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| 2. |
- Enberg, U., et al.
(author)
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Increased ratio of mRNA expression of the genes CYP17 and CYP11B1 indicates autonomous cortisol production in adrenocortical tumors
- 2009
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In: Journal of Endocrinological Investigation. - 0391-4097 .- 1720-8386. ; 32:10, s. 810-815
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Due to increased use of imaging techniques, adrenal incidentalomas are frequently detected. The majority are non-hyperfunctioning adrenocortical tumors. We have previously shown that expression of the gene CYP17, coding for the enzyme in the cortisol pathway, correlates with cortisol release from adrenocortical tumors in vitro. The aim of this study was to compare clinical data with mRNA expression of CYP17 and CYP11B1 in adrenocortical tumors from patients with and without Cushing's syndrome and to identify adrenal tumors that may cause subclinical Cushing's syndrome. DESIGN: A retrospective study of 34 patients undergoing adrenalectomy due to an adrenal tumor. METHODS: Clinical data were collected. In the adrenal gland the mRNA expression of the genes CYP17 and CYP11B1 was studied with in situ hybridisation technique. RESULTS: The median ratio of CYP17/CYP11B1 expression in tumors from patients with Cushing's syndrome was significantly higher than the median ratio in the non-hyperfunctioning tumors. Tumors from 2 patients with subclinical Cushing's syndrome had ratios within the upper range for non-hyperfunctioning tumors. CONCLUSIONS: The ratio between the expression of the genes CYP17 and CYP11B1 in tumors from patients with Cushing's syndrome is significantly higher than in the non-hyperfunctioning tumors. This indicates that 17alpha-hydroxylase is a major determinant of cortisol overproduction. The patients with subclinical Cushing's syndrome in this study are too few to draw any firm conclusions although the results suggest that subclinical Cushing's syndrome may be identified post-operatively with this method.
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| 3. |
- Hellman, A, et al.
(author)
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Predicting catalysis : understanding ammonia synthesis from first-principles calculations
- 2006
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In: Journal of Physical Chemistry B. - 1520-6106 .- 1520-5207. ; 110, s. 17719-17735
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Journal article (peer-reviewed)abstract
- Here, we give a full account of a large collaborative effort toward an atomic-scale understanding of modern industrial ammonia production over ruthenium catalysts. We show that overall rates of ammonia production can be determined by applying various levels of theory (including transition state theory with or without tunneling corrections, and quantum dynamics) to a range of relevant elementary reaction steps, such as N(2) dissociation, H(2) dissociation, and hydrogenation of the intermediate reactants. A complete kinetic model based on the most relevant elementary steps can be established for any given point along an industrial reactor, and the kinetic results can be integrated over the catalyst bed to determine the industrial reactor yield. We find that, given the present uncertainties, the rate of ammonia production is well-determined directly from our atomic-scale calculations. Furthermore, our studies provide new insight into several related fields, for instance, gas-phase and electrochemical ammonia synthesis. The success of predicting the outcome of a catalytic reaction from first-principles calculations supports our point of view that, in the future, theory will be a fully integrated tool in the search for the next generation of catalysts.
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| 4. |
- Rahman-Roblick, R., et al.
(author)
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Proteomic identification of p53-dependent protein phosphorylation
- 2008
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In: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 27:35, s. 4854-4859
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Journal article (peer-reviewed)abstract
- The p53 tumor suppressor regulates transcription of target genes. We have previously analysed the p53-dependent proteome and identified novel protein targets. Here we have examined p53-dependent phosphorylation using two-dimensional gel electrophoresis and staining with the fluorescent phosphoprotein dye Pro-Q Diamond. We report that p53 induces phosphorylation of a subset of proteins including Nm23, DJ-1, ANXA1 and PrxII. Our identification of p53-dependent phosphorylation of specific target proteins reveals new aspects of the p53-dependent cellular response and suggests that such posttranslational modifications may contribute to p53-mediated tumor suppression.
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| 5. |
- Roblick, U.J., et al.
(author)
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Undifferentiated pelvic adenocarcinomas : diagnostic potential of protein profiling and multivariate analysis
- 2008
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In: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 23:5, s. 483-491
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Despite improved techniques, the determination of tumor origin in poorly differentiated adenocarcinomas still remains a challenge for the pathologist. Here we report the use of protein profiling combined with principal component analysis to improve diagnostic decision-making in tumor samples, in which standard pathologic investigations cannot present reliable results. MATERIALS AND METHODS: A poorly differentiated adenocarcinoma of unknown origin located in the pelvis, infiltrating the sigmoid colon as well as the ovary, served as a model to evaluate our proteomic approach. Firstly, we characterized the protein expression profiles from eight advanced colon and seven ovarian adenocarcinomas using two-dimensional gel electrophoresis (2-DE). Qualitative and quantitative patterns were recorded and compared to the tumor of unknown origin. Based on these protein profiles, match sets from the different tumors were created. Finally, a multivariate principal component analysis was applied to the entire 2-DE data to disclose differences in protein patterns between the different tumors. RESULTS: Over 89% of the unknown tumor sample spots could be matched with the colon standard gel, whereas only 63% of the spots could be matched with the ovarian standard. In addition, principal component analysis impressively displayed the clustering of the unknown case within the colon cancer samples, whereas this case did not cluster at all within the group of ovarian adenocarcinomas. CONCLUSION: These results show that 2-DE protein expression profiling combined with principal component analysis is a sensitive method for diagnosing undifferentiated adenocarcinomas of unknown origin. The described approach can contribute greatly to diagnostic decision-making and, with further technical improvements and a higher throughput, become a powerful tool in the armentarium of the pathologist.
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| 6. |
- Stasyk, T, et al.
(author)
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Phosphoproteome profiling of transforming growth factor (TGF)-beta signaling: abrogation of TGFbeta1-dependent phosphorylation of transcription factor-II-I (TFII-I) enhances cooperation of TFII-I and Smad3 in transcription
- 2005
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In: Molecular biology of the cell. - : American Society for Cell Biology (ASCB). - 1059-1524 .- 1939-4586. ; 16:10, s. 4765-4780
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Journal article (peer-reviewed)abstract
- Transforming growth factor-β (TGFβ) signaling involves activation of a number of signaling pathways, several of which are controlled by phosphorylation events. Here, we describe a phosphoproteome profiling of MCF-7 human breast epithelial cells treated with TGFβ1. We identified 32 proteins that change their phosphorylation upon treatment with TGFβ1; 26 of these proteins are novel targets of TGFβ1. We show that Smad2 and Smad3 have different effects on the dynamics of TGFβ1-induced protein phosphorylation. The identified proteins belong to nine functional groups, e.g., proteins regulating RNA processing, cytoskeletal rearrangements, and proteasomal degradation. To evaluate the proteomics findings, we explored the functional importance of TGFβ1-dependent phosphorylation of one of the targets, i.e., transcription factor-II-I (TFII-I). We confirmed that TGFβ1 stimulated TFII-I phosphorylation at serine residues 371 and 743. Abrogation of the phosphorylation by replacement of Ser371 and Ser743 with alanine residues resulted in enhanced complex formation between TFII-I and Smad3, and enhanced cooperation between TFII-I and Smad3 in transcriptional regulation, as evaluated by a microarray-based measurement of expression of endogenous cyclin D2, cyclin D3, and E2F2 genes, and by a luciferase reporter assay. Thus, TGFβ1-dependent phosphorylation of TFII-I may modulate TGFβ signaling at the transcriptional level.
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