| 191. |
- Lu, Donghao, et al.
(författare)
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Expression and Genetic Variation in Neuroendocrine Signaling Pathways in Lethal and Nonlethal Prostate Cancer among Men Diagnosed with Localized Disease
- 2017
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 26:12, s. 1781-1787
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent data suggest that neuroendocrine signaling pathways may play a role in the progression of prostate cancer, particularly for early-stage disease. We aimed to explore whether expression of selected genes in the adrenergic, serotoninergic, glucocorticoid, and dopaminergic pathways differs in prostate tumor tissue from men with lethal disease compared to men with nonlethal disease.METHODS: Based on the Swedish Watchful Waiting Cohort, we included 511 men diagnosed with incidental prostate cancer through TURP during 1977-1998 with follow-up up to 30 years. For those with tumor tissue (N=262), we measured mRNA expression of 223 selected genes included in neuroendocrine pathways. Using DNA from normal prostate tissue (N=396), we genotyped 36 SNPs from 14 receptor genes. Lethal prostate cancer was the primary outcome in analyses with pathway gene expression and genetic variants.RESULTS: Differential expression of genes in the serotoninergic pathway was associated with risk of lethal prostate cancer (P=0.007); similar but weaker associations were noted for the adrenergic (P=0.014) and glucocorticoid (P=0.020) pathways. Variants of the HTR2A (rs2296972; P=0.002) and NR3CI (rs33388; P=0.035) genes (within the serotoninergic and glucocorticoid pathways) were associated with lethal cancer in over-dominant models. These genetic variants were correlated with expression of several genes in corresponding pathways (P<0.05).CONCLUSIONS: Our findings lend support to hypothesis that the neuroendocrine pathways, particularly serotoninergic pathway, are associated with lethal outcome in the natural course of localized prostate cancer.IMPACT: The current study provides evidence of the role of neuroendocrine pathways in prostate cancer progression which may have clinical utility.
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| 192. |
- Lyth, Johan, et al.
(författare)
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A decision support model for cost-effectiveness of radical prostatectomy in localized prostate cancer
- 2012
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Ingår i: Scandinavian Journal of Urology and Nephrology. - London, United Kingdom : Informa Healthcare. - 0036-5599 .- 1651-2065. ; 46:1, s. 19-25
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to develop a probabilistic decision support model to calculate the lifetime incremental cost-effectiveness ratio (ICER) between radical prostatectomy and watchful waiting for different patient groups.Material and methods: A randomized trial (SPCG-4) provided most data for this study. Data on survival, costs and quality of life were inputs in a decision analysis, and a decision support model was developed. The model can generate cost-effectiveness information on subgroups of patients with different characteristics.Results: Age was the most important independent factor explaining cost-effectiveness. The cost-effectiveness value varied from 21,026 Swedish kronor (SEK) to 858,703 SEK for those aged 65 to 75 years, depending on Gleason scores and prostate-specific antigen (PSA) values. Information from the decision support model can support decision makers in judging whether or not radical prostatectomy (RP) should be used to treat a specific patient group.Conclusions: The cost-effectiveness ratio for RP varies with age, Gleason scores, and PSA values. Assuming a threshold value of 200,000 SEK per quality-adjusted life-year (QALY) gained, for patients aged ≤70 years the treatment was always cost-effective, except at age 70, Gleason 0-4 and PSA ≤10. Using the same threshold value at age 75, Gleason 7-9 (regardless of PSA) and Gleason 5-6 (with PSA >20) were cost-effective. Hence, RP was not perceived to be cost-effective in men aged 75 years with low Gleason and low PSA. Higher threshold values for patients with clinically localized prostate cancer could be discussed
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| 193. |
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| 194. |
- Malkiewicz, Katarzyna, et al.
(författare)
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Human experts' judgment of chemicals reactivity for identification of hazardous chemicals
- 2009
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Ingår i: Toxicology Letters. - : Elsevier BV. - 0378-4274 .- 1879-3169. ; 189, s. S243-S243
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The development of non-testing approaches for the identification of chemicals with the potential to cause environmental hazards, have gained increased attention. In this study the hypothesis that experts’ judgement of chemical reactivity could be used for this purpose has been tested. The judgments of chemical reactivity for 200 organic chemicals, based on their molecular structure were performed by four senior organic and environmental chemists. Potentials for reactivity (namely: oxidative/reductive reactivity, hydrolysis, direct photolysis, reactivity towards radicals) were scored on the 1– scale. Both the experts’ individual judgment, and a compromised judgment after joint discussion for clarification of cases with divergent opinions, was analysed. Furthermore we searched for relations between the expert judgement data and: (a) the chemical characteristics representedby 40 chemical descriptors using partial least squares regression (PLS), and (b) experimental and in silico data for different toxicological and physico-chemical end-points. The results of on-going analyses indicate that for the majority of the chemicals, the individual judgments differed significantly between experts but after discussion among the experts for clarification, the judgments becamemuch more concurrent. The relation between averaged experts’ predicted photolytic degradation potential and chemical characteristic based on a PLS model (with three significant components explaining 76% of the variation) was found. We have also found that in the group of the chemicals with the higher score of the experts judged oxidative reactivity there was higher percentage of biodegradable chemicals when compar
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| 195. |
- Martin, Neil E., et al.
(författare)
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Measuring PI3K Activation : Clinicopathologic, Immunohistochemical, and RNA Expression Analysis in Prostate Cancer
- 2015
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Ingår i: Molecular Cancer Research. - : American Association for Cancer Research. - 1541-7786 .- 1557-3125. ; 13:10, s. 1431-1440
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Tidskriftsartikel (refereegranskat)abstract
- Assessing the extent of PI3K pathway activity in cancer is vital to predicting sensitivity to PI3K-targeting drugs, but the best biomarker of PI3K pathway activity in archival tumor specimens is unclear. Here, PI3K pathway activation was assessed, in clinical tissue from 1,021 men with prostate cancers, using multiple pathway nodes that include PTEN, phosphorylated AKT (pAKT), phosphorylated ribosomal protein S6 (pS6), and stathmin. Based on these markers, a 9-point score of PI3K activation was created using the combined intensity of the 4-markers and analyzed its association with proliferation (Ki67), apoptosis (TUNEL), and androgen receptor (AR) status, as well as pathologic features and cancer-specific outcomes. In addition, the PI3K activation score was compared with mRNA expression profiling data for a large subset of men. Interestingly, those tumors with higher PI3K activation scores also had higher Gleason grade (P = 0.006), increased AR (r = 0.37; P < 0.001) and Ki67 (r = 0.24; P < 0.001), and decreased TUNEL (r = -0.12; P = 0.003). Although the PI3K activation score was not associated with an increased risk of lethal outcome, a significant interaction between lethal outcome, Gleason and high PI3K score (P = 0.03) was observed. Finally, enrichment of PI3K-specific pathways was found in the mRNA expression patterns differentiating the low and high PI3K activation scores; thus, the 4-marker IHC score of PI3K pathway activity correlates with features of PI3K activation.
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| 196. |
- Mazloum, Nafiseh Seyed, et al.
(författare)
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Improving practical sensitivity of energy optimized wake-up receivers : Proof of concept in 65nm CMOS
- 2016
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Ingår i: IEEE Sensors Journal. - 1530-437X. ; PP:99, s. 8158-8166
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Tidskriftsartikel (refereegranskat)abstract
- We present a high performance low-power digital base-band architecture, specially designed for an energy optimized duty-cycled wake-up receiver scheme. Based on a careful wake-up beacon design, a structured wake-up beacon detection technique leads to an architecture that compensates for the implementation loss of a low-power wake-up receiver front-end at low energy and area costs. Design parameters are selected by energy optimization and the architecture is easily scalable to support various network sizes. Fabricated in 65nm CMOS, the digital base-band consumes 0:9μW (VDD = 0:37V) in sub-threshold operation at 250kbps, with appropriate 97% wake-up beacon detection and 0:04% false alarm probabilities. The circuit is fully functional at a minimum VDD of 0:23V at fmax = 5kHz and 0:018μW power consumption. Based on these results we show that our digital base-band can be used as a companion to compensate for front-end implementation losses resulting from the limited wake-up receiver power budget at a negligible cost. This implies an improvement of the practical sensitivity of the wake-up receiver, compared to what is traditionally reported.
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| 197. |
- Melby, V, et al.
(författare)
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Patient comfort in pre-hospital emergency care : A challenge to clinicians.
- 2012
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Ingår i: Journal of Paramedic Practice. - : M A Healthcare Ltd.. - 1759-1376. ; 4:7, s. 389-399
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of this paper is to report on a study that compared ambulance clinicians' views of two different types of patient coverings, focusing on core caring concepts such as comfort, dignity, and safety. Design: Ambulance clinicians' views were gathered in respect of two types of patient coverings, and 128 ambulance patients were randomly distributed into a control or experimental group receiving respectively either the traditional cotton blanket or a multi-layered TelesPro rescue covering. Views were gathered using a short questionnaire developed by the authors. Findings: Ambulance clinicians, in their own view, maintained the core caring concepts no matter which type of covering was used. Findings suggest strongly that the rescue covering provided for a superior patient experience in respect of all core concepts and one functional aspect. Conclusions: Ambulance clinicians undertake caring that encompasses the core caring concepts of comfort, safety, and dignity, while remaining vigilant to threats to these constituents of caring.
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| 198. |
- Meyer, Mara S., et al.
(författare)
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Homogeneous prostate cancer mortality in the Nordic countries over four decades
- 2010
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 58:3, s. 427-32
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Incidence of prostate cancer (PCa) has greatly increased in the Nordic region over the past two decades, following the advent of prostate-specific antigen (PSA) screening. Consequently, interpreting temporal trends in PCa has become difficult, and the impact of changes in exposure to causal factors is uncertain.OBJECTIVE: To reveal geographic differences and temporal trends in PCa in the Nordic countries. Because the recorded incidence of PCa has been profoundly influenced by PSA screening, we focused our analyses primarily on PCa mortality.DESIGN, SETTING, AND PARTICIPANTS: We analyzed national PCa incidence and mortality data from Denmark, Finland, Norway, and Sweden from 1965 to 2006 using the PC-NORDCAN software program and the online NORDCAN database.MEASUREMENTS: Cumulative incidence and cumulative mortality from PCa were calculated for selected calendar years during four decades, along with age-standardized mortality rates. Incidence data in NORDCAN come from individual countries' cancer registries, and mortality data come from national mortality registries.RESULTS AND LIMITATIONS: From 1965 to 2006, 172 613 deaths from PCa were reported in the four Nordic countries. A substantial rise in incidence was observed across the region, with some geographic variation, since the late 1980s. In contrast, both disease-specific mortality rates and cumulative risk of PCa mortality lacked consistent temporal trends over the same period. Cumulative mortality from PCa ranged between 3.5% and 7.5% in the region over four decades, whereas cumulative incidence jumped from about 9% to >20%. Mortality has remained fairly constant among the countries, with a minimally lower risk in Finland.CONCLUSIONS: Unlike most malignancies, the occurrence of lethal PCa showed minimal geographic variation and lacked consistent temporal trends over four decades. These findings may guide our search for important causes of PCa, a malignancy with etiology that is still largely unknown.
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| 199. |
- Moltesen, Maria, et al.
(författare)
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Effects of acute and chronic stress on telencephalic neurochemistry and gene expression in rainbow trout (Oncorhynchus mykiss)
- 2016
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 219:24, s. 3907-3914
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Tidskriftsartikel (refereegranskat)abstract
- By filtering relevant sensory inputs and initiating stress responses, the brain is an essential organ in stress coping and adaptation. However, exposure to chronic or repeated stress can lead to allostatic overload, where neuroendocrinal and behavioral reactions to stress become maladaptive. This work examines forebrain mechanisms involved in allostatic processes in teleost fishes. Plasma cortisol, forebrain serotonergic (5-HTergic) neurochemistry, and mRNA levels of corticotropin-releasing factor (CRF), CRF-binding protein (CRFBP), CRF receptors (CRFR1 and CRFR2), mineralocorticoid receptor (MR), glucocorticoid receptors (GR1 and GR2) and serotonin type 1A (5-HT1A) receptors (5-HT1Aα and 5-HT1Aβ) were investigated at 1 h before and 0, 1 and 4 h after acute stress, in two groups of rainbow trout held in densities of 25 and 140 kg m-3 for 28 days. Generally, being held at 140 kg m-3 resulted in a less pronounced cortisol response. This effect was also reflected in lower forebrain 5-HTergic turnover, but not in mRNA levels in any of the investigated genes. This lends further support to reports that allostatic load causes fish to be incapable of mounting a proper cortisol response to an acute stressor, and suggests that changes in forebrain 5-HT metabolism are involved in allostatic processes in fish. Independent of rearing densities, mRNA levels of 5-HT1Aα and MR were downregulated 4 h post-stress compared with values 1 h post-stress, suggesting that these receptors are under feedback control and take part in the downregulation of the hypothalamic-pituitary-interrenal (HPI) axis after exposure to an acute stressor.
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| 200. |
- Mucci, Lorelei A., et al.
(författare)
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Nine-gene molecular signature is not associated with prostate cancer death in a watchful waiting cohort
- 2008
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Baltimore : Waverly Press. - 1055-9965 .- 1538-7755. ; 17:1, s. 249-251
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Tidskriftsartikel (refereegranskat)abstract
- Tumor molecular markers hold promise to distinguish potentially lethal from indolent prostate cancer and to guide treatment choices. A previous study identified a nine-gene molecular signature in tumors associated with prostate-specific antigen relapse after prostatectomy. We examined this molecular model in relation to prostate cancer death among 172 men with initially localized disease. We quantified protein expression of the nine genes in tumors to classify progression risk. Accounting for clinical prognostic factors, the nine-gene model did not provide discrimination to predict lethal and indolent prostate cancer.
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