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  • Mantero, Juan, et al. (författare)
  • Pit lakes from Southern Sweden: natural radioactivity and elementary characterization
  • 2020
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Natural radioactivity in the environment is a field gaining more attention in last decades. This work is focused on the study of natural radioactivity complemented with elementary characterization at former non-uraniferous mining areas in Sweden. This aim is addressed through the study of mining lakes, called pit lakes, which are water bodies generated after opencast mining. Environmental matrices (water, sediments and rocks) from 32 Swedish pit lakes, commonly used for recreational purposes were radiometrically characterized via alpha (238U, 234U, 232Th, 230Th, 210Po isotopes) and gamma spectrometry (238U and 232Th series radionuclides). Additionally, ambient dose rate equivalent in the immediate surrounding of each pit lake was quantified. Physico-chemical parameters (pH, specific conductivity, dissolved oxygen, oxidation–reduction potential) and elemental composition (major and trace elements by ICP-MS) were analysed in water samples and elementary composition of sediments/rocks was measured by XRF and SEM–EDX in some specific cases. A non-negligible number of pit lakes (26%) with enhanced U levels in water was found. At some sites, rocks contained up to 4% of U in areas with high degree of interaction with local population. Concerning the elementary perspective, another popular site (due to its turquoise water) was found to have elevated dissolved heavy metal levels. Results obtained in this work prove that measurement of natural radioactivity is another component that should be included in routine analysis of characterization in mining areas, especially if restauration of post-mining sites is intended for human recreational.
  • Ziegelitz, Doerthe, et al. (författare)
  • Absolute quantification of cerebral blood flow in neurologically normal volunteers: dynamic-susceptibility contrast MRI-perfusion compared with computed tomography (CT)-perfusion.
  • 2009
  • Ingår i: Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. - : John Wiley and Sons. - 1522-2594. ; 62:1, s. 56-65
  • Tidskriftsartikel (refereegranskat)abstract
    • To improve the reproducibility of arterial input function (AIF) registration and absolute cerebral blood flow (CBF) quantification in dynamic-susceptibility MRI-perfusion (MRP) at 1.5T, we rescaled the AIF by use of a venous output function (VOF). We compared CBF estimates of 20 healthy, elderly volunteers, obtained by computed tomography (CT)-perfusion (CTP) and MRP on two consecutive days. MRP, calculated without the AIF correction, did not result in any significant correlation with CTP. The rescaled MRP showed fair to moderate correlation with CTP for the central gray matter (GM) and the whole brain. Our results indicate that the method used for correction of partial volume effects (PVEs) improves MRP experiments by reducing AIF-introduced variance at 1.5T.
  • Zou, Zhiyuan V., et al. (författare)
  • Genomic profiling of the transcription factor Zfp148 and its impact on the p53 pathway
  • 2020
  • Ingår i: Scientific Reports. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent data suggest that the transcription factor Zfp148 represses activation of the tumor suppressor p53 in mice and that therapeutic targeting of the human orthologue ZNF148 could activate the p53 pathway without causing detrimental side effects. We have previously shown that Zfp148 deficiency promotes p53-dependent proliferation arrest of mouse embryonic fibroblasts (MEFs), but the underlying mechanism is not clear. Here, we showed that Zfp148 deficiency downregulated cell cycle genes in MEFs in a p53-dependent manner. Proliferation arrest of Zfp148-deficient cells required increased expression of ARF, a potent activator of the p53 pathway. Chromatin immunoprecipitation showed that Zfp148 bound to the ARF promoter, suggesting that Zfp148 represses ARF transcription. However, Zfp148 preferentially bound to promoters of other transcription factors, indicating that deletion of Zfp148 may have pleiotropic effects that activate ARF and p53 indirectly. In line with this, we found no evidence of genetic interaction between TP53 and ZNF148 in CRISPR and siRNA screen data from hundreds of human cancer cell lines. We conclude that Zfp148 deficiency, by increasing ARF transcription, downregulates cell cycle genes and cell proliferation in a p53-dependent manner. However, the lack of genetic interaction between ZNF148 and TP53 in human cancer cells suggests that therapeutic targeting of ZNF148 may not increase p53 activity in humans.
  • Biermann, Jana, et al. (författare)
  • Clonal relatedness in tumour pairs of breast cancer patients.
  • 2018
  • Ingår i: Breast cancer research : BCR. - 1465-542X. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Molecular classification of tumour clonality is currently not evaluated in multiple invasive breast carcinomas, despite evidence suggesting common clonal origins. There is no consensus about which type of data (e.g. copy number, mutation, histology) and especially which statistical method is most suitable to distinguish clonal recurrences from independent primary tumours.Thirty-seven invasive breast tumour pairs were stratified according to laterality and time interval between the diagnoses of the two tumours. In a multi-omics approach, tumour clonality was analysed by integrating clinical characteristics (n = 37), DNA copy number (n = 37), DNA methylation (n = 8), gene expression microarray (n = 7), RNA sequencing (n = 3), and SNP genotyping data (n = 3). Different statistical methods, e.g. the diagnostic similarity index (SI), were used to classify the tumours as clonally related recurrences or independent primary tumours.The SI and hierarchical clustering showed similar tendencies and the highest concordance with the other methods. Concordant evidence for tumour clonality was found in 46% (17/37) of patients. Notably, no association was found between the current clinical guidelines and molecular tumour features.A more accurate classification of clonal relatedness between multiple breast tumours may help to mitigate treatment failure and relapse by integrating tumour-associated molecular features, clinical parameters, and statistical methods. Guidelines need to be defined with exact thresholds to standardise clonality testing in a routine diagnostic setting.
  • Biermann, Jana, et al. (författare)
  • Tumour clonality in paired invasive breast carcinomas
  • 2019
  • Ingår i: Cancer Research. - 0008-5472.
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • Background: Multiple invasive breast tumours may represent either independent primary tumours or clonal recurrences of the first tumour, where the same progenitor cell gives rise to all of the detected tumours. Consequently, the driver events for the progenitor cell need to have been identical in early tumour development. Molecular classification of tumour clonality is not currently evaluated in multiple invasive breast carcinomas, despite evidence suggesting common clonal origins. Furthermore, there is no consensus about which type of biological data (e.g. copy number, mutation, histology) and especially which statistical method is most suitable to distinguish clonal recurrences from independent primary tumours. Methods: Thirty-seven invasive breast tumour pairs were stratified by laterality (bilateral vs. ipsilateral) and the time interval between the diagnoses of the first and second tumours (synchronous vs. metachronous). Both tumours from the same patient were analysed by integrating clinical characteristics (n = 37), DNA copy number (n = 37), DNA methylation (n = 8), gene expression microarray (n = 7), RNA sequencing (n = 3), and SNP genotyping data (n = 3). Different statistical methods, e.g. the diagnostic similarity index (SI), distance measure, shared segment analysis etc., were used to classify the tumours from the same patient as clonally related recurrences or independent primary tumours. Results: The SI applied on DNA copy numbers derived from aCGH (array comparative genomic hybridization) data was determined as the strongest indicator of clonal relatedness as it showed the highest concordance with all other methods. The distance measure was the most conservative method and the shared segment analysis most liberal. Concordant evidence for tumour clonality was found in 46% (17/37) of the patients. Notably, no significant association was found between the clinical characteristics and molecular tumour features. Conclusions: A more accurate classification of clonal relatedness between multiple breast tumours may help to mitigate treatment failure and relapse by integrating tumour-associated molecular features, clinical parameters, and statistical methods. In cases of extremely similar or different tumour pairs, the results showed consistency regardless of the method used. The SI can be easily integrated into clinical routine using FFPE samples to obtain copy number data. However, clinical guidelines with exact thresholds need to be defined to standardize clonality testing in a routine diagnostic setting.
  • Brandberg, John, 1966, et al. (författare)
  • Accurate tissue area measurements with considerably reduced radiation dose achieved by patient-specific CT scan parameters
  • 2008
  • Ingår i: British Journal of Radiology. - 1748-880X. ; 81:970, s. 801-8
  • Tidskriftsartikel (refereegranskat)abstract
    • A low-dose technique was compared with a standard diagnostic technique for measuring areas of adipose and muscle tissue and CT numbers for muscles in a body composition application. The low-dose technique was intended to keep the expected deviation in the measured area of adipose and muscle tissue to <1% of the total tissue area. The largest diameter of the patient determined the parameters for the low-dose technique. 17 patients - chosen to cover a wide range of diameters (31-47 cm) for both abdomen and thighs - were examined using both techniques. Tissue areas were compared, as were CT numbers for muscle tissue. Image noise was quantified by standard deviation measurements. The area deviation was <1%, except in the smallest subjects, in whom it was <2%. The integral radiation dose of the low-dose technique was reduced to 2-3% for diameters of 31-35 cm and to 7.5-50% for diameters of 36-47 cm as compared with the integral dose by the standard diagnostic technique. The CT numbers of muscle tissue remained unchanged with reduced radiation dose. Image noise was on average 20.9 HU (Hounsfield units) for subjects with diameters of 31-35 cm and 11.2 HU for subjects with diameters in the range of 36-47 cm. In conclusion, for body composition studies with CT, scan protocols can be adjusted so that the integral dose is lowered to 2-60% of the standard diagnostic technique at our centre without adversely altering area measurements of adipose and muscle tissue and without altering CT numbers of muscle tissue.
  • Larsson, Peter, et al. (författare)
  • Optimization of cell viability assays to improve replicability and reproducibility of cancer drug sensitivity screens.
  • 2020
  • Ingår i: Scientific Reports. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer drug development has been riddled with high attrition rates, in part, due to poor reproducibility of preclinical models for drug discovery. Poor experimental design and lack of scientific transparency may cause experimental biases that in turn affect data quality, robustness and reproducibility. Here, we pinpoint sources of experimental variability in conventional 2D cell-based cancer drug screens to determine the effect of confounders on cell viability for MCF7 and HCC38 breast cancer cell lines treated with platinum agents (cisplatin and carboplatin) and a proteasome inhibitor (bortezomib). Variance component analysis demonstrated that variations in cell viability were primarily associated with the choice of pharmaceutical drug and cell line, and less likely to be due to the type of growth medium or assay incubation time. Furthermore, careful consideration should be given to different methods of storing diluted pharmaceutical drugs and use of DMSO controls due to the potential risk of evaporation and the subsequent effect on dose-response curves. Optimization of experimental parameters not only improved data quality substantially but also resulted in reproducible results for bortezomib- and cisplatin-treated HCC38, MCF7, MCF-10A, and MDA-MB-436 cells. Taken together, these findings indicate that replicability (the same analyst re-performs the same experiment multiple times) and reproducibility (different analysts perform the same experiment using different experimental conditions) for cell-based drug screens can be improved by identifying potential confounders and subsequent optimization of experimental parameters for each cell line.
  • Magnander, Tobias, et al. (författare)
  • Comparison of the accuracy in kidney activity concentration estimates by the conjugate view and posterior view methods
  • 2015
  • Ingår i: Optimisation in X-ray and Molecular Imaging 2015 - the Fourth Malmö Conference on Medical Imaging, Gothenburg, Sweden, 28-30 May 2015.
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • Purpose: In nuclear medicine the conjugate view method (CV) is the most common method for activity quantifications in planar images. The advantage with the CV method is its depth independence, i.e. the activity concentrations can be calculated from two opposite planar images without the knowledge of depth. However, one disadvantage of the method that the signal to background ratio is dependent on the location of the object. This effect might increase the inaccuracy in the activity concentration estimates. Therefore, the activity in off-center objects might be better estimated by the camera projection with the shortest camera to object distance. The aim of the present study was to compare the CV method with a posterior-anterior (PA) projection method for estimation of 177Lu activity concentrations in the kidneys. Methods: The two methods were used to retrospectively determine and compare the left and right kidney activity concentration in 20 patients treated with 177Lu-DOTA-octreotate at Sahlgrenska University Hospital. The kidney was segmented in the SPECT or CT image using an appropriate segmentation algorithm. An attenuation map for 177Lu was created from the CT. Attenuated planar AP and PA projections were created from the SPECT and the attenuation map. The kidney VOI was projected onto the AP and PA projections. The activity concentration in the kidney was calculated using both the PA projection method (ACPA) and the CV method (ACCV) and the results were compared to the concentration in the kidney VOI in the SPECT. Results: The mean ratio between ACCV and the SPECT determined activity concentration was 1.99 with a standard deviation (SD) equal to 1.03 and the mean ratio between ACPA and the SPECT determined concentration was 1.66 with SD=0.80. Both methods demonstrated that the main problems with activity estimates from planar images are the influences of attenuation and the activity concentration in the under and overlying tissues. Conclusions: The present study shows that a true background estimate cannot be accurately performed with neither the CV nor the PA method and that the difficulties in obtaining a true background affect the CV method more than the PA method. The study indicates that the PA method gives a more accurate estimate of the kidney activity concentration than the CV method.
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