Local haemostasis in brain tumours.

The thromboplastic activity and the fibrinolytic activity were examined in 7 human meningiomas and 6 gliomas obtained at neurosurgery. Two different haemostatic patterns emerged, meningiomas having lower thromboplastic and higher fibrinolytic activity than that of gliomas. This difference might help to explain the better haemostatic capacity of gliomas during and after operation than that of meningiomas.     

Characterization and antithrombotic action of tissue plasminogen activator

Summary An extractive fibrinolytic enzyme has been characterized and found to belong to the class of vascular plasminogen activators. The agent has been found to have an antithrombotic action in the rabbit.Provided by Dr L. Dussourd d'Hinterland, Laboratoires Pierre Fabre, Castres, France. 1000 units have a fibrinolytic activity of about 15 PU urokinase.     

Quantitation of fibrinolytic agents released in tissue culture

Zusammenfassung Es wird eine neue Methode zur Bestimmung der freigesetzten Menge fibrinolytisch wirksamer Stoffe in Gewebekulturen beschrieben. Das Gewebe wird in Leightonröhrchen mit einem standardisierten Fibringerinnsel gezüchtet. Die abgebaute Fibrinmenge — als Mass der fibrinolytischen Aktivität — wird durch immunologische Bestimmung der Spaltprodukte gemessen.     

The p66shc adaptor protein controls oxidative stress response and life span in mammals

Gene mutations in invertebrates have been identified that extend life span and enhance resistance to environmental stresses such as ultraviolet light or reactive oxygen species. In mammals, the mechanisms that regulate stress response are poorly understood and no genes are known to increase individual life span. Here we report that targeted mutation of the mouse p66shc gene induces stress resistance and prolongs life span. p66shc is a splice variant of p52shc/p46shc (ref. 2), a cytoplasmic signal transducer involved in the transmission of mitogenic signals from activated receptors to Ras. We show that: (1) p66shc is serine phosphorylated upon treatment with hydrogen peroxide (H2O2) or irradiation with ultraviolet light; (2) ablation of p66shc enhances cellular resistance to apoptosis induced by H2O2 or ultraviolet light; (3) a serine-phosphorylation defective mutant of p66shc cannot restore the normal stress response in p66shc-/- cells; (4) the p53 and p21 stress response is impaired in p66shc-/- cells; (5) p66shc-/- mice have increased resistance to paraquat and a 30% increase in life span. We propose that p66shc is part of a signal transduction pathway that regulates stress apoptotic responses and life span in mammals.     

Antifibrinolytic properties of oxyphenbutazone in vitro

Summary The authors found that oxyphenbutazone (Tanderil^®) added to culture medium, in amounts giving a final concentration of 10–100 g/ml, causes a decrease in the liberation of fibrinolytic agents from explants of various tissues cultured in vitro.     

PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR

Loss of the promyelocytic leukaemia (PML) tumour suppressor has been observed in several human cancers. The tumour-suppressive function of PML has been attributed to its ability to induce growth arrest, cellular senescence and apoptosis. Here we identify PML as a critical inhibitor of neoangiogenesis (the formation of new blood vessels) in vivo, in both ischaemic and neoplastic conditions, through the control of protein translation. We demonstrate that in hypoxic conditions PML acts as a negative regulator of the synthesis rate of hypoxia-inducible factor 1alpha (HIF-1alpha) by repressing mammalian target of rapamycin (mTOR). PML physically interacts with mTOR and negatively regulates its association with the small GTPase Rheb by favouring mTOR nuclear accumulation. Notably, Pml-/- cells and tumours display higher sensitivity both in vitro and in vivo to growth inhibition by rapamycin, and lack of PML inversely correlates with phosphorylation of ribosomal protein S6 and tumour angiogenesis in mouse and human tumours. Thus, our findings identify PML as a novel suppressor of mTOR and neoangiogenesis.