Tyrosine kinases as molecular targets to inhibit cancer progression and metastasis.

During the last decades, the improvement of our knowledge of the mechanisms responsible for cancer development has led to the introduction of new promising strategies of treatment, based on "molecular targeted" drugs. These drugs are designed to act on specific molecules, identified as major players in the maintenance of the malignant status. The development of inhibitors, mainly monoclonal antibodies and small-molecules, directed against activated oncogenes has been the most widely used approach for this kind of treatment. Among the oncogenes implicated in human cancers, tyrosine kinases play a critical role. This observation, together with the discovery that cancer cells can be dependent for their survival from the continuous expression of activated oncogenes (a concept defined as "oncogene addiction"), has made protein kinases ideal targets for targeted therapy in cancer. As the field of targeted therapies is now rapidly growing and a comprehensive survey would be too wide, this review will thus mainly focus on strategies aimed at inhibiting tyrosine kinases and their signal transduction pathways.

Pentoxifylline reduces proteinuria in insulin-dependent and non insulin-dependent diabetic patients.

Pentoxifylline is a drug with hemorheological actions used in the management of microcirculatory abnormalities, such as those usually seen in diabetic patients. The drug has been successfully used in improving peripheral and central circulation, as well as proteinuria of long-term diabetes. With the hypothesis that pentoxifylline reduces proteinuria in patients with IDDM and NIDDM, with a wide range of urinary protein excretion, 86 diabetic patients were studied. Forty-one patients with IDDM were stratified in 2 subgroups: one of 18 patients with microalbuminuria, and the other of 23 patients with overt proteinuria. In the same way, 45 patients with NIDDM were divided in 2 subgroups: one of 23 patients with microalbuminuria, and the other of 22 patients with proteinuria. Patients in each subgroup were randomized to receive either placebo or pentoxifylline 1,200 mg/d, during 4 months, using a double blind design. At the beginning of the study and after treatment, 24-hour urinary albumin excretion was measured by nephelometry in each patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Zinc and copper concentration in plasma and erythrocytes of patients with chronic renal failure.

Zinc (Zn) and copper (Cu) concentrations were studied in plasma and erythrocytes in patients with chronic renal failure that were on hemo or peritoneal dialysis together with the effect of dialysis treatment on these element concentrations. Plasma Zn was found to be significantly reduced in both groups of patients. On the other hand, erythrocyte zinc levels were higher. This considered more as a metabolic adaptation than as a pathological fact. Plasma Cu increase was observed in hemodialysis patients; however in the group on peritoneal dialysis it was found to be normal. Dialysis did not alter significantly plasma levels in any of these two elements; on the contrary, Zn and Cu levels were decreased in erythrocytes. Ceruloplasmin increased with hemodialysis and decreased with peritoneal dialysis possible due to protein loss resulting in this procedure.

Concentracion de cinc y cobre en plasma y eritrocitos en pacientes con insuficiencia renal cronica. / Zinc and copper concentration in plasma and erythrocytes of patients with chronic renal failure

Se estudiaron la concentracion de cinc (Zn) y de cobre (Cu) en el plasma y los eritrocitos de pacientes con insuficiencia renal cronica (IRC) que recebian tratamiento con hemodialisis o dialisis peritoneal, y el efecto que tiene la terapeutica dialitica sobre la concentracion de esos elementos. El Zn plasmatico se encontro significativamente disminuido en los dos grupos de pacientes.En contraste, el Zn del eritrocito estuvo elevado. Esto se interpreta como una adaptacion metabolica mas que como un hecho patologico. Se encontro aumento del Cu plasmatico en los pacientes en hemodialisis; en cambio, en el grupo de dialisis peritoneal fue normal. La dialisis no altero significativamente los niveles plasmaticos de ninguno de los dos elementos; por lo contrario, en el eritrocito se observo una disminucion tanto del Zn como del Cu. La ceruloplasmina se incremento con la hemodialisis y disminuyo con la dialisis peritoneal, posiblemente por la perdida de proteinas que se produce cuando se realiza este procedimiento