibody complexes formed near equivalence were most effective in induction of a cytokine response. PGE2 could augment the immune complex-induced IL-6 and IL-10 secretion, but alone, did not induce cytokine secretion. IL-10 was capable of down-regulating the release of IL-6 and PGE2. Additionally, we demonstrated that endogenously synthesized IL-10 limited the immune complex-induced secretion of proinflammatory cytokines tumor necrosis factor-alpha and IL-1 beta. All three regulatory factors examined here share anti-inflammatory properties and are closely associated with the T helper type 2 (Th2) immune response. We conclude that immune complexes, besides their well-known ability no cause acute and chronic inflammation, can mediate immunosuppressive effects and influence the balance of Th1/Th2 responses.

The source of labor-associated release of tumor-necrosis-factor-alpha from placental tissues are macrophages, whereas interleukin-1beta and interleukin-6 are released from placental endothelial cells.