| 61. |
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| 62. |
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| 63. |
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| 64. |
- Siegel, G., et al.
(författare)
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Lipoprotein binding to anionic biopolyelectrolytes and the effect of glucose on nanoplaque formation in arteriosclerosis and Alzheimer's disease
- 2016
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Ingår i: Advances in Colloid and Interface Science. - : Elsevier BV. - 0001-8686 .- 1873-3727. ; 232, s. 25-35
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Tidskriftsartikel (refereegranskat)abstract
- Arteriosclerosis with its clinical sequelae (cardiac infarction, stroke, peripheral arterial occlusive disease) and vascular/Alzheimer dementia not only result in far more than half of all deaths but also represent dramatic economic problems. The reason is, among others, that diabetes mellitus is an independent risk factor for both disorders, and the number of diabetics strongly increases worldwide. More than one-half of infants in the first 6 months of life have already small collections of macrophages and macrophages filled with lipid droplets in susceptible segments of the coronary arteries. On the other hand, the authors of the Bogalusa Heart Study found a strong increase in the prevalence of obesity in childhood that is paralleled by an increase in blood pressure, blood lipid concentration, and type 2 diabetes mellitus. Thus, there is a clear linkage between arteriosclerosis/Alzheimer's disease on the one hand and diabetes mellitus on the other hand. Furthermore, it has been demonstrated that distinct apoE isoforms on the blood lipids further both arteriosclerotic and Alzheimer nanoplaque formation and therefore impair flow-mediated vascular reactivity as well. Nanoplaque build-up seems to be the starting point for arteriosclerosis and Alzheimer's disease in their later full clinical manifestation. In earlier work, we could portray the anionic biopolyelectrolytes syndecan/perlecan as blood flow sensors and lipoprotein receptors in cell membrane and vascular matrix. We described extensively molecular composition, conformation, form and function of the macromolecule heparan sulfate proteoglycan (HS-PG). In two supplementary experimental settings (ellipsometry, myography), we utilized isolated HS-PG for in vitro nanoplaque investigations and isolated human coronary artery segments for in vivo tension measurements. With the ellipsometry-based approach, we were successful in establishing a direct connection on a molecular level between diabetes mellitus on the one side and arteriosclerosis/Alzheimer's disease on the other side. Application of glucose at a concentration representative for diabetics and leading to glycation of proteins and lipids, entailed a significant increase in arteriosclerotic and Alzheimer nanoplaque formation. IDLapoE4/E4 was by far superior to IDLapoE3/E3 in plaque build-up, both in diabetic and non-diabetic patients. Recording vascular tension of flow-dependent reactivity in blood substitute solution and under application of different IDLapoE isoforms showed an impaired vasorelaxation for pooled IDL and IDLapoE4/E4, thus confirming the ellipsometric investigations. Incubation in IDLapoE0/E0 (apoE "knockout man"), however, resulted in a massive flow mediated contraction, also complemented" by strongly aggregated nanoplaques. In contrast, HDL was shown to present a powerful protection against nanoplaque formation on principle, both in the in vitro model and the in vivo scenario on the endothelial cell membrane. The competitive interplay with LDL is highlighted through the flow experiment, where flow-mediated, HDL-induced vasodilatation remains untouched by additional incubation with LDL. This is due to the four times higher affinity for the proteoglycan receptor of HDL as compared to LDL. Taken together, the studies demonstrate that while simplistic, the ellipsometry approach and the endothelial mimicking proteoglycan-modified surfaces provide information on the initial steps of lipoprotein-related plaque formation, which correlates with findings on endothelial cells and blood vessels, and afford insight into the role of lipoprotein deposition and exchange phenomena at the onset of these pathophysiologies.
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| 65. |
- Staaf, Johan, et al.
(författare)
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RNA sequencing-based single sample predictors of molecular subtype and risk of recurrence for clinical assessment of early-stage breast cancer
- 2022
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Ingår i: npj Breast Cancer. - : Nature Publishing Group. - 2374-4677. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Multigene assays for molecular subtypes and biomarkers can aid management of early invasive breast cancer. Using RNA-sequencing we aimed to develop single-sample predictor (SSP) models for clinical markers, subtypes, and risk of recurrence (ROR). A cohort of 7743 patients was divided into training and test set. We trained SSPs for subtypes and ROR assigned by nearest-centroid (NC) methods and SSPs for biomarkers from histopathology. Classifications were compared with Prosigna in two external cohorts (ABiM, n = 100 and OSLO2-EMIT0, n = 103). Prognostic value was assessed using distant recurrence-free interval. Agreement between SSP and NC for PAM50 {five subtypes) was high (85%, Kappa = 0.78) for Subtype (four subtypes) very high {90%, Kappa = 0.84) and for ROR risk category high (84%, Kappa = 0.75, weighted Kappa = 0.90). Prognostic value was assessed as equivalent and clinically relevant. Agreement with histopathology was very high or high for receptor status, while moderate for Ki67 status and poor for Nottingham histological grade. SSP and Prosigna concordance was high for subtype (OSLO-EMIT0 83%, Kappa = 0.73 and ABiM 80%, Kappa = 0.72) and moderate and high for ROR risk category (68 and 84%, Kappa = 0.50 and 0.70, weighted Kappa = 0.70 and 0.78). Pooled concordance for emulated treatment recommendation dichotomized for chemotherapy was high (85%, Kappa = 0.66). Retrospective evaluation suggested that SSP application could change chemotherapy recommendations for up to 17% of postmenopausal ER+/HER2-/N0 patients with balanced escalation and de-escalation. Results suggest that NC and SSP models are interchangeable on a group-level and nearly so on a patient level and that SSP models can be derived to closely match clinical tests.
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| 66. |
- Strandberg, E., et al.
(författare)
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Effects of heavy-load resistance training during (neo-)adjuvant chemotherapy on muscle cellular outcomes in women with breast cancer
- 2021
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Ingår i: Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 0025-7974 .- 1536-5964. ; 100:10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: (Neo-)adjuvant chemotherapy for breast cancer has a deleterious impact on muscle tissue resulting in reduced cardiorespiratory fitness, skeletal muscle mass and function. Physical exercise during treatment may counteract some of these negative effects. However, the effects of resistance training (RT) alone have never been explored. The present study aims to investigate if heavy-load RT during (neo-)adjuvant chemotherapy counteracts deleterious effects on skeletal muscle in women diagnosed with breast cancer. We hypothesize that (neo-)adjuvant treatment with chemotherapy will reduce muscle fiber size, impair mitochondrial function, and increase indicators of cellular stress and that RT during treatment will counteract these negative effects. We also hypothesize that RT during (neo-)adjuvant chemotherapy will increase muscle and blood levels of potential antitumor myokines and reduce treatment-related side effects on muscle strength and cardiorespiratory fitness. Methods: Fifty women recently diagnosed with breast cancer scheduled to start (neo-)adjuvant chemotherapy will be randomized to either randomized to either intervention group or to control group. The intervention group will perform supervised heavy-load RT twice a week over the course of chemotherapy (approximately 16-weeks) whereas the control group will be encouraged to continue with their usual activities. Muscle biopsies from m. vastus lateralis will be collected before the first cycle of chemotherapy (T0), after chemotherapy (T1), and 6 months later (T2) for assessment of muscle cellular outcomes. The primary outcome for this study is muscle fiber size. Secondary outcomes are: regulators of muscle fiber size and function, indicators of cellular stress and mitochondrial function, myokines with potential antitumor effects, muscle strength, and cardiorespiratory fitness. Ethics and dissemination: Ethical approval has been obtained from the Regional Ethical Review Board in Uppsala, Sweden (Dnr:2016/230/2). Results will be disseminated through presentations at scientific meetings, publications in peer-reviewed journals, social media, and patient organizations.
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| 67. |
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| 68. |
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| 69. |
- Thunberg, S., et al.
(författare)
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Dose reduction in mammography with photon counting imaging
- 2004
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. ; , s. 457-465
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Konferensbidrag (refereegranskat)abstract
- The purpose of this study was to investigate if the glandular dose to the breast in mammography can significantly be reduced without compromising image quality, when using photon counting technology, in a multi-slit scanning photon counting detector, compared to a conventional film mammography system and commercial available digital mammography systems with TFT-array detectors. A CDMAM phantom study, with two different thicknesses of additional PMMA absorber, 4 cm and 7 cm respectively, has shown that multi-slit scanning photon counting detector technology can reduce the dose, without reducing the image quality. This comparison was made to two commercial available digital mammography systems Senographe 2000D (from GEMS) and Selenia (from Lorad). The results show that dose can be reduced with 63% to 77%, depending on object thickness, when using XCT for mammography. This dose reduction has also been verified clinically through a small pilot study with patients and specimen, where the comparison was made between XCT and film.
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| 70. |
- Valachis, A., 1984-, et al.
(författare)
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Palbociclib dose patterns in Swedish patients with metastatic breast cancer : 5-year update from the SIRI study
- 2023
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Ingår i: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 34:Suppl. 2, s. S362-S362
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Although palbociclib combined with endocrine therapy is a well-established treatment option in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), there is limited evidence on patterns of dose reductions in real-world setting. The Swedish Ibrance Registries Insights (SIRI) study investigated real-world dose patterns using a nationwide cohort of palbociclib-treated MBC patients...Methods: This was a retrospective study utilizing population-based Swedish Health Data Registers. The cohort included all patients ≥ 18 years with ≥ 1 dispensation of palbociclib from January 2017 – June 2022. Minimum follow-up was 3 months. Starting dose and dose changes for the full population and for different age groups, in total and over time, was investigated...Results: 2058 patients were identified and the median (IQR) age at treatment initiation was 68.4 (15.7) years. Patients were stratified into three age groups: <50, 50-69, ≥70 years, with the following distribution: 9.9%, 46.1%, and 44.0%, respectively. Most patients were initiated on 125 mg (82.0%), with a lower share for older patients (≥70 years; 74.4%). In total, 45.5% of patients had ≥ 1 dose reduction, with a higher frequency for older patients (≥70 years; 48.5%). Median (IQR) time to first dose...Conclusions: Most Swedish palbociclib-treated patients were initiated on the recommended dose, but a lower starting dose and a higher frequency of dose reductions were observed for older patients. The time to dose reduction was equal across age groups, whereas the probability for dose reduction increased over time for older patients, and for patients with a start dose of 100 mg...
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