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
tirsdag 17. august 2010
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
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
tirsdag 10. august 2010
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.
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.
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.
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.
Hedgehog antagonist cyclopamine isomerizes to less potent forms when acidified.
Wilson SR, Strand MF, Krapp A, Rise F, Petersen D, Krauss S.
J Pharm Biomed Anal. 2010 Sep 5;52(5):707-13.
The effect of acid treatment of cyclopamine, a natural antagonist of the hedgehog (Hh) signaling pathway and a potential anti-cancer drug, has been studied. Previous reports have shown that under acidic conditions, as in the stomach, cyclopamine is less effective. Also, it has been stated that cyclopamine converts to veratramine, which has side effects such as hemolysis. In this study, we examined in detail the influence of acidification on structure and activity of cyclopamine. We found that of acidified cyclopamine converts to two previously unreported isomers, which we have called cyclopamine (S) and cyclopamine (X). These have likely gone undetected because cyclopamine is often analyzed with fast and hence lower resolving chromatographic methods. Compared to natural cyclopamine, these cyclopamine isomers have a significantly reduced effect on the ciliary transport of the Hh receptor smoothened, and reduced inhibition on the Hedgehog signaling pathway. The side effects of these isomers are unknown. Our findings can partly explain a reduced efficiency of cyclopamine in a gastric environment, and may help with the rational design of more pH independent cyclopamine analogues.
J Pharm Biomed Anal. 2010 Sep 5;52(5):707-13.
The effect of acid treatment of cyclopamine, a natural antagonist of the hedgehog (Hh) signaling pathway and a potential anti-cancer drug, has been studied. Previous reports have shown that under acidic conditions, as in the stomach, cyclopamine is less effective. Also, it has been stated that cyclopamine converts to veratramine, which has side effects such as hemolysis. In this study, we examined in detail the influence of acidification on structure and activity of cyclopamine. We found that of acidified cyclopamine converts to two previously unreported isomers, which we have called cyclopamine (S) and cyclopamine (X). These have likely gone undetected because cyclopamine is often analyzed with fast and hence lower resolving chromatographic methods. Compared to natural cyclopamine, these cyclopamine isomers have a significantly reduced effect on the ciliary transport of the Hh receptor smoothened, and reduced inhibition on the Hedgehog signaling pathway. The side effects of these isomers are unknown. Our findings can partly explain a reduced efficiency of cyclopamine in a gastric environment, and may help with the rational design of more pH independent cyclopamine analogues.
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