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  • 1
    In: Placenta, Elsevier BV, Vol. 112 ( 2021-09), p. e18-e19
    Type of Medium: Online Resource
    ISSN: 0143-4004
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
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  • 2
    In: Metabolites, MDPI AG, Vol. 13, No. 3 ( 2023-03-12), p. 417-
    Abstract: High-grade serous ovarian carcinoma (HGSOC) is the most common and deadliest ovarian cancer subtype. Despite advances in treatment, the overall prognosis remains poor. Regardless of efforts to develop biomarkers to predict surgical outcome and recurrence risk and resistance, reproducible indicators are scarce. Exploring the complex tumor heterogeneity, serum profiling of metabolites and lipoprotein subfractions that reflect both systemic and local biological processes were utilized. Furthermore, the overall impact on the patient from the tumor and the treatment was investigated. The aim was to characterize the systemic metabolic effects of primary treatment in patients with advanced HGSOC. In total 28 metabolites and 112 lipoproteins were analyzed by nuclear magnetic resonance (NMR) spectroscopy in longitudinal serum samples (n = 112) from patients with advanced HGSOC (n = 24) from the IMPACT trial with linear mixed effect models and repeated measures ANOVA simultaneous component analysis. The serum profiling revealed treatment-induced changes in both lipoprotein subfractions and circulating metabolites. The development of a more atherogenic lipid profile throughout the treatment, which was more evident in patients with short time to recurrence, indicates an enhanced systemic inflammation and increased risk of cardiovascular disease after treatment. The findings suggest that treatment-induced changes in the metabolome reflect mechanisms behind the diversity in disease-related outcomes.
    Type of Medium: Online Resource
    ISSN: 2218-1989
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
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  • 3
    In: IJC Heart & Vasculature, Elsevier BV, Vol. 46 ( 2023-06), p. 101215-
    Type of Medium: Online Resource
    ISSN: 2352-9067
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
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  • 4
    In: Physiological Genomics, American Physiological Society, Vol. 55, No. 1 ( 2023-01-01), p. 16-26
    Abstract: Lipoprotein subfractions currently represent a new source of cardiovascular disease (CVD) risk markers that may provide more information than conventional lipid measures. We aimed to investigate whether lipoprotein subfractions are associated with coronary atherosclerosis in patients without prior known CVD. Fasting serum samples from 60 patients with suspected coronary artery disease (CAD) were collected before coronary angiography and analyzed by nuclear magnetic resonance (NMR) spectroscopy. The severity of coronary atherosclerosis was quantified by the Gensini score (≤20.5 = nonsignificant coronary atherosclerosis, 20.6–30.0 = intermediate coronary atherosclerosis, ≥30.1 = significant CAD). Differences in lipoprotein subfractions between the three Gensini groups were assessed by two-way ANOVA, adjusted for statin use. Despite no differences in conventional lipid measures between the three Gensini groups, patients with significant CAD had higher apolipoprotein-B/apolipoprotein-A1 ratio, 30% more small and dense low-density lipoprotein 5 (LDL-5) particles, and increased levels of cholesterol, triglycerides, and phospholipids within LDL-5 compared with patients with nonsignificant coronary atherosclerosis and intermediate coronary atherosclerosis ( P ≤ 0.001). In addition, the low-density lipoprotein (LDL) cholesterol/high-density lipoprotein cholesterol ratio, and triglyceride levels of LDL 4 were significantly increased in patients with significant CAD compared with patients with nonsignificant coronary atherosclerosis. In conclusion, small and dense lipoprotein subfractions were associated with coronary atherosclerosis in patients without prior CVD. Additional studies are needed to explore whether lipoprotein subfractions may represent biomarkers offering a clinically meaningful improvement in the risk prediction of CAD.
    Type of Medium: Online Resource
    ISSN: 1094-8341 , 1531-2267
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2023
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  • 5
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. P1-13-01-P1-13-01
    Abstract: Background: Adjuvant breast cancer treatment may cause metabolic perturbations, such as dyslipidaemia, potentially exacerbating risk of cardiometabolic disease as well as risk of breast cancer recurrence. Physical exercise may have beneficial metabolic effects, but it’s effect on serum lipoprotein- and metabolite profiles during adjuvant breast cancer treatment including chemotherapy is not yet well established. Methods: The women participating in this pilot study of Energy Balance and Breast Cancer Aspects (EBBA)-II, were aged 38-69 years and diagnosed with stage I-II breast cancer. 60 breast cancer patients were randomized after surgery to a control group (n = 29, usual care) or an intervention group (n = 31, intervention), stratified by menopausal status. The patients in the intervention group received a detailed exercise program and met for supervised training sessions in groups of 10-12 women for 60 minutes twice a week during a 12 month period, and were in addition asked to perform at least 60 minutes of exercise at home (a total of 180 minutes of exercise weekly). Fasting serum samples were collected pre-surgery and after six months, and analysed by nuclear magnetic resonance (NMR)-spectroscopy and mass spectrometry. 170 metabolites and 109 lipoprotein subclass variables were quantified and analysed using orthogonalized partial least squares discriminant analysis. Statistical significance was assessed by permutation testing. Single variables were tested with Mann Whitney U-tests or multiple linear regression (NCT02240836). Results: The breast cancer patients (n = 60) had at pre-surgery the following means: Age at diagnosis of 55.4 years (38-69 years), low density lipoprotein (LDL)-cholesterol 145.4 mg/dl (3.76 mmol/L), high density lipoprotein (HDL)-cholesterol 70.4 mg/dl (1.82 mmol/L), and triglycerides 101.9 mg/dl (1.15 mmol/L), and 58.3 % of the patients underwent chemotherapy (paclitaxel/docetaxel/5-FU/epirubicin/cyclophosphamide based adjuvant chemotherapy). Physical exercise ameliorated chemotherapy-induced increases in very low density lipoprotein (VLDL)- and intermediate density lipoprotein (IDL)-associated lipids, and reduced triglyceride enrichment in LDL and HDL compared with chemotherapy controls (p = 0.003). Physical exercise also significantly increased apoA1 (4.6 % increase vs 11.3 % decrease, q = 0.02) and apoA2 (5.2 % increase vs 13.0 % decrease, q = 0.01) compared with chemotherapy control patients. The NMR-measured lipid signal at 1.55-1.60 ppm increased after six months in chemotherapy recipients, but this was attenuated among chemotherapy recipients in the intervention group. No statistically significant effect of physical exercise on serum levels of small-molecular metabolites was detected. Conclusion: Our findings suggest that physical exercise may prevent atherogenic alterations in lipoprotein profile induced by chemotherapy. The results indicate increased HDL particle number- and function, as well as increased triglyceride clearance in the intervention group. Thus, atherogenic alterations in lipoprotein profile may play a role in evaluating breast cancer treatment, and could potentially be biomarkers of importance for breast cancer prognosis and co-morbidity. Citation Format: Torfinn Støve Madssen, Vidar Gordon Flote, Inger Thune, Gro Falkener Bertheussen, Anders Husøy, Steinar Lundgren, Hanne Frydenberg, Erik Wist, Ellen Schlichting, Jon Lømo, Anne McTiernan, Tone Frost Bathen, Guro Fanneløb Giskeødegård. Lipoprotein and metabolite responses to physical exercise during adjuvant breast cancer treatment [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-13-01.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e23043-e23043
    Abstract: e23043 Serum metabolism during breast cancer treatment Background: Breast cancer treatment may include surgery, systemic therapy and radiation, often involving side-effects. Many patients experience weight gain during treatment, which is associated with decreased survival rates 1 . The purpose of this study was to describe serum metabolic alterations in breast cancer patients undergoing treatment, and relate these alterations to weight gain during treatment. Methods: This pilot study includes 60 breast cancer patients, aged 35-75 years, with histologically verified stage I/II disease. All patients underwent tumor surgery, and were treated according to national guidelines. Samples were collected before and 6 months after surgery, and analyzed by MR spectroscopy (MRS) and mass spectrometry (MS). 170 metabolites and 105 lipoprotein subfractions were quantified by combined MRS and MS analyses. Results: Multilevel PLS-DA showed significant alterations in serum metabolite profiles post-treatment, both in patients receiving (n = 35) and not receiving (n = 25) chemotherapy (classification accuracy: 86.7% and 77.0%, resp., p 〈 0.001). Lipoprotein profiles were also significantly altered in both groups (p 〈 0.001). Chemotherapy recipients had decreased levels of citrate, ornithine, and methionine after treatment, while non-recipients had increased levels of glutamate, alanine, proline and two biogenic amines, and decreased levels of acylcarnitines. 17/52 patients (32.7%) gained weight (≥ 1.5 kg) during treatment. Weight gain was predicted from pre-treatment samples with accuracy 67.0% (p = 0.020). Weight gain patients had lower levels of three acylcarnitines and 20 phosphocholines, and higher levels of lysine and isoleucine, suggesting aberrant lipid and amino acid metabolism. Weight gain was also reflected in the post-treatment samples (accuracy 66.8%, p = 0.015), with weight gain patients having higher levels of five acylcarnitines, and lower levels of glycine, isoleucine and valine. Conclusions: This study indicates that treatment induces changes in serum metabolite levels. Patients gaining weight had significantly different metabolite profiles than those not gaining weight both before and after treatment. 1. Chan et al, Ann Oncol 25: 1901-14, 2014.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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  • 7
    In: Diagnostics, MDPI AG, Vol. 12, No. 6 ( 2022-06-08), p. 1420-
    Abstract: High intensity interval training (HIIT) has been shown to benefit patients with psoriatic arthritis (PsA). However, magnetic resonance (MR) imaging has uncovered bone marrow edema (BME) in healthy volunteers after vigorous exercise. The purpose of this study was to investigate MR images of the spine of PsA patients for changes in BME after HIIT. PsA patients went through 11 weeks of HIIT (N = 19, 4 men, median age 52 years) or no change in physical exercise habits (N = 20, 8 men, median age 45 years). We acquired scores for joint affection and pain and short tau inversion recovery (STIR) and T1-weighted MR images of the spine at baseline and after 11 weeks. MR images were evaluated for BME by a trained radiologist, by SpondyloArthritis Research Consortium of Canada (SPARCC) scoring, and by extraction of textural features. No significant changes of BME were detected in MR images of the spine after HIIT. This was consistent for MR image evaluation by a radiologist, by SPARCC, and by texture analysis. Values of textural features were significantly different in BME compared to healthy bone marrow. In conclusion, BME in spine was not changed after HIIT, supporting that HIIT is safe for PsA patients.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 8
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e23095-e23095
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e23095-e23095
    Abstract: e23095 Background: Breast tumors are highly heterogeneous due to subpopulations of cancer cells that differ in genetic and phenotypic characteristics. Tumor heterogeneity has been associated with treatment resistance and relapse. Therefore, it can be questioned how representative one biopsy is for the whole tumor. Tumor phenotypic heterogeneity cannot be solely attributed to genetic differences, as epigenetics and interaction with the tumor microenvironment also contribute. In this study we have examined intra-tumor heterogeneity by measuring metabolite expression in breast cancer tissue compared with fibroadenomas. Methods: Fresh frozen tissue slices from surgically removed breast tumors were used. Five cores from different areas of the slices were drilled out from 10 tumors; 6 invasive ductal carcinomas grade 2-3, and 4 fibroadenomas. Histological examination of HES-stained sections from each core was done, and metabolic profiling was performed by magnetic resonance spectroscopy (MRS). The relative concentrations of 23 metabolites were quantified. Metabolic heterogeneity was assessed by coefficient of variation (CoV) and PLSDA classification was used for prediction of tumor origin. Results: Cancer tissue showed significantly higher heterogeneity than fibroadenomas for 16/23 metabolites (mean CoV range: 0.15-0.94 for cancer samples, 0.09-0.37 for fibroadenomas, p 〈 0.05). However, 23/50 samples did not contain tumor tissue on histological examination. After exclusion of tumor-free samples, the heterogeneity of 3 metabolites (glycine, glycerophosphocholine (GPC) and phosphocholine (PCho) remained significantly different between cancer and fibroadenomas (mean CoV range: 0.12-0.65 for cancer, 0.07-0.42 for fibroadenomas, p 〈 0.05). GPC and PCho are involved in building of cell membranes and may reflect cell-turnover. Multivariate classification could correctly predict which patient a sample belonged to with 78% accuracy. Conclusions: Metabolic heterogeneity could partly be explained by differences in tumor cell and stromal content, and the origin of an unknown sample could be successfully predicted, showing that metabolic intratumor heterogeneity is smaller than the heterogeneity between patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 9
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-10-14)
    Abstract: Pregnancy implies delicate immunological balance between two individuals, with constant changes and adaptions in response to maternal capacity and fetal demands. We performed cytokine profiling of 1149 longitudinal serum samples from 707 pregnant women to map immunological changes from first trimester to term and beyond. The serum levels of 22 cytokines and C-reactive protein (CRP) followed diverse but characteristic trajectories throughout pregnancy, consistent with staged immunological adaptions. Eotaxin showed a particularly robust decrease throughout pregnancy. A strong surge in cytokine levels developed when pregnancies progressed beyond term and the increase was amplified as labor approached. Maternal obesity, smoking and pregnancies with large fetuses showed sustained increase in distinct cytokines throughout pregnancy. Multiparous women had increased cytokine levels in the first trimester compared to nulliparous women with higher cytokine levels in the third trimester. Fetal sex affected first trimester cytokine levels with increased levels in pregnancies with a female fetus. These findings unravel important immunological dynamics of pregnancy, demonstrate how both maternal and fetal factors influence maternal systemic cytokines, and serve as a comprehensive reference for cytokine profiles in normal pregnancies.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 10
    In: Acta Radiologica, SAGE Publications, Vol. 61, No. 7 ( 2020-07), p. 875-884
    Abstract: The prognosis for women with locally advanced breast cancer (LABC) is poor and there is a need for better treatment stratification. Gray-level co-occurrence matrix (GLCM) texture analysis of magnetic resonance (MR) images has been shown to predict pathological response and could become useful in stratifying patients to more targeted treatments. Purpose To evaluate the ability of GLCM textural features obtained before neoadjuvant chemotherapy to predict overall survival (OS) seven years after diagnosis of patients with LABC. Material and Methods This retrospective study includes data from 55 patients with LABC. GLCM textural features were extracted from segmented tumors in pre-treatment dynamic contrast-enhanced 3-T MR images. Prediction of OS by GLCM textural features was assessed and compared to predictions using traditional clinical variables. Results Linear mixed-effect models showed significant differences in five GLCM features (f 1 , f 2 , f 5 , f 10 , f 11 ) between survivors and non-survivors. Using discriminant analysis for prediction of survival, GLCM features from 2 min post-contrast images achieved a classification accuracy of 73% ( P  〈  0.001), whereas traditional prognostic factors resulted in a classification accuracy of 67% ( P = 0.005). Using a combination of both yielded the highest classification accuracy (78%, P  〈  0.001). Median values for features f 1 , f 2 , f 10 , and f 11 provided significantly different survival curves in Kaplan–Meier analysis. Conclusion This study shows a clear association between textural features from post-contrast images obtained before neoadjuvant chemotherapy and OS seven years after diagnosis. Further studies in larger cohorts should be undertaken to investigate how this prognostic information can be used to benefit treatment stratification.
    Type of Medium: Online Resource
    ISSN: 0284-1851 , 1600-0455
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    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
    detail.hit.zdb_id: 2024579-8
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