| 1. |
- Iles, Mark M., et al.
(författare)
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A variant in FTO shows association with melanoma risk not due to BMI
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:4, s. 428-432
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 x 10(-12), per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanomasusceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.
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| 2. |
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| 3. |
- Pérez-Perarnau, Alba, et al.
(författare)
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A trifluorinated thiazoline scaffold leading to pro-apoptotic agents targeting prohibitins
- 2014
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 53:38, s. 10150-10154
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Tidskriftsartikel (refereegranskat)abstract
- A new class of small molecules, with an unprecedented trifluorothiazoline scaffold, were synthesized and their pro-apoptotic activity was evaluated. With an EC50 in the low micromolar range, these compounds proved to be potent inducers of apoptosis in a broad spectrum of tumor cell lines, regardless of the functional status of p53. Fast structure-activity relationship studies allowed the preparation of the strongest apoptosis-inducing candidate. Using a high performance affinity purification approach, we identified prohibitins 1 and 2, key proteins involved in the maintenance of cell viability, as the targets for these compounds.
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| 4. |
- Sun, Ying, et al.
(författare)
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Asymmetrical effects of mesophyll conductance on fundamental photosynthetic parameters and their relationships estimated from leaf gas exchange measurements
- 2014
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Ingår i: Plant, Cell and Environment. - : John Wiley & Sons. - 0140-7791 .- 1365-3040. ; 37:4, s. 978-994
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Tidskriftsartikel (refereegranskat)abstract
- Worldwide measurements of nearly 130 C3 species covering all major plant functional types are analysed in conjunction with model simulations to determine the effects of mesophyll conductance (gm) on photosynthetic parameters and their relationships estimated fromA/Ci curves. We find that an assumption of infinite gm results in up to 75% underestimation for maximum carboxylation rate Vcmax, 60% for maximum electron transport rate Jmax, and 40% for triose phosphate utilization rate Tu. Vcmax is most sensitive, Jmax is less sensitive, and Tuhas the least sensitivity to the variation of gm. Because of this asymmetrical effect of gm, the ratios of Jmax to Vcmax, Tu to Vcmax and Tu toJmax are all overestimated. An infinite gm assumption also limits the freedom of variation of estimated parameters and artificially constrains parameter relationships to stronger shapes. These findings suggest the importance of quantifying gm for understanding in situphotosynthetic machinery functioning. We show that a nonzero resistance to CO2 movement in chloroplasts has small effects on estimated parameters. A non-linear function with gm as input is developed to convert the parameters estimated under an assumption of infinite gm to proper values. This function will facilitate gm representation in global carbon cycle models.
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| 5. |
- Bjartell, Anders, et al.
(författare)
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Tumour markers in prostate cancer II: diagnostic and prognostic cellular biomarkers.
- 2011
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 50 Suppl 1, s. 76-84
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Tidskriftsartikel (refereegranskat)abstract
- The main goal of prostate cancer tissue biomarkers is to improve diagnostic and prognostic accuracy. A particularly important question is whether the cancer needs immediate treatment or if treatment can be deferred. It is highly unlikely that a single biomarker that provides comprehensive prognostic information about a newly diagnosed prostate cancer will be forthcoming. Despite extensive research efforts, very few biomarkers of prostate cancer have been successfully implemented into clinical practice today. This can be partly explained by a lack of standardised methods for performance and interpretation of immunohistochemistry, but also by poor study design with insufficient biomaterial or inappropriate statistical analysis. Also appropriate cohorts to test prostate cancer biomarkers do not exist. It must be kept in mind that unsuccessful integration of new biomarkers in nomograms can also be explained by the good performance of the clinical and pathological base model with serum PSA as the only independent biomarker. A new biomarker must be powerful enough to improve this prediction model and not merely replace.
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| 6. |
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| 7. |
- Fine, Samson W., et al.
(författare)
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A Contemporary Update on Pathology Reporting for Prostate Cancer: Biopsy and Radical Prostatectomy Specimens
- 2012
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 62:1, s. 20-39
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Forskningsöversikt (refereegranskat)abstract
- Context: The diagnosis of and reporting parameters for prostate cancer (PCa) have evolved over time, yet they remain key components in predicting clinical outcomes. Objective: Update pathology reporting standards for PCa. Evidence acquisition: A thorough literature review was performed for articles discussing PCa handling, grading, staging, and reporting published as of September 15, 2011. Electronic articles published ahead of print were also considered. Proceedings of recent international conferences addressing these areas were extensively reviewed. Evidence synthesis: Two main areas of reporting were examined: (1) prostatic needle biopsy, including handling, contemporary Gleason grading, extent of involvement, and high-risk lesions/precursors and (2) radical prostatectomy (RP), including sectioning, multifocality, Gleason grading, staging of organ-confined and extraprostatic disease, lymph node involvement, tumor volume, and lymphovascular invasion. For each category, consensus views, controversial areas, and clinical import were reviewed. Conclusions: Modern prostate needle biopsy and RP reports are extremely detailed so as to maximize clinical utility. Accurate diagnosis of cancer-specific features requires up-to-date knowledge of grading, quantitation, and staging criteria. While some areas remain controversial, efforts to codify existing knowledge have had a significant impact on pathology practice. (C) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 8. |
- Montironi, Rodolfo, et al.
(författare)
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Role of histopathology and molecular markers in the active surveillance of prostate cancer
- 2011
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Ingår i: Acta Oncologica. - 1651-226X. ; 50, s. 56-60
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Forskningsöversikt (refereegranskat)abstract
- Surgery or radiation therapy remain the standard curative treatments for newly diagnosed prostate cancer patients. Nonetheless, these aggressive treatments are associated with decreased quality of life with altered sexual and urinary functions. The objective was a systematic review of active surveillance protocols to investigate the role of histopathology and molecular markers in the active surveillance of prostate cancer. Medline was searched using the following terms: prostate cancer, active surveillance and expectant management. Selection criteria, follow-up strategies and outcomes. Using modern risk stratification, several centres have gained significant experience in identifying patients with a low risk of prostate cancer progression and have adopted an active surveillance program with delayed curative therapy. Interestingly, only limited numbers of patients under active surveillance require additional treatment. Recent data suggest that delayed treatment does not appear to alter the clinical outcome among those highly selected patients. The future and conclusions. A better understanding of the molecular determinants of prostate cancer behaviour would not only enable healthcare professionals to identify which cases need aggressive treatment but, perhaps more importantly, would also indicate potential targets for the development of novel therapeutic strategies.
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| 9. |
- Ramos Ramos, Oswaldo Eduardo, et al.
(författare)
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Sources and behavior of arsenic and trace elements in groundwater and surface water in the Poopó Lake Basin, Bolivian Altiplano
- 2012
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Ingår i: Environmental Earth Sciences. - : Springer Science and Business Media LLC. - 1866-6280 .- 1866-6299. ; 66:3, s. 793-807
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Tidskriftsartikel (refereegranskat)abstract
- Water management in semiarid and arid catchments such as the Poopó Lake Basin requires improved understanding of the complex behavior of the various contaminants, which affect the drinking water quality and considered as crucial for sustainable development of the region. Mechanisms of arsenic (As) release in the surface and groundwater were studied. Hydrochemical data for surface water (4 samples) and groundwater (28 samples) were collected in a small watershed in the Poopó catchment at the highland of the Bolivian Andes (Altiplano). All of them show high electrical conductivity values and moderately oxidizing conditions. The surface water contains high concentration of sulfate and the trace elements As, Zn and Pb in the zone affected by acid mine drainage. There is a large variability of the concentration of As and of the trace elements in the groundwater in the five different regions within the Poopó catchment. The metal concentrations sensitive to changes of redox state and results of speciation modeling suggest that As (V) is a predominant aqueous species, which conforms to the prevailing oxidizing conditions in the shallow groundwater environment. Two generalized trends for As distribution were identified in groundwater: (a) high concentrations are found in the arid zone (100-250 Όg/L) in the southern (region III) and in the northwestern (region V) regions, and (b) low concentrations (< 50 Όg/L) are found in the remaining part of the basin (region I, II and IV). However, the spatial distribution within these regions needs to be investigated further. A conclusion from the present study is that there are multiple sources of As as well as other trace elements (such as Cd, Mn and Zn) in the Poopó Lake Basin. Among the sources and the processes which led to the mobility of As and other trace metals in the region are: (a) weathering of sulfide minerals, (b) oxidation of pyrite and/or arsenopyrite in mineralized areas and (c) desorption from hydrous ferric oxide (HFO) surfaces. In non-mining areas, volcanic ash is suggested to be a significant source of As.
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| 10. |
- Rundle, Andrew, et al.
(författare)
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Physical activity and lung cancer among non-smokers : a pilot molecular epidemiological study within EPIC
- 2010
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Ingår i: Biomarkers. - : Taylor & Francis. - 1354-750X .- 1366-5804. ; 15:1, s. 20-30
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Tidskriftsartikel (refereegranskat)abstract
- The association between physical activity, potential intermediate biomarkers and lung cancer risk was investigated in a study of 230 cases and 648 controls nested within the European Prospective Investigation of Cancer and Nutrition. Data on white blood cell aromatic-DNA adducts by 32P-post-labelling and glutathione (GSH) in red blood cells were available from a subset of cases and controls. Compared with the first quartile, the fourth quartile of recreational physical activity was associated with a lower lung cancer risk (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35-0.90), higher GSH levels (+1.87 μmol GSH g-1 haemoglobin, p = 0.04) but not with the presence of high levels of adducts (OR 1.05, 95% CI 0.38-2.86). Despite being associated with recreational physical activity, in these small-scale pilot analyses GSH levels were not associated with lung cancer risk (OR 0.95, 95% CI 0.84-1.07 per unit increase in GSH levels). Household and occupational activity was not associated with lung cancer risk or biomarker levels.
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