| 1. |
- Bratt, Ola, et al.
(författare)
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The Study of Active Monitoring in Sweden (SAMS) : A randomized study comparing two different follow-up schedules for active surveillance of low-risk prostate cancer
- 2013
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 47:5, s. 347-355
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Forskningsöversikt (refereegranskat)abstract
- Objective. Only a minority of patients with low-risk prostate cancer needs treatment, but the methods for optimal selection of patients for treatment are not established. This article describes the Study of Active Monitoring in Sweden (SAMS), which aims to improve those methods. Material and methods. SAMS is a prospective, multicentre study of active surveillance for low-risk prostate cancer. It consists of a randomized part comparing standard rebiopsy and follow-up with an extensive initial rebiopsy coupled with less intensive follow-up and no further scheduled biopsies (SAMS-FU), as well as an observational part (SAMS-ObsQoL). Quality of life is assessed with questionnaires and compared with patients receiving primary curative treatment. SAMS-FU is planned to randomize 500 patients and SAMS-ObsQoL to include at least 500 patients during 5 years. The primary endpoint is conversion to active treatment. The secondary endpoints include symptoms, distant metastases and mortality. All patients will be followed for 10-15 years. Results. Inclusion started in October 2011. In March 2013, 148 patients were included at 13 Swedish urological centres. Conclusions. It is hoped that the results of SAMS will contribute to fewer patients with indolent, low-risk prostate cancer receiving unnecessary treatment and more patients on active surveillance who need treatment receiving it when the disease is still curable. The less intensive investigational follow-up in the SAMS-FU trial would reduce the healthcare resources allocated to this large group of patients if it replaced the present standard schedule.
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| 2. |
- Fowler, Christopher J., et al.
(författare)
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Tumour epithelial expression levels of endocannabinoid markers modulate the value of endoglin-positive vascular density as a prognostic marker in prostate cancer
- 2013
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Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981 .- 1879-2618. ; 1831:10, s. 1579-1587
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Tidskriftsartikel (refereegranskat)abstract
- Fatty acid amide hydrolase (FAAH) is responsible for the hydrolysis of the endogenous cannabinoid (CB) receptor ligand anandamide. Here we have investigated whether the expression levels of FAAH and CB1 receptors influence the prognostic value of markers of angiogenesis in prostate cancer. Data from a cohort of 419 patients who were diagnosed with prostate cancer at transurethral resection for lower urinary tract symptoms, of whom approximately 2/3 had been followed by expectancy, were used. Scores for the angiogenesis markers endoglin and von Willebrand factor (vWf), the endocannabinoid markers fatty acid amide hydrolase (FAAH) and cannabinoid CB1 receptors and the cell proliferation marker Ki-67 were available in the database. For the cases followed by expectancy, the prognostic value of endoglin was dependent upon the tumour epithelial FAAH immunoreactivity (FAAH-IR) and CB1IR scores, and the non-malignant epithelial FAAH-IR scores, but not the non-malignant CB1IR scores or the tumour blood vessel FAAH-IR scores. This dependency upon the tumour epithelial FAAH-IR or CB1IR scores was less apparent for vWf, and was not seen for Ki-67. Using an endoglin cut-off value of 10 positively stained vessels per core and a median split of tumour FAAH-IR, four groups could be generated, with 15 year of disease-specific survival (%) of 68 +/- 7 (low endoglin, low FAAH), 45 +/- 11 (high endoglin, low FAAH), 77 +/- 6 (low endoglin, high FAAH) and 21 +/- 10 (high endoglin, high FAAH). Thus, the cases with high endoglin and high FAAH scores have the poorest rate of disease-specific survival. At diagnosis, the number of cases with tumour stages 1a-1b relative to stages 2-4 was sensitive to the endoglin score in a manner dependent upon the tumour FAAH-IR. It is concluded that the prognostic value of endoglin as a marker of neovascularisation in prostate cancer can be influenced by the expression level of markers of the endocannabinoid system. This article is part of a Special Issue entitled Lipid Metabolism in Cancer.
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| 3. |
- Hammarsten, Peter, et al.
(författare)
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Low levels of phosphorylated epidermal growth factor receptor in nonmalignant and malignant prostate tissue predict favorable outcome in prostate cancer patients.
- 2010
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 16:4, s. 1245-1255
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To explore if the expression of phosphorylated epidermal growth factor receptor (pEGFR) in nonmalignant and malignant prostate tissue is a potential prognostic marker for outcome in prostate cancer patients. EXPERIMENTAL DESIGN: We used formalin-fixed tissues obtained through the transurethral resection of the prostate from 259 patients diagnosed with prostate cancer after the transurethral resection of the prostate, and patients were then followed with watchful waiting. Tissue microarrays of nonmalignant and malignant prostate tissue were stained with an antibody against pEGFR. The staining pattern was scored and related to clinicopathologic parameters and to outcome. RESULTS: Low phosphorylation of EGFR in prostate epithelial cells, both in the tumor and surprisingly also in the surrounding nonmalignant tissue, was associated with significantly longer cancer-specific survival in prostate cancer patients. This association remained significant when Gleason score and local tumor stage were added together with pEGFR to a Cox regression model. Tumor epithelial pEGFR immunoreactivity was significantly correlated to tumor cell proliferation, tumor vascular density, and nonmalignant epithelial pEGFR immunoreactivity. Patients with metastases had significantly higher immunoreactivity for tumor and nonmalignant epithelial pEGFR compared with patients without metastases. CONCLUSIONS: Low pEGFR immunoreactivity is associated with the favorable prognosis in prostate cancer patients and may provide information about which patients with Gleason score 6 and 7 tumors that will survive their disease even without treatment. Changes in the nonmalignant tissue adjacent to prostate tumors give prognostic information.
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| 4. |
- Hammarsten, Peter, et al.
(författare)
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Phospho-Akt Immunoreactivity in Prostate Cancer : Relationship to Disease Severity and Outcome, Ki67 and Phosphorylated EGFR Expression
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10, s. e47994-
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the present study, we have investigated the prognostic usefulness of phosphorylated Akt immunoreactivity (pAkt-IR) in prostate cancer using a well-characterised tissue microarray from men who had undergone transurethral resection due to lower urinary tract symptoms. Methodology/Principal Findings: pAkt-IR in prostate epithelial and tumour cells was assessed using a monoclonal anti-pAkt (Ser(473)) antibody. Immunoreactive intensity was determined for 282 (tumour) and 240 (non-mlignant tissue) cases. Tumour pAkt-IR scores correlated with Gleason score, tumour Ki67-IR (a marker of cell proliferation) and tumour phosphorylated epidermal growth factor receptor (pEGFR)-IR. For cases followed with expectancy, a high tumour pAkt-IR was associated with a poor disease-specific survival, and the prognostic information provided by this biomarker was additive to that provided by either (but not both) tumour pEFGR-IR or Ki67-IR. Upon division of the cases with respect to their Gleason scores, the prognostic value of pAkt-IR was seen for patients with Gleason score 8-10, but not for patients with Gleason score 6-7. Conclusions/Significance: Tumour pAkt-IR is associated with both disease severity and disease-specific survival. However, its clinical use as a biomarker is limited, since it does not provide prognostic information in patients with Gleason scores 6-7.
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| 5. |
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| 6. |
- Hägglöf, Christina, et al.
(författare)
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TMPRSS2-ERG Expression Predicts Prostate Cancer Survival and Associates with Stromal Biomarkers
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- The TMPRSS2-ERG gene fusion is found in approximately half of all prostate cancers. The functional and prognostic significance of TMPRSS2-ERG is, however, not fully understood. Based on a historical watchful waiting cohort, an association between TMPRSS2-ERG, evaluated as positive immune staining, and shorter survival of prostate cancer patients was identified. Expression of ERG was also associated with clinical markers such as advanced tumor stage, high Gleason score, presence of metastasis and prognostic tumor cell markers such as high Ki67, pEGFR and pAkt. Novel associations between TMPRSS2-ERG and alterations in the tumor stroma, for example, increased vascular density, hyaluronan and PDGFR beta and decreased Caveolin-1, all known to be associated with an aggressive disease, were found. The present study suggests that the TMPRSS2-ERG fusion gene is associated with a more aggressive prostate cancer phenotype, supported by changes in the tumor stroma.
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| 7. |
- Jonsson, Linus, 1986, et al.
(författare)
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Self-Determination Theory in Pratice
- 2013
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Ingår i: Book of Abstract. ENYSSP 9th Annual International Workshop. ; 9
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Josefsson, Andreas, et al.
(författare)
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Bias errors due to leakage effects when estimating frequency response functions
- 2012
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Ingår i: Shock and Vibration. - : IOS Press. - 1070-9622 .- 1875-9203. ; 19:6, s. 1257-1266
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Tidskriftsartikel (refereegranskat)abstract
- Frequency response functions are often utilized to characterize a system's dynamic response. For a wide range of engineering applications, it is desirable to determine frequency response functions for a system under stochastic excitation. In practice, the measurement data is contaminated by noise and some form of averaging is needed in order to obtain a consistent estimator. With Welch's method, the discrete Fourier transform is used and the data is segmented into smaller blocks so that averaging can be performed when estimating the spectrum. However, this segmentation introduces leakage effects. As a result, the estimated frequency response function suffers from both systematic (bias) and random errors due to leakage. In this paper the bias error in the H 1 and H2-estimate is studied and a new method is proposed to derive an approximate expression for the relative bias error at the resonance frequency with different window functions. The method is based on using a sum of real exponentials to describe the window's deterministic autocorrelation function. Simple expressions are derived for a rectangular window and a Hanning window. The theoretical expressions are verified with numerical simulations and a very good agreement is found between the results from the proposed bias expressions and the empirical results.
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| 9. |
- Josefsson, Andreas
(författare)
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Identification and Simulation Methods for Nonlinear Mechanical Systems Subjected to Stochastic Excitation
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- With an ongoing desire to improve product performance, in combination with the continuously growing complexity of engineering structures, there is a need for well-tested and reliable engineering tools that can aid the decision making and facilitate an efficient and effective product development. The technical assessment of the dynamic characteristics of mechanical systems often relies on linear analysis techniques which are well developed and generally accepted. However, sometimes the errors due to linearization are too large to be acceptable, making it necessary to take nonlinear effects into account. Many existing analysis techniques for nonlinear mechanical systems build on the assumption that the input excitation of the system is periodic and deterministic. This often results in highly inefficient analysis procedures when nonlinear mechanical systems are studied in a non-deterministic environment where the excitation of the system is stochastic. The aim of this thesis is to develop and validate new efficient analysis methods for the theoretical and experimental study of nonlinear mechanical systems under stochastic excitation, with emphasis on two specific problem areas; forced response simulation and system identification from measurement data. A fundamental concept in the presented methodology is to model the nonlinearities as external forces acting on an underlying linear system, and thereby making it possible to use much of the linear theories for simulation and identification. The developed simulation methods utilize a digital filter to achieve a stable and condensed representation of the linear subparts of the system which is then solved recursively at each time step together with the counteracting nonlinear forces. The result is computationally efficient simulation routines, which are particularly suitable for performance predictions when the input excitation consist of long segments of discrete data representing a realization of the stochastic excitation of the system. Similarly, the presented identification methods take advantage of linear Multiple-Input-Multiple-Output theories for random data by using the measured responses to create artificial inputs which can separate the linear system from the nonlinear parameters. The developed methods have been tested with extensive numerical simulations and with experimental test rigs with promising results. Furthermore, an industrial case study of a wave energy converter, with nonlinear characteristics, has been carried out and an analysis procedure capable of evaluating the performance of the system in non-deterministic ocean waves is presented.
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| 10. |
- Josefsson, Andreas, 1979-, et al.
(författare)
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Low endoglin vascular density and Ki67 index in Gleason score 6 tumours may identify prostate cancer patients suitable for surveillance
- 2012
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa Healthcare. - 0036-5599 .- 1651-2065. ; 46:4, s. 247-257
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to explore whether vascular density and tumour cell proliferation are related to the risk of prostate cancer death in patients managed by watchful waiting. Material and methods. From a consecutive series of men diagnosed with prostate cancer at transurethral resection in 1975-1990, tissue microarrays (TMAs) were constructed. A majority of men had no metastases at diagnosis and were followed by watchful waiting (n = 295). The TMAs were stained for Ki67, endoglin and factor VIII-related antigen (vWf).Results: In univariate Cox analyses, increased Ki67 index, endoglin vascular density and vWf vascular density were associated with shorter cancer-specific survival. Ki67 index and endoglin vascular density added independent prognostic information to clinical stage, estimated tumour size and Gleason score (GS) in multivariate Cox analysis. In GS 6 tumours, high Ki67 index and high endoglin vascular density identified patients with poor outcome. After 15 years of follow-up not a single man out of 34 men with low staining for both markers (35% of all GS 6 tumours) had died of prostate cancer, in contrast to 15 prostate cancer deaths among the remaining 63 men with GS 6 tumours (65% cumulative risk of prostate cancer death). vWf vascular density in benign areas was a prognostic marker in GS 6 and 7 tumours.Conclusions: Men with GS 6 tumours with both low Ki67 index and endoglin vascular density staining scores have a low risk of progression. Additional studies are needed to test whether these two markers can be applied to core biopsies to select patients suitable for surveillance.
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