In the VEGFR TKI patients we found that higher levels of ESR, CRP and neutrophils were associated with worse objective cognitive functioning, and higher levels of ESR, CRP en LDH with depressive symptoms. Especially the ESR level seems relevant as it showed correlations with all cognitive domains. Our data suggest that markers of systemic inflammatory response, probably as a symptom of tumor progression, selleck chemical Cisplatin are corre lated with worse cognitive performance and more de pressive feelings in patients treated with VEGFR TKI. This is consistent with the work of others who found that higher CRP levels were associated with depression and worse cognitive functioning. Recently a review was published addressing the role of VEGF in the brain and the role of VEGF inhibitors on cognitive impairment. Ng et a.

concluded that VEGF plays an important role in the Central Nervous System such as neurogenesis and neuroprotection, and that studies suggest that VEGF may affect cognitive function ing through its effects on neurogenesis, cerebral blood flow and modulation of long term potentiation. We demonstrated no differences Inhibitors,Modulators,Libraries in plasma VEGF concentra tion between the two patient groups, and no influence of VEGF levels on cognitive functioning was observed. However, in the VEGFR TKI group the intracellular effect of VEGF is prevented by receptor blockade, and therefore VEGF plasma concentrations are not reflecting the intracellular concentrations and effects of VEGF in this group.

A possible explanation for the difference in cognitive Inhibitors,Modulators,Libraries functioning between the two patient groups is that, as a result of blocking the cerebral VEGF receptor through the VEGFR TKI, the capacity of neuronal repair and neurogenesis and learning is decreased. Further more, in the patient controls we found a strong negative Inhibitors,Modulators,Libraries correlation between subjective complaints and VEGF concentration, suggesting that VEGF indeed is important for psychological well being. Conclusions In summary, our data suggest that treatment with VEGFR TKI has a negative impact on cognitive functioning, and that subjective complaints can be corroborated by object ive neuropsychological Inhibitors,Modulators,Libraries testing. However this should be confirmed in a longitudinal Inhibitors,Modulators,Libraries study. Our results also war rant further studies on the underlying mechanism of the impairment of cognitive functioning during VEGF TKI therapy for example with functional imaging such as dynamic inhibitor Trichostatin A MRI imaging. We propose that patients who are treated with VEGFR TKI are monitored and informed for possible signs or symptoms associated with cognitive impairment. Background When activated, cell surface growth factor receptor tyrosine kinases become phosphorylated at a number of tyro sine residues.