| 1. |
- Filipowicz, Natalia, et al.
(författare)
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Comprehensive cancer-oriented biobanking resource of human samples for studies of post-zygotic genetic variation involved in cancer predisposition
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:4
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Tidskriftsartikel (refereegranskat)abstract
- The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available "-omics" approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups.
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| 2. |
- Wójcik, Magdalena, et al.
(författare)
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Loss of Y in regulatory T lymphocytes in the tumor micro-environment of primary colorectal cancers and liver metastases
- 2024
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Male sex is a risk factor for colorectal cancer (CRC) with higher illness burden and earlier onset. Thus, we hypothesized that loss of chromosome Y (LOY) in the tumor micro-environment (TME) might be involved in oncogenesis. Previous studies show that LOY in circulating leukocytes of aging men was associated with shorter survival and non-hematological cancer, as well as higher LOY in CD4 + T-lymphocytes in men with prostate cancer vs. controls. However, nothing is known about LOY in leukocytes infiltrating TME and we address this aspect here. We studied frequency and functional effects of LOY in blood, TME and non-tumorous tissue. Regulatory T-lymphocytes (Tregs) in TME had the highest frequency of LOY (22%) in comparison to CD4 + T-lymphocytes and cytotoxic CD8 + T-lymphocytes. LOY score using scRNA-seq was also linked to higher expression of PDCD1, TIGIT and IKZF2 in Tregs. PDCD1 and TIGIT encode immune checkpoint receptors involved in the regulation of Tregs function. Our study sets the direction for further functional research regarding a probable role of LOY in intensifying features related to the suppressive phenotype of Tregs in TME and consequently a possible influence on immunotherapy response in CRC patients.
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| 3. |
- Aad, G., et al.
(författare)
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Readiness of the ATLAS Tile Calorimeter for LHC collisions
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:4, s. 1193-1236
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Tidskriftsartikel (refereegranskat)abstract
- The Tile hadronic calorimeter of the ATLAS detector has undergone extensive testing in the experimental hall since its installation in late 2005. The readout, control and calibration systems have been fully operational since 2007 and the detector has successfully collected data from the LHC single beams in 2008 and first collisions in 2009. This paper gives an overview of the Tile Calorimeter performance as measured using random triggers, calibration data, data from cosmic ray muons and single beam data. The detector operation status, noise characteristics and performance of the calibration systems are presented, as well as the validation of the timing and energy calibration carried out with minimum ionising cosmic ray muons data. The calibration systems' precision is well below the design value of 1%. The determination of the global energy scale was performed with an uncertainty of 4%.
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| 4. |
- Aad, G., et al.
(författare)
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Studies of the performance of the ATLAS detector using cosmic-ray muons
- 2011
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 71:3
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Tidskriftsartikel (refereegranskat)abstract
- Muons from cosmic-ray interactions in the atmosphere provide a high-statistics source of particles that can be used to study the performance and calibration of the ATLAS detector. Cosmic-ray muons can penetrate to the cavern and deposit energy in all detector subsystems. Such events have played an important role in the commissioning of the detector since the start of the installation phase in 2005 and were particularly important for understanding the detector performance in the time prior to the arrival of the first LHC beams. Global cosmic-ray runs were undertaken in both 2008 and 2009 and these data have been used through to the early phases of collision data-taking as a tool for calibration, alignment and detector monitoring. These large datasets have also been used for detector performance studies, including investigations that rely on the combined performance of different subsystems. This paper presents the results of performance studies related to combined tracking, lepton identification and the reconstruction of jets and missing transverse energy. Results are compared to expectations based on a cosmic-ray event generator and a full simulation of the detector response.
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| 5. |
- Aad, G., et al.
(författare)
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The ATLAS Inner Detector commissioning and calibration
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 787-821
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS Inner Detector is a composite tracking system consisting of silicon pixels, silicon strips and straw tubes in a 2 T magnetic field. Its installation was completed in August 2008 and the detector took part in data-taking with single LHC beams and cosmic rays. The initial detector operation, hardware commissioning and in-situ calibrations are described. Tracking performance has been measured with 7.6 million cosmic-ray events, collected using a tracking trigger and reconstructed with modular pattern-recognition and fitting software. The intrinsic hit efficiency and tracking trigger efficiencies are close to 100%. Lorentz angle measurements for both electrons and holes, specific energy-loss calibration and transition radiation turn-on measurements have been performed. Different alignment techniques have been used to reconstruct the detector geometry. After the initial alignment, a transverse impact parameter resolution of 22.1 +/- 0.9 mu m and a relative momentum resolution sigma (p) /p=(4.83 +/- 0.16)x10(-4) GeV(-1)xp (T) have been measured for high momentum tracks.
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| 6. |
- Benetkiewicz, Magdalena, et al.
(författare)
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Chromosome 22 array-CGH profiling of breast cancer delimited minimal common regions of genomic imbalances and revealed frequent intra-tumoral genetic heterogeneity
- 2006
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 29:4, s. 935-945
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a common malignancy and the second most frequent cause of death among women. Our aim was to perform DNA copy number profiling of 22q in breast tumors using a methodology which is superior, as compared to the ones applied previously. We studied 83 biopsies from 63 tumors obtained from 60 female patients. A general conclusion is that multiple distinct patterns of genetic aberrations were observed, which included deletion(s) and/or gain(s), ranging in size from affecting the whole chromosome to only a few hundred kb. Overall, the analysis revealed genomic imbalances of 22q in 22% (14 out of 63) of tumors. The predominant profile (11%) was monosomy 22. The smallest identified candidate region, in the vicinity of telomere of 22q, encompasses approximately 220 kb and was involved in all but one of the tumors with aberrations on chromosome 22. This segment is dense in genes and contains 11 confirmed and one predicted gene. The availability of multiple biopsies from a single tumor provides an excellent opportunity for analysis of possible intra-tumor differences in genetic profiles. In 15 tumors we had access to two or three biopsies derived from the same lesion and these were studied independently. Four out of 15 (26.6%) tumors displayed indications of clonal intra-tumor genotypic differences, which should be viewed as a high number, considering that we studied in detail only a single human chromosome. Our results open up several avenues for continued genetic research of breast cancer.
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| 7. |
- Forsberg, Lars A., et al.
(författare)
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Signatures of post-zygotic structural genetic aberrations in the cells of histologically normal breast tissue that can predispose to sporadic breast cancer
- 2015
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 25:10, s. 1521-1535
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Tidskriftsartikel (refereegranskat)abstract
- Sporadic breast cancer (SBC) is a common disease without robust means of early risk prediction in the population. We studied 282 females with SBC, focusing on copy number aberrations in cancer-free breast tissue (uninvolved margin, UM) outside the primary tumor (PT). In total, 1162 UMs (1-14 per breast) were studied. Comparative analysis between UM(s), PT(s), and blood/skin from the same patient as a control is the core of the study design. We identified 108 patients with at least one aberrant UM, representing 38.3% of cases. Gains in gene copy number were the principal type of mutations in microscopically normal breast cells, suggesting that oncogenic activation of genes via increased gene copy number is a predominant mechanism for initiation of SBC pathogenesis. The gain of ERBB2, with overexpression of HER2 protein, was the most common aberration in normal cells. Five additional growth factor receptor genes (EGFR, FGFR1, IGF1R, LIFR, and NGFR) also showed recurrent gains, and these were occasionally present in combination with the gain of ERBB2. All the aberrations found in the normal breast cells were previously described in cancer literature, suggesting their causative, driving role in pathogenesis of SBC. We demonstrate that analysis of normal cells from cancer patients leads to identification of signatures that may increase risk of SBC and our results could influence the choice of surgical intervention to remove all predisposing cells. Early detection of copy number gains suggesting a predisposition toward cancer development, long before detectable tumors are formed, is a key to the anticipated shift into a preventive paradigm of personalized medicine for breast cancer.
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| 8. |
- Jankowski, Michal, et al.
(författare)
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Authorizing Grid Resource Access and Consumption
- 2009
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Ingår i: Grid and Services Evolution. - Boston, MA : Springer-Verlag. - 9780387859651 - 0387859659 ; , s. 157-168
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Konferensbidrag (refereegranskat)abstract
- The tasks to authorize users access to grid resources and to authorize their regulated consumption is studied and some key functionality is identified. A novel authorization infrastructure is proposed by combining the Virtual User System (VUS) for dynamically assigning local pool-accounts to grid-users and the SweGrid Accounting System (SGAS) for grid-wide usage logging and real-time enforcement of resource pre-allocations.
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| 9. |
- Li, Jun, et al.
(författare)
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CFD Approach for Unburned Carbon Reduction in Pulverized Coal Boilers
- 2012
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Ingår i: Energy & Fuels. - : American Chemical Society (ACS). - 0887-0624 .- 1520-5029. ; 26:2, s. 926-937
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Tidskriftsartikel (refereegranskat)abstract
- Low-NO, technologies are widely used in pulverized coal boilers, but they usually produce high levels of carbon in the fly ash. High levels of unburned carbon represent fuel loss, so the overall boiler efficiency is reduced. Additionally, the higher carbon content affects the suitability of fly ash for cement applications. The purpose of this paper is to provide a CFD approach for unburned carbon reduction by optimizing operating conditions. In this paper, three different boiler loads were simulated: 200 MW, 170 MW, and 140 MW. The air supply System was simulated previously for preparing as precise as possible boundary conditions. At last, the unburned carbon level of every burner was investigated, and the effects of residue residence time and the local fuel air momentum ratio are discussed in detail. According to the predicted results, operating conditions and the residence time of the coal particles affects the unburned carbon level in fly ash. Operating conditions play a more significant role during the combustion process, while the residence time affects char burnout only when the burner's location is low. Therefore, it is concluded that a cost-effective method could be developed for reducing the unburned carbon level in ash and correspondingly, the loss on ignition level. First, it is necessary to determine which burners are operating under poor conditions through CFD analysis. Then, the fuel air momentum ratios of those burners should be modified by changing the operating conditions, meanwhile increasing the residence time of coal particles to ensure complete combustion.
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| 10. |
- Małyszko, Jolanta, et al.
(författare)
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Do we know more about hypertension in Poland after the May Measurement Month 2017? - Europe
- 2019
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Ingår i: European Heart Journal, Supplement. - : Oxford University Press (OUP). - 1520-765X .- 1554-2815. ; 21, s. 97-100
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Forskningsöversikt (refereegranskat)abstract
- Elevated blood pressure (BP) is a worldwide burden, leading to over 10 million deaths yearly. May Measurement Month (MMM) is a global initiative organized by the International Society of Hypertension aimed at raising awareness of hypertension and the need for BP screening. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. BP measurement, the definition of hypertension and statistical analysis followed the globally approved MMM17 Study Protocol. In Poland 5834 (98.9%, Caucasian) individuals were screened. After multiple imputation, 2601 (35.3%) had hypertension. Of individuals not receiving anti-hypertensive medication, 976 (20.6%) were hypertensive. Of individuals receiving anti-hypertensive medication, 532 (49.1%) had uncontrolled BP. In the crude screened group, 81.4% declared to not receive any anti-hypertensive treatment, while the remaining 18.6% were on such medications. In overweight and obese patients both systolic and diastolic BP were significantly higher than in normal weight and underweight subjects. In addition, BP measured on Sundays was significantly lower than on Mondays. MMM17 was one of the largest recent BP screening campaigns in Poland. We found that over 1/3 of participants were hypertensive. Almost half of the treated subjects had uncontrolled BP. These results suggest that opportunistic screening can identify substantial numbers with raised BP.
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| 11. |
- Poplawski, Andrzej B., et al.
(författare)
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Frequent genetic differences between matched primary and metastatic breast cancer provide an approach to identification of biomarkers for disease progression
- 2010
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 18:5, s. 560-568
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a major cause of morbidity and mortality in women and its metastatic spread is the principal reason behind the fatal outcome. Metastasis-related research of breast cancer is however underdeveloped when compared with the abundant literature on primary tumors. We applied an unexplored approach comparing at high resolution the genomic profiles of primary tumors and synchronous axillary lymph node metastases from 13 patients with breast cancer. Overall, primary tumors displayed 20% higher number of aberrations than metastases. In all but two patients, we detected in total 157 statistically significant differences between primary lesions and matched metastases. We further observed differences that can be linked to metastatic disease and there was also an overlapping pattern of changes between different patients. Many of the differences described here have been previously linked to poor patient survival, suggesting that this is a viable approach toward finding biomarkers for disease progression and definition of new targets useful for development of anticancer drugs. Frequent genetic differences between primary tumors and metastases in breast cancer also question, at least to some extent, the role of primary tumors as a surrogate subject of study for the systemic disease. European Journal of Human Genetics (2010) 18, 560-568; doi:10.1038/ejhg.2009.230; published online 6 January 2010
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| 12. |
- Razzaghian, Hamid Reza, et al.
(författare)
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Post-Zygotic and Inter-Individual Structural Genetic Variation in a Presumptive Enhancer Element of the Locus between the IL10Rβ and IFNAR1 Genes
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9, s. e67752-
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Tidskriftsartikel (refereegranskat)abstract
- Although historically considered as junk-DNA, tandemly repeated sequence motifs can affect human phenotype. For example, variable number tandem repeats (VNTR) with embedded enhancers have been shown to regulate gene transcription. The post-zygotic variation is the presence of genetically distinct populations of cells in an individual derived from a single zygote, and this is an understudied aspect of genome biology. We report somatically variable VNTR with sequence properties of an enhancer, located upstream of IFNAR1. Initially, SNP genotyping of 63 monozygotic twin pairs and multiple tissues from 21 breast cancer patients suggested a frequent post-zygotic mosaicism. The VNTR displayed a repeated 32 bp core motif in the center of the repeat, which was flanked by similar variable motifs. A total of 14 alleles were characterized based on combinations of segments, which showed post-zygotic and inter-individual variation, with up to 6 alleles in a single subject. Somatic variation occurred in similar to 24% of cases. In this hypervariable region, we found a clustering of transcription factor binding sites with strongest sequence similarity to mouse Foxg1 transcription factor binding motif. This study describes a VNTR with sequence properties of an enhancer that displays post-zygotic and inter-individual genetic variation. This element is within a locus containing four related cytokine receptors: IFNAR2, IL10R beta, IFNAR1 and IFNGR2, and we hypothesize that it might function in transcriptional regulation of several genes in this cluster. Our findings add another level of complexity to the variation among VNTR-based enhancers. Further work may unveil the normal function of this VNTR in transcriptional control and its possible involvement in diseases connected with these receptors, such as autoimmune conditions and cancer.
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| 13. |
- Urbiola-Salvador, Victor, et al.
(författare)
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Plasma protein changes reflect colorectal cancer development and associated inflammation
- 2023
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Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of death worldwide. Efficient non-invasive blood-based biomarkers for CRC early detection and prognosis are urgently needed.Methods: To identify novel potential plasma biomarkers, we applied a proximity extension assay (PEA), an antibody-based proteomics strategy to quantify the abundance of plasma proteins in CRC development and cancer-associated inflammation from few mu L of plasma sample.Results: Among the 690 quantified proteins, levels of 202 plasma proteins were significantly changed in CRC patients compared to age-and-sex-matched healthy subjects. We identified novel protein changes involved in Th17 activity, oncogenic pathways, and cancer-related inflammation with potential implications in the CRC diagnosis. Moreover, the interferon gamma (IFNG), interleukin (IL) 32, and IL17C were identified as associated with the early stages of CRC, whereas lysophosphatidic acid phosphatase type 6 (ACP6), Fms-related tyrosine kinase 4 (FLT4), and MANSC domain-containing protein 1 (MANSC1) were correlated with the late-stages of CRC.Discussion: Further study to characterize the newly identified plasma protein changes from larger cohorts will facilitate the identification of potential novel diagnostic, prognostic biomarkers for CRC.
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| 14. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 15. |
- Aad, G., et al.
(författare)
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- 2011
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Tidskriftsartikel (refereegranskat)
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| 16. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 17. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 18. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 19. |
- Aad, G., et al.
(författare)
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- 2013
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swepub:Mat__t (refereegranskat)
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| 20. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 21. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 22. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 23. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 24. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 25. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 26. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 27. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 28. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 29. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 30. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 31. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 32. |
- Aad, G., et al.
(författare)
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- 2012
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Tidskriftsartikel (refereegranskat)
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| 33. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 34. |
- Aad, G., et al.
(författare)
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- 2013
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swepub:Mat__t (refereegranskat)
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| 35. |
- Aad, G., et al.
(författare)
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- 2012
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Tidskriftsartikel (refereegranskat)
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| 36. |
- Aad, G., et al.
(författare)
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- 2012
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| 37. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 38. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 39. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 40. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 41. |
- Aad, G., et al.
(författare)
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- 2011
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| 42. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 43. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 44. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 45. |
- Aad, G., et al.
(författare)
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- 2012
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| 46. |
- Aad, G., et al.
(författare)
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- 2011
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| 47. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 48. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 49. |
- Aad, G., et al.
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- 2011
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| 50. |
- Aad, G., et al.
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- 2011
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