Increase in ascorbate-glutathione metabolism as local and precocious systemic responses induced by cadmium in durum wheat plants.

Durum wheat plants (Triticum durum cv Creso) were grown in the presence of cadmium (0-40 microM) and analysed after 3 and 7 d for their growth, oxidative stress markers, phytochelatins, and enzymes and metabolites of the ascorbate (ASC)-glutathione (GSH) cycle. Cd exposure produced a dose-dependent inhibition of growth in both roots and leaves. Lipid peroxidation, protein oxidation and the decrease in the ascorbate redox state indicate the presence of oxidative stress in the roots, where H2O2 overproduction and phytochelatin synthesis also occurred. The activity of the ASC-GSH cycle enzymes significantly increased in roots. Consistently, a dose-dependent accumulation of Cd was evident in these organs. On the other hand, no oxidative stress symptoms or phytochelatin synthesis occurred in the leaves; where, at least during the time of our analysis, the levels of Cd remained irrelevant. In spite of this, enzymes of the ASC-GSH cycle significantly increased their activity in the leaves. When ASC biosynthesis was enhanced, by feeding plants with its last precursor, L-galactono-gamma-lactone (GL), Cd uptake was not affected. On the other hand, the oxidative stress induced in the roots by the heavy metal was alleviated. GL treatment also inhibited the Cd-dependent phytochelatin biosynthesis. These results suggest that different strategies can successfully cope with heavy metal toxicity. The changes that occurred in the ASC-GSH cycle enzymes of the leaves also suggest that the whole plant improved its antioxidant defense, even in those parts which had not yet been reached by Cd. This precocious increase in the enzymes of the ASC-GSH cycle further highlight the tight regulation and the relevance of this cycle in the defense against heavy metals.

C-reactive protein: a biomarker of survival in patients with metastatic renal cell carcinoma treated with subcutaneous interleukin-2 based immunotherapy.

PURPOSE: In patients with metastatic renal cell carcinoma treated with low dose subcutaneous interleukin-2 based immunotherapy we evaluated a panel of biohumoral and clinical parameters before treatment to verify their correlation with clinical outcome. MATERIALS AND METHODS: We analyzed the records of 110 patients treated at our institution. Before treatment total lymphocytes, lactate dehydrogenase, the erythrocyte sedimentation rate, albumin, C-reactive protein (CRP) and fibrinogen were analyzed and correlated with clinical parameters, namely performance status, patient age, sex, prior nephrectomy, number and sites of disease, and disease-free interval (DFI) from nephrectomy to metastatic disease. RESULTS: Median survival was 12 months (partial and complete response 33, stable disease 14 and progression 7). The overall response was 24% for a partial and complete response, 37% for stable disease and 39% for progression. On univariate analysis good performance status (p = 0.0000), prior nephrectomy (p = 0.0001), DFI longer than 12 months (p = 0.0003), bone disease site (p = 0.0013), a low number of metastatic sites (p = 0.0449), normal albumin (p = 0.0001), low/normal fibrinogen (p = 0.0140), low/normal lactate dehydrogenase (p = 0.0430) and low/normal CRP (p = 0.0000) were related to better survival. On final multivariate analysis only CRP (p = 0.002) and DFI (p = 0.0497) were found to have an independent role in survival. When we correlated clinical and biohumoral factors, only CRP correlated with DFI (p = 0.021) and prior nephrectomy (p = 0.041). CONCLUSIONS: Our data confirm that some clinical and biohumoral factors may be strongly related to survival in metastatic renal cell carcinoma. The interesting new aspect emerging from this study is the prognostic value of CRP and fibrinogen, which are able to discriminate a good from a poor prognosis.