| 1. |
- Fernö, Mårten, et al.
(författare)
-
Results of two or five years of adjuvant tamoxifen correlated to steroid receptor and S-phase levels
- 2000
-
Ingår i: Breast Cancer Research and Treatment. - 1573-7217 .- 0167-6806. ; 59:1, s. 69-76
-
Tidskriftsartikel (refereegranskat)abstract
- A Swedish cooperative trial demonstrated that 5 years of adjuvant tamoxifen was more beneficial than 2 years of tamoxifen in the treatment of postmenopausal women with estrogen receptor (ER) positive, early stage, invasive breast cancer. The main aim of the present study was to investigate the importance of progesterone receptor (PgR) and ER concentration levels for patients participating in the trial and still distant recurrence free two years after the primary operation. Subgroup analyses revealed that only patients with ER positive and PgR positive breast cancer had improved distant recurrence free survival (DRFS) by prolonged tamoxifen therapy (p = 0.0016). Patients with ER negative and PgR negative as well as ER positive and PgR negative tumors showed no significant effect of prolonged tamoxifen (p = 0.53 and p = 0.80, respectively). The percentage of ER negative and PgR positive breast cancers was too small (2.2%) for any meaningful subgroup analysis. There was a significant positive trend that the concentration level of PgR (high positive vs. low positive vs. negative) decreased the recurrence rate for those with prolonged therapy. No corresponding pattern was found for the ER content. S-phase fraction did not correlate to the recurrence rate of PgR positive breast cancers. Patients recurring during tamoxifen therapy had receptor negative tumors to a greater extent than those recurring after tamoxifen treatment. In conclusion, prolonged tamoxifen therapy for 5 years instead of 2 years was found to be beneficial for patients with ER positive and PgR positive breast cancer, whereas three extra years of tamoxifen had little or no effect for patients with ER positive but PgR negative tumors as well as for steroid receptor negative patients.
|
|
| 2. |
|
|
| 3. |
- Alkner, Sara, et al.
(författare)
-
Tamoxifen reduces the risk of contralateral breast cancer in premenopausal women : Results from a controlled randomised trial
- 2009
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 45:14, s. 2496-2502
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Adjuvant treatment with tamoxifen reduces the risk of contralateral breast cancer in hormone-responsive postmenopausal patients, whereas the effect in premenopausal women has not been fully elucidated. We have therefore studied the effect of tamoxifen on contralateral breast cancer in premenopausal women in a controlled randomised trial. Patients and methods: Premenopausal women (564) with stage II breast cancers were randomised to 2 years of tamoxifen versus control irrespective of oestrogen receptor (ER) and progesterone receptor (PgR) status. The median follow-up for patients not developing a contralateral cancer was 14 years. Results: In the control group 35 women, and in the tamoxifen group 17 women, developed a contralateral breast cancer as a primary event. Tamoxifen significantly reduced the risk of contralateral breast cancer in all women regardless of age (hazard ratio (HR) 0.5, p = 0.02). In subgroup analysis the risk reduction was most pronounced in patients less than40 years of age (HR 0.09, p = 0.02). A risk reduction was also seen in women 40-49 years of age or ≥50 years of age, although in these subgroups this did not reach statistical significance. The reduced risk of contralateral breast cancer was persistent during the whole follow-up time. Conclusion: In this randomised trial, adjuvant treatment using tamoxifen for 2 years reduced the incidence of contralateral breast cancer by 50% in all premenopausal women, and by 90% in women less than40 years of age. The effect of tamoxifen was not significantly dependent on time.
|
|
| 4. |
- Asif, Sana, M.D, PhD student, et al.
(författare)
-
Validation of an MPC polymer coating to attenuate surface- induced cross-talk between the complement and coagulation systems in whole blood in in vitro and in vivo models
- 2019
-
Ingår i: Macromolecular Bioscience. - : Wiley-VCH Verlagsgesellschaft. - 1616-5187 .- 1616-5195. ; 19:5
-
Tidskriftsartikel (refereegranskat)abstract
- Artificial surfaces that come into contact with blood induce an immediate activation of the cascade systems of the blood, leading to a thrombotic and/or inflammatory response that can eventually cause damage to the biomaterial or the patient, or to both. Heparin coating has been used to improve hemocompatibility, and another approach is 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer coatings. Here, the aim is to evaluate the hemocompatibility of MPC polymer coating by studying the interactions with coagulation and complement systems using human blood in vitro model and pig in vivo model. The stability of the coatings is investigated in vitro and MPC polymer-coated catheters are tested in vivo by insertion into the external jugular vein of pigs to monitor the catheters' antithrombotic properties. There is no significant activation of platelets or of the coagulation and complement systems in the MPC polymer-coated one, which was superior in hemocompatibility to non-coated matrix surfaces. The protective effect of the MPC polymer coat does not decline after incubation in human plasma for up to 2 weeks. With MPC polymer-coated catheters, it is possible to easily draw blood from pig for 4 days in contrast to the case for non-coated catheters, in which substantial clotting is seen.
|
|
| 5. |
- Asif, Sana, M.D, PhD student, et al.
(författare)
-
Validation of an MPC polymer coating to reduce surface-induced cascade system activation in whole blood in in vitroand in vivo models
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- ABSTRACTBackground: Artificial surfaces that come into contact with blood (e.g., when used in various forms of biomedical device) induce an immediate activation of the cascade systems of the blood, the coagulation and complement systems. These reactions may lead to a thrombotic and/or inflammatory response that can eventually cause damage to the biomaterial or the patient, or to both. Multiple strategies to dampen these reactions have been employed, with heparin conjugation to the material surface being the most successfulthus far. Another approach to improving hemocompatibility is to use 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer coatings.Experimental: In the present study, we evaluated the effectiveness of MPC polymer coating and compared it to a commercially available heparin coating in various in vitromodels using fresh human blood with the aim to replace the costly heparin-coated equipment with the more economic MPC. We then investigated the stability of the various coatings in human plasma in vitrofor 2 weeks. Finally, we inserted MPC polymer-coated catheters into the external jugular vein of pigs and monitored the catheters’ antithrombotic properties for 4 days.Results: 1) There was no significant activation of platelets and of the coagulation and complement systems on the MPC polymer-coated or the commercially available heparin surface. 2) Both coats were superior in hemocompatibility to non-coated matrix surfaces. 3) The protective effect of the MPC polymer coat did not decline after incubation in plasma for up to 2 weeks. 4) With MPC polymer-coated catheters, it was possible to easily draw blood from experimental animals for 4 days, in contrast to the case for heparin-flushed commercially available non-coated catheters, in which substantial clotting was seen.
|
|
| 6. |
- Berglund, Pontus, et al.
(författare)
-
Cyclin E confers a prognostic value in premenopausal breast cancer patients with tumours exhibiting an infiltrative growth pattern
- 2008
-
Ingår i: Journal of Clinical Pathology. - : BMJ. - 0021-9746 .- 1472-4146. ; 61:2, s. 184-191
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate the prognostic value of cyclin E in relation to tumour growth pattern by analysing stage II primary breast cancers from premenopausal women not subjected to any further adjuvant treatment. To analyse the value of cyclin E as a predictor of tamoxifen response, by comparing untreated and treated patients with oestrogen receptor positive tumours. Methods: Breast cancer samples, assembled in tissue microarrays, were immunohistochemically stained for cyclin E and evaluated regarding the presence of nuclear staining. The overall growth characteristics of each tumour were assessed using whole tissue sections. Results: Tumours displaying a pushing margin phenotype were strongly associated with high cyclin E levels, lymph node negative disease, a high histological grade and oestrogen receptor negativity, and exhibited a better prognosis compared to tumours with an infiltrative growth pattern. In the total cohort of non-treated patients (n = 187), cyclin E was not associated with recurrence free survival (RFS). However, when analysing the subgroup of tumours lacking a pushing growth pattern (n = 141), cyclin E was significantly associated with RFS, independent of histological grade and node status. There was no significant difference in tamoxifen response with regard to different cyclin E levels. Conclusion: The prognostic value of cyclin E in premenopausal breast cancer is limited to patients with breast carcinomas exhibiting an exclusively infiltrative growth pattern. This limitation could be explained by the presence of a small but distinct subgroup of cyclin E-high breast cancers with a pushing margin phenotype and a more favourable outcome.
|
|
| 7. |
- Borg, Åke, et al.
(författare)
-
ERBB2 amplification is associated with tamoxifen resistance in steroid-receptor positive breast cancer
- 1994
-
Ingår i: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 81:2, s. 137-144
-
Tidskriftsartikel (refereegranskat)abstract
- Amplification and overexpression of the ERBB2 (HER-2/neu) oncogene has been implicated as contributing to the development of human breast cancer, and as a predictor of poor survival. In the present non-randomized study of 871 primary invasive breast tumours, ERBB2 activation was significantly correlated to a shorter disease-free and overall survival in the subgroup of patients receiving adjuvant tamoxifen therapy, but not in the untreated group. Further subcategorization demonstrated the relationship to poor prognosis to be confined to lymph node positive and steroid receptor-positive tumours. We suggest that steroid receptor and ERBB2-positive breast tumours are resistant to tamoxifen therapy and, supported by experimental evidence showing an oestrogen receptor dependent up-regulation of ERBB2 expression upon tamoxifen administration, possibly even growth stimulated by the drug.
|
|
| 8. |
- Chen, Changchun, et al.
(författare)
-
Elongator Complex Influences Telomeric Gene Silencing and DNA Damage Response by Its Role in Wobble Uridine tRNA Modification
- 2011
-
Ingår i: PLoS genetics. - : Public Library of Science. - 1553-7404. ; 7:9, s. e1002258-
-
Tidskriftsartikel (refereegranskat)abstract
- Elongator complex is required for formation of the side chains at position 5 of modified nucleosides 5-carbamoylmethyluridine (ncm(5)U(34)), 5-methoxycarbonylmethyluridine (mcm(5)U(34)), and 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U(34)) at wobble position in tRNA. These modified nucleosides are important for efficient decoding during translation. In a recent publication, Elongator complex was implicated to participate in telomeric gene silencing and DNA damage response by interacting with proliferating cell nuclear antigen (PCNA). Here we show that elevated levels of tRNA(Lys) (s(2) ) (UUU), tRNA(Gln) (s(2) ) (UUG), and tRNA(Glu) (s(2) ) (UUC), which in a wild-type background contain the mcm(5)s(2)U nucleoside at position 34, suppress the defects in telomeric gene silencing and DNA damage response observed in the Elongator mutants. We also found that the reported differences in telomeric gene silencing and DNA damage response of various elp3 alleles correlated with the levels of modified nucleosides at U(34). Defects in telomeric gene silencing and DNA damage response are also observed in strains with the tuc2Δ mutation, which abolish the formation of the 2-thio group of the mcm(5)s(2)U nucleoside in tRNA(Lys) (mcm(5) (s(2) ) (UUU) ), tRNA(Gln) (mcm(5) (s(2) ) (UUG) ), and tRNA(Glu) (mcm(5) (s(2) ) (UUC) ). These observations show that Elongator complex does not directly participate in telomeric gene silencing and DNA damage response, but rather that modified nucleosides at U(34) are important for efficient expression of gene products involved in these processes. Consistent with this notion, we found that expression of Sir4, a silent information regulator required for assembly of silent chromatin at telomeres, was decreased in the elp3Δ mutants.
|
|
| 9. |
- Ekholm, M., et al.
(författare)
-
Effects of adjuvant tamoxifen over three decades on breast cancer–free and distant recurrence–free interval among premenopausal women with oestrogen receptor–positive breast cancer randomised in the Swedish SBII:2pre trial
- 2019
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 110, s. 53-61
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: The primary aim was to compare 2 years of adjuvant tamoxifen versus no systemic treatment in premenopausal patients with oestrogen receptor (ER)–positive tumours, regarding breast cancer–free interval (BCFi) and distant recurrence–free interval (D-RFi), with 30 years of follow-up and for specified intervals. Moreover, we aimed to investigate the effects of adjuvant tamoxifen on the incidence of secondary malignancies and survival after distant recurrence. Methods: Premenopausal patients with primary breast cancer were randomised to 2 years of tamoxifen (n = 277) or no systemic treatment (n = 287), irrespective of ER status. Information regarding events was collected by a review of medical records and from national registers. Results: The median follow-up for all patients without events was 28 years, and only four of the patients alive had a follow-up of <20 years. With 30 years of follow-up, tamoxifen prolonged BCFi in the intention-to-treat population (hazard ratio [HR] = 0.76, 95% confidence interval (CI) 0.61–0.94, p = 0.011) compared with no treatment. In patients with ER-positive tumours (n = 362), tamoxifen prolonged BCFi (HR = 0.62, 95% CI 0.47–0.82, p = 0.001) and D-RFi (HR = 0.73, 95% CI 0.54–0.99, p = 0.043). The positive effect on BCFi was significant also for the interval >15–30 years (HR = 0.53, 95% CI 0.28–0.98, p = 0.042). For patients with ER-positive tumours who were diagnosed with distant recurrence (n = 165), survival after distant recurrence was shorter among tamoxifen-treated patients (median, 29 months versus 43 months). The incidence of contralateral breast cancer was 42% lower in the tamoxifen group (HR = 0.58, 95% CI 0.35–0.96, p = 0.035), whereas no differences were observed regarding other secondary malignancies. Conclusions: With three decades of follow-up, 2 years of adjuvant tamoxifen reduced the incidence of breast cancer–related events and distant recurrence, and the carryover effect seems to extend beyond 15 years. Moreover, adjuvant tamoxifen seems to be associated with shorter survival after diagnosis of distant recurrence.
|
|
| 10. |
- Ekholm, Maria, et al.
(författare)
-
Two Years of Adjuvant Tamoxifen Provides a Survival Benefit Compared With No Systemic Treatment in Premenopausal Patients With Primary Breast Cancer: Long-Term Follow-Up (> 25 years) of the Phase III SBII:2pre Trial
- 2016
-
Ingår i: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 34:19, s. 2232-
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose The aim of this study was to evaluate the long-term effect of 2 years of adjuvant tamoxifen compared with no systemic treatment (control) in premenopausal patients with breast cancer over different time periods through long-term (amp;gt; 25 years) follow-up. Patients and Methods Premenopausal patients with primary breast cancer (N = 564) were randomly assigned to 2 years of tamoxifen (n = 276) or no systemic treatment (n = 288). Data regarding date and cause of death were obtained from the Swedish Cause of Death Register. End points were cumulative mortality (CM) and cumulative breast cancer-related mortality (CBCM). The median follow-up for the 250 patients still alive in April 2014 was 26.3 years (range, 22.7 to 29.7 years). Results In patients with estrogen receptor-positive tumors (n = 362), tamoxifen was associated with a marginal reduction in CM (hazard ratio [HR], 0.77; 95% CI, 0.58 to 1.03; P = .075) and a significant reduction in CBCM (HR, 0.73; 95% CI, 0.53 to 0.99; P = .046). The effect seemed to vary over time (CM years 0 to 5: HR, 1.05; 95% CI, 0.64 to 1.73; years amp;gt;5 to 15: HR, 0.58; 95% CI, 0.37 to 0.91; and after 15 years: HR, 0.82; 95% CI, 0.48 to 1.42; CBCM years 0 to 5: HR, 1.09; 95% CI, 0.65 to 1.82; years amp;gt;5 to 15: HR, 0.53; 95% CI, 0.33 to 0.86; and after 15 years: HR, 0.72; 95% CI, 0.36 to 1.44). Conclusion Two years of adjuvant tamoxifen resulted in a long-term survival benefit in premenopausal patients with estrogen receptor-positive primary breast cancer. (C) 2016 by American Society of Clinical Oncology. Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/
|
|
| 11. |
- Engström, Terese, et al.
(författare)
-
Hormone receptor mRNA and protein levels as predictors of premenopausal tamoxifen benefit
- 2024
-
Ingår i: Acta Oncologica. - : Medical Journal Sweden AB. - 0284-186X .- 1651-226X. ; 63, s. 125-136
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Tamoxifen remains an important adjuvant treatment in premenopausal patients with hormone receptor-positive breast cancer. Thus, determination of hormone receptors is important. Here, we compare cytosol-based methods, immunohistochemistry (IHC), and gene expression (GEX) analysis for determining hormone receptor status in premenopausal breast cancer patients from a randomised tamoxifen trial, to evaluate their performance in identifying patients that benefit from tamoxifen. Patients and Methods: Premenopausal patients (n=564) were randomised to 2 years of tamoxifen or no systemic treatment. Estrogen receptor (ER) and progesterone receptor (PR) status by protein expression measured by cytosol-based methods and IHC, and mRNA by GEX analysis were compared in 313 patients with available data from all methods. Kaplan Meier estimates and Cox regression were used to evaluate the treatment-predictive value for recurrence-free interval (RFi) and overall survival (OS). Median follow-up for event-free patients was 26 (RFi) and 33 (OS) years. Results: The mRNA data of ESR1 and PGR distributed bimodally, patterns confirmed in an independent cohort. Kappa-values between all methods were 0.76 and 0.79 for ER and PR, respectively. Tamoxifen improved RFi in patients with ER-positive (ER+) or PR-positive (PR+) tumours (Hazard Ratio [HR] and 95% confidence interval [CI]), cytosol-ER+ 0.53 [0.36–0.79]; IHC-ER+ 0.55 [0.38–0.79]; GEX-ER+ 0.54 [0.37–0.77]; cytosol-PR+ 0.49 [0.34–0.72]; IHC-PR+ 0.58 [0.40–0.85]; GEX-PR+ 0.55 [0.38–0.80]). Results were similar for OS. Interpretation: These methods can all identify patients that benefit from 2 years of tamoxifen with equal performance, indicating that GEX data might be used to guide adjuvant tamoxifen therapy.
|
|
| 12. |
|
|
| 13. |
- Ewers, Sven-Börje, et al.
(författare)
-
Flow cytometry DNA analysis and prediction of loco-regional recurrences after mastectomy in breast cancer
- 1992
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 31:7, s. 733-740
-
Tidskriftsartikel (refereegranskat)abstract
- The study concerns whether DNA flow cytometry and estrogen receptor analysis might help predict which breast cancer patients, particularly node-positive ones, were at the greatest risk of developing loco-regional recurrence (LRR). Such patients would best benefit from postoperative radiotherapy following modified radical mastectomy and axillary lymph node dissection. After this type of surgery, 506 patients were followed up for a median time of nearly 5 years. Among the 235 patients given postoperative radiotherapy, the loco-regional control rate was 100% in N0 cases (n = 93), 94% in cases with 1-3 positive nodes (n = 90), 93% in cases with 4-9 positive nodes (n = 43), and 67% in cases with 10 or more positive nodes (n = 9). Among the 271 non-irradiated patients, the corresponding figures for loco-regional control were 91% in N0 cases (n = 141), 71% in cases with 1-3 positive nodes (n = 84), 65% in cases with 4-9 positive nodes (n = 31), and 67% in cases with 10 or more positive nodes (n = 15). Ploidy status, level of S-phase fraction, estrogen receptor content, and primary tumor size did not, in the present material, yield significant additional information with regard to the risk of LRR in the different nodal subgroups, a finding confirmed in multivariate analysis where the only significant predictor of LRR was the number of positive nodes (p = 0.01). Adjuvant tamoxifen treatment could not replace postoperative radiotherapy for achieving loco-regional tumor control, the overall rate of which was 81% among patients treated with tamoxifen only (n = 117), as compared with 98% among those also treated with radiotherapy (n = 54) (p = 0.003).
|
|
| 14. |
- Fernö, Mårten, et al.
(författare)
-
Recurrence-free survival in breast cancer improved by adjuvant tamoxifen--especially for progesterone receptor positive tumors with a high proliferation
- 1995
-
Ingår i: Breast Cancer Research and Treatment. - 1573-7217. ; 36:1, s. 23-34
-
Tidskriftsartikel (refereegranskat)abstract
- Although the beneficial effect on breast cancer of adjuvant tamoxifen (TAM) is well established, in the series studied by our group this effect seems to have been restricted to patients with steroid receptor (especially progesterone receptor (PgR)) positive tumors. However, as some patients with PgR-positive tumors manifested recurrence despite adjuvant TAM treatment, the question arose whether some other biological factor(s) could be used to identify these non-responding cases. The level of the S-phase fraction (SPF), as measured by flow cytometry, has been shown to be a useful prognostic marker, prognosis being better in cases where the SPF is low than in those where it is high. The aim of the present study was to relate the prognosis after adjuvant TAM to SPF among patients with PgR-positive tumors. In the PgR-positive group as a whole, the effect of TAM on prognosis was more pronounced in the high SPF group than in the low SPF group (p = 0.005) the respective decrease in 3 year recurrence rate was from 19 to 43% and from 17 to 9%. Multivariate analysis of the data for the TAM-treated group showed the level of PgR concentration (low positive vs. high positive), lymph node status, and tumor size to be independent predictive factors, but not the level of SPF (i.e. high vs. low). By contrast, among patients not treated with TAM, the SPF was a strong independent prognostic factor. To sum up, SPF was a strong independent predictor of outcome only for patients receiving no systemic adjuvant therapy, but not in patients receiving adjuvant TAM. Patients with PgR-positive and high S-phase tumors derived more benefit from TAM than patients with PgR-positive and low SPF tumors.
|
|
| 15. |
- Fohlin, Helena, et al.
(författare)
-
Breast cancer hormone receptor levels and benefit from adjuvant tamoxifen in a randomized trial with long-term follow-up
- 2024
-
Ingår i: ACTA ONCOLOGICA. - : Medical Journal Sweden AB. - 0284-186X .- 1651-226X. ; 63, s. 535-541
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Hormone receptor positivity predicts benefit from endocrine therapy but the knowledge about the long-term survival of patients with different tumor receptor levels is limited. In this study, we describe the 25 years outcome of tamoxifen (TAM) treated patients. Patients and methods: Between 1983 and 1992, a total of 4,610 postmenopausal patients with early-stage breast cancer were randomized to receive totally 2 or 5 years of TAM therapy. After 2 years, 4,124 were alive and free of breast cancer recurrence. Among these, 2,481 had demonstrated estrogen receptor positive (ER+) disease. From 1988, the Abbot enzyme immunoassay became available and provided quantitative receptor levels for 1,210 patients, for which our analyses were done. Results: After 5 years of follow-up, when all TAM treatment was finished, until 15 years of follow-up, breast cancer mortality for patients with ER+ disease was significantly reduced in the 5-year group as compared with the 2-year group (hazard ratios [HR] 0.67, 95% confidence intervals [CI] 0.55-0.83, p < 0.001). After 15 years, the difference between the groups remained but did not increase further. A substantial benefit from prolonged TAM therapy was only observed for the subgroup of patients with ER levels below the median (HR = 0.62, 95% CI 0.46-0.84, p = 0.002). Similarly, patients with progesterone receptor negative (PR-) disease did benefit from prolonged TAM treatment. For patients with progesterone receptor positive (PR+) disease, there was no statistically significant benefit from more than 2 years of TAM. Interpretation: As compared with 2 years of adjuvant TAM, 5 years significantly prolonged breast cancer-specific survival. The benefit from prolonged TAM therapy was statistically significant for patients with ER levels below median or PR-negative disease. There was no evident benefit from prolonged TAM for patients with high ER levels or with PR+ tumors.
|
|
| 16. |
- Gottsäter, Anders, et al.
(författare)
-
Cardiovascular autonomic neuropathy associated with carotid atherosclerosis in Type 2 diabetic patients.
- 2003
-
Ingår i: Diabetic Medicine. - : Wiley. - 1464-5491 .- 0742-3071. ; 20:6, s. 495-499
-
Tidskriftsartikel (refereegranskat)abstract
- AimsTo clarify if cardiovascular autonomic neuropathy is associated with carotid artery atherosclerotic plaques in Type 2 diabetic patients. MethodsCardiovascular autonomic nerve function was related to carotid artery ultrasound in 61 Type 2 diabetic patients 5-6 years after diagnosis of diabetes. ResultsCardiovascular autonomic neuropathy [abnormal age corrected expiration/inspiration (E/I) ratio or acceleration index (AI)] was found in 13/61 (21%) patients. Patients with cardiovascular autonomic neuropathy showed increased degree of stenosis in the common carotid artery (24.6 ± 13.2% vs. 14.7 ± 9.2%; P = 0.014) and a tendency towards a higher plaque score (4.0 ± 1.7 vs. 3.2 ± 1.6; P = 0.064). Controlled for age, AI correlated inversely with degree of stenosis (r = -0.39; P = 0.005), plaque score (r = -0.39; P = 0.005), and mean (r = -0.33; P = 0.018) and maximum (r = -0.39; P = 0.004) intima-media thickness in the common carotid artery. In contrast, E/I ratio correlated only slightly with mean intima-media thickness in the common carotid artery (r = -0.28; P = 0.049). ConclusionsCardiovascular autonomic neuropathy was associated with carotid atherosclerosis in Type 2 diabetic patients. Abnormal E/I ratios reflect efferent structural damage to parasympathetic nerves whereas abnormal AI reflects afferent autonomic dysfunction possibly due to impaired baroreceptor sensitivity secondary to carotid atherosclerosis.
|
|
| 17. |
- Huang, Bo, 1965-
(författare)
-
Formation and function of wobble uridine modifications in transfer RNA of Saccharomyces cerevisiae
- 2007
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Transfer RNAs (tRNAs) act as adaptor molecules in decoding messenger RNA into protein. Frequently found in tRNAs are different modified nucleosides, which are derivatives of the four normal nucleosides, adenosine (A), guanosine (G), cytidine (C), and uridine (U). Although modified nucleosides are present at many positions in tRNAs, two positions in the anticodon region, position 34 (wobble position) and position 37, show the largest variety of modified nucleosides. In Saccharomyces cerevisiae, the xm5U type of modified uridines found at position 34 are 5-carbamoylmethyluridine (ncm5U), 5-carbamoylmethyl-2´-O-methyluridine, (ncm5Um), 5-methoxycarbonylmethyluridine (mcm5U), and 5-methoxycarbonyl-methyl-2-thiouridine (mcm5s2U). Based on the complex structure of these nucleosides, it is likely that their formation requires several synthesis steps. The Elongator complex consisting of proteins Elp1p - Elp6p, and the proteins Kti11p - Kti14p, Sit4p, Sap185p, and Sap190p were shown to be involved in 5-carbamoylmethyl (ncm5) and 5-methoxycarbonylmethyl (mcm5) side-chain synthesis at position 34 in eleven tRNA species. The proteins Urm1p, Uba4p, Ncs2p, Ncs6p, and Yor251cp were also identified to be required for the 2-thio (s2) group formation of the modified nucleoside mcm5s2U at wobble position. Modified nucleosides in the anticodon region of tRNA influence the efficiency and fidelity of translation. The identification of mutants lacking ncm5-, mcm5-, or s2-group at the wobble position allowed the investigation of the in vivo role of these nucleosides in the tRNA decoding process. It was revealed that the presence of ncm5-, mcm5- or s2-group promotes reading of G-ending codons. The concurrent presence of the mcm5- and the s2-groups in the wobble nucleoside mcm5s2U improves reading of A- and G-ending codons, whereas absence of both groups is lethal to the yeast cell. The Elongator complex was previously proposed to regulate polarized exocytosis and to participate in elongation of RNA polymerase II transcription. The pleiotropic phenotypes observed in Elongator mutants were therefore suggested to be caused by defects in exocytosis and transcription of many genes. Here it is shown that elevated levels of hypomodified tRNALys [mcm5s2UUU] and tRNAGln[mcm5s2UUG] can efficiently suppress these pleiotropic phenotypes, suggesting that the defects in transcription and exocytosis are indirectly caused by inefficient translation of mRNAs encoding proteins important in these processes.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Jirström, Karin, et al.
(författare)
-
Pathology parameters and adjuvant tamoxifen response in a randomised premenopausal breast cancer trial
- 2005
-
Ingår i: Journal of Clinical Pathology. - : BMJ. - 0021-9746 .- 1472-4146. ; 58:11, s. 1135-1142
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Subgroups of breast cancer that have an impaired response to endocrine treatment, despite hormone receptor positivity, are still poorly defined. Breast cancer can be subdivided according to standard pathological parameters including histological type, grade, and assessment of proliferation. These parameters are the net result of combinations of genetic alterations effecting tumour behaviour and could potentially reflect subtypes that respond differently to endocrine treatment.Aims: To investigate the usefulness of these parameters as predictors of the response to tamoxifen in premenopausal women with breast cancer.Materials/methods: Clinically established pathological parameters were assessed and related to the tamoxifen response in 500 available tumour specimens from 564 premenopausal patients with breast cancer randomised to either two years of tamoxifen or no treatment with 14 years of follow up. Proliferation was further evaluated by immunohistochemical Ki-67 expression.Results: Oestrogen receptor positive ductal carcinomas responded as expected to tamoxifen, whereas the difference in recurrence free survival between control and tamoxifen treated patients was less apparent in the relatively few lobular carcinomas. For histological grade, there was no obvious difference in treatment response between the groups. The relation between proliferation and tamoxifen response seemed to be more complex, with a clear response in tumours with high and low proliferation, whereas tumours with intermediate proliferation defined by Ki-67 responded more poorly.Conclusions: Clinically established pathology parameters seem to mirror the endocrine treatment response and could potentially be valuable in future treatment decisions for patients with breast cancer.
|
|
| 21. |
- Kallstrom, Ann-Christine, et al.
(författare)
-
17 beta-Hydroxysteroid dehydrogenase type 1 as predictor of tamoxifen response in premenopausal breast cancer
- 2010
-
Ingår i: EUROPEAN JOURNAL OF CANCER. - : Elsevier Science B.V., Amsterdam.. - 0959-8049 .- 1879-0852. ; 46:5, s. 892-900
-
Tidskriftsartikel (refereegranskat)abstract
- 17 beta-Hydroxysteroid dehydrogenases (17HSDs) are involved in the local regulation of sex steroids. 17HSD1 converts oestrone (El) to the more potent oestradiol (E2) and 17HSD2 catalyses the reverse reaction. The aim of this study was to investigate the expression of these enzymes in premenopausal breast cancers and to analyse if they have any prognostic or tamoxifen predictive value. Premenopausal patients with invasive breast cancer, stage II (UICC), were randomised to either 2 years of adjuvant tamoxifen (n = 276) or no tamoxifen (n = 288). The median follow-up was 13.9 years (range 10.5-17.5). The expression of 17HSD1 and 17HSD2 was analysed with immunohistochemistry using tissue microarrays. The enzyme expression level (-/+/++/+++) was successfully determined in 396 and 373 tumours, respectively. Women with hormone-receptor positive tumours, with low levels (-/+/++) of 17HSD1, had a 43% reduced risk of recurrence, when treated with tamoxifen (Hazard Ratio (HR) = 0.57; 95% confidence interval (CI), 0.37-0.86; p = 0.0086). On the other hand high expression (+++) of 17HSD1 was associated with no significant difference between the two treatment arms (HR = 0.91; 95% CI, 0.43-1.95; p = 0.82). The interaction between 17HSD1 and tamoxifen was significant during the first 5 years of follow-up (p = 0.023). In the cohort of systemically untreated patients no prognostic importance was observed for 17HSD1. We found no predictive or prognostic value for 17HSD2. This is the first report of 17HSD1 in a cohort of premenopausal women with breast cancer randomised to tamoxifen. Our data suggest that 17HSD1 might be a predictive factor in this group of patients.
|
|
| 22. |
- Korsgren, Olle, et al.
(författare)
-
Optimising islet engraftment is critical for successful clinical islet transplantation
- 2008
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 51:2, s. 227-32
-
Tidskriftsartikel (refereegranskat)abstract
- Clinical islet transplantation is currently being explored as a treatment for persons with type 1 diabetes and hypoglycaemia unawareness. Although 'proof-of-principle' has been established in recent clinical studies, the procedure suffers from low efficacy. At the time of transplantation, the isolated islets are allowed to embolise the liver after injection in the portal vein, a procedure that is unique in the area of transplantation. A novel view on the engraftment of intraportally transplanted islets is presented that could explain the low efficacy of the procedure.
|
|
| 23. |
- Kronblad, Åsa, et al.
(författare)
-
Hypoxia inducible factor-1alpha is a prognostic marker in premenopausal patients with intermediate to highly differentiated breast cancer but not a predictive marker for tamoxifen response.
- 2006
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 118:10, s. 2609-2616
-
Tidskriftsartikel (refereegranskat)abstract
- Hypoxia is common in many solid tumours, including breast cancer. Hypoxia triggers the expression of hypoxia inducible factor-1 alpha (HIF-1 alpha), and HIF-1 alpha has been associated with an impaired prognosis in breast cancer and down-regulation of the oestrogen receptor (ER), potentially affecting the treatment efficiency of antioestrogens. The role of HIF-1 alpha regarding prognostic and treatment predictive information in breast cancer has not been established and we therefore analyzed HIF-1 alpha using immunohistochemistry in a cohort of 377 premenopausal stage II breast cancers arranged in a tissue microarray. The patients were included in a randomized trial with either 2 years of tamoxifen or no adjuvant treatment. The tamoxifen treatment effect could be studied in subgroups of breast cancer and pure prognostic information could be scrutinized for untreated control patients. HIF-1 alpha was scored as positive in 24% of the tumours and correlated positively to tumour size, Nottingham histological grade (NHG), Ki-67, Her2 and cyclin E expression and negatively to lymph node status, cyclin D1, ER and PR (progesterone receptor) expression. Surprisingly, there was no difference in tamoxifen response for patients with high or low HIF-1 alpha expressing tumours. In lymph node-positive patients as well as NHG 1/2 tumours, high HIF-1 alpha protein expression was significantly associated with an impaired recurrence-free survival (p = 0.014, 0.0.18). When analyzing the subgroup of NHG 1/2 tumours, a high HIF-1 alpha expression was the only independent significant prognostic marker in multivariate analysis, including standard prognostic markers, suggesting that HIF-1a might be a useful prognostic marker in this subgroup of breast cancer, with a rather good but diverse prognosis. (c) 2005 Wiley-Liss, Inc.
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
- Lundgren, Christine, et al.
(författare)
-
PAM50 subtyping and ROR score add long-term prognostic information in premenopausal breast cancer patients
- 2022
-
Ingår i: Npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- PAM50 intrinsic subtyping and risk of recurrence (ROR) score are approved for risk profiling in postmenopausal women. We aimed to examine their long-term prognostic value in terms of breast cancer-free interval (BCFi) and overall survival (OS) (n = 437) in premenopausal women randomised to 2 years of tamoxifen versus no systemic treatment irrespective of hormone-receptor status. Intrinsic subtyping added independent prognostic information in patients with oestrogen receptor-positive/human epidermal growth factor 2-negative tumours for BCFi and OS after maximum follow-up (overall P-value 0.02 and 0.006, respectively) and those with high versus low ROR had worse prognosis (maximum follow-up: hazard ratio (HR)(BCFi): 1.70, P 0.04). The prognostic information by ROR was similar regarding OS and in multivariable analysis. These results support that PAM50 subtyping and ROR score provide long-term prognostic information in premenopausal women. Moreover, tamoxifen reduced the incidence of breast cancer events only in patients with Luminal A(PAM50) tumours (0-10 years: HRBCFi(Luminal A): 0.41, HRBCFi(Luminal B): 1.19, P-interaction = 0.02).
|
|
| 27. |
- Lundgren, Christine, et al.
(författare)
-
Tamoxifen-predictive value of gene expression signatures in premenopausal breast cancer : data from the randomized SBII:2 trial
- 2023
-
Ingår i: Breast Cancer Research. - : BMC. - 1465-5411 .- 1465-542X. ; 25:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Gene expression (GEX) signatures in breast cancer provide prognostic information, but little is known about their predictive value for tamoxifen treatment. We examined the tamoxifen-predictive value and prognostic effects of different GEX signatures in premenopausal women with early breast cancer. Methods: RNA from formalin-fixed paraffin-embedded tumor tissue from premenopausal women randomized between two years of tamoxifen treatment and no systemic treatment was extracted and successfully subjected to GEX profiling (n = 437, NanoString Breast Cancer 360™ panel). The median follow-up periods for a recurrence-free interval (RFi) and overall survival (OS) were 28 and 33 years, respectively. Associations between GEX signatures and tamoxifen effect were assessed in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+ /HER2−) tumors using Kaplan–Meier estimates and Cox regression. The prognostic effects of GEX signatures were studied in the entire cohort. False discovery rate adjustments (q-values) were applied to account for multiple hypothesis testing. Results: In patients with ER+/HER2− tumors, FOXA1 expression below the median was associated with an improved effect of tamoxifen after 10 years with regard to RFi (hazard ratio [HR] FOXA1(high) = 1.04, 95% CI = 0.61–1.76, HR FOXA1(low) = 0.30, 95% CI = 0.14–0.67, q interaction = 0.0013), and a resembling trend was observed for AR (HR AR(high) = 1.15, 95% CI = 0.60–2.20, HR AR(low) = 0.42, 95% CI = 0.24–0.75, q interaction = 0.87). Similar patterns were observed for OS. Tamoxifen was in the same subgroup most beneficial for RFi in patients with low ESR1 expression (HRRFi ESR1(high) = 0.76, 95% CI = 0.43–1.35, HRRFi, ESR1(low) = 0.56, 95% CI = 0.29–1.06, q interaction = 0.37). Irrespective of molecular subtype, higher levels of ESR1, Mast cells, and PGR on a continuous scale were correlated with improved 10 years RFi (HR ESR1 = 0.80, 95% CI = 0.69–0.92, q = 0.005; HRMast cells = 0.74, 95% CI = 0.65–0.85, q < 0.0001; and HR PGR = 0.78, 95% CI = 0.68–0.89, q = 0.002). For BC proliferation and Hypoxia, higher scores associated with worse outcomes (HRBCproliferation = 1.54, 95% CI = 1.33–1.79, q < 0.0001; HRHypoxia = 1.38, 95% CI = 1.20–1.58, q < 0.0001). The results were similar for OS. Conclusions: Expression of FOXA1 is a promising predictive biomarker for tamoxifen effect in ER+/HER2− premenopausal breast cancer. In addition, each of the signatures BC proliferation, Hypoxia, Mast cells, and the GEX of AR, ESR1, and PGR had prognostic value, also after adjusting for established prognostic factors. Trial registration This trial was retrospectively registered in the ISRCTN database the 6th of December 2019, trial ID: https://clinicaltrials.gov/ct2/show/ISRCTN12474687 .
|
|
| 28. |
- Lundgren, Christine, et al.
(författare)
-
Tumour-infiltrating lymphocytes as a prognostic and tamoxifen predictive marker in premenopausal breast cancer : data from a randomised trial with long-term follow-up
- 2020
-
Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 22:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Tumour-infiltrating lymphocytes (TILs) are of important prognostic and predictive value in human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) and triple-negative breast cancer (TNBC), but their clinical relevance in oestrogen receptor-positive/HER2-negative (ER+/HER2−) remains unknown. The primary study aim was to analyse the prognostic effect of TILs on the BC-free interval (BCFi) in premenopausal patients stratified by BC subtypes. The secondary aim was to investigate if TILs are predictive of tamoxifen (TAM) benefit. Methods: Archival tissues from primary breast tumours were collected from patients from the SBII:2pre trial, in which 564 premenopausal women were randomised to 2 years of adjuvant TAM or no systemic treatment, regardless of hormone receptor status. TILs were scored on whole tissue sections from 447 patients with available ER status. Tumours were divided into ER+/HER2−, HER2+ and TNBC subtypes by immunohistochemistry and in situ hybridisation. The prognostic value of TILs was analysed in systemically untreated patients (n = 221); the predictive information was investigated in the ER+ subgroup (n = 321) by cumulative incidence curves and Cox regression analyses. The median follow-up was 28 years. Results: High (≥ 50%) infiltration of TILs was a favourable prognostic factor in terms of BCFi (univariable analysis: hazard ratioBCFi (HRBCFi) 0.40; 95% confidence interval (CI) 0.22–0.71; P = 0.002). Similar effects were observed across all BC subtypes. The effect of adjuvant TAM was stronger in patients with ER+ tumours and TILs < 50% (HRBCFi 0.63; 95% CI 0.47–0.84; P = 0.002) than in patients with high immune infiltration (≥ 50%) (HRBCFi 0.84; 95% CI (0.24–2.86); P = 0.77). However, evidence for differential effects of TAM in categories of TILs, i.e. interaction, was weak. Conclusions: We demonstrate a long-term favourable prognostic value of high infiltration of TILs in a cohort of premenopausal BC patients and the positive prognostic effect was extended to the ER+/HER2− subgroup. A beneficial effect of TAM in ER+ patients was observed in patients with tumours of low TIL infiltration, but evidence for a treatment predictive effect was weak. Trial registration: This trial is registered in the ISRCTN database, trial ID: ISRCTN12474687.
|
|
| 29. |
- Mattila, Robert
(författare)
-
Hidden Markov Models: Identification, Inverse Filtering and Applications
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A hidden Markov model (HMM) comprises a state with Markovian dynamics that is hidden in the sense that it can only be observed via a noisy sensor. This thesis considers three themes in relation to HMMs, namely, identification, inverse filtering and applications.In order to employ an HMM, its parameters have first to be identified (or, estimated) from data. Traditional maximum-likelihood estimation procedures may, in practice, suffer from convergence to bad local optima and high computational cost. Recently proposed methods of moments address these shortcomings, but are less accurate. We explore how such methods can be extended to incorporate non-consecutive correlations in data so as to improve their accuracy (while still retaining their attractive properties).Motivated by applications in the design of counter-adversarial autonomous (CAA) systems, we then ask the question: Is it possible to estimate the parameters of an HMM from other data sources than just raw measurements from its sensor? To answer this question, we consider a number of inverse filtering problems. First, we demonstrate how HMM parameters and sensor measurements can be reconstructed from posterior distributions from an HMM filter. Next, we show how to estimate such posterior distributions from actions taken by a rational agent. Finally, we bridge our results to provide a solution to the CAA problem of remotely estimating the accuracy of an adversary’s sensor based on its actions.Throughout the thesis, we motivate our results with applications in various domains. A real-world application that we investigate in particular detail is how the treatment of abdominal aortic aneurysms can be modeled in the Markovian framework. Our findings suggest that the structural properties of the optimal treatment policy are different than those recommended by current clinical guidelines – in particular, that younger patients could benefit from earlier surgery. This indicates an opportunity for improved care of patients with the disease.
|
|
| 30. |
- Nordenskjöld, Anna, 1969, et al.
(författare)
-
Breast cancer survival and incidence of second primary cancers after 30 years in a randomized study of two versus five years of adjuvant tamoxifen therapy
- 2023
-
Ingår i: Breast. - : CHURCHILL LIVINGSTONE. - 0960-9776 .- 1532-3080. ; 71, s. 63-68
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Tamoxifen is an established treatment for breast cancer, but its long-term effects on survival and on secondary cancers are not fully evaluated. Material and methods: We studied 30 years outcome of 4124 postmenopausal patients who were randomized to receive (totally) two or five years of adjuvant tamoxifen.Results: After 5 years of follow-up, when tamoxifen treatment was finished in both groups, until 15 years of follow-up, overall mortality (HR 0.80, 95% CI 0.72-0.90, p < 0.001), breast cancer mortality for all patients (HR 0.80, 95% CI 0.68-0.94, p = 0.006) and breast cancer mortality for patients with estrogen receptor positive disease (HR 0.67, 95% CI 0.55-0.83, p < 0.001) were significantly reduced in the five-year group as compared to the two-year group. After 15 years, the difference remained but did not further increase. In the five-year group, the incidence of contralateral breast cancer was gradually reduced during the entire period of observation. The incidence of lung cancer was also reduced in the five-year group. In contrast there was an increased endometrial cancer incidence in the five-year group and for those receiving 40 mg of tamoxifen this incidence was further increased.Conclusion: Three more years of tamoxifen therapy reduced the risk of breast cancer mortality. The difference was established during the first 15 years after randomization. Moreover, the incidence of contralateral breast cancer gradually decreased for 30 years. The incidence of lung cancer was reduced in the five-year group. In contrast the incidence of endometrial cancer was increased.
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
- Ortenlöf, Niklas, et al.
(författare)
-
Characterization of choroid plexus in the preterm rabbit pup following subcutaneous administration of recombinant human IGF-1/IGFBP-3
- 2023
-
Ingår i: Fluids and Barriers of the CNS. - 2045-8118. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates essential processes of vascular maturation and stabilization. Importantly, preterm birth is associated with reduced serum levels of IGF-1 as compared to in utero levels. Using a preterm rabbit pup model, we investigated the uptake of systemic recombinant human (rh) IGF-1 in complex with its main binding protein IGF-binding protein 3 (BP-3) to the brain parenchyma via the choroid plexus. Five hours after subcutaneous administration, labeled rhIGF-1/rhIGFBP-3 displayed a widespread presence in the choroid plexus of the lateral and third ventricle, however, to a less degree in the fourth, as well as in the perivascular and subarachnoid space. We found a time-dependent uptake of IGF-1 in cerebrospinal fluid, decreasing with postnatal age, and a translocation of IGF-1 through the choroid plexus. The impact of systemic rhIGF-1/rhIGFBP-3 on IGF-1 receptor activation in the choroid plexus decreased with postnatal age, correlating with IGF-1 uptake in cerebrospinal fluid. In addition, choroid plexus gene expression was observed to increase with postnatal age. Moreover, using choroid plexus in vitro cell cultures, gene expression and protein synthesis were further investigated upon rhIGF-1/rhIGFBP-3 stimulation as compared to rhIGF-1 alone, and found not to be differently altered. Here, we characterize the uptake of systemic rhIGF-1/rhIGFBP-3 to the preterm brain, and show that the interaction between systemic rhIGF-1/rhIGFBP-3 and choroid plexus varies over time.
|
|
| 35. |
- Rafael, Ehab, et al.
(författare)
-
Intramuscular autotransplantation of pancreatic islets in a 7-year-old child : a 2-year follow-up
- 2008
-
Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 8:2, s. 458-62
-
Tidskriftsartikel (refereegranskat)abstract
- A 7-year-old girl with severe hereditary pancreatitis underwent total pancreatectomy. A total of 160,000 islet equivalents (6400 islet/kg) were transplanted to the brachioradialis muscle of the right forearm. Her plasma C-peptide level was undetectable after pancreatectomy but increased to 1.37 ng/mL after 17 days; at this time point, her insulin requirement was 0.75 units of insulin/kg/day. At 5- and 27-months, her hemoglobin A1c (HbA1c) and insulin requirements were 4.5 and 5.3% and 0.3 and 0.18 units/kg/day, respectively. Basal and stimulated C-peptide levels were 0.67 +/- 0.07 and 3.36 +/- 1.37 ng/mL, respectively. Stimulated insulin levels were 30% higher in the islet-bearing arm compared to the contralateral arm after glucagon stimulation. After surgery and islet transplantation, the quality of life improved dramatically and she gained 8 kg of weight. In summary, a normal HbA1c, a low insulin requirement and the absence of recurrent hypoglycemia and the gradient of insulin between the arms indicate that the intramuscularly transplanted islets contribute to a long-term clinically significant metabolic control.
|
|
| 36. |
- Rydén, Bo, 1957, et al.
(författare)
-
Fjärrvärmens Affärsmodeller: Slutrapport för Fjärrsynprojekt
- 2013
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Fjärrvärmen är en integrerad del av det framtida hållbara energisystemet, med ambitionen att i än högre grad bidra till de samhälleliga målen om låga utsläpp från uppvärmning, minskad användning av primärenergi och synergier med andra sektorer, exempelvis energiåtervinning från avfall, industrier och avloppsrening. Som produkt och bransch har fjärrvärmen gjort en betydande resa sedan starten för mer än 50 år sedan och den har genomgått en omfattande utveckling, framför allt inom teknikområdet. Nya utmaningar och förändrade omvärldsförhållanden ställer dock nya och ökade krav på fjärrvärmeaffären och fjärrvärmeföretagens affärsmodeller. Fjärrvärmens Affärsmodeller är ett tvärvetenskapligt forskningsprojekt som genomförts inom ramen för forskningsprogrammet Fjärrsyn. Projektet har pågått under 2010-2013. Målsättningen har varit att generera ny kunskap och bättre verktyg för att konkurrenskraftiga affärsmodeller skall kunna utvecklas. Syftet är att stärka fjärrvärmen, att uppmuntra affärsutveckling och att skapa resurseffektiva lösningar för framtidens hållbara energisystem, till nytta för fjärrvärmebranschen, kunderna, miljön och samhället i stort. Inom ramen för olika delstudier har vi bland annat undersökt hur fjärrvärmeföretag skapar och levererar värde, möter sina kunder, använder sina nyckelresurser, hur intäkter uppstår och hur väl organisationen utnyttjas. Vi har även analyserat de utmaningar företagen står inför, fjärrvärmeaffärens möjligheter att tackla dagens komplexa problem, liksom dess förutsättningar för att utvecklas och generera långsiktigt uthålligt värde. Denna slutrapport redovisar projektets forskningsresultat och slutsatser, samt beskriver det breda tvärvetenskapliga arbetssättet och den aktiva och omfattande kommunikation som tillämpas mellan forskningsprojektet och dess intressenter. I tre lättlästa temaböcker har projektet också redovisat resultat och metoder om hur dagens prismodeller kan utvecklas, hur kunddialogen och kundens förtroende kan stärkas och hur fjärrvärmeaffären som helhet kan utvecklas.
|
|
| 37. |
|
|
| 38. |
- Rydén, Bo, et al.
(författare)
-
Lokala värmemarknader
- 2017
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Huvudsyftet med denna temabok är att beskriva och problematisera kring värmemarknaderna ur ett lokalt och regionalt perspektiv. Vi ger även underlag till att – i senare etapp av projektet – kunna analysera dessa lokala och regionala värmemarknaders hållbara utveckling under de kommande decennierna. I denna temabok gör vi dock inte någon sådan analys eller några scenarier för hur enskilda lokala eller regionala värmemarknader kan utvecklas.
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
- Rydén, Lisa, et al.
(författare)
-
HER2 status in hormone receptor positive premenopausal primary breast cancer adds prognostic, but not tamoxifen treatment predictive, information
- 2008
-
Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 109:2, s. 351-357
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundOverexpression of human epidermal growth factor receptor 2 (HER2) or amplification of its gene is a prognostic factor in primary breast cancer and a predictor for tamoxifen treatment efficacy in oestrogen receptor (ER) positive disease. In the present study we explored a defined cohort of breast cancer patients included in a randomised trial in order to assess prognostic and tamoxifen treatment information yielded by HER2 status.MethodsPremenopausal breast cancer patients with stage II tumours (n = 564) were included and allocated to 2 years of adjuvant tamoxifen treatment versus no adjuvant treatment. ER, progesterone receptor (PR) status and HER2 status was determined by immunohistochemistry using a tissue microarray. HER2 amplification was analysed by fluorescent in situ hybridisation and tumours being amplified and/or HER2 3+ were considered HER2+. HER2 status was evaluable in 83% of the patients and 12.6% were HER2+. In untreated patients, HER2 was a negative prognostic factor in ER+ patients, HR 2.95; 95% CI: 1.61–5.38, p < 0.001, but not in ER- patients, HR 0.67; 95% CI: 0.28–1.61, p = 0.4, and a significant interaction between the two markers was found, p < 0.01. HER2 status was not related to tamoxifen treatment efficacy in ER+ patients (term of interaction p = 0.95). When stratifying for PR status, similar results were achieved.DiscussionHER2+ and ER+ breast cancer constituted a subgroup of tumours with poor prognosis in premenopausal breast cancer, whereas no treatment interaction was found between HER2 status and tamoxifen in ER+ tumours. The poor prognosis in HER2+ and ER+ patients may interfere with the interpretation of HER2 data in non-randomised trials of adjuvant tamoxifen.
|
|
| 42. |
- Rydén, Lisa, et al.
(författare)
-
Tumor-specific expression of vascular endothelial growth factor receptor 2 but not vascular endothelial growth factor or human epidermal growth factor receptor 2 is associated with impaired response to adjuvant tamoxifen in premenopausal breast cancer
- 2005
-
Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 23:21, s. 4695-4704
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) are often coexpressed in breast cancer, and potentially affect cellular pathways and key proteins such as the estrogen receptor (ER) targeted by endocrine treatment. We therefore explored the association between adjuvant tamoxifen treatment in breast cancer and expression of VEGF-A and VEGFR2, as well as human epidermal growth factor receptor 2 (HER2), which represents a candidate gene product involved in tamoxifen resistance.Patients and Methods Immunohistochemical expression of tumor-specific VEGF-A, VEGFR2, and HER2 was evaluated in tumor specimens from premenopausal breast cancer patients randomly assigned to 2 years of tamoxifen or no treatment (n = 564), with 14 years of follow-up. Hormone receptor status was determined in 96% of the tumors.Results VEGF-A, VEGFR2, and HER2 were assessable in 460, 472, and 428 of the tumors, respectively. In patients with ER–positive and VEGFR2-low tumors, adjuvant tamoxifen significantly increased recurrence-free survival (RFS; [HR] hazard ratio for RFS, 0.53; P = .001). In contrast, tamoxifen treatment had no effect in patients with VEGFR2-high tumors (HR for RFS, 2.44; P = .2). When multivariate interaction analyses were used, this difference in treatment efficacy relative to VEGFR2 expression status was statistically significant for both ER-positive (P = .04) plus ER-positive and progesterone receptor–positive tumors. We found no significant difference in tamoxifen treatment effects in relation to VEGF-A or HER2 status.Conclusion Tumor-specific expression of VEGFR2 was associated with an impaired tamoxifen effect in hormone receptor–positive premenopausal breast cancer. Tamoxifen in combination with VEGFR2 inhibitors might be a novel treatment approach for VEGFR2-expressing breast cancer, and such a treatment might restore the tamoxifen response.
|
|
| 43. |
- Rydén, Lisa, et al.
(författare)
-
Two years of adjuvant tamoxifen in premenopausal patients with breast cancer : a randomised, controlled trial with long-term follow-up
- 2005
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 41:2, s. 256-264
-
Tidskriftsartikel (refereegranskat)abstract
- Adjuvant tamoxifen treatment increases recurrence-free survival (RFS) and overall survival (OS) in early breast cancer, although in premenopausal patients the number of studies comparing tamoxifen vs no treatment are limited. We report herein the effect on RFS of adjuvant tamoxifen treatment in a multicentre trial of premenopausal patients with stage II breast cancer patients randomised between 1986 and 1991 to 2 years of tamoxifen treatment (n = 276) or no treatment (n = 288). The receptor status of the tumour was known for 541 (96%) of the patients included. Tamoxifen treatment significantly increased RFS in patients with hormone receptor-positive (oestrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+)) tumours (Relative Risk (RR) 0.65; 95% Confidence Interval (CI): 0.48–0.89, P = 0.006), and the beneficial effect of tamoxifen was extended to patients with indicators of poor prognosis, such as young age and nodal-positivity. PR status was a significant predictor of response to tamoxifen in multivariate models with testing of interactions of hormone receptor status and adjuvant therapy.
|
|
| 44. |
- Rydén, Mireille, et al.
(författare)
-
Does Stress Reduction Change the Levels of Cortisol Secretion in Patients With Coronary Artery Disease?
- 2009
-
Ingår i: JOURNAL OF CARDIOPULMONARY REHABILITATION AND PREVENTION. - 1932-7501. ; 29:5, s. 314-317
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: It has been shown that behavioral therapy has effects on Stress behavior in patients with coronary artery disease Salivary cortisol measurements are widely used to assess psychological stress, stress reactivity or both The aim of this study was to investigate whether improved stress behavior in type A patients with coronary artery disease involved changes in cortisol secretion pattern METHODS: Twenty-four male patients were identified as type A individuals and completed a 12-month cognitive-behavioral stress management program Stress behavior was evaluated by using a validated questionnaire Morning and evening salivary cortisol levels were measured over 3 consecutive clays at baseline and after 12 months. RESULTS: Although the patients showed a significant improvement in psychosocial well-being after 12 months, their basal cortisol levels of diurnal rhythm of cortisol did not change There was no Correlation between stress score and cortisol levels CONCLUSIONS. The value of salivary cortisol as both a stress marker and a new cardiovasular risk factor has been discussed but the data from this small Pilot Study raise the question of its utility as a stress marker in cardiac rehabilitation
|
|
| 45. |
- Schaad, Gabriela, 1967, et al.
(författare)
-
Conflicting sustainability goals on the Swedish heating market - Where does the green race take us?
- 2017
-
Ingår i: 8th International Sustainability Transitions Conference, Gothenburg, 18-21 June 2017..
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This study was conducted within the frame of the collaborative cross-industry project “Heating market Sweden”, stage two (2015-2017), in which 30 market participants and governmental organizations took part. Its purpose was to investigate heating market actors’ sustainability goals and their potential consequences. This study shows a multi-faceted set of sustainability ambitions pursued by heating market actors. All actors have distinct sustainability goals relating to energy efficiency, renewable fuels or their climate impact at large. These goals are frequently highly ambitious and similar within each organizational field, but widely divergent in-between these fields. Such uncoordinated ambitions are most pronounced between the district heating sector and the housing sector. There are inherent difficulties and trade-offs resulting from the fact that each sector maximizes its own sustainability outcomes. Actors intend to contribute to increased sustainability, but disregard the overall perspective of costs, the climate and resource efficiency on a higher level.
|
|
| 46. |
- Sköld, Martin, et al.
(författare)
-
Regression analysis and modelling of data acquisition for SELDI-TOF mass spectrometry
- 2007
-
Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811 .- 1460-2059. ; 23:11, s. 1401-1409
-
Tidskriftsartikel (refereegranskat)abstract
- Motivation: Pre-processing of SELDI-TOF mass spectrometry data is currently performed on a largel y ad hoc basis. This makes comparison of results from independent analyses troublesome and does not provide a framework for distinguishing different sources of variation in data. Results: In this article, we consider the task of pooling a large number of single-shot spectra, a task commonly performed automatically by the instrument software. By viewing the underlying statistical problem as one of heteroscedastic linear regression, we provide a framework for introducing robust methods and for dealing with missing data resulting from a limited span of recordable intensity values provided by the instrument. Our framework provides an interpretation of currently used methods as a maximum-likelihood estimator and allows theoretical derivation of its variance. We observe that this variance depends crucially on the total number of ionic species, which can vary considerably between different pooled spectra. This variation in variance can potentially invalidate the results from naive methods of discrimination/classification and we outline appropriate data transformations. Introducing methods from robust statistics did not improve the standard errors of the pooled samples. Imputing missing values however—using the EM algorithm—had a notable effect on the result; for our data, the pooled height of peaks which were frequently truncated increased by up to 30%.
|
|
| 47. |
- Stendahl, Maria, et al.
(författare)
-
High progesterone receptor expression correlates to the effect of adjuvant tamoxifen in premenopausal breast cancer patients
- 2006
-
Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 12:15, s. 4614-4618
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Tamoxifen has long been the drug of choice in adjuvant endocrine therapy of steroid hormone receptor-positive breast cancer, and it still remains important due to its well-documented beneficial effect. Hormone receptor status is often reported as "positive" or "negative" using 10% positive nuclei as a cutoff. In this study, we aimed to assess whether a further subclassification of hormone receptor status could enhance the treatment predictive value. Experimental Design: The immunohistochemical expression of estrogen receptor (ER) and progesterone receptor (PR) was quantified in tissue microarrays with tumors from 500 premenopausal breast cancer patients previously included in a randomized trial of adjuvant tamoxifen compared with an untreated control group. Results: Our findings show a gradually increasing tamoxifen effect in tumors with >10% ER-positive nuclei. However, when analyzing tamoxifen response according to various PR fractions, we found that it was primarily patients with tumors showing >75% PR-positive nuclei that responded to tamoxifen treatment, with an improved recurrence-free [relative risk, 0.42 (0.25-0.70), P = 0.001] as well as overall [relative risk, 0.49 (0.28-0.84), P = 0.010] survival. Conclusions: Adjuvant tamoxifen improved recurrence-free and overall survival for premenopausal patients with tumors showing >75% PR-positive nuclei. No effect could be shown in tumors with fewer PR-positive nuclei. The PR was a stronger predictor of treatment response than the ER. Based on these findings, we suggest the implementation of a fractioned rather than dichotomized immunohistochemical evaluation of hormone receptors in clinical practice, possibly with greater emphasis on the PR than the ER. © 2006 American Association for Cancer Research.
|
|
| 48. |
- Svensson, Bo S, et al.
(författare)
-
Vad korten berättar - Tarot hos Yeats, Meyrink, Kafka, T.S. Eliot och Sigrid Combüchen
- 2010
-
Ingår i: Ferlin och alla de andra. En festskrift till Jenny Westerström 21 januari 2010. - 1102-5522. ; , s. 237-251
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- En ockult våg svepte fram över Europa kring förra sekelskiftet. Poeten W.B. Yeats var, liksom den store auktoriteten på Tarot-kort A.E. Waite, medlemmar av the Golden Dawn, en sluten ockult frimurarorden, som hade grundats i London 1887 och som hade ett både sociokulturellt och litterärt inflytande i speciellt England och USA, men också på kontinenten. Sin inspiration hämtade Golden Dawn från renässansens ockulta naturfilosofer, bl.a. Agrippa, Paracelsus och John Dee. Den mest spridda kortleken, Rider-Waite, består av 78 kort med bilder som har korta och ofta arketypiska namn, som "Dåren", "Eremiten", "Trollkarlen" och "Lyckohjulet". De läggs ut enligt speciella regler och ger då upphov till skilda spådomar eller historier av delfisk karaktär. Det senare har fascinerat många författare. Den keltiske renässansens mästare, William Butler Yeats, använde sig av Tarot litterärt, t.ex. i en historia där han suggererar fram ett tillstånd bortom tid och rum i samband med en keltisk festivalnatt vid slutet av skördesäsongen. Österrikaren Gustav Meyrink bodde en tid i Prag och hans mest bekanta berättelse, Golem, utspelas i det judiska gettot under renässanshumanisten Rabbi Löövs tid. Den bygger på en legend och utförandet tycks vara influerat av Tarot-leken. Golem rymmer mustiga krogscener, teosofiska utläggningar, trånande kärlek och en deckarliknande mordgåta. Allt sammansmält till en feberhet och egenartad berättelse där det råder vilda kast mellan extas och förtvivlan. En amerikansk litteraturforskare har upptäckt att Kafka uppenbarligen har låtit sitt berättande inspireras av Tarot, t.ex. i berättelserna Slottet och Amerika. I T.S. Eliots berömda dikt The Waste Land, från 1922, förekommer en sierska, kallad Madame Sosostris. Hon lägger kort åt den anonyme sökaren i dikten, men hindrad av en svår förkylning säger hon mer om vad hon inte kan se i korten än vad som faktiskt kan ses. Dessutom förser poeten henne i hemlighet med några kort som han själv har hittat på och lägger till egna luriga kommentarer i diktens avslutande fotnoter. Åtminstone en sak har Eliots huvudperson gemensamt med huvudpersonen Perle i Sigrid Combüchens berättelse Parsifal (1998) - de är båda gralsökare i en depressiv efterkrigsvärld. I Eliots fall efter första världskriget, då en generation unga män, hans generation, hade förlorat livet i skyttegravarna. I Combüchens Parsifal, en dystopi som utspelar sig i ett ödelagt Europa under 2050-talet, finns det både spår av en rad småkrig och radioaktivitet efter ett utkämpat kärnvapenkrig. I Combüchens Parsifal lägger den lögnaktiga astrologen Livia ett keltiskt kors för en dagligen återkommande kund, "Georg" - lika anonym som Eliots sökare. Situationen är gåtfull - är det den åldrande och cancersjuke generalen Piscator som är denne Georg? Och är denne Piscator egentligen en historisk dubbelgångare till Parsifalmytens Fiskarkung? Författaren lägger ut spår. Hon är också ganska fräck. Hur då? I berättelsen beskrivs i detalj själva utlägget, ett keltiskt kors, men vad vi samtidigt får veta är att vad sierskan Livia berättar för Georg är en stor fet lögn. Men lagt kort ligger - genom att använda spelets regler med hjälp av Rider-Waite får läsaren själv möjlighet att tolka detta keltiska kors. Och blir på köpet själv en gralsökare.
|
|
| 49. |
- Svensson, Johanna, et al.
(författare)
-
A novel planar image-based method for bone marrow dosimetry in (177)Lu-DOTATATE treatment correlates with haematological toxicity.
- 2016
-
Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- (177)Lu-DOTATATE is a valuable treatment option for patients with advanced neuroendocrine tumours overexpressing somatostatin receptors. Though well tolerated in general, bone marrow toxicity can, besides renal exposure, become dose limiting and affect the ability to sustain future therapies. The aim of this study was to develop a novel planar image-based method for bone marrow dosimetry and evaluate its correlation with haematological toxicity during (177)Lu-DOTATATE treatment. In this study, 46 patients with advanced neuroendocrine tumours were treated with 7.2GBq (3.5-8.3GBq) of (177)Lu-DOTATATE on two to five occasions. Planar gamma camera images were acquired at 2, 24, 48 and 168h post-injection. Whole-body regions of interest were created in the images, and a threshold-based segmentation algorithm was applied to separate the uptake of (177)Lu-DOTATATE into high and low uptake compartments. The conjugate view method was used to quantify the activity, the accumulated activity was calculated and the absorbed dose to the bone marrow was estimated according to the MIRD scheme. Patients were monitored for haematological toxicity based on haemoglobin (Hb), white blood cell (WBC) and platelet (PLT) counts every other week during the treatment period.The mean absorbed dose to the bone marrow was estimated to 0.20Gy (0.11-0.37Gy) per 7.4GBq of (177)Lu-DOTATATE, and the mean dose per fraction correlated with a decrease in Hb (p=0.01), WBC (p<0.01) and PLT (p<0.01) counts. The total mean absorbed dose to the bone marrow was 0.64Gy (0.30-1.5Gy) per 24GBq (8.2-37GBq) of (177)Lu-DOTATATE and also correlated with a decrease in Hb (p<0.01), WBC (p=0.01) and PLT (p<0.01) counts.The planar image-based method developed in this study resulted in similar absorbed doses to the bone marrow as reported in earlier studies with blood-based bone marrow dosimetry. The results correlated with haematological toxicity, making it a promising method for estimating bone marrow doses in (177)Lu-DOTATATE treatment without the need for blood and urine sampling.
|
|
| 50. |
- Tevell, Staffan, 1975-, et al.
(författare)
-
Handläggning av infektioner vid ortopediska implantat en utmaning för vården : [Treatment of orthopedic implant-associated infections]
- 2019
-
Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 116:43
-
Forskningsöversikt (refereegranskat)abstract
- The Swedish National Guidelines for Bone and Joint Infections were revised during 2018. The work was carried out on behalf of the Swedish Society for Infectious Diseases. The study group consists of senior consultants in infectious diseases, supported by specialists in orthopedic surgery, clinical microbiology and allergology when needed. The study group emphasizes that implant associated infections are challenging and requires multidisciplinary cooperation, including, but not limited to, specialists in orthopedic surgery, infectious diseases, clinical microbiology and radiology for optimal treatment results. All aspects of the clinical management are equally important; selecting the optimal antibiotic prophylaxis in arthroplasty as well as fracture surgery, early diagnosis of infection, adequate treatment, follow-up, and finally a structured evaluation of outcome. Profound and updated knowledge of treatment of biofilm related infection is necessary to achieve optimal results in patients with implant-associated infections. Future challenges include improved decision support for combining surgical treatment with selection of proper antibiotics, as well as management of antibiotic resistance, drug-drug interactions and adverse effects of antibiotic treatment.
|
|
