Cancer Research; 71(1); 197–205. 2010

Novel Synthetic Antagonists of Canonical Wnt Signaling Inhibit Colorectal Cancer Cell Growth 

Jo Waaler, Ondrej Machon, Jens Peter von Kries, Steven Ray Wilson, Elsa Lundenes, Doris Wedlich, Dietmar Gradl, Jan Erik Paulsen, Olga Machonova, Jennifer L. Dembinski, Huyen Dinh, Stefan Krauss

Canonical Wnt signaling is deregulated in several types of human cancer where it plays a central role in tumor cell growth and progression. Here we report the identification of 2 new small molecules that specifically inhibit canonical Wnt pathway at the level of the destruction complex. Specificity was verified in various cellular reporter systems, a Xenopus double-axis formation assay and a gene expression profile analysis. In human colorectal cancer (CRC) cells, the new compounds JW67 and JW74 rapidly reduced active β-catenin with a subsequent downregulation of Wnt target genes, including AXIN2, SP5, and NKD1. Notably, AXIN2 protein levels were strongly increased after compound exposure. Long-term treatment with JW74 inhibited the growth of tumor cells in both a mouse xenograft model of CRC and in Apc^Min mice (multiple intestinal neoplasia, Min). Our findings rationalize further preclinical and clinical evaluation of these new compounds as novel modalities for cancer treatment.

http://cancerres.aacrjournals.org/content/71/1/197.abstract

CAST attacks cancer stem cells

Here is a link (Norwegian) to a recent article in on the group I am working in (CAST). We are working on ways to attack cancer by killing cancer stem cells (CSCs). Roughly, you can compare it to killing the seeds of an ugly plant so it doesn´t spread.
I will be posting links to our recent findings as soon as they are published online.

 http://www.forskningsradet.no/no/Nyheter/Stamcelleforskning_kan_lose_kreftgaten/1253961224567?WT.mc_id=nyhetsbrev-ForskningsradetNorsk

The Fenton and sono-Fenton processes applied for pesticide degradation.

Iordache I, Wilson SR, Lundanes E, Iordache M, Pavel VL, Aelenei N.
Env Engin Man Journ. 2010 April; 9 (4): 519-525


In this study, the authors explore the potential of ultrasound and wet catalyzed peroxide oxidation into the wastewater treatment processes. The processes applied for degradation of pesticides were carried out using Fenton reagent and sonochemical treatment. The Fenton and the sono-Fenton decomposition of 2,4-dichlorophenoxyacetic acid (2,4 D), 4-(2,4-dichlorophenoxy)butyric acid (2,4 DB), 4-chloro-o-tolyoxyacetic acid (MCPA), 3,5-dibromo-4-hidroxybenzonitrile (bromoxynil), and 3-(4-chlorophenyl)-1,1-
dimethylurea (monuron) showed that, in all cases ultrasound irradiation of wastewater improved the wet oxidation process.

Hedgehog antogonists cyclopamine and dihydroveratramine can be mistaken for each other in Veratrum Album.

Wilson SR, Strand MF, Rise F, Malterud KE, Krauss S
J. Pharm Biomed Anal. 2010 Volume 53, Issue 3, Nov 2; 53 (3): 497-502


A toxic plant, Veratrum album (ssp. viriscens), was found to have an inhibitory effect on Hedgehog (Hh), a developmental signaling pathway that has been shown to be active during development, in adult stem cells and in numerous human tumors. Based on earlier studies it was believed that the known Hh inhibitor cyclopamine was present in V. album (ssp. viriscens). Here we show that instead of cyclopamine, dihydroveratramine (DHV) was found in V. album (ssp. viriscens). These compounds are easily mistaken for each other, as both substances share the same molecular weight, and the same main MS/MS fragments. DHV was found to be a less potent Hh inhibitor compared to cyclopamine. This is the first reported occurrence of DVH in nature.

Separation of intact proteins on porous layer open tubular (PLOT) columns.

Magnus Rogeberg, Steven Ray Wilson, Tyge Greibrokk and Elsa Lundanes
Journal of Chromatography A
Volume 1217, Issue 17, 23 April 2010, Pages 2782-2786

Porous layer open tubular (PLOT) polystyrene divinylbenzene columns have been used for separating intact proteins with gradient elution. The 10 microm I.D. x 3 m columns were easily coupled to standard liquid chromatography-mass spectrometry (LC-MS) instrumentation with commercially available fittings. Standard proteins separated on PLOT columns appeared as narrow and symmetrical peaks with good resolution. Average peak width increased linearly with gradient time (tG) from 0.14 to 0.33 min (tG 20 and 120 min, respectively) using a 3 m column. With shorter columns, peak widths were larger and increased more steeply with gradient time. Theoretical peak capacity (nc) increased with column length (tested up to 3 m). The nc increased with tG until a plateau was reached. The highest peak capacity achieved (nc=185) was obtained with a 3 m column, where a plateau was reached with tG 90 min. The within- and between column retention time repeatabilities were below 0.6% and below 2.5% (relative standard deviation, RSD), respectively. The carry-over following injection of 0.5 ng per protein was less than 1.1%. The retention time dependence on column temperature was investigated in the range 20-50 degrees C. Proteins in a skimmed milk sample were separated using the method.