The European Medicines Agency review of Tegafur/Gimeracil/Oteracil (Teysuno™) for the treatment of advanced gastric cancer when given in combination with cisplatin: summary of the Scientific Assessment of the Committee for medicinal products for human use (CHMP).

The product Teysuno™ (S-1) contains tegafur, a prodrug of 5-fluorouracil (5-FU), and two modulators of 5-FU metabolism, gimeracil and oteracil. The main clinical study in this application was a randomized controlled study comparing S-1 plus cisplatin with 5-FU plus cisplatin. In this study, median overall survival times of 8.

Impact of the C-N status on the amino acid profile in tobacco source leaves.

This paper investigates the influence of the carbon (C) and nitrogen (N) status on the amino acid profile in tobacco source leaves. Treatments used included growing plants at different light intensities, using an antisense RBCS (small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase) construct to inhibit Rubisco activity, growing plants on 12 or 0.5 mM nitrate, comparing wild-types with genotypes that have small and large decreases in nitrate reductase (NIA) activity, and sampling plants at different times during the diurnal cycle.

Decreased Rubisco activity leads to dramatic changes of nitrate metabolism, amino acid metabolism and the levels of phenylpropanoids and nicotine in tobacco antisense RBCS transformants.

Tobacco transformants that express an antisense RBCS construct were used to investigate the consequences of a lesion in photosynthetic carbon metabolism for nitrogen metabolism and secondary metabolism. The results show that an inhibition of photosynthesis and decrease in sugar levels leads to a general inhibition of nitrogen metabolism, and dramatic changes in the levels of secondary metabolites. The response was particularly clear in plants that received excess nitrogen.

Steps towards an integrated view of nitrogen metabolism.

This article discusses how nitrate assimilation is integrated with nitrate uptake, with ammonium assimilation and amino acid synthesis, with pH regulation, and with the sugar supply in tobacco leaves. During the first part of the light period, nitrate assimilation exceeds nitrate uptake by 2-fold and ammonium assimilation by 50%, leading to rapid depletion of nitrate and accumulation of ammonium, glutamine, glycine and serine. NIA, NII and PPC expression show a shared maximum early in the diurnal cycle to direct carbon towards malate synthesis for pH regulation.