Patients with small cell lung cancer (SCLC) die because of chemoresistance. Fibroblast growth factor-2 (FGF-2) increases the expression of antiapoptotic proteins, XIAP and Bcl-X L , and triggers chemoresistance in SCLC cells. Here we show that these effects are mediated through the formation of a specific multiprotein complex comprising B-Raf, PKCe and S6K2. S6K1, Raf-1 and other PKC isoforms do not form similar complexes. RNAi-mediated downregulation of B-Raf, PKCe or S6K2 abolishes FGF-2-mediated survival. In contrast, overexpression of PKCe increases XIAP and Bcl-X L levels and chemoresistance in SCLC cells. In a tetracycline-inducible system, increased S6K2 kinase activity triggers upregulation of XIAP, Bcl-X L and prosurvival effects. However, increased S6K1 kinase activity has no such effect. Thus, S6K2 but not S6K1 mediates prosurvival/chemoresistance signalling.
Summary and conclusionsIn 12 consecutive unselected patients admitted to a consultant maternity unit one single injection of subarachnoid morphine sulphate 15 mg abolished pain during the first stage of labour. Pain in the second stage was abolished in four patients and lessened in three. During the early puerperium, pain at the site of the episiotomy was much reduced. Side effects included itching of the face, nausea and vomiting, and frontal headache, but these were mild and simply treated. They were even less severe in the last four patients, in whom barbotage was not used in administering the morphine. The high rate of forceps delivery and caesarean section (three cases of each) was not thought to be associated with the use of intrathecal morphine.These findings show that intrathecal morphine can abolish the pain of labour, whether spontaneous or induced, while preserving the mother's full awareness of labour and her co-operation in the second and third stages of labour. Further, controlled, trials are warranted.
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