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- Godtman, Rebecka Arnsrud, 1981, et al.
(författare)
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Men's Acceptance of Screening for Prostate Cancer with Prostate-specific Antigen, Magnetic Resonance Imaging, and Prostate Biopsy
- 2024
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Ingår i: EUROPEAN UROLOGY ONCOLOGY. - 2588-9311. ; 7:3, s. 553-562
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Tidskriftsartikel (refereegranskat)abstract
- Background: A prerequisite before introducing a screening program is that the screening examinations are acceptable to participants. Objective: To evaluate the acceptance and bother of prostate cancer screening examinations. Design, setting, and participants: The randomized population -based G & Ouml;TEBORG-2 prostate cancer screening trial invited >37 000 men for prostate -specific antigen (PSA) testing followed by magnetic resonance imaging (MRI) in case of elevated PSA and prostate biopsy (targeted and/or systematic) if indicated. Outcome measurements and statistical analysis: Participants were asked to fill out a questionnaire and rate the level of bother associated with each examination (PSA, MRI, and prostate biopsy) on a categorical scale ranging from 1 to 5 (1 = "not at all bothersome" and 5 = "very bothersome"), and to rate their willingness to repeat the examinations, by marking an X on a continuous scale ranging from 0 to 10 (0 = "yes, without any hesitation" and 10 = "no, absolutely not''). Wilcoxon signed rank test was used. Results and limitations: Compliance with MRI was 96% (1790/1872), compliance with biopsy was 89% (810/907), and the response rate to the questionnaire was 75% (608/810). Men who underwent all examinations ( n = 577) responded that biopsy was more bothersome than PSA test ( p < 0.001) and MRI ( p < 0.001). High levels of bother (>= 4 out of 5) were reported by 2% (12/577) for PSA test, 8% (46/577) for MRI, and 43% (247/577) for biopsy. Men were more willing to repeat MRI than biopsy ( p < 0.001), but the difference was small (median 0.2 [interquartile range 0.1-0.6] vs 0.5 [0.1-2.0]). Conclusions: Biopsies are more bothersome than MRI, but a large majority of men accept to repeat both examinations if necessary. Omitting biopsy for MRI-negative men and shifting to targeted biopsies only will reduce bother for men participating in prostate cancer screening. Patient summary: We asked men how bothersome they found the prostate -specific antigen (PSA) test, magnetic resonance imaging (MRI), and prostate biopsies. Biopsies were more bothersome than PSA and MRI, but most men were willing to repeat all procedures if necessary. (c) 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 3. |
- Östlund, Pernilla, et al.
(författare)
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Altered insulin receptor processing and function in scrapie-infected neuroblastoma cell lines
- 2001
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Ingår i: Brain Research. Molecular Brain Research. - : Elsevier. - 0169-328X .- 1872-6941. ; 97:2, s. 161-170
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Tidskriftsartikel (refereegranskat)abstract
- The underlying neurochemical changes contributing to prion-induced neurodegeneration remain largely unknown. This study showsthat scrapie infection induced a 2-fold increase of insulin receptor (IR) protein and aberrantly processed IR b-chain in scrapie-infectedN2a neuroblastoma cells (ScN2a) as measured byWestern blot of immunoprecipitated IR, in the absence of increased IR mRNA. ElevatedIR protein level was further confirmed in an independently scrapie-infected neuroblastoma cell line N1E-115 (ScN1E-115). Proliferationstudies showed that the increased IR level in ScN2a did not result in an increased insulin-mediated cell growth compared to normal N2a125 cells. Binding studies indicated that this apparent paradox was due to a 65% decrease in specific [ I]insulin binding sites in ScN2a whencompared to the amount of immunoreactive IR, although the IR binding affinity was unchanged. Analysis of insulin stimulated IR tyrosinephosphorylation showed a slight but not significant reduction in ScN2a, when related to the increased level of immunoreactive IR.However, comparing the IR tyrosine phosphorylation to the loss of binding sites in ScN2a, we demonstrated an increased IR tyrosinephosphorylation of the remaining functional IR. In addition to these differences in IR properties, the basal extracellular signal regulatedkinase-2 (ERK2) phosphorylation detected by Western blot, was significantly elevated and the insulin stimulated ERK2 phosphorylationwas subsequently decreased in ScN2a. Together, these data show that scrapie infection affects the level and processing of the IR andsignal transduction mediated by the IR in neuroblastoma cells, as well as induces an elevated basal ERK2 phosphorylation. Aberrantregulation of neuroprotective receptors may contribute to neurodegeneration in prion diseases.
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| 4. |
- Östlund, Pernilla, et al.
(författare)
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Up-regulation of functionally impaired insulin-like growth factor-1 receptor in scrapie-infected neuroblastoma cells
- 2001
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 276:39, s. 36110-36115
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Tidskriftsartikel (refereegranskat)abstract
- A growing body of evidence suggests that an altered level or function of the neurotrophic insulin-like growth factor-1 receptor (IGF-1R), which supports neuronal survival, may underlie neurodegeneration. This study has focused on the expression and function of the IGF-1R in scrapie-infected neuroblastoma cell lines. Our results show that scrapie infection induces a 4-fold increase in the level of IGF-1R in two independently scrapie-infected neuroblastomas, ScN2a and ScN1E-115 cells, and that the increased IGF-1R level was accompanied by increased IGF-1R mRNA levels. In contrast to the elevated IGF-IR expression in ScN2a, receptor binding studies revealed an 80% decrease in specific I-125-IGF-1-binding sites compared with N2a cells. This decrease in IGF-1R-binding sites was shown to be caused by a 7-fold decrease in IGF-1R affinity. Furthermore, ScN2a showed no significant difference in IGF-1 induced proliferative response, despite the noticeable elevated IGF-1R expression, putatively explained by the reduced IGF-1R binding affinity. Additionally, IGF-1 stimulated IGF-1R beta tyrosine phosphorylation showed no major change in the dose-response between the cell types, possibly due to altered tyrosine kinase signaling in scrapie-infected neuroblastoma cells. Altogether these data indicate that scrapie infection affects the expression, binding affinity, and signal transduction mediated by the IGF-1R in neuroblastoma cells. Altered IGF-1R expression and function may weaken the trophic support in scrapie-infected neurons and thereby contribute to neurodegeneration in prion diseases
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