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- Schnorr, Kirsten, et al.
(author)
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Tracing the 267 nm-Induced Radical Formation in Dimethyl Disulfide Using Time-Resolved X-ray Absorption Spectroscopy
- 2019
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In: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 10:6, s. 1382-1387
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Journal article (peer-reviewed)abstract
- Disulfide bonds are pivotal for the structure, function, and stability of proteins, and understanding ultraviolet (UV)-induced S–S bond cleavage is highly relevant for elucidating the fundamental mechanisms underlying protein photochemistry. Here, the near-UV photodecomposition mechanisms in gas-phase dimethyl disulfide, a prototype system with a S–S bond, are probed by ultrafast transient X-ray absorption spectroscopy. The evolving electronic structure during and after the dissociation is simultaneously monitored at the sulfur L1,2,3-edges and the carbon K-edge with 100 fs (FWHM) temporal resolution using the broadband soft X-ray spectrum from a femtosecond high-order harmonics light source. Dissociation products are identified with the help of ADC and RASPT2 electronic-structure calculations. Rapid dissociation into two CH3S radicals within 120 ± 30 fs is identified as the major relaxation pathway after excitation with 267 nm radiation. Additionally, a 30 ± 10% contribution from asymmetric CH3S2 + CH3 dissociation is indicated by the appearance of CH3 radicals, which is, however, at least partly the result of multiphoton excitation.
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2. |
- Ullenhag, Gustav J., et al.
(author)
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The TRAIL system is over-expressed in breast cancer and FLIP a marker of good prognosis
- 2015
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In: Journal of Cancer Research and Clinical Oncology. - : Springer Science and Business Media LLC. - 0171-5216 .- 1432-1335. ; 141:3, s. 505-514
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Journal article (peer-reviewed)abstract
- Background Breast cancer is the most common cancer in women. The tumor necrosis factor-related apoptosisinducing ligand (TRAIL) pathway transmits apoptotic signals. Novel anticancer agents that activate this system are in clinical development, including anti-breast cancer. Methods The tissue microarray technique was applied. We used an array of breast cancer tissues from a large group of patients (> 800) to assess the protein expression of TRAIL-R1, TRAIL-R2, the long isoform of FLICE-inhibitory protein and total FLICE-inhibitory protein (FLIPL and FLIPT). Disease-free survival was examined by Kaplan-Meier estimates and the log-rank test. The independence of prognostic factors was determined by Cox multivariate analysis. Results High intra-tumoral expression of all these proteins of the TRAIL pathway was found. The TRAIL receptors and FLIPL were not associated with survival. On univariate analysis, strong FLIPT expression was associated with a significantly better survival (p = 0.001). On multivariate analysis using the Cox proportional hazards model, FLIPT phenotype was significantly associated with a good prognosis in this series (HR 0.52, 95 % CI 0.35-0.78, p = 0.039). Results indicate that this association is valid for all the biological subtypes of breast cancer. The expression of FLIPT was especially high in the luminal subtype, known for its good prognosis. Conclusions These findings support the use of agonistic TRAIL antibodies and drugs targeting FLIP in breast cancer patients. Over-expression of FLIPT but not TRAIL-R1, TRAIL-R2 or FLIPL provides stage-independent prognostic information in breast cancer patients. This indicates a clinically less aggressive phenotype.
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