| 1. |
- Andrén, Ove, 1963-, et al.
(författare)
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MUC-1 gene is associated with prostate cancer death : a 20-year follow-up of a population-based study in Sweden
- 2007
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Ingår i: British Journal of Cancer. - London : Harcourt Publishers. - 0007-0920 .- 1532-1827. ; 97:6, s. 730-734
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Tidskriftsartikel (refereegranskat)abstract
- Anti-adhesion mucins have proven to play an important part in the biology of several types of cancer. Therefore, we test the hypothesis that altered expression of MUC-1 is associated with prostate cancer progression. We retrieved archival tumour tissue from a population-based cohort of 195 men with localised prostate cancer (T1a-b, Nx, M0) that has been followed for up to 20 years with watchful waiting. Semi-automated, quantitative immunohistochemistry was undertaken to evaluate MUC-1 expression. We modelled prostate cancer-specific death as a function of MUC-1 levels accounting for age, Gleason grade and tumour extent, and calculated age-adjusted and multivariate adjusted hazard ratios (HR). Men that had tumours with an MUC-intensity lower or higher than normal tissue had a higher risk of dying in prostate cancer, independent of tumour extent and Gleason score (HR 5.1 and 4.5, respectively). Adjustment for Gleason grade and tumour stage did not alter the results. Men with a Gleason score >=7 and MUC-1 deviating from the normal had a 17 (RR=17.1 95% confidence interval=2.3–128) times higher risk to die in prostate cancer compared with men with Gleason score <7 and normal MUC-1 intensity. In summary, our data show that MUC-1 is an independent prognostic marker for prostate cancer death.
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| 2. |
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| 3. |
- Bize, Ariane, et al.
(författare)
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A unique virus release mechanism in the Archaea
- 2009
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:27, s. 11306-11311
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the infection cycles of viruses infecting cells from Archaea, the third domain of life. Here, we demonstrate that the virions of the archaeal Sulfolobus islandicus rod-shaped virus 2 (SIRV2) are released from the host cell through a mechanism, involving the formation of specific cellular structures. Large pyramidal virus-induced protrusions transect the cell envelope at several positions, rupturing the S-layer; they eventually open out, thus creating large apertures through which virions escape the cell. We also demonstrate that massive degradation of the host chromosomes occurs because of virus infection, and that virion assembly occurs in the cytoplasm. Furthermore, intracellular viral DNA is visualized by flow cytometry. The results show that SIRV2 is a lytic virus, and that the host cell dies as a consequence of elaborated mechanisms orchestrated by the virus. The generation of specific cellular structures for a distinct step of virus life cycle is known in eukaryal virus-host systems but is unprecedented in cells from other domains.
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| 4. |
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| 5. |
- Hartman, Ola, et al.
(författare)
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Neutron Compton scattering anomaly verified with Rh-resonance foil
- 2008
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Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 20:10, s. 104248-
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Tidskriftsartikel (refereegranskat)abstract
- Compton scattering experiments with neutrons usually employ Au- or U-foils for energy selection of the scattered neutrons. A series of experiments on various H-containing materials have shown a large deficit in the scattering intensity of protons using Au-foils and it has been claimed that the anomalies arise from a faulty analysis of the data by neglecting effects of the tails of the Au- resonance lines. In the present experiments a Rh-103 resonance foil is used. It has considerably different resonance characteristics, but the H/metal ratio derived shows nearly the same anomalous value as with Au- foils. The present result therefore supports the existence of the mentioned anomalies.
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| 6. |
- Johnston, Eric V., et al.
(författare)
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Efficient synthesis of hybrid (hydroquinone-Schiff base)cobalt oxidation catalysts
- 2009
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Ingår i: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; :23, s. 3973-3976
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Tidskriftsartikel (refereegranskat)abstract
- Hybrid catalysts A and B have recently been found to efficiently transfer electrons from a metal catalyst to molecular oxygen in biomimetic oxidations. In the present work hybrid catalysts A and B were synthesized in high yield from inexpensive starting materials. The key step is an efficient Suzuki cross-coupling, which allows the use of unprotected aldehyde 5. The new synthesis of the title hybrid catalysts is easy to carry out and can be scaled up.
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| 7. |
- Kalén, Mattias, et al.
(författare)
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Combination of reverse and chemical genetic screens reveals angiogenesis inhibitors and targets.
- 2009
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Ingår i: Chemistry & biology. - : Elsevier BV. - 1879-1301 .- 1074-5521. ; 16:4, s. 432-41
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Tidskriftsartikel (refereegranskat)abstract
- We combined reverse and chemical genetics to identify targets and compounds modulating blood vessel development. Through transcript profiling in mice, we identified 150 potentially druggable microvessel-enriched gene products. Orthologs of 50 of these were knocked down in a reverse genetic screen in zebrafish, demonstrating that 16 were necessary for developmental angiogenesis. In parallel, 1280 pharmacologically active compounds were screened in a human cell-based assay, identifying 28 compounds selectively inhibiting endothelial sprouting. Several links were revealed between the results of the reverse and chemical genetic screens, including the serine/threonine (S/T) phosphatases ppp1ca, ppp1cc, and ppp4c and an inhibitor of this gene family; Endothall. Our results suggest that the combination of reverse and chemical genetic screens, in vertebrates, is an efficient strategy for the identification of drug targets and compounds that modulate complex biological systems, such as angiogenesis.
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| 8. |
- Karlsson, Erik A., et al.
(författare)
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Mechanism of the palladium-catalyzed carbohydroxylation of allene-substituted conjugated dienes: rationalization of the recently observed nucleophilic attack by water on a (pi-allyl)palladium intermediate
- 2008
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 14:30, s. 9175-9180
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism of the palladium-catalyzed oxidative carbohydroxylation of allene-substituted 1,3-cyclohexadiene was studied by DFT calculations. All intermediates and transition states of the reaction were identified and their structures were calculated. The calculations confirm the mechanism previously proposed and show that the CC bond-forming step occurs via insertion of one of the double bonds of 1,3-cyclohexadiene into a Pdvinyl bond of a vinylpalladium intermediate. This reaction leads to a (π-allyl)palladium intermediate, and coordination of benzoquinone and a double bond in the molecule to Pd creates a highly reactive cationic π-allyl complex, which is readily attacked by water according to the calculations.
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| 9. |
- Karlsson, Erik A., et al.
(författare)
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Oxidation of ethers, alcohols, and unfunctionalized hydrocarbons by the methyltrioxorhenium/H2O2 system: a computational study on catalytic C-H bond activation
- 2009
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Ingår i: Abstracts of Papers, 238th ACS National Meeting, Washington, DC, United States, August 16-20, 2009. - Washington DC : American Chemical Society.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Karlsson, Erik A., et al.
(författare)
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Oxidation of ethers, alcohols, and unfunctionalized hydrocarbons by the methyltrioxorhenium/H2O2 system: a computational study on catalytic C-H bond activation
- 2009
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 15:8, s. 1862-1869
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Tidskriftsartikel (refereegranskat)abstract
- A concerted mechanism that does not involve an ionic intermediate was revealed by a DFT study on oxidation of ethers, alcohols, and unfunctionalized hydrocarbons by methyltrioxorhenium/H2O2. Instead, CH insertion occurs through hydride transfer and then turns into a hydroxide transfer/rebound in a concerted fashion. The picture shows selected frames from an intrinsic reaction coordinate scan from the transition state to the product for the oxidation of cis-1,2-dimethylcyclohexane. The potential-energy surfaces (PESs) of methyltrioxorhenium (MTO)-catalyzed CH insertion reactions in the presence of hydrogen peroxide were studied by accurate DFT methods for a series of substrates including unsaturated hydrocarbons, an ether, and an alcohol. Based on the comprehensive analysis of transition states and intrinsic reaction coordinate (IRC) scans, CH insertion was found to proceed by a concerted mechanism that does not require, as previously thought, a side-on or a butterfly-like transition state. We found that a typical transition state follows requirements of the SN2 reaction instead. Furthermore, by exploring the PESs of several CH insertion reactions, we discovered that no ionic intermediate is formed even in a polar solvent. The latter was modeled within the self-consistent reaction field approach in a polarizable continuum model (PB-SCRF/PCM). According to our study, CH insertion occurs by a concerted but highly asynchronous mechanism that first proceeds by hydride transfer and then turns into hydroxide transfer/rebound. For the oxidation of alcohols, CH bond cleavage occurs without formation of alkoxide intermediates on the dominant pathway. The computed deuterium kinetic isotope effect of 2.9 for the hydride-transfer transition state for alcohol oxidation is in good agreement with the experimental kH/kD ration of 3.2 reported by Zauche and Espenson. As confirmed by IRC and PES scans in different solvents, the OH-rebound phase of the CH insertion pathway demonstrates strong similarities with the rebound mechanism that was previously proposed for cytochrome P450 and metalloporphyrin-catalyzed oxidations.
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