Purpose In the present study, we screened a compound library containing 1,600 clinically used compounds with the aim to identify compounds, which potentially could be repositioned for colon cancer therapy.Methods Two established colon cancer cell lines were tested using the fluorometric microculture cytotoxicity assay (FMCA). For compound comparison connectivity map (CMAP) analysis, NCI 60 data mining and protein kinase binding measurements were performed.ResultsSixty-eight compounds were defined as hits with activity in both of these cell lines (<40 % cell survival compared with control) at 10 μM drug concentration. Analysis of chemical similarity of the hit compounds revealed several distinct clusters, among them the antiparasitic benzimidazole group. Two of these compounds, mebendazole (MBZ) and albendazole (ABZ) are registered for human use. Data from the NCI 60 cell line panel revealed only modest correlation between MBZ and ABZ, indicating differences in mechanism of action. This was further supported when gene expression signatures were compared in the CMAP database; ABZ ranked very low when MBZ was used as the query signature. Furthermore, MBZ, but not ABZ, was found to significantly interact with several protein kinases including BCR–ABL and BRAF. Analysis of the diagnosis-specific activity of MBZ showed activity in 80 % of the colon cancer cell lines in the NCI 60 panel. Three additional colon cancer cell lines and three cell models with non-malignant phenotypes were subsequently tested, confirming selective colon cancer activity of MBZ.ConclusionMBZ seemingly has repositioning potential for colorectal cancer therapy.

A B S T R A C T The present experiments were performed to quantify the effect of changes in distal tubular sodium delivery on glomerular flow dynamics both below and above the normal physiologic range. Glomerular capillary pressure as derived from the tubular stop flow pressure was assessed while the loop of Henle of the same nephron was perfused with varying flow rates. During Ringer perfusion no change of glomerular capillary pressure was observed when flow was increased from 0 to 13 nl/min. Further increasing flow to 27 nl/ min was associated with a reduction of glomerular hydrostatic pressure by an average of 7.0±4.4 cm H20 (+SD). During

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Glycerol has been injected intravenously in guinea pig and its effects on the pressure in the cochlear fluids have been studied. Simultaneously, arterial and cerebro-spinal pressures have been recorded. Glycerol lowered the intracochlear as well as cerebro-spinal and blood pressures, the latter only temporarily. Different possible mechanisms for the glycerol effect on the intracochlear pressure and its transient effect on hearing in Menière's disease are discussed.