| 1. |
- Beilmann-Lehtonen, Ines, et al.
(författare)
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The Relationship between the Tissue Expression of TLR2, TLR4, TLR5, and TLR7 and Systemic Inflammatory Responses in Colorectal Cancer Patients
- 2021
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Ingår i: Oncology. - : S. Karger. - 0030-2414 .- 1423-0232. ; 99:12, s. 790-801
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Tidskriftsartikel (refereegranskat)abstract
- Background: Colorectal cancer (CRC) is the third most commonly diagnosed malignancy globally. CRC patients with elevated plasma C-reactive protein (CRP) levels exhibit compromised prognoses. Toll-like receptors (TLRs), activating the innate and adaptive immune systems, may contribute to pro- and antitumorigenic inflammatory responses. We aimed to identify a possible link between local and systemic inflammatory responses in CRC patients by investigating the association between tissue TLRs and plasma CRP.Methods: Tissue expressions of TLR2, TLR4, TLR5, and TLR7 were assessed using immunohistochemistry of tissue microarray slides from 549 CRC patients surgically treated between 1998 and 2005. Blood samples were drawn preoperatively, centrifuged, aliquoted, and stored at −80°C until analysis. Plasma CRP was determined through high-sensitivity time-resolved immunofluorometric assay. We investigated the association of TLRs to clinicopathologic variables, plasma CRP, and survival.Results: High TLR2 expression (hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.41–0.85; p = 0.005), high TLR5 expression (HR 0.60; 95% CI 0.45–0.83; p = 0.002), positive TLR7 expression (HR 0.49; 95% CI 0.33–0.72; p < 0.001), and low CRP (HR 1.48; 95% CI 1.08–2.11; p = 0.017) were associated with a better prognosis. A high TLR2 immunoexpression was associated with a better prognosis among low-CRP patients (HR 0.53; 95% CI 0.35–0.80; p = 0.002), high TLR4 expression among high-CRP patients (HR 2.04; 95% CI 1.04–4.00; p = 0.038), high TLR5 expression among low-CRP patients (HR 0.059; 95% CI 0.37–0.92; p = 0.021), and positive TLR7 expression among low-CRP patients (HR 0.53; 95% CI 0.28–1.00; p = 0.049). In multivariate analyses, no biomarkers emerged as significant independent variables.Conclusions: High tissue TLR2, TLR5, and TLR7 levels were associated with a better prognosis. Among low-CRP patients, those with high TLR2, TLR5, and TLR7 immunoexpressions exhibited a better prognosis. Among high CRP patients, a high TLR4 immunoexpression was associated with a better prognosis.
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| 2. |
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| 3. |
- Johansson, Daniel, et al.
(författare)
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Shock front curvature measurements of emulsion explosives
- 2019
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Ingår i: Tenth EFEE World Conferenceon Explosives and Blasting. - : European Federation of Explosives Engineers. - 9780955029066 ; , s. 409-416
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Konferensbidrag (refereegranskat)abstract
- This paper will discuss a suggested methodology and data collection carried out within the EU-project SLIM (Sustainable Low Impact solution for exploitation of small Mineral deposits based on advanced rock blasting and environmental technologies). The field work took place during 2017 at a test site near Stockholm, Sweden. This paper suggests a method to measure the detonation front curvature and the velocity of detonation of explosives. The purpose for this is to increase the understanding of the detonation properties of emulsion explosives as used in many blasting operations around the world. In this study, the key parameters of the performance of the emulsion explosive are its non-ideal detonation front curvature and its velocity of detonation (VOD). The charge diameters have been varied Ø25 mm up to Ø65 mm i.e. from nearly critical diameters for a steady detonation up to diameters used in mining/quarrying and tunnelling. The suggested methodology also introduces a heavy and thick-walled mortar as a confiner for the explosive. This to simulate similar conditions as in blasting in rock. Additional to the proposed methodology and set-up, a scheme to analyse and evaluate the measurements is also proposed.
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| 4. |
- Petropoulos, Nikolaos, et al.
(författare)
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A Method to Measure Detonation Front Curvature of Emulsion Explosives
- 2020
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Konferensbidrag (refereegranskat)abstract
- The optimization of the explosive performance is of great importance since blasting is extensively usedin civil projects and mining industry. An improved understanding of how the energy from thedetonation of an explosive is transmitted to the surrounding rock mass is critical information for theproper selection of an explosive. Therefore, an extensive study was done on the influence of theblasthole diameter on the Velocity of Detonation (VoD) and the detonation front curvature. In thisstudy, pure emulsion was tested in confined conditions to better simulate the behavior of the detonationof the explosive in rock mass conditions. A methodology is proposed for carrying out the evaluationof the explosive performance. The blasthole diameter of the samples varied from Ø 25 mm (0.98 in)up to Ø 65 mm (2.55 in). The confiner was a magnetic mortar cylindrical sample with mechanicalproperties similar to a rock mass. A streak camera and VoD probes were used to measure detonationfront curvature and VoD. The data was analyzed and correlated with the physical parameters of theexplosive. Additional to this, the data was further used to calibrate numerical models in LS-Dyna.
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| 5. |
- Schallmeiner, Edith, et al.
(författare)
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Sensitive protein detection via triple-binder proximity ligation assays
- 2007
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Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 4:2, s. 135-137
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Tidskriftsartikel (refereegranskat)abstract
- The detection of weakly expressed proteins and protein complexes in biological samples represents a fundamental challenge. We have developed a new proximity-ligation strategy named 3PLA that uses three recognition events for the highly specific and sensitive detection of as little as a hundred molecules of the vascular endothelial growth factor (VEGF), the biomarkers troponin I, and prostate-specific antigen (PSA) alone or in complex with an inhibitor--demonstrating the versatility of 3PLA.
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| 6. |
- Zhu, Lei, et al.
(författare)
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Proximity ligation measurement of the complex between prostate specific antigen and alpha1-protease inhibitor
- 2009
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 55:9, s. 1665-1671
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate specific antigen (PSA)-alpha1-protease inhibitor complex (PSA-API) is a minor form of PSA in serum. It may be useful for prostate cancer (PCa) diagnosis, but its specific detection is hampered by nonspecific background. To avoid this, we developed an immunoassay for PSA-API based on proximity ligation. METHODS: We used a monoclonal antibody (mAb) to total PSA (tPSA) to capture PSA, while using another anti-tPSA mAb together with an anti-API mAb as probes. We measured PSA-API by quantification of amplified DNA strands conjugated to the probes. We measured serum PSA-API in 84 controls and 55 men with PCa who had PSA concentrations of 4.0-10 microg/L. RESULTS: The detection limit of the assay was 6.6 ng/L. The proportion of PSA-API to tPSA (%PSA-API) tended to be lower in men with PCa (2.8%) than without cancer (3.3%) but was not statistically significant (P = 0.363). When used alone, %PSA-API [area under the curve (AUC) 0.546] did not improve detection of PCa, whereas %fPSA (AUC 0.710) and the sum of %fPSA and %PSA-API (AUC 0.723) did. At 90% diagnostic sensitivity, the diagnostic specificity for cancer was not significantly better for %f PSA + %PSA-API than for %fPSA alone (36% vs 30%). CONCLUSIONS: Proximity ligation eliminated nonspecific background, enabling accurate measurement of PSA-API in serum specimens with moderately increased tPSA. The combined use of %PSA-API and %fPSA provided a modest improvement for PCa detection, but based on the current study cohort, it is uncertain whether the improvement has clinical utility.
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| 7. |
- Assel, Melissa, et al.
(författare)
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A Four-kallikrein Panel and β-Microseminoprotein in Predicting High-grade Prostate Cancer on Biopsy : An Independent Replication from the Finnish Section of the European Randomized Study of Screening for Prostate Cancer
- 2019
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Ingår i: European Urology Focus. - : Elsevier BV. - 2405-4569. ; 5:4, s. 561-567
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Tidskriftsartikel (refereegranskat)abstract
- Background: A panel of four kallikrein markers (total, free, and intact prostate-specific antigen [PSA] and human kallikrein-related peptidase 2 [hK2]) improves predictive accuracy for Gleason score ≥7 (high-grade) prostate cancer among men biopsied for elevated PSA. A four-kallikrein panel model was originally developed and validated by the Dutch center of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The kallikrein panel is now commercially available as 4Kscore™. Objective: To assess whether these findings could be replicated among participants in the Finnish section of ERSPC (FinRSPC) and whether β-microseminoprotein (MSP), a candidate prostate cancer biomarker, adds predictive value. Design, setting, and participants: Among 4861 biopsied screening-positive participants in the first three screening rounds of FinRSPC, a case-control subset was selected that included 1632 biopsy-positive cases matched by age at biopsy to biopsy-negative controls. Outcome measurements and statistical analysis: The predictive accuracy of prespecified prediction models was compared with biopsy outcomes. Results and limitations: Among men with PSA of 4.0-25. ng/ml, 1111 had prostate cancer, 318 of whom had high-grade disease. Total PSA and age predicted high-grade cancer with an area under the curve of 0.648 (95% confidence interval [CI] 0.614-0.681) and the four-kallikrein panel increased discrimination to 0.746 (95% CI 0.717-0.774). Adding MSP to the four-kallikrein panel led to a significant (Wald test; p = 0.015) but small increase (0.003) in discrimination. Limitations include a risk of verification bias among men with PSA of 3.0-3.99. ng/ml and the absence of digital rectal examination results. Conclusions: These findings provide additional evidence that kallikrein markers can be used to inform biopsy decision-making. Further studies are needed to define the role of MSP. Patient summary: Four kallikrein markers and β-microseminoprotein in blood improve discrimination of high-grade prostate cancer at biopsy in men with elevated prostate-specific antigen. Four kallikrein markers and β-microseminoprotein (MSP) in blood improve discrimination of high-grade cancer at biopsy in men with elevated prostate-specific antigen. These kallikrein markers can be used to inform biopsy decision-making. Further studies are needed to define the role of MSP.
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| 8. |
- Birgisson, Helgi, et al.
(författare)
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Serum concentrations of human chorionic gonadotropin beta and its association with survival in patients with colorectal cancer
- 2012
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Ingår i: CANCER BIOMARK. - 1574-0153 .- 1875-8592. ; 11:4, s. 173-181
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Tidskriftsartikel (refereegranskat)abstract
- Increased serum concentrations of the beta subunit of human chorionic gonadotropin (hCG beta) are associated with adverse prognosis in several cancers. The aim of the present study was to analyse the association between serum hCG beta recurrence, and survival, in patients with colorectal cancer. The concentrations of hCG beta were determined in serum collected preoperatively from 324 patients with colorectal cancer, of whom 270 were curatively treated. The serum concentrations of hCG beta were associated with increasing age and they were higher in women than in men. Using the 75th percentile (1.55 pmol/L) as a cut-off for serum hCG beta, overall survival (OS) was shorter in patients with elevated concentrations (HR 1.95; 95% CI 1.39-2.74; P = 0.004), and this association was stronger in women (P = 0.022) than in men (P = 0.061). In multivariate analyses including age, disease stage, tumour differentiation, vascular invasion and CEA, high serum hCG beta concentrations remained an independent prognostic factor for adverse OS in women (HR 2.26; 95% CI 1.39-3.67), but not in men (HR 0.78; 95% CI 0.41-1.51). The same trend was observed for disease free-and cancer specific survival. High serum concentration of hCG beta is an independent prognostic factor for adverse outcome in women with colorectal cancer.
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| 9. |
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| 10. |
- Björk, Thomas, et al.
(författare)
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Comparison of analysis of the different prostate-specific antigen forms in serum for detection of clinically localized prostate cancer
- 1996
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Ingår i: Urology. - 1527-9995. ; 48:6, s. 882-888
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To compare different forms and ratios of serum prostate-specific antigen (PSA) to determine which form or ratio provides optimal diagnostic specificity and sensitivity in distinguishing between benign prostatic hyperplasia (BPH) and clinically localized prostate cancer. METHODS: Serum samples were obtained from 47 patients with BPH and 39 with clinically localized prostate cancer. Patients with BPH underwent either transurethral resection of the prostate or transurethral microwave thermotherapy. Patients with prostate cancer, all of whom had no metastases on radionucleotide bone scans and no pelvic lymph node involvement, underwent either radical external beam radiation therapy or radical retropubic prostatectomy. All patients had pretreatment serum PSA levels between 1 and 20 ng/mL. The different forms of serum PSA (free PSA [PSA-F], PSA complexed to alpha 1-antichymotrypsin [PSA-ACT], and total PSA [PSA-T]) were measured using different monoclonal antibodies against PSA and ACT and immunofluorometric assay techniques. Furthermore, three ratios (PSA-F/PSA-T, PSA-ACT/PSA-T, and PSA-F/PSA-ACT) were calculated. RESULTS: By receiver operating characteristic curve analysis, the performance of the different forms and ratios were compared. The PSA-F/PSA-T ratio had the greatest area under the curve (AUC, 0.776), significantly larger than that for PSA-T (0.612; P = 0.024). For PSA-ACT/PSA-T, the AUC was 0.695 (P = 0.283 versus PSA-T) and 0.773 for PSA-F/PSA-ACT (P = 0.051 versus PSA-T). At a cutoff level < 0.17, PSA-F/PSA-T had a sensitivity of 79%, a specificity of 66%, and a positive predictive value of 66% compared with 74%, 38%, and 50%, respectively, for PSA-T at a cutoff level > 4.0 ng/mL. CONCLUSIONS: The PSA-F/PSA-T ratio gives the best diagnostic performance compared with that for other forms and ratios of PSA and will reduce the number of prostatic biopsies in patients with BPH.
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