| 1. |
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| 2. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 3. |
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| 5. |
- Wilking, N., et al.
(författare)
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Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
- 2007
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
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| 6. |
- Dahlrot, R. H., et al.
(författare)
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Prognostic value of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression in glioblastoma excluding nontumour cells from the analysis
- 2018
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Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 44:2, s. 172-184
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Tidskriftsartikel (refereegranskat)abstract
- Aims: It is important to predict response to treatment with temozolomide (TMZ) in glioblastoma (GBM) patients. Both MGMT protein expression and MGMT promoter methylation status have been reported to predict the response to TMZ. We investigated the prognostic value of quantified MGMT protein levels in tumour cells and the prognostic importance of combining information of MGMT protein level and MGMT promoter methylation status.Methods: MGMT protein expression was quantified in tumour cells in 171 GBMs from the population‐based Region of Southern Denmark (RSD)‐cohort using a double immunofluorescence approach. Pyrosequencing was performed in 157 patients. For validation we used GBM‐patients from a Nordic Study (NS) investigating the effect of radiotherapy and different TMZ schedules.Results: When divided at the median, patients with low expression of MGMT protein (AF‐low) had the best prognosis (HR = 1.5, P = 0.01). Similar results were observed in the subgroup of patients receiving the Stupp regimen (HR = 2.0, P = 0.001). In the NS‐cohort a trend towards superior survival (HR = 1.6, P = 0.08) was seen in patients with AF‐low. Including MGMT promoter methylation status, we found for both cohorts that patients with methylated MGMT promoter and AF‐low had the best outcome; median OS 23.1 and 20.0 months, respectively.Conclusion: Our data indicate that MGMT protein expression in tumour cells has an independent prognostic significance. Exclusion of nontumour cells contributed to a more exact analysis of tumour‐specific MGMT protein expression. This should be incorporated in future studies evaluating MGMT status before potential integration into clinical practice.
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| 7. |
- Boman, Karolina, et al.
(författare)
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Membranous expression of podocalyxin-like protein is an independent factor of poor prognosis in urothelial bladder cancer
- 2013
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 108:11, s. 2321-2328
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Tidskriftsartikel (refereegranskat)abstract
- Background: Membranous expression of the anti-adhesive glycoprotein podocalyxin-like (PODXL) has previously been found to correlate with poor prognosis in several major cancer forms. Here we examined the prognostic impact of PODXL expression in urothelial bladder cancer. Methods: Immunohistochemical PODXL expression was examined in tissue microarrays with tumours from two independent cohorts of patients with urothelial bladder cancer: n = 100 (Cohort I) and n = 343 (Cohort II). The impact of PODXL expression on disease-specific survival (DSS; Cohort II), 5-year overall survival (OS; both cohorts) and 2-year progression-free survival (PFS; Cohort II) was assessed. Results: Membranous PODXL expression was significantly associated with more advanced tumour (T) stage and high-grade tumours in both cohorts, and a significantly reduced 5-year OS (unadjusted HR = 2.25 in Cohort I and 3.10 in Cohort II, adjusted HR = 2.05 in Cohort I and 2.18 in Cohort II) and DSS (unadjusted HR = 4.36, adjusted HR = 2.70). In patients with Ta and T1 tumours, membranous PODXL expression was an independent predictor of a reduced 2-year PFS (unadjusted HR = 6.19, adjusted HR = 4.60) and DSS (unadjusted HR = 8.34, adjusted HR = 7.16). Conclusion: Membranous PODXL expression is an independent risk factor for progressive disease and death in patients with urothelial bladder cancer.
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| 8. |
- Coullerez, G., et al.
(författare)
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Insights into ToF-SIMS analysis of dendritic macromolecules : cationization and PCA to probe their molecular weight on surfaces
- 2003
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Ingår i: Applied Surface Science. - 0169-4332 .- 1873-5584. ; 203, s. 620-624
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Tidskriftsartikel (refereegranskat)abstract
- Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is utilized to study dendrons, dendrimers and hyperbranched derivatives prepared from the 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) or the 3-ethyl-3-(hydroxymethyl)oxetane (TMPO). We show that the cationization experiments of the intact molecules with alkali or metal ions such as Na+, Cu+ or Ag+ allow to detect whole molecular species up to 3000 Da (low generation). It allows to probe directly their molecular TM weight and end-functionality. However, when the molecule lift-off fails for series of hyperbranched polyesters Boltorn(TM), the fingerprint part of the SIMS spectra (m/z < 300 Da) is instead used. The low-mass fragments are mainly assigned to the bis-MP repeating unit. Ions due to the core molecule are also distinguished. Data treatment is combined with the principal component analysis (PCA) multivariate statistical method to highlight the main differences between the spectra. Only one principal component (PC1) is needed to describe most of the variance between the samples taking into account the generation effect. PC1 plotted as a function of the molecular weight gives a calibration curve. Normalization of the data set by ion intensities from the core molecule allows the linearization of the SIMS intensities vs. the molecular weight.
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| 9. |
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| 13. |
- Mahdi, H, et al.
(författare)
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Specific interaction between genotype, smoking and autoimmunity to citrullinated alpha-enolase in the etiology of rheumatoid arthritis
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:12, s. 1319-1324
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Tidskriftsartikel (refereegranskat)abstract
- Gene-environment associations are important in rheumatoid arthritis (RA) susceptibility, with an association existing between smoking, HLA- DRB1 'shared epitope' alleles, PTPN22 and antibodies to cyclic citrullinated peptides (CCP). Here, we test the hypothesis that a subset of the anti-CCP response, with specific autoimmunity to citrullinated alpha-enolase, accounts for an important portion of these associations. In 1,497 individuals from three RA cohorts, antibodies to the immunodominant citrullinated alpha-enolase CEP-1 epitope were detected in 43-63% of the anti-CCP-positive individuals, and this subset was preferentially linked to HLA-DRB1*04. In a case-control analysis of 1,000 affected individuals and 872 controls, the combined effect of shared epitope, PTPN22 and smoking showed the strongest association with the anti-CEP-1-positive subset (odds ratio (OR) of 37, compared to an OR of 2 for the corresponding anti-CEP-1-negative, anti-CCP-positive subset). We conclude that citrullinated alpha-enolase is a specific citrullinated autoantigen that links smoking to genetic risk factors in the development of RA.
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| 14. |
- Malmström, Johan, et al.
(författare)
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Proteome annotations and identifications of the human pulmonary fibroblast.
- 2004
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 3:3, s. 525-537
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Tidskriftsartikel (refereegranskat)abstract
- We hereby report on a three year project initiative undertaken by our research team encompassing large-scale protein expression profiling and annotations of human primary lung fibroblast cells. An overview is given of proteomic studies of the fibroblast target cell involved in several diseases such as asthma, idiopatic pulmonary disease, and COPD. It has been the objective within our research team to map and identify the protein expressions occurring in both activated-, as well as resting cell states. The JGGL database www.2DDB.org has been built around these data, allowing advanced hypothesis building using the interactive query bioinformatic tools developed. Gene ontology has been applied to these annotations, classifying and correlating protein expressions to function. The localization as well as the biological processes involved for the annotations are being presented including an annotation-, and sequence-identification strategy, resulting in close to 2000 protein identities. Both gel based, high resolution 2D-gels, and liquid-phase separation (three-dimensional HPLC), as well as the combination of gel- and LC-based approaches (1D-gels and nano-capillary LC, reversed-phase) were utilized. Protein sequencing and structure identities were acquired by a combination of MALDI-, and electrospray-mass spectrometry techniques. Phenotypical and morphological characterizations were also made for this human disease target cell in both stimulated- and resting-cell states. The use of functional assays that demonstrate the key regulating role of growth factors and cytokine stimuli such as PDGF, TGF-, and EGF and the effect of ECM molecules such as Biglycan, are also presented and discussed.
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| 15. |
- Mani, K, et al.
(författare)
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Heparan/chondroitin/dermatan sulfate primer 2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside preferentially inhibits growth of transformed cells
- 1998
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Ingår i: Cancer Research. - 0008-5472. ; 58:6, s. 104-1099
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Tidskriftsartikel (refereegranskat)abstract
- Xylose forms the direct carbohydrate-protein link in extra- or pericellular proteoglycans (PGs) that are substituted with either chondroitin sulfate (CS)/dermatan sulfate (DS) and/or heparan sulfate (HS). Cell surface PGs carrying HS are important regulators of cell growth. Xylose coupled to an aromatic compound can enter cells and initiate either CS/DS synthesis or both HS and CS/DS synthesis, depending on the nature of the aromatic adduct. Here, we show that 2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside, which can prime both types of glycan chains, inhibits growth of a set of normal and transformed cells. Transformed cells are preferentially inhibited, and at a concentration of 0.15-0.20 mM xyloside, transformed cells are totally growth arrested, whereas normal cells are only < or = 50% inhibited. No inhibition of growth is observed with the stereoisomeric 2-(6-hydroxynaphthyl)-O-beta-L-xylopyranoside, which does not prime glycosaminoglycan synthesis at all; with the nonhydroxylated 2-naphthyl-O-beta-D-xylopyranoside, which only primes CS/DS synthesis under these conditions; or with p-nitrophenyl-O-beta-D-xylopyranoside, which is known to prime only CS/DS synthesis. We conclude that growth inhibition is due to priming of HS and/or CS/DS synthesis, which may either lead to the formation of specific antiproliferative glycans or glycan fragments or to interference with endogenous PG synthesis and turnover.
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| 16. |
- Ritchie, C., et al.
(författare)
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A systematic review shows minimal evidence for measurement properties of psychological functioning outcomes in whiplash
- 2022
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier Inc.. - 0895-4356 .- 1878-5921. ; 151, s. 29-44
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to systematically identify, synthesize, and appraise studies on the measurement properties of patient-reported outcome measures (PROMs) for anxiety, depression, fear of movement, pain catastrophizing, post-traumatic stress, self-efficacy, and stress in people with whiplash-associated disorders (WAD). Study Design and Setting: PsycINFO, MEDLINE, EMBASE, CINAHL, PILOTS, Web of Science, and Scopus were searched (November 9, 2021). Studies evaluating any measurement property of relevant PROMs in WAD were included. Two reviewers independently screened the studies and assessed the measurement properties in accordance with the COSMIN guidelines. Results: Measurement properties of 10 PROMs were evaluated in WAD: Pictorial Fear of Activity Scale-Cervical (PFActS-C), Tampa Scale of Kinesiophobia-11, Pain Catastrophizing Scale (PCS), Pain Self-Efficacy Questionnaire (PSEQ), PSEQ-4 item, PSEQ-2a, PSEQ-2b, Self-Efficacy Scale, Harvard Trauma Questionnaire, and Post-Traumatic Stress Diagnostic Scale. Content validity was not examined in any of these PROMs in whiplash. Moderate- or high-quality evidence showed adequate internal structure for the PSEQ, PCS, and PFActS-C, whereas the original structures of the remaining seven PROMs were not confirmed in whiplash. Conclusion: Until further research on the measurement properties of these PROMs is available, researchers may opt to use the PSEQ, PCS, or PFActS-C if the construct is aligned with research aims. © 2022 Elsevier Inc.
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| 17. |
- Van Den Berg, F. D., et al.
(författare)
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Product uniformity control - A research collaboration of european steel industries to non-destructive evaluation of microstructure and mechanical properties
- 2018
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Ingår i: Stud. Appl. Electromagn. Mech.. - : IOS Press. - 9781614998358 ; 43, s. 120-129
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Konferensbidrag (refereegranskat)abstract
- In steel manufacturing, the conventional method to determine the mechanical properties and microstructure is by offline, destructive (lab-)characterisation of sample material that is typically taken from the head or the tail of the coil. Since coils can be up to 7 km long, the samples are not always representative for the main coil body. Also, the time delay (typically a few days) between the actual production and the availability of the characterisation results implies that these results cannot be exploited for real-time adaptation of the process settings. Information about the microstructure and material properties can also be obtained from electromagnetic (EM) and ultrasonic (US) parameters, which can be measured in real-time, non-destructively, and over the full length of the steel strip product. With the aim to improve the consistency in product quality by use of inline EM and US measurements, a European project called "Product Uniformity Control" (PUC) has been set up as a broad collaboration between 4 major European Steel Manufacturers and 10 Universities / Research institutes. Using both numerical simulations and experimental characterisations, we study the inline measured EM and US parameters in regard of the microstructural and mechanical properties. In this way, we aim to establish an improved understanding of their mutual relationships, and to apply this knowledge in existing and new nondestructive evaluation techniques. In this paper, the concerted approach of modelling and experimental validation will be addressed, and results of this work will be shown in combination with inline measured data.
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| 18. |
- Wulaningsih, W., et al.
(författare)
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A competing risks analysis of the association between prediagnostic serum glucose and lipids and breast cancer survival
- 2016
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Ingår i: Cancer Research. - Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London WC2R 2LS, England. Kings Coll London, Inst Math & Mol Biomed, London WC2R 2LS, England. Uppsala Univ, Uppsala, Sweden. Reg Canc Ctr, Uppsala, Sweden. Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. Karolinska Inst, S-10401 Stockholm, Sweden. AstraZeneca R&D, Mlndal, Switzerland. CALAB Res, Madrid, Spain.. - 0008-5472 .- 1538-7445. ; 76
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 19. |
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| 20. |
- Ahlström, Håkan, et al.
(författare)
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Positron emission tomography in the diagnosis and staging of urinary bladder cancer
- 1996
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Ingår i: Acta Radiologica. - 0284-1851 .- 1600-0455. ; 37:2, s. 180-185
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Evaluation of positron emission tomography (PET) using (18)fl 18F-2-fluoro-2-deoxy-D-glucose (18FDG) and L-methyl-11C-methionine in the diagnosis and staging of urinary bladder carcinoma. MATERIAL AND METHODS: Twenty-three patients with biopsy-proven urinary bladder carcinoma were examined with PET after intravenous injection of 11C-methionine; 2 were also examined with 18FDG. The results from the PET investigations were compared with CT or MR findings and TNM classification before and after treatment. RESULTS: The urinary excretion of 18FDG prevented distinction of the primary tumour from the surrounding tracer. With 11C-methionine it was possible to detect 18/23 primary tumours. A trend was seen, suggesting that the higher the uptake values of 11C-methionine in the tumour, the greater the tumour stage. CONCLUSION: It is possible to visualize urinary bladder tumours larger than 1 cm in diameter with PET using (11)C-methionine, but the value of the method in the staging of the lesions is not superior to conventional methods.
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| 21. |
- Andersson, Lennart, et al.
(författare)
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Chairmen's summary
- 2008
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Ingår i: Scandinavian Journal of Urology and Nephrology, Supplementum. - : Informa UK Limited. - 0300-8886 .- 1651-2537 .- 0036-5599 .- 1651-2065. ; :218, s. 7-11
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Tidskriftsartikel (refereegranskat)
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| 22. |
- Asem, H., et al.
(författare)
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Functional Nanocarriers for Drug Delivery by Surface Engineering of Polymeric Nanoparticle Post-Polymerization-Induced Self-Assembly
- 2021
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Ingår i: ACS Applied Bio Materials. - : American Chemical Society. - 2576-6422. ; 4:1, s. 1045-1056
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Tidskriftsartikel (refereegranskat)abstract
- Engineered polymeric nanoparticles (NPs) have been comprehensively explored as potential platforms for diagnosis and targeted therapy for several diseases including cancer. Herein, we designed functional poly(acrylic acid)-b-poly(butyl acrylate) (PAA-b-PBA) NPs using reversible addition-fragmentation chain-transfer (RAFT)-mediated emulsion polymerization via polymerization-induced self-assembly (PISA). The hydrophilic PAA-macroRAFT, forming a stabilizing shell (i.e., corona), was chain-extended using the hydrophobic monomer n-butyl acrylate (n-BA), resulting in stable, monodisperse, and reproducible PAA-b-PBA NPs, typically having a diameter of 130 nm. The surface engineering of the PAA-b-PBA NP post-PISA were explored using a two-step approach. The hydrophilic NP-shell corona was modified with allyl groups under mild conditions, using allylamine in water, which resulted in stable allyl-functional NPs (allyl-NPs) suitable for further bioconjugation. The allyl-NPs were subsequently conjugated with a thiol-functional fluorescent dye (BODIPY-SH) to the allyl groups using "thiol-ene"-click chemistry, to mimic the attachment of a thiol-functional target ligand. The successful attachment of BODIPY-SH to the allyl-NPs was corroborated by UV-vis spectroscopy, showing the characteristic absorbance of the BODIPY-fluorophore at 500 nm. Despite modification of NPs with allyl groups and attachment of BODIPY-SH, the NPs retained their colloidal stability and monodispersity as indicated by DLS. This demonstrates that post-PISA functionalization is a robust method for synthesizing functional NPs. Neither the NPs nor allyl-NPs showed significant cytotoxicity toward RAW264.7 or MCF-7 cell lines, which indicates their desirable safety profile. The cellular uptake of the NPs using J774A cells in vitro was found to be time and concentration dependent. The anti-cancer drug doxorubicin was efficiently (90%) encapsulated into the PAA-b-PBA NPs during NP formation. After a small initial burst release during the first 2 h, a controlled release pattern over 7 days was observed. The present investigation demonstrates a potential method for functionalizing polymeric NP post-PISA to produce carriers designed for targeted drug delivery.
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| 23. |
- Bady, Pierre, et al.
(författare)
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DNA methylation-based age acceleration observed in IDH wild-type glioblastoma is associated with better outcome - including in elderly patients
- 2022
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Ingår i: Acta neuropathologica communications. - : BMC. - 2051-5960. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Elderly patients represent a growing proportion of individuals with glioblastoma, who however, are often excluded from clinical trials owing to poor expected prognosis. We aimed at identifying age-related molecular differences that would justify and guide distinct treatment decisions in elderly glioblastoma patients. The combined DNA methylome (450 k) of four IDH wild-type glioblastoma datasets, comprising two clinical trial cohorts, was interrogated for differences based on the patients age, DNA methylation (DNAm) age acceleration (DNAm age "Horvath-clock" minus patient age), DNA methylation-based tumor classification (Heidelberg), entropy, and functional methylation of DNA damage response (DDR) genes. Age dependent methylation included 19 CpGs (p-value <= 0.1, Bonferroni corrected), comprising a CpG located in the ELOVL2 gene that is part of a 13-gene forensic age predictor. Most of the age related CpGs (n = 16) were also associated with age acceleration that itself was associated with a large number of CpGs (n = 50,551). Over 70% age acceleration-associated CpGs (n = 36,348) overlapped with those associated with the DNA methylation based tumor classification (n = 170,759). Gene set enrichment analysis identified associated pathways, providing insights into the biology of DNAm age acceleration and respective commonalities with glioblastoma classification. Functional methylation of several DDR genes, defined as correlation of methylation with gene expression (r <= -0.3), was associated with age acceleration (n = 8), tumor classification (n = 12), or both (n = 4), the latter including MGMT. DNAm age acceleration was significantly associated with better outcome in both clinical trial cohorts, whereof one comprised only elderly patients. Multivariate analysis included treatment (RT, RT/TMZ -> TMZ; TMZ, RT), MGMT promoter methylation status, and interaction with treatment. In conclusion, DNA methylation features of age acceleration are an integrative part of the methylation-based tumor classification (RTK I, RTK II, MES), while patient age seems hardly reflected in the glioblastoma DNA methylome. We found no molecular evidence justifying other treatments in elderly patients, not owing to frailty or co-morbidities.
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| 24. |
- Bartolini, Barbara, et al.
(författare)
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Iduronic Acid in chondroitin/dermatan sulfate affects directional migration of aortic smooth muscle cells.
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Aortic smooth muscle cells produce chondroitin/dermatan sulfate (CS/DS) proteoglycans that regulate extracellular matrix organization and cell behavior in normal and pathological conditions. A unique feature of CS/DS proteoglycans is the presence of iduronic acid (IdoA), catalyzed by two DS epimerases. Functional ablation of DS-epi1, the main epimerase in these cells, resulted in a major reduction of IdoA both on cell surface and in secreted CS/DS proteoglycans. Downregulation of IdoA led to delayed ability to re-populate wounded areas due to loss of directional persistence of migration. DS-epi1-/- aortic smooth muscle cells, however, had not lost the general property of migration showing even increased speed of movement compared to wild type cells. Where the cell membrane adheres to the substratum, stress fibers were denser whereas focal adhesion sites were fewer. Total cellular expression of focal adhesion kinase (FAK) and phospho-FAK (pFAK) was decreased in mutant cells compared to control cells. As many pathological conditions are dependent on migration, modulation of IdoA content may point to therapeutic strategies for diseases such as cancer and atherosclerosis.
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| 25. |
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| 26. |
- Berg, Frenk van den, et al.
(författare)
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Results of the European collaborative project "Product Uniformity Control" to improve the inline sensing of mechanical properties and microstructure of automotive steels
- 2018
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Ingår i: e-Journal of Nondestructive Testing (eJNDT). - 1435-4934. ; 23:8
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Tidskriftsartikel (refereegranskat)abstract
- A European consortium consisting of four major steel manufacturers and ten academic technology institutes has conducted a research and development project, called “Product Uniformity Control“ (PUC) in the period 2013 to 2017. This project aimed to develop and improve non-destructive (inline) measurement techniques to characterise the (uniformity of the) microstructure of steel strip products. In this project, a multitude of strip steel samples from various stages of production have been collected from the four participating steel manufacturers. The samples have been characterised in various ways, namely on their (1) non-destructive measurement parameters using different techniques suited for inline evaluation, (2) fundamental ultrasonic and electromagnetic properties (wave speed, ultrasonic attenuation, magnetisation loops, coercive field), (3) tensile properties (stress-strain curves) and (4) microstructure (by optical micrographs and EBSD images). The correlations between these different characterisations will be addressed. Besides the experimental characterisation, a strong accent has been on modelling activities: during the project, fundamental models have been developed to describe, starting from 2D and 3D microstructures, the ultrasonic and magnetic properties, which are next used as input to sensor models that predict the output of the inline measurement systems. This contribution presents the recent results of experimental work, which underlines the importance of associated modelling studies for the interpretation of the measurement data for the benefit of inline characterisation of the mechanical properties complementary to traditional destructive tensile testing.
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| 27. |
- Bergengren, Oskar, et al.
(författare)
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Short term outcomes after robot assisted and open cystectomy- A nation-wide population-based study
- 2023
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Ingår i: Ejso. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 49:4, s. 868-874
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: We aimed to compare short term outcomes after robot assisted radical cystectomy (RARC) and open radical cystectomy (ORC) for urinary bladder cancer in a large population.Materials and methods: We included all patients without distant metastases who underwent either RARC or ORC with ileal conduit between 2011 and 2019 registered in the Bladder cancer data Base Sweden (BladderBaSe) 2.0. Primary outcome was unplanned readmissions within 90 days, and secondary out-comes within 90 days of surgery were reoperations, Clavien 3-5 complications, total days alive and out of hospital, and mortality. The analysis was carried out using multivariate regression models.Results: Out of 2905 patients, 832 were operated with RARC and 2073 with ORC. Robotic procedures were to a larger extent performed during later years, at high volume centers (47% vs 17%), more often for organ-confined disease (82% vs. 72%) and more frequently in patients with high socioeconomic status (26% vs. 21%). Patients operated with RARC were more commonly readmitted (29% vs. 25%). In multi -variable analysis RARC was associated with decreased risk of Clavien 3-5 complications (OR 0.58, 95% CI 0.47-0.72), reoperations (OR 0.53, 95% CI 0.39-0.71) and had more days alive and out of hospital (mean difference 3.7 days, 95% CI 2.4-5.0).Conclusion: This study illustrates the "real-world" effects of a gradual and nation-wide introduction of RARC. Patients operated with RARC had fewer major complications and reoperations but were more frequently readmitted compared to ORC. The observed differences were largely due to more wound related complications among patients treated with ORC.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 28. |
- Bernhardson, Britt-Marie, et al.
(författare)
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Sensations, symptoms, and then what? : Early bodily experiences prior to diagnosis of lung cancer
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:3
-
Tidskriftsartikel (refereegranskat)abstract
- Lung cancer (LC) generally lacks unique core symptoms or signs. However, there are a multitude of bodily sensations that are often non-specific, not easily understood, and many times initially not recognized as indicative of LC by the affected person, which often leads to late diagnosis. In this international qualitative study, we inductively analyzed retrospective accounts of 61 people diagnosed with LC in Denmark, England and Sweden. Using the bodily sensations they most commonly spoke about (tiredness, breathlessness, pain, and cough), we constructed four sensation-based cases to understand the pre-diagnostic processes of reasoning and practice triggered by these key indicators of LC. We thereafter critically applied Hay's model of sensations to symptoms transformation, examining its central concepts of duration, disability and vulnerability, to support understanding of these processes. We found that while duration and disability are clearly relevant, vulnerability is more implicitly expressed in relation to perceived threat. Tiredness, even when of long duration and causing disability, was often related to normal aging, rather than a health threat. Regardless of duration, breathlessness was disturbing and threatening enough to lead to care-seeking. Pain varied by location, duration and degree of disability, and thus also varied in degree of threat perceived. Preconceived, but unmet expectations of what LC-related cough and pain would entail could cause delays by misleading participants; if cough lasted long enough, it could trigger health care contact. Duration, disability, and sense of threat, rather than vulnerability, were found to be relevant concepts for understanding the trajectory to diagnosis for LC among these participants. The process by which an individual, their family and health care providers legitimize sensations, allowing them to be seen as potential symptoms of disease, is also an essential, but varying part of the diagnostic processes described here.
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| 29. |
- Bonnefoi, H., et al.
(författare)
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Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial
- 2014
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 25:6, s. 1128-1136
-
Tidskriftsartikel (refereegranskat)abstract
- Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes. Patients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses. Sufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS [hazard ratio (HR) = 0.40, P < 0.001 in favour of pCR], DMFS (HR = 0.32, P < 0.001) and OS (HR = 0.32, P < 0.001). Chemotherapy arm was an independent predictor only for EFS (HR = 0.73, P = 0.004 in favour of T-ET). The interaction between TP53, intrinsic subtypes and survival outcomes only approached statistical significance for EFS (P = 0.1). pCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis.
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| 30. |
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| 31. |
- Cohen, Helen S., et al.
(författare)
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International guidelines for education in vestibular rehabilitation therapy
- 2011
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Ingår i: Journal of Vestibular Research. - 1878-6464. ; 21:5, s. 243-250
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Tidskriftsartikel (refereegranskat)abstract
- The Barany Society Ad Hoc Committee on Vestibular Rehabilitation Therapy has developed guidelines for developing educational programs for continuing education. These guidelines may be useful to individual therapists who seek to learn about vestibular rehabilitation or who seek to improve their knowledge bases. These guidelines may also be useful to professional organizations or therapists who provide continuing education in vestibular rehabilitation. We recommend a thorough background in basic vestibular science as well as an understating of current objective diagnostic testing and diagnoses, understanding of common tests used by therapists to assess postural control, vertigo and ability to perform activities of daily living. We recommend that therapists be familiar with the evidence supporting efficacy of available treatments as well as with limitations in the current research.
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| 32. |
- Cohen, Helen S., et al.
(författare)
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International survey of vestibular rehabilitation therapists by the Barany Society Ad Hoc Committee on Vestibular Rehabilitation Therapy
- 2009
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Ingår i: Journal of Vestibular Research. - 1878-6464. ; 19:1-2, s. 15-20
-
Tidskriftsartikel (refereegranskat)abstract
- The goal of this study was to determine how occupational and physical therapists learn about vestibular rehabilitation therapy, their educational backgrounds, referral patterns, and their ideas about entry-level and advanced continuing education in vestibular rehabilitation therapy. The Barany Society Ad Hoc Committee for Vestibular Rehabilitation Therapy invited therapists around the world to complete an E-mail survey. Participants were either known to committee members or other Barany Society members, known to other participants, identified from their self-listings on the Internet, or volunteered after reading notices published in publications read by therapists. Responses were received from 133 therapists in 19 countries. They had a range of educational backgrounds, practice settings, and referral patterns. Few respondents had had any training about vestibular rehabilitation during their professional entry-level education. Most respondents learned about vestibular rehabilitation from continuing education courses, interactions with their colleagues, and reading. All of them endorsed the concept of developing standards and educating therapists about vestibular anatomy and physiology, vestibular diagnostic testing, vestibular disorders and current intervention strategies. Therefore, the Committee recommends the development of international standards for education and practice in vestibular rehabilitation therapy.
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| 33. |
- Coullerez, G., et al.
(författare)
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ToF-SIMS for the characterization of hyperbranched aliphatic polyesters : probing their molecular weight on surfaces based on principal component analysis (PCA)
- 2003
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Ingår i: Surface and Interface Analysis. - : Wiley. - 0142-2421 .- 1096-9918. ; 35:8, s. 693-708
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Tidskriftsartikel (refereegranskat)abstract
- A series of 2,2-bis(hydroxymethyl)propionic acid (Bis-MPA) hyperbranched aliphatic polyesters with different molecular weights (generations) is analysed for the first time by time-of-flight secondary ion mass spectrometry (ToF-SIMS). The main negative and positive low-mass fragments are identified in the fingerprint part of the spectra (m/z < 400) and are principally assigned to fragmentation of the Bis-MPA repeating units. In addition, it is shown that the fragmentation pattern is highly affected by the functional end-groups. This is illustrated for a phthalic acid end-capped hyperbranched polymer and for an acetonide-terminated dendrimer analog. Also, typical fragments assigned to the ethoxylated pentaerythritol core molecule are detected. These ions show decreasing intensities with increasing molecular weight. This intensity dependency on the generation is used to calibrate the molecular weight of hyperbranched polyesters on the surface. To obtain quantitative information, a principal component analysis WCA) multivariate statistical method is applied to the ToF-SIMS data. The influence of different normalization procedures prior to PCA calculation is tested, e.g. normalization to the total intensity, to the intensities of ions assigned to the Bis-MPA repeating unit or to intensities of fragments due to the core molecule. It is shown that only one principal component (PC1) is needed to describe most of the variance between the samples. In addition, PC1 takes into account the generation effect. However, different relationships between the PC1 scores and the hyperbranched mass average molecular weights are observed depending on the normalization procedure used. Normalization of data set ion intensities by ion intensities from the core molecule allows linearization of the SIMS intensities versus the molecular weight and allows the hyperbranched polymers to be discriminated up to the highest generations. In addition, PCA applied to ToF-SIMS data provides an extended interpretation of the spectra leading to further identification of the correlated mass peaks, such as those of the Bis-MPA repeating unit (terminal, dendritic and linear) and those of the core molecule. Finally, the work presented demonstrates the extreme potential of the static ToF-SIMS and PCA techniques in the analysis of dendritic molecules on solid surfaces.
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| 34. |
- Dalhammar, Karin, et al.
(författare)
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Striving towards normality in an unpredictable situation. A qualitative interview study of how persons newly diagnosed with incurable oesophageal and gastric cancer manage everyday life
- 2023
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Ingår i: European Journal of Oncology Nursing. - : Elsevier BV. - 1462-3889. ; 63
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Getting an incurable oesophageal or gastric cancer diagnosis is a major stressful life event associated with severe physical, psychosocial and existential challenges. To provide timely and efficient support, based on patients' experiences, the aim of the study was to explore how patients newly diagnosed with incurable oesophageal and gastric cancer manage everyday life. Method: Semi-structured interviews were conducted with 12 patients 1–3 months after being diagnosed with incurable oesophageal or gastric cancer. Four participants were interviewed twice, which resulted in 16 interviews. Data were analysed with qualitative content analysis. Results: An overall theme, “Striving towards normality in an unpredictable situation”, with three related themes – “Trying to comprehend the disease”, “Dealing with the consequences of illness” and “Re-evaluating what is important in everyday life” – and seven sub-themes were identified. The participants described an unexpected and unpredictable situation, in which they strived to maintain their normal life. Amidst struggling to manage problems related to eating, fatigue and an incurable diagnosis the participants talked about the importance of focusing on the positive and normal aspects of life. Conclusions: The findings in this study point to the importance of supporting patients’ confidence and skills, particularly with regard to managing eating, so that they can hold on to their normal life as much as possible. The findings further point to the possible benefit of integrating an early palliative care approach and could provide guidance for nurses and other professionals on how to support patients post diagnosis.
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| 35. |
- Dalhammar, Karin, et al.
(författare)
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Symptoms, problems and quality of life in patients newly diagnosed with oesophageal and gastric cancer - a comparative study of treatment strategy
- 2022
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 22, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with oesophageal and gastric cancer have a low likelihood of being cured and suffer from a broad spectrum of symptoms and problems that negatively affect their quality-of-life (QOL). Although the majority (67-75%) of patients at the time of diagnosis suffer from an incurable disease, research has primarily focused on the pre- and postoperative phase among patients treated with curative intent, with little attention to symptoms and problems in the diagnostic phase, especially in those who cannot be offered a cure.METHODS: In this cross-sectional study 158 patients newly diagnosed with oesophageal and gastric cancer visiting the surgical outpatient department for a preplanned care visit were included consecutively during 2018-2020. The validated instruments QLQ-C30 and QLQ-OG25, developed by the European Organization for Research and Treatment of Cancer (EORTC), and selected items from the Integrated Patient Outcome Scale (IPOS) were used to assess QOL, symptoms and problems. Differences between patients with a curative and a palliative treatment strategy were analysed using t-test and Mann-Whitney U test. The QLQ-C30 and QLQ-OG25 scores were compared to published reference data on the general Swedish population.RESULTS: Among all, the QOL was markedly lower, compared with general Swedish population (mean ± SD, 55.9 ± 24.7 vs 76.4 ± 22.8, p < 0.001). Compared to general population, the patients had significant impairment in all QOL aspects, particularly for role and emotional functioning and for symptoms such as eating-related problems, fatigue, insomnia and dyspnea. Majority of patients also reported severe anxiety among family and friends. Among patients with oesophageal cancer those with a palliative treatment strategy, compared with curative strategy, reported significantly lower QOL (mean ± SD, 50.8 ± 28.6 vs 62.0 ± 22.9 p = 0.030), physical (65.5 ± 22.6 vs 83.9 ± 16.5, p < 0.001) and role functioning (55.7 ± 36.6 vs 73.9 ± 33.3, p = 0.012), and a higher burden of several symptoms and problems. No significant differences between treatment groups were shown among patients with gastric cancer.CONCLUSIONS: Patients newly diagnosed with oesophageal and gastric cancer, and especially those with incurable oesophageal cancer, have a severely affected QOL and several burdensome symptoms and problems. To better address patients' needs, it seems important to integrate a palliative approach into oesophageal and gastric cancer care.
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| 36. |
- Davies, C, et al.
(författare)
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Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen : patient-level meta-analysis of randomised trials
- 2011
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 378:9793, s. 771-784
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: As trials of 5 years of tamoxifen in early breast cancer mature, the relevance of hormone receptor measurements (and other patient characteristics) to long-term outcome can be assessed increasingly reliably. We report updated meta-analyses of the trials of 5 years of adjuvant tamoxifen. METHODS: We undertook a collaborative meta-analysis of individual patient data from 20 trials (n=21,457) in early breast cancer of about 5 years of tamoxifen versus no adjuvant tamoxifen, with about 80% compliance. Recurrence and death rate ratios (RRs) were from log-rank analyses by allocated treatment. FINDINGS: In oestrogen receptor (ER)-positive disease (n=10,645), allocation to about 5 years of tamoxifen substantially reduced recurrence rates throughout the first 10 years (RR 0·53 [SE 0·03] during years 0-4 and RR 0·68 [0·06] during years 5-9 [both 2p<0·00001]; but RR 0·97 [0·10] during years 10-14, suggesting no further gain or loss after year 10). Even in marginally ER-positive disease (10-19 fmol/mg cytosol protein) the recurrence reduction was substantial (RR 0·67 [0·08]). In ER-positive disease, the RR was approximately independent of progesterone receptor status (or level), age, nodal status, or use of chemotherapy. Breast cancer mortality was reduced by about a third throughout the first 15 years (RR 0·71 [0·05] during years 0-4, 0·66 [0·05] during years 5-9, and 0·68 [0·08] during years 10-14; p<0·0001 for extra mortality reduction during each separate time period). Overall non-breast-cancer mortality was little affected, despite small absolute increases in thromboembolic and uterine cancer mortality (both only in women older than 55 years), so all-cause mortality was substantially reduced. In ER-negative disease, tamoxifen had little or no effect on breast cancer recurrence or mortality. INTERPRETATION: 5 years of adjuvant tamoxifen safely reduces 15-year risks of breast cancer recurrence and death. ER status was the only recorded factor importantly predictive of the proportional reductions. Hence, the absolute risk reductions produced by tamoxifen depend on the absolute breast cancer risks (after any chemotherapy) without tamoxifen. FUNDING: Cancer Research UK, British Heart Foundation, and Medical Research Council.
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| 37. |
- De Marchi, Tommaso, et al.
(författare)
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Proteomic profiling reveals that ESR1 mutations enhance cyclin-dependent kinase signaling
- 2024
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Ingår i: Scientific Reports. - 2045-2322. ; 14, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- Three quarters of all breast cancers express the estrogen receptor (ER, ESR1 gene), which promotes tumor growth and constitutes a direct target for endocrine therapies. ESR1 mutations have been implicated in therapy resistance in metastatic breast cancer, in particular to aromatase inhibitors. ESR1 mutations promote constitutive ER activity and affect other signaling pathways, allowing cancer cells to proliferate by employing mechanisms within and without direct regulation by the ER. Although subjected to extensive genetic and transcriptomic analyses, understanding of protein alterations remains poorly investigated. Towards this, we employed an integrated mass spectrometry based proteomic approach to profile the protein and phosphoprotein differences in breast cancer cell lines expressing the frequent Y537N and Y537S ER mutations. Global proteome analysis revealed enrichment of mitotic and immune signaling pathways in ER mutant cells, while phosphoprotein analysis evidenced enriched activity of proliferation associated kinases, in particular CDKs and mTOR. Integration of protein expression and phosphorylation data revealed pathway-dependent discrepancies (motility vs proliferation) that were observed at varying degrees across mutant and wt ER cells. Additionally, protein expression and phosphorylation patterns, while under different regulation, still recapitulated the estrogen-independent phenotype of ER mutant cells. Our study is the first proteome-centric characterization of ESR1 mutant models, out of which we confirm estrogen independence of ER mutants and reveal the enrichment of immune signaling pathways at the proteomic level.
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| 38. |
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| 39. |
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| 40. |
- Flodgren, P, et al.
(författare)
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Immune functions in melanoma patients during treatment with interferon [HuIFN-alpha (Le)] alone or in combination with cimetidine
- 1985
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Ingår i: Anticancer research. - 0250-7005. ; 5:2, s. 197-204
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Tidskriftsartikel (refereegranskat)abstract
- While leukocyte interferon was found therapeutically ineffective in a series of 20 patients with metastatic malignant melanoma, subsequent combination treatment with interferon and cimetidine induced 5 complete and 1 partial tumour remissions. Prior to interferon therapy initiation, regressor patients demonstrated a significantly greater ability to mediate antibody-dependent cellular cytotoxicity than progressor patients and also tended to have higher natural killer-cell activity. These differences were more pronounced following in vitro exposure of effector cells to interferon alone or in combination with cimetidine. During therapy the differences decreased to statistically nonsignificant levels. The number of immunoglobulin producing cells and lymphocyte proliferative responses to Con A were found to increase in both patient groups after interferon therapy initiation; but this augmentation vanished gradually upon combined treatment with cimetidine. A gradual decrease of the number of T lymphocytes and granulocytes was also recorded. None of the demonstrated alterations in the activities of circulating lymphocytes appears to be a relevant correlate to the efficacy of combined therapy compared to interferon alone.
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| 41. |
- Forsberg, Ole, 1979-, et al.
(författare)
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High frequency of prostate antigen-directed T cells in cancer patients compared to healthy age-matched individuals
- 2009
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 69:1, s. 70-81
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. In order to obtain a sustained cytotoxic T lymphocyte (CTL) response against cancer cells it is preferable to have CTLs directed against multiple peptide epitopes from numerous tumor-associated antigens. METHODS. We used a flow cytometry-based interferon (IFN)-g secretion assay to analyze whether CD8+ T cells directed against any of 24 HLA-A*0201-binding peptides from 15 prostate-associated proteins can be found in the peripheral blood of patients with localized prostate cancer. We also investigated whether multiple prostate antigen-specific CD8+ T cells can be generated simultaneously, from a naïve T cell repertoire. In that case, dendritic cells (DCs) from peripheral blood of healthy donors were divided in six portions and separately pulsed with six peptides. The peptide-pulsed DCs were then pooled and used to stimulate autologous T cells. The T cells were re-stimulated with peptide-pulsed monocytes. RESULTS. We found prostate antigen-restricted CD8+ T cells in the peripheral blood in 48 out of 184 (26.1%) analyzed samples from 25 cancer patients. This is significantly higher than 17 out of 214 analyzed samples (7.9%) from 10 healthy age-matched male individuals (p = 0.0249). In the cases when antigen-specific T cells could not be detected, we were able to generate IFN-g-producing CD8+ T cells specific for up to three prostate antigens simultaneously from a naïve T cell repertoire. CONCLUSIONS. CD8+ T cells directed against prostate antigen peptides can be found in, or generated from, peripheral blood. This indicates that such T cells could be expanded ex vivo for adoptive transfer to prostate cancer patients.
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| 42. |
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| 43. |
- Gruvberger, Sofia, et al.
(författare)
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Estrogen receptor beta expression is associated with tamoxifen response in ER alpha-negative breast carcinoma
- 2007
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 13:7, s. 1987-1994
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Endocrine therapies, such as tamoxifen, are commonly given to most patients with estrogen receptor (ERalpha)-positive breast carcinoma but are not indicated for persons with ERalpha-negative cancer. The factors responsible for response to tamoxifen in 5% to 10% of patients with ERalpha-negative tumors are not clear. The aim of the present study was to elucidate the biology and prognostic role of the second ER, ERbeta, in patients treated with adjuvant tamoxifen.EXPERIMENTAL DESIGN: We investigated ERbeta by immunohistochemistry in 353 stage II primary breast tumors from patients treated with 2 years adjuvant tamoxifen, and generated gene expression profiles for a representative subset of 88 tumors.RESULTS: ERbeta was associated with increased survival (distant disease-free survival, P = 0.01; overall survival, P = 0.22), and in particular within ERalpha-negative patients (P = 0.003; P = 0.04), but not in the ERalpha-positive subgroup (P = 0.49; P = 0.88). Lack of ERbeta conferred early relapse (hazard ratio, 14; 95% confidence interval, 1.8-106; P = 0.01) within the ERalpha-negative subgroup even after adjustment for other markers. ERalpha was an independent marker only within the ERbeta-negative tumors (hazard ratio, 0.44; 95% confidence interval, 0.21-0.89; P = 0.02). An ERbeta gene expression profile was identified and was markedly different from the ERalpha signature.CONCLUSION: Expression of ERbeta is an independent marker for favorable prognosis after adjuvant tamoxifen treatment in ERalpha-negative breast cancer patients and involves a gene expression program distinct from ERalpha. These results may be highly clinically significant, because in the United States alone, approximately 10,000 women are diagnosed annually with ERalpha-negative/ERbeta-positive breast carcinoma and may benefit from adjuvant tamoxifen.
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| 44. |
- Grönwall, Caroline, et al.
(författare)
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A Comprehensive Evaluation of the Relationship Between Different IgG and IgA Anti-Modified Protein Autoantibodies in Rheumatoid Arthritis
- 2021
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Seropositive rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified protein autoantibodies (AMPA), e.g. anti-carbamylated (Carb), -acetylated (KAc), and malondialdehyde acetaldehyde (MAA) modified protein antibodies, have been described. In this comprehensive study, we analyze 30 different IgG and IgA AMPA reactivities to Cit, Carb, KAc, and MAA antigens detected by ELISA and autoantigen arrays in N=1985 newly diagnosed RA patients. Association with patient characteristics such as smoking and disease activity were explored. Carb and KAc reactivities by different assays were primarily seen in patients also positive for anti-citrulline reactivity. Modified vimentin (mod-Vim) peptides were used for direct comparison of different AMPA reactivities, revealing that IgA AMPA recognizing mod-Vim was mainly detected in subsets of patients with high IgG anti-Cit-Vim levels and a history of smoking. IgG reactivity to acetylation was mainly detected in a subset of patients with Cit and Carb reactivity. Anti-acetylated histone reactivity was RA-specific and associated with high anti-CCP2 IgG levels, multiple ACPA fine-specificities, and smoking status. This reactivity was also found to be present in CCP2+ RA-risk individuals without arthritis. Our data further demonstrate that IgG autoreactivity to MAA was increased in RA compared to controls with highest levels in CCP2+ RA, but was not RA-specific, and showed low correlation with other AMPA. Anti-MAA was instead associated with disease activity and was not significantly increased in CCP2+ individuals at risk of RA. Notably, RA patients could be subdivided into four different subsets based on their AMPA IgG and IgA reactivity profiles. Our serology results were complemented by screening of monoclonal antibodies derived from single B cells from RA patients for the same antigens as the RA cohort. Certain CCP2+ clones had Carb or Carb+KAc+ multireactivity, while such reactivities were not found in CCP2- clones. We conclude that autoantibodies exhibiting different patterns of ACPA fine-specificities as well as Carb and KAc reactivity are present in RA and may be derived from multireactive B-cell clones. Carb and KAc could be considered reactivities within the "Cit-umbrella" similar to ACPA fine-specificities, while MAA reactivity is distinctly different.
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| 45. |
- Hao, X. J., et al.
(författare)
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Dendrimers as scaffolds for multifunctional reversible addition-fragmentation chain transfer agents : Syntheses and polymerization
- 2004
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Ingår i: Journal of Polymer Science Part A. - : Wiley. - 0887-624X .- 1099-0518. ; 42:23, s. 5877-5890
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis and characterization of novel first- and second-generation true dendritic reversible addition-fragmentation chain transfer (RAFT) agents carrying 6 or 12 pendant 3-benzylsulfanylthiocarbonylsulfanylpropionic acid RAFT end groups with Z-group architecture based on 1,1,1-hydroxyphenyl ethane and trimethylolpropane cores are described in detail. The multifunctional dendritic RAFT agents have been used to prepare star polymers of poly(butyl acrylate) (PBA) and polystyrene (PS) of narrow polydispersities (1.4 < polydispersity index < 1.1 for PBA and 1.5 < polydispersity index < 1.3 for PS) via bulk free-radical polymerization at 60 degreesC. The novel dendrimer-based multifunctional RAFT agents effect an efficient living polymerization process, as evidenced by the linear evolution of the number-average molecular weight (M.) with the monomer-polymer conversion, yielding star polymers with molecular weights of up to M-n = 160,000 g mol(-1) for PBA (based on a linear PBA calibration) and up to M. = 70,000 g mol(-1) for PS (based on a linear PS calibration). A structural change in the chemical nature of the dendritic core (i.e., 1,1,1-hydroxyphenyl ethane vs trimethylolpropane) has no influence on the observed molecular weight distributions. The star-shaped structure of the generated polymers has been confirmed through the cleavage of the pendant arms off the core of the star-shaped polymeric materials.
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| 46. |
- Hao, X. J., et al.
(författare)
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Dendrimers as scaffolds for reversible addition fragmentation chain transfer (RAFT) agents : A route to star-shaped block copolymers
- 2005
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Ingår i: Australian journal of chemistry (Print). - 0004-9425 .- 1445-0038. ; 58:6, s. 483-491
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Tidskriftsartikel (refereegranskat)abstract
- Star-shaped block copolymers of styrene and n-butyl acrylate having three, six, and twelve pendent arms were successfully synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization. Dendritic cores ( based on 1,1,1-trimethylolpropane) of generation 0, 1, and 2 have been functionalized with 3-benzylsulfanylthiocarbonylsulfanylpropionic ester groups and have subsequently been employed to mediate the polymerization of styrene and n-butyl acrylate to generate macro-star-RAFT agents as starting materials for chain extension. The chain extension of the macro-star-RAFT agents with either styrene or n-butyl acrylate by bulk free radical polymerization at 60 degrees C gives narrowly distributed polymer (final polydispersities close to 1.2) increasing linearly in molecular weight with increasing monomer-to-polymer conversion. However, with an increasing number of arms (i.e., when going from three- to twelve-armed star polymers), the chain extension becomes significantly less efficient. The molecular weight of the generated block copolymers was assessed using H-1 NMR spectroscopy as well as size exclusion chromatography calibrated with linear polystyrene standards. The hydrodynamic radius, R-h, of the star block copolymers as well as the precursor star polymers was determined in tetrahydrofuran by dynamic light scattering (90 degrees) at 25 degrees C. Interestingly, the observed R-h-M-n relationships indicate a stronger dependence of R-h on M-n for poly(butyl acrylate) stars than for the corresponding styrene polymers. R-h increases significantly when the macro-star-RAFT agent is chain extended with either styrene or n-butyl acrylate.
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| 47. |
- Jesberger, M., et al.
(författare)
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Hyperbranched polymers as scaffolds for multifunctional reversible addition-fragmentation chain-transfer agents : A route to polystyrene-core-polyesters and polystyrene-block-poly(butyl acrylate)-core-polyesters
- 2003
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Ingår i: Journal of Polymer Science Part A. - : Wiley. - 0887-624X .- 1099-0518. ; 41:23, s. 3847-3861
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Tidskriftsartikel (refereegranskat)abstract
- Polydisperse hyperbranched polyesters were modified for use as novel multifunctional reversible addition-fragmentation chain-transfer (RAFT) agents. The polyester-core-based RAFT agents were subsequently employed to synthesize star polymers of n-butyl acrylate and styrene with low polydispersity (polydispersity index < 1.3) in a living free-radical process. Although the polyester-core-based RAFT agent mediated polymerization of n-butyl acrylate displayed a linear evolution of the number-average molecular weight (M.) up to high monomer conversions (>70%) and molecular weights [M-n > 140,000 g mol(-1), linear poly(methyl methacrylate) equivalents)], the corresponding styrene-based system reached a maximum molecular weight at low conversions (approximate to30%, M-n = 45,500 g mol(-1), linear polystyrene equivalents). The resulting star polymers were subsequently used as platforms for the preparation of star block copolymers of styrene and n-butyl acrylate with a polyester core with low polydispersities (polydispersity index < 1.25). The generated polystyrene-based star polymers were successfully cast into highly regular honeycomb-structured microarrays.
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| 48. |
- Jingili, Nuru, et al.
(författare)
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A Two-Stage co-Design Process of Battleship-AST Persuasive Game for Active School Transportation in Northern Sweden
- 2024
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Ingår i: International Journal of Human-Computer Interaction. - : Taylor & Francis. - 1044-7318 .- 1532-7590.
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Tidskriftsartikel (refereegranskat)abstract
- This research delves into the dynamics of active school transport (AST) by utilizing a two-stage co-design process and leveraging persuasive technology within a game for promoting AST called Battleship-AST. The primary aim of this research is to thoroughly investigate the two-stage game co-design process employed in creating a Battleship-AST game. Moreover, our research aims to evaluate participants’ perceptions regarding the motivating and engaging potential of the persuasive technology and gamification features embedded within the final iteration of the game. This evaluation aims to understand how these features influence participants’ motivation to increase their usage of AST through gameplay. In pursuit of these objectives, the research builds upon the existing Battleship-AST prototype and actively engages school children in a collaborative two-stage co-design process. Their valuable insights and preferences were harnessed in refining the game, which was subsequently tested during a tech event in Skellefteå, Sweden. The findings shed light on various aspects of the game’s impact, from its reception to the gamification features integrated within. Notably, the research highlights the positive impact of the co-design process, with increased motivation and engagement observed among the participants. Their involvement in shaping the game’s design resulted in a more engaging and enjoyable experience. The persuasive technology features, encompassing competition, collaboration, auditory cues, a virtual reward system, and an emphasis on similarity, played a pivotal role in sustaining engagement and motivating players. Elements such as rewards, leaderboard progression, and badges proved highly effective in encouraging continued participation and fostering a positive feedback loop. However, the study also identifies areas for potential improvement, including the need to measure real-life progress and refine the game’s levelling system. The research indicates that refining feedback mechanisms and tailoring game content to individual preferences could create an even more engaging experience. Additionally, long-term playtesting is proposed to assess the game’s extended impact. The findings offer promising avenues for enhancing motivation and engagement in AST, which can contribute to the promotion of healthier and more sustainable transportation choices among school children.
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| 49. |
- Jingili, Nuru, et al.
(författare)
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Adolescents’ perceptions of active school transport in northern Sweden
- 2023
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Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Active school transport (AST) refers to using active means of transport such as walking, cycling, or riding a non-motorised scooter to school. It can help improve adolescents’ physical activity levels and create a more sustainable environment. The study involved 70 adolescents (45 boys and 25 girls) aged 13 to 14 from one school in Skellefteå, in Northern Sweden. In an online questionnaire, they were asked about their perceptions of cycling, walking, and riding a non-motorised scooter to school. This study used descriptive statistics, multiple regression analysis, and hypothesis testing with ANOVA to analyse the collected data and compare the perceptions of different types of transport on safety, environmental, and personal factors among adolescents in Northern Sweden. According to the results, more adolescents walked to school than cycled, and significantly few rode a non-motorised scooter to school. Most adolescents believe walking or cycling to school is a great way to exercise. Furthermore, the study also revealed that many adolescents avoid using AST due to the time it takes. Although the study showed that adolescents felt sufficient support for using AST from schools and parents, the number of adolescents using motorised transport is higher during winter than in summer. Additionally, most of them were more confident about cycling and walking to school than riding a non-motorised scooter and thought using AST was nice. Finally, most adolescents perceived having complete control over their transport options when going to school. The research indicates that it is crucial to implement interventions that inspire children to be interested and excited about using AST. These strategies should include fostering an AST culture that is fun and positive, as well as creating environments that are safe and supportive. The research results will guide the creation of a persuasive game that can motivate adolescents to use AST and measure its effectiveness.
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| 50. |
- Johansson, Maria H., et al.
(författare)
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Chiral platinum(II) complexes. Crystal and molecular structures of cis-[PtPhCl((R,R)-CHIRAPHOS)] and cis-[PtCl2((R,R)-CHIRAPHOS)]
- 2001
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Ingår i: Inorganica Chimica Acta. - 0020-1693. ; 316:1-2, s. 149-152
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Tidskriftsartikel (refereegranskat)abstract
- The reaction between trans-PtPhCl(SMe2)2 and (R,R)-CHIRAPHOS gives cis-[PtPhCl((R,R)-CHIRAPHOS)] (1). The crystals of which are monoclinic, space group P21 with a = 12.875(3), b = 18.012(4), c = 13.864(3) Å, β = 109.71(3)° and Z = 4. In CDCl3 1 reacts with Ph2P(C6H4)CH2N(Me)(COEt) to give cis[PtCl2((R,R)-CHIRAPHOS)] (2), the crystals of which are monoclinic, space group P21 with a = 7.8052(16), b = 17.679(4), c = 9.843(2) Å, β = 100.67(3)° and Z = 2.
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