| 31. |
- Kurbasic, Emila, et al.
(författare)
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Changes in glycoprotein expression between primary breast tumour and synchronous lymph node metastases or asynchronous distant metastases.
- 2015
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Ingår i: Clinical Proteomics. - : Springer Science and Business Media LLC. - 1559-0275 .- 1542-6416. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a very heterogeneous disease and some patients are cured by the surgical removal of the primary tumour whilst other patients suffer from metastasis and spreading of the disease, despite adjuvant therapy. A number of prognostic and treatment predictive factors have been identified such as tumour size, oestrogen (ER) and progesterone (PgR) receptor status, human epidermal growth factor receptor type 2 (HER2) status, histological grade, Ki67 and age. Lymph node involvement is also assessed during surgery to determine if the tumour has spread which requires dissection of the axilla and adjuvant treatment. The prognostic and treatment predictive factors assessing the nature of the tumour are all routinely based on the status of the primary tumour.
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| 32. |
- Labbé, David P., et al.
(författare)
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TOP2A and EZH2 provide early detection of an aggressive prostate cancer subgroup
- 2017
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 23:22, s. 7072-7083
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient's progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches.
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| 33. |
- Leemann, Simon, et al.
(författare)
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Status of the MAX IV Storage Rings
- 2010
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Ingår i: Proceedings of IPAC’10. - 9789290833529 ; , s. 2618-2620
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Konferensbidrag (refereegranskat)abstract
- In 2009 the MAX IV facility was granted funding by Swedish authorities. Construction of the facility will begin this summer and user operation is expected by 2015. MAX IV will consist of a 3.4 GeV linac as a driver for a short-pulse radiation facility (with planned upgrade to a seeded/cascaded FEL) as well as an injector for two storage rings at different energies serving user communities in separate spectral ranges. Thanks to a novel compact multibend-achromat design, the 3 GeV ring will deliver a 500 mA electron beam with a horizontal emittance below 0.3 nmrad to x-ray insertion devices located in 19 dispersion-free 5 m straight sections. When the 3 GeV ring goes into operation in 2015 it is expected to become the highest electron-brightness storage ring light source world-wide. The 1.5 GeV ring will serve as a replacement for both present-day MAX II and MAX III storage rings. Its below 6 nm rad horizontal emittance electron beam will be delivered to IR and UV insertion devices in twelve 3.5 m straight sections. We report on design progress for the two new storage rings of the MAX IV facility.
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| 34. |
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| 35. |
- Lewis, Jeffrey, et al.
(författare)
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PFAS – A threat for groundwater and drinking water supply in Sweden?
- 2015
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Ingår i: EGU General Assembly 2015. ; 17
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Perfluoroalkyl substances (PFAS) are a group of anthropogenic environmental pollutants that are widely distributed in the global environment. They have multiple industrial uses, including water repellents in clothing, paper coatings and firefighting foam. According to a study released by the Environmental Directorate of the OECD, they are persistent, bioaccumulative and toxic to mammalian species (OECD, 2002). In some municipal drinking water wells in Sweden, measured concentrations of PFAS found to be several hundred times higher than the allowed threshold values. This has created a huge public concern and has recently attracted much media attention in Sweden (e.g. Afzelius et al., 2014; Bergman et al., 2014; Lewis et al., 2014). PFAS findings raised questions such as “What can we do to solve the problem?” When it comes to drinking water, there are a number of techniques that can ensure that PFAS levels are reduced to acceptable levels. This may be a costly challenge, but from a technical point of view it is possible. To ensure the safety of drinking water from a public health perspective is obviously a top priority. However, international experience shows that the cost of cleaning up PFAS in groundwater may be significantly higher than continuously treat drinking water in water works. Approximately fifty percent of Sweden’s drinking water comes from groundwater. As a result, there are several ongoing and planned PFAS-related environmental and drinking-water investigations in Sweden. Many aquifers that supply municipal water plants are located in areas of sand and gravel deposits. Such soils have relatively high permeabilities, which permits extraction of large volumes of water. However, the downside to high permeabilities is that they also allow dissolved contaminants as PFAS to spread over large areas. If one disregards the health risks linked to its presence in drinking water, PFAS have an impact on three of Sweden’s national environmental quality objectives, namely, A Non-Toxic Environment, Flourishing Lakes and Streams and Good-Quality Groundwater. Although the survey of PFAS in our groundwater supplies will take time, it is feasible. Much research in the field of hydrogeology and geochemistry remains before a viable and cost-effective groundwater remediation method can be operational. Until then, it is essential that measures are taken to identify the present distribution and magnitude of PFAS in groundwater and prevents its further spread in our most important aquifers. Afzelius, H. et al., 2014. Vågar vi dricka kranvattnet? (Do we dare drinking tap water?), Svenska Dagbladet. Bergman, Å., Hansson, S.O., Hellsten, E., 2014. En miljöskandal av historiska mått (An environmental scandal of historic proportions), Svenska Dagbladet. Lewis, J. et al., 2014. Kartlägg det förorenade dricksvattnet (Survey the contaminated drinking water), Svenska Dagbladet. OECD, 2002. Hazard Assessment of Perfluorooctane Sulfonate (PFOS) and its Salt.
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| 36. |
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| 37. |
- Link, Siim, et al.
(författare)
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Atmospheric fluidized bed gasification of untreated and leached olive residue, and co-gasification of olive residue, reed, pine pellets and Douglas fir wood chips
- 2012
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Ingår i: Applied Energy. - : Elsevier BV. - 0306-2619 .- 1872-9118. ; 94, s. 89-97
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Tidskriftsartikel (refereegranskat)abstract
- The fluidized bed gasification of untreated and pre-treated olive residue and pre-treated olive residue mixed with reed, pine pellets and Douglas fir wood chips is studied. Leaching is used as a pre-treatment process targeted on the elimination of alkali metals such as K and Na as well as chlorine to reduce/eliminate the ash-related problems during gasification. The leaching pre-treatment process could affect the producer gas composition toward the lower or higher yield of CO and H-2 of the producer gas depending on the moisture content of parent fuels. The lower total tar yield of the producer gas in the case of leached olive residue was observed compared to untreated olive residue. At the same time, there are present wider varieties of different tar components in the producer gas of the leached olive residue compared to the untreated one. The distinctions in tar composition and content between the leached and untreated olive residue are attributed to the alkali and alkali earth metal and chorine chemistry affected by leaching pre-treatment. The addition of woody fuels and reed at elevated proportions resulted in the lower LHV value compared to the leached olive residue. The tar content of the producer gas is seen to increase adding reed and woody fuels to the leached olive residue, i.e. the producer gas contained additional variety of tar components whereas phenol becomes one of the key components determining the total tar content, apart from benzene, toluene and naphthalene. This is seen to be due to the higher cellulose, hemicelluloses, lignin as well as higher chlorine content of the reed and woody fuels compared to the leached olive residue. The olive residue is seen to be better fuel for gasification compared with woody fuels and reed. Even more, we believe that the leached olive residue is better compared to all other tested fuel/mixtures in this study. It is seen that the proportions of different fuels in the mixture play role in the composition of the producer gas.
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| 38. |
- Narbe, Ulrik, et al.
(författare)
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AIB1 is a new putative prognostic biomarker in the luminal A and B-like (HER2-negative) classification of invasive lobular carcinoma
- 2017
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Ingår i: ; , s. 1-07
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Konferensbidrag (refereegranskat)abstract
- Body: Background: Estrogen receptor (ER) positive HER2-negative breast cancer comprises 75–80% of all breast cancer. Thisfraction is even higher (>90%) in invasive lobular carcinoma (ILC). According to the St Gallen surrogate definitions of the intrinsicsubtypes, Ki67 and progesterone receptor (PgR) are used to classify these tumors as luminal A- and luminal B-like(HER2-negative). These guidelines are based on information derived from patient materials with mixed histological types, wherethe vast majority of the patients have invasive ductal carcinoma. The `luminal-like classification´ together with histological grade,tumor size and lymph node status is widely used in the clinic for prognostication. The aim of the present study was to investigateif the same markers are applicable for ILC, and furthermore, if additional biomarkers involved in the endocrine signaling system,e.g. Amplified in breast cancer 1 (AIB1) and the putative G protein-coupled estrogen receptor (GPER), might providecomplementary prognostic information.Patients: Two hundred and thirty-three (N = 233) well-characterized patients with primary ILC, diagnosed between 1980 and1991 were included. Forty-two percent of the patients received adjuvant endocrine treatment and 2 % received adjuvantchemotherapy. All biomarkers were analyzed immunohistochemically on tissue microarray, whereas histological grade wasevaluated on whole sections according to Elston and Ellis (NHG). The primary endpoint was breast cancer mortality (BCM).Results: In univariable analyses with 10-year follow-up, Ki67 (high vs. low), NHG (3 vs. 1+2) and AIB1 (high vs. low) weresignificantly associated to BCM (Hazard Ratio: 4.7, 95% CI: 2.1–10.4, p 95% CI: 1.4–7.2, p = 0.005 respectively), whereas PgR (respectively). Essentially the same effect was seen after multivariable adjustment for lymph node status (+ vs. -), tumor size (>20mm vs. according to St Gallen surrogate definitions did not show significant prognostic differences between the two groups (p = 0.12).Patients with AIB1) had a 10-year BCM of 4.2% (95% CI: 1.4–12%). This group constituted 34% of the patients included in the present study.Conclusions: In contrast to other previous studies, where breast cancers of mixed histological types were included, PgR was notsignificantly associated to prognosis in the ER-positive HER2-negative subgroup in the present study, consisting only of ILC. Theprognostic role of PgR and the clinical usefulness of the luminal A and B-like (HER2-negative) classification (using only Ki67 andPgR) in ILC is still to be further investigated. The prognostic importance of Ki67 and NHG in this subgroup was, however,confirmed also in ILC, and AIB1 might be a new putative prognostic factor. By combining Ki67, NHG, and AIB1, together withlymph node status and tumor size, a group of patients with an excellent prognosis could be identified.
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| 39. |
- Narbe, Ulrik, et al.
(författare)
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The estrogen receptor coactivator AIB1 is a new putative prognostic biomarker in ER-positive/HER2-negative invasive lobular carcinoma of the breast
- 2019
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 175:2, s. 305-316
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: According to the 2017 St Gallen surrogate definitions of the intrinsic subtypes, Ki67, progesterone receptor (PR) and Nottingham histological grade (NHG) are used for prognostic classification of estrogen receptor (ER) positive/HER2-negative breast cancer into luminal A- or luminal B-like. The aim of the present study was to investigate if additional biomarkers, related to endocrine signaling pathways, e.g., amplified in breast cancer 1 (AIB1), androgen receptor (AR), and G protein-coupled estrogen receptor (GPER), can provide complementary prognostic information in a subset of ER-positive/HER-negative invasive lobular carcinoma (ILC). Methods: Biomarkers from 224 patients were analyzed immunohistochemically on tissue microarray. The primary endpoint was breast cancer mortality (BCM), analyzed with 10- and 25-year follow-up (FU). In addition, the prognostic value of gene expression data for these biomarkers was analyzed in three publicly available ILC datasets. Results: AIB1 (high vs. low) was associated to BCM in multivariable analysis (adjusted for age, tumor size, nodal status, NHG, Ki67, luminal-like classification, and adjuvant systemic therapy) with 10-year FU (HR 6.8, 95% CI 2.3–20, P = 0.001) and 25-year FU (HR 3.0, 95% CI 1.1–7.8, P = 0.03). The evidence of a prognostic effect of AIB1 could be confirmed by linking gene expression data to outcome in independent publicly available ILC datasets. AR and GPER were neither associated to BCM with 10-year nor with 25-year FU (P > 0.33). Furthermore, Ki67 and NHG were prognostic for BCM at both 10-year and 25-year FU, whereas PR was not. Conclusions: AIB1 is a new putative prognostic biomarker in ER-positive/HER2-negative ILC.
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| 40. |
- Neovius, Martin, et al.
(författare)
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Health Care Use During 20 Years Following Bariatric Surgery
- 2012
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 308:11, s. 1132-1141
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Tidskriftsartikel (refereegranskat)abstract
- Context Bariatric surgery results in sustained weight loss; reduced incidence of diabetes, cardiovascular events, and cancer; and improved survival. The long-term effect on health care use is unknown. Objective To assess health care use over 20 years by obese patients treated conventionally or with bariatric surgery. Design, Setting, and Participants The Swedish Obese Subjects study is an ongoing, prospective, nonrandomized, controlled intervention study conducted in the Swedish health care system that included 2010 adults who underwent bariatric surgery and 2037 contemporaneously matched controls recruited between 1987 and 2001. Inclusion criteria were age 37 years to 60 years and body mass index of 34 or higher in men and 38 or higher in women. Exclusion criteria were identical in both groups. Interventions Of the surgery patients, 13% underwent gastric bypass, 19% gastric banding, and 68% vertical-banded gastroplasty. Controls received conventional obesity treatment. Main Outcome Measures Annual hospital days (follow-up years 1 to 20; data capture 1987-2009; median follow-up 15 years) and nonprimary care outpatient visits (years 2-20; data capture 2001-2009; median follow-up 9 years) were retrieved from the National Patient Register, and drug costs from the Prescribed Drug Register (years 7-20; data capture 2005-2011; median follow-up 6 years). Registry linkage was complete for more than 99% of patients (4044 of 4047). Mean differences were adjusted for baseline age, sex, smoking, diabetes status, body mass index, inclusion period, and (for the inpatient care analysis) hospital days the year before the index date. Results In the 20 years following their bariatric procedure, surgery patients used a total of 54 mean cumulative hospital days compared with 40 used by those in the control group (adjusted difference, 15; 95% CI, 2-27; P = .03). During the years 2 through 6, surgery patients had an accumulated annual mean of 1.7 hospital days vs 1.2 days among control patients (adjusted difference, 0.5; 95% CI, 0.2 to 0.7; P < .001). From year 7 to 20, both groups had a mean annual 1.8 hospital days (adjusted difference, 0.0; 95% CI, −0.3 to 0.3; P = .95). Surgery patients had a mean annual 1.3 nonprimary care outpatient visits during the years 2 through 6 vs 1.1 among the controls (adjusted difference, 0.3; 95% CI, 0.1 to 0.4; P = .003), but from year 7, the 2 groups did not differ (1.8 vs 1.9 mean annual visits; adjusted difference, −0.2; 95% CI, −0.4 to 0.1; P = .12). From year 7 to 20, the surgery group incurred a mean annual drug cost of US $930; the control patients, $1123 (adjusted difference, −$228; 95% CI, −$335 to −$121; P < .001). Conclusions Compared with controls, surgically treated patients used more inpatient and nonprimary outpatient care during the first 6-year period after undergoing bariatric surgery but not thereafter. Drug costs from years 7 through 20 were lower for surgery patients than for control patients.
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