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- Pelttari, LM, et al.
(författare)
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RAD51B in Familial Breast Cancer
- 2016
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5, s. e0153788-
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Tidskriftsartikel (refereegranskat)
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- Ahearn, Thomas U., et al.
(författare)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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- Bain, C. C., et al.
(författare)
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Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6C(hi) monocyte precursors
- 2013
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Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 6:3, s. 498-510
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages (m phi) are essential for intestinal homeostasis and the pathology of inflammatory bowel disease (IBD), but it is unclear whether discrete m phi populations carry out these distinct functions or if resident m phi change during inflammation. We show here that most resident m phi in resting mouse colon express very high levels of CX3CR1, are avidly phagocytic and MHCII hi, but are resistant to Toll-like receptor (TLR) stimulation, produce interleukin 10 constitutively, and express CD163 and CD206. A smaller population of CX3CR1(int) cells is present in resting colon and it expands during experimental colitis. Ly6C(hi) CCR2(+) monocytes can give rise to all m phi subsets in both healthy and inflamed colon and we show that the CX3CR1int pool represents a continuum in which newly arrived, recently divided monocytes develop into resident CX3CR1 hi m phi. This process is arrested during experimental colitis, resulting in the accumulation of TLR-responsive pro-inflammatory m phi. Phenotypic analysis of human intestinal m phi indicates that analogous processes occur in the normal and Crohn's disease ileum. These studies show for the first time that resident and inflammatory m phi in the intestine represent alternative differentiation outcomes of the same precursor and targeting these events could offer routes for therapeutic intervention in IBD.
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- Escala-Garcia, M, et al.
(författare)
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Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 19787-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10−8 and 4.42 × 10−8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.
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- Grip, Carl-Erik, et al.
(författare)
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BioODRI: forestry meets steel : A techno-economic study on us of biomass gasification to produce a gas sutiable for production of CO2 lean iron
- 2015
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Konferensbidrag (refereegranskat)abstract
- A major part of the world’s iron production is presently using fossil reductants. The climate effect would be improved if renewable raw material could be used instead. One way could be to gasify biomass and use the gas to produce DRI (Direct reduced Iron). This is studied in a cooperative project. LTU, MEFOS, ETC and five industries in the areas forestry & pulp, mining, iron and gas are involved. The production chain Biomass production and distribution-Gasification-DRI production-DRI use is investigated in four work packages: WP1: Biomass supply, WP2: Gasification, WP3: Metallurgical processes and WP4: Process integration. The paper will focus on the studies and modeling of biomass supply, harvesting and transport and gasification as well as on the system studies. The use of the gas in the metallurgical application is briefly described as background.
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- Grip, Carl-Erik, et al.
(författare)
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Forestry meets Steel. A Technoeconomic study of the possible DRI production using biomass
- 2015
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Konferensbidrag (refereegranskat)abstract
- The possibility to produce DRI using gasified Biomass is studied in a cooperative project. LTU, MEFOS, ETC and five industries in the areas forestry & pulp, mining, iron and gas are involved. The production chain Biomass production and distribution -Gasification-DRI production-DRI use is investigated in four work packages:WP1: Biomass supply: A large amount of Biomass has to be delivered into a single site to exchange a large amount of fossil reductant. It is important to use forestry by- products as a major part of round wood is reserved for other uses. Harvesting, logistics and economics have to be considered. Available data were collected and used to make a system model on harvesting treatment and transport. The simulations indicated that the supply of residuals is possible but will need material from a large part of the north Sweden wood area. WP2: Gasification. The aim is to use to produce hot gas that can be used directly. Pilot experiments are carried out using oxygen in an entrained flow gasifier. WP3: Metallurgical processes. Reduction tests are carried out with gas that can be produced in the gasifier. The limitations of the gas content are studied as well as the effect on DRI. Also the suitability of the DRI product is evaluated WP4: Process integration. A system model is built using the results from work packages 1-3 and used for technical economic optimization the whole system harvesting-transport-gasifier-direct reduction- use of DRI. The process chain is technically possible; however there are problems to be solved, e.g., gas quality vs. demands from DRI process, Biomass supply and logistics. The result is important to evaluate for industrial application, but also to get information of the effect of different governmental control instruments.
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| 29. |
- Grip, L, et al.
(författare)
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Coronary angioplasty in patients with unstable angina, with special reference to preceding treatment with antithrombin III and heparin
- 1996
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Ingår i: CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS. - : SAGE Publications. - 1076-0296 .- 1938-2723. ; 2:2, s. 107-115
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Seventy-nine patients undergoing percutane ous transluminal coronary angioplasty (PTCA) for unsta ble angina were analyzed with respect to preceding an tithrombin treatment; group I comprised patients (n = 26) without antecedent antithrombin therapy; group II, pa tients (n = 30) with heparin infusion for ≥24 h, and group III patients (n = 23) with ongoing heparin infusion and given antithrombin III concentrate immediately before the procedure because of plasma antithrombin III <85%. Immediate results were 89% (70 of 79) angiographic suc cess, five (6%) subacute occlusions (two subsequent non-Q wave infarctions), no emergency coronary artery bypass grafting (CABG), and no immediate mortality. There were no differences between the groups. From dis charge to 4 months, one patient died, one had a nonfatal infarction, and 24 (30%) had repeated PTCA or CABG. The cumulative 4-month event rate was 11 of 26 (42%) in group I, 10 of 30 (33%) in group II, and 7 of 23 (30%) in group III (NS). During PTCA, heparin bolus administra tion was guided by activated clotting time (ACT), aiming at>300 s. Baseline ACT was significantly less in patients not treated with heparin (129 ± 34 s in group I vs. 179 ± 38 and 162 ± 29 s in groups II and III, respectively; p < 0.05), but during the procedure, patients from all groups required the same amount of heparin (13,900 ± 4,800, 13,000 ± 6,800, and 13,000 ± 5,700 IU, respectively; NS) to reach similar maximum ACT levels (334 ± 36, 312 ± 32, and 319 ± 44 s, respectively; NS). Patients receiving warfarin ( n = 8) responded with a higher ACT (456 ± 110 s; p < 0.05) on lower doses of heparin (10,000 ± 3,800 IU). In conclusion, patients with unstable angina receiv ing individualized antithrombotic therapy can be success fully treated with PTCA, with an acute complication rate and long-term results comparable with those expected in patients undergoing elective procedures. The value of an tithrombin III substitution must be evaluated in random ized trials. Preprocedural heparin infusion does not re duce the need of extra heparin during the procedure. Key Words: Antithrombin III—Heparin—PTCA (percutane ous transluminal coronary angioplasty)—Unstable angina pectoris.
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- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 36. |
- Karlsson, Lars O, 1975, et al.
(författare)
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Dose-dependent cardioprotection of enkephalin analogue Eribis peptide 94 and cardiac expression of opioid receptors in a porcine model of ischaemia and reperfusion
- 2012
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Ingår i: European journal of pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 674:2-3, s. 378-383
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Tidskriftsartikel (refereegranskat)abstract
- Opioids confer cardioprotection after myocardial ischaemia and reperfusion. The primary aim of the present study was to evaluate the cardioprotective effect of different doses of enkephalin analogue Eribis peptide 94 (EP 94) in a porcine model of ischaemia and reperfusion. A secondary aim was to analyse the impact of ischaemia and reperfusion on the expression of opioid receptor subtypes in the porcine heart. Thirty-four anesthetised pigs underwent 40 min of balloon occlusion of the left anterior descending coronary artery followed by four hours of reperfusion. Pigs were given either vehicle (0.9% NaCl) or one of four doses of EP 94 (0.2, 1, 5 or 25 ug/kg at each administration, respectively), intravenously after 26, 33 and 40 min of ischaemia. Hearts were stained to quantify area at risk and infarct size. mRNA and protein expressions of the opioid receptor subtypes were detected with RT-PCR, immunoblotting and immunohistochemistry in the control and ischaemic/reperfused areas. There was a significant dose-response relationship between higher doses of EP 94 and reduced infarct size. Expression of kappa- and delta-opioid receptors was detected at both mRNA and protein levels. In ischaemic/reperfused areas, an increased expression of mRNA for both receptors was observed, whereas only protein expression for the delta subtype was up-regulated. The mu-opioid receptor was not detected.
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- Sabourova, Natalia, 1975-, et al.
(författare)
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Detection of sparse damages in plates
- 2020
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Ingår i: IABSE Symposium, Wroclaw 2020. - Zürich : International Association For Bridge And Structural Engineering (IABSE). ; , s. 1141-1148
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Konferensbidrag (refereegranskat)abstract
- Structural damage is often a spatially sparse phenomenon, i.e. it occurs only in a small part of the structure. This property of damage has not been utilized in the field of structural damage identification until quite recently, when the sparsity-based regularization developed in compressed sensing problems found its application in this field. In this paper we consider classical sensitivity-based finite element model updating combined with a regularization technique appropriate for the expected type of sparse damage. The validity of the proposed methods is demonstrated using simulations on a bridge. The pros and cons of these methods are discussed.
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