| 1. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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| 2. |
- Colomé, Núria, et al.
(author)
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Multi-laboratory experiment PME11 for the standardization of phosphoproteome analysis
- 2022
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In: Journal of Proteomics. - : Elsevier. - 1874-3919 .- 1876-7737. ; 251
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Journal article (peer-reviewed)abstract
- Global analysis of protein phosphorylation by mass spectrometry proteomic techniques has emerged in the last decades as a powerful tool in biological and biomedical research. However, there are several factors that make the global study of the phosphoproteome more challenging than measuring non-modified proteins. The low stoichiometry of the phosphorylated species and the need to retrieve residue specific information require particular attention on sample preparation, data acquisition and processing to ensure reproducibility, qualitative and quantitative robustness and ample phosphoproteome coverage in phosphoproteomic workflows. Aiming to investigate the effect of different variables in the performance of proteome wide phosphoprotein analysis protocols, ProteoRed-ISCIII and EuPA launched the Proteomics Multicentric Experiment 11 (PME11). A reference sample consisting of a yeast protein extract spiked in with different amounts of a phosphomix standard (Sigma/Merck) was distributed to 31 laboratories around the globe. Thirty-six datasets from 23 laboratories were analyzed. Our results indicate the suitability of the PME11 reference sample to benchmark and optimize phosphoproteomics strategies, weighing the influence of different factors, as well as to rank intra and inter laboratory performance.
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| 3. |
- Sánchez-de-la-Torre, Manuel, et al.
(author)
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Adherence to CPAP Treatment and the Risk of Recurrent Cardiovascular Events: A Meta-Analysis.
- 2023
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In: JAMA. - 1538-3598. ; 330:13, s. 1255-1265
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Journal article (peer-reviewed)abstract
- The effect of continuous positive airway pressure (CPAP) on secondary cardiovascular disease prevention is highly debated.To assess the effect of CPAP treatment for obstructive sleep apnea (OSA) on the risk of adverse cardiovascular events in randomized clinical trials.PubMed (MEDLINE), EMBASE, Current Controlled Trials: metaRegister of Controlled Trials, ISRCTN Registry, European Union clinical trials database, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov databases were systematically searched through June 22, 2023.For qualitative and individual participant data (IPD) meta-analysis, randomized clinical trials addressing the therapeutic effect of CPAP on cardiovascular outcomes and mortality in adults with cardiovascular disease and OSA were included.Two reviewers independently screened records, evaluated potentially eligible primary studies in full text, extracted data, and cross-checked errors. IPD were requested from authors of the selected studies (SAVE [NCT00738179], ISAACC [NCT01335087], and RICCADSA [NCT00519597]).One-stage and 2-stage IPD meta-analyses were completed to estimate the effect of CPAP treatment on risk of recurrent major adverse cardiac and cerebrovascular events (MACCEs) using mixed-effect Cox regression models. Additionally, an on-treatment analysis with marginal structural Cox models using inverse probability of treatment weighting was fitted to assess the effect of good adherence to CPAP (≥4 hours per day).A total of 4186 individual participants were evaluated (82.1% men; mean [SD] body mass index, 28.9 [4.5]; mean [SD] age, 61.2 [8.7] years; mean [SD] apnea-hypopnea index, 31.2 [17] events per hour; 71% with hypertension; 50.1% receiving CPAP [mean {SD} adherence, 3.1 {2.4} hours per day]; 49.9% not receiving CPAP [usual care], mean [SD] follow-up, 3.25 [1.8] years). The main outcome was defined as the first MACCE, which was similar for the CPAP and no CPAP groups (hazard ratio, 1.01 [95% CI, 0.87-1.17]). However, an on-treatment analysis by marginal structural model revealed a reduced risk of MACCEs associated with good adherence to CPAP (hazard ratio, 0.69 [95% CI, 0.52-0.92]).Adherence to CPAP was associated with a reduced MACCE recurrence risk, suggesting that treatment adherence is a key factor in secondary cardiovascular prevention in patients with OSA.
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| 4. |
- Vialas, Vital, et al.
(author)
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A multicentric study to evaluate the use of relative retention times in targeted proteomics
- 2017
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In: Journal of Proteomics. - : Elsevier BV. - 1874-3919. ; 152, s. 138-149
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Journal article (peer-reviewed)abstract
- Despite the maturity reached by targeted proteomic strategies, reliable and standardized protocols are urgently needed to enhance reproducibility among different laboratories and analytical platforms, facilitating a more widespread use in biomedical research. To achieve this goal, the use of dimensionless relative retention times (iRT), defined on the basis of peptide standard retention times (RT), has lately emerged as a powerful tool. The robustness, reproducibility and utility of this strategy were examined for the first time in a multicentric setting, involving 28 laboratories that included 24 of the Spanish network of proteomics laboratories (ProteoRed-ISCIII). According to the results obtained in this study, dimensionless retention time values (iRTs) demonstrated to be a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups both intra- and inter-laboratories. iRT values also showed very low variability over long time periods. Furthermore, parallel quantitative analyses showed a high reproducibility despite the variety of experimental strategies used, either MRM (multiple reaction monitoring) or pseudoMRM, and the diversity of analytical platforms employed. Biological significance From the very beginning of proteomics as an analytical science there has been a growing interest in developing standardized methods and experimental procedures in order to ensure the highest quality and reproducibility of the results. In this regard, the recent (2012) introduction of the dimensionless retention time concept has been a significant advance. In our multicentric (28 laboratories) study we explore the usefulness of this concept in the context of a targeted proteomics experiment, demonstrating that dimensionless retention time values is a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups.
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| 5. |
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| 6. |
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| 7. |
- Bill-Axelson, Anna, et al.
(author)
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Radical prostatectomy versus watchful waiting in localized prostate cancer : the Scandinavian prostate cancer group-4 randomized trial
- 2008
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In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:16, s. 1144-1154
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Journal article (peer-reviewed)abstract
- BACKGROUND: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up.METHODS: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided.RESULTS: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001).CONCLUSION: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery.
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| 8. |
- Carlsson, Jörgen, et al.
(author)
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EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides
- 2015
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In: Radiology and Oncology. - : Walter de Gruyter GmbH. - 1318-2099 .- 1581-3207. ; 49:1, s. 50-58
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Journal article (peer-reviewed)abstract
- Background. There is limited effect of tyrosine kinase inhibitors or "naked" antibodies binding EGFR or HER2 for therapy of metastasized urinary bladder canter and these methods are therefore not routinely used. Targeting radionuclides to the extracellular domain of the receptors is potentially a better possibility. Methods. EGFR- and HER2-expression was analyzed for primary tumors and corresponding metastases from 72 patients using immunohistochemistry and the internationally recommended HercepTest. Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose. Results. EGFR was positive in 71% of the primary tumors and 69% of corresponding metastases. Local and distant metastases were EGFR-positive in 75% and 66% of the cases, respectively. The expression frequency of HER2 in related lesions was slightly higher (data from previous study). The EGFR-positive tumors expressed EGFR in metastases in 86% of the cases. The co-expression of EGFR and HER2 was 57% for tumors and 53% for metastases. Only 3% and 10% of the lesions were negative for both receptors in tumors and metastases, respectively. Thus, targeting these receptors with radionuclides might be applied for most patients. Conclusions. At least one of the EGFR- or HER2-receptors was present in most cases and co-expressed in more than half the cases. It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy. This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention.
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| 9. |
- Dyrskjøt, Lars, et al.
(author)
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Gene expression signatures predict outcome in non-muscle-invasive bladder carcinoma : a multicenter validation study
- 2007
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:12, s. 3545-3551
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Journal article (peer-reviewed)abstract
- Purpose: Clinically useful molecular markers predicting the clinical course of patients diagnosed with non–muscle-invasive bladder cancer are needed to improve treatment outcome. Here, we validated four previously reported gene expression signatures for molecular diagnosis of disease stage and carcinoma in situ (CIS) and for predicting disease recurrence and progression. Experimental Design: We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain, and France using custom microarrays. Molecular classifications were compared with pathologic diagnosis and clinical outcome. Results: Classification of disease stage using a 52-gene classifier was found to be highly significantly correlated with pathologic stage (P < 0.001). Furthermore, the classifier added information regarding disease progression of Ta or T1 tumors (P < 0.001). The molecular 88-gene progression classifier was highly significantly correlated with progression-free survival (P < 0.001) and cancer-specific survival (P = 0.001). Multivariate Cox regression analysis showed the progression classifier to be an independently significant variable associated with disease progression after adjustment for age, sex, stage, grade, and treatment (hazard ratio, 2.3; P = 0.007). The diagnosis of CIS using a 68-gene classifier showed a highly significant correlation with histopathologic CIS diagnosis (odds ratio, 5.8; P < 0.001) in multivariate logistic regression analysis. Conclusion: This multicenter validation study confirms in an independent series the clinical utility of molecular classifiers to predict the outcome of patients initially diagnosed with non–muscle-invasive bladder cancer. This information may be useful to better guide patient treatment.
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| 10. |
- Gkogkou, A., et al.
(author)
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CONCERTO: Simulating the CO, [CII], and [CI] line emission of galaxies in a 117 deg2 field and the impact of field-to-field variance
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 670
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Journal article (peer-reviewed)abstract
- In the submillimeter regime, spectral line scans and line intensity mapping (LIM) are new promising probes for the cold gas content and star formation rate of galaxies across cosmic time. However, both of these two measurements suffer from field-to-field variance. We study the effect of field-to-field variance on the predicted CO and [CII] power spectra from future LIM experiments such as CONCERTO, as well as on the line luminosity functions (LFs) and the cosmic molecular gas mass density that are currently derived from spectral line scans. We combined a 117 deg2 dark matter lightcone from the Uchuu cosmological simulation with the simulated infrared dusty extragalactic sky (SIDES) approach. The clustering of the dusty galaxies in the SIDES-Uchuu product is validated by reproducing the cosmic infrared background anisotropies measured by Herschel and Planck. We find that in order to constrain the CO LF with an uncertainty below 20%, we need survey sizes of at least 0.1 deg2. Furthermore, accounting for the field-to-field variance using only the Poisson variance can underestimate the total variance by up to 80%. The lower the luminosity is and the larger the survey size is, the higher the level of underestimate. At z < 3, the impact of field-to-field variance on the cosmic molecular gas density can be as high as 40% for the 4.6 arcmin2 field, but drops below 10% for areas larger than 0.2 deg2. However, at z > 3 the variance decreases more slowly with survey size and for example drops below 10% for 1 deg2 fields. Finally, we find that the CO and [CII] LIM power spectra can vary by up to 50% in 1 deg2 fields. This limits the accuracy of the constraints provided by the first 1 deg2 surveys. In addition the level of the shot noise power is always dominated by the sources that are just below the detection thresholds, which limits its potential for deriving number densities of faint [CII] emitters. We provide an analytical formula to estimate the field-to-field variance of current or future LIM experiments given their observed frequency and survey size. The underlying code to derive the field-to-field variance and the full SIDES-Uchuu products (catalogs, cubes, and maps) are publicly available.
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| 11. |
- Gullbo, Joachim, et al.
(author)
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Antitumor efficacy and acute toxicity of the novel dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) in vivo.
- 2004
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In: Investigational new drugs. - 0167-6997. ; 22:4, s. 411-20
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Journal article (peer-reviewed)abstract
- The novel alkylating dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) was evaluated for acute toxicity and antitumor activity in mice, with melphalan as a reference. To determine a safe and tolerable dose for efficacy studies the acute toxicity following intravenous injection in the tail vein was monitored using a 14-day schedule with up to four doses. The highest tested dose, 25 micromoles/kg, was considered close to this level, with minor effects on body weight gain but significant effects on hematological parameters. Melphalan and J1 appeared equitoxic with no statistically significant differences. Subsequently a mouse hollow fiber model was employed with subcutaneous implantation of fibers containing human tumor cells. Three different human tumor cell lines as well as two samples of primary human tumor cells (ovarian carcinoma and chronic lymphatic leukemia) were used as tumor models. At the dose level tested there was a marked and statistically significant decrease in both T-cell leukemia CCRF-CEM and small cell lung cancer NCI-H69 tumor cell growth and viability in response to J1 as compared with both placebo and melphalan treated groups. In primary ovarian carcinoma cells only J1 treatment resulted in significant tumor regression (net cell kill). In summary the results indicate that, despite an expected short half time in the blood circulation, the promising in vitro data from the previous studies of J1 seems translatable into the in vivo situation. At equal doses of alkylating units J1, compared to melphalan, was more active in the mouse hollow-fiber model, but showed similar general toxicity.
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| 12. |
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| 13. |
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| 14. |
- Gårdmark, Truls, et al.
(author)
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Analysis of HER2 expression in primary urinary bladder carcinoma and corresponding metastases
- 2005
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In: BJU International. - 1464-4096 .- 1464-410X. ; 95:7, s. 982-986
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To evaluate the expression of HER2 receptors (previously reported to be over-expressed in malignant urothelium) in both primary tumours and metastases of transitional cell cancer, using two different staining methods and two different scoring techniques, considering the potential use of these receptors as targets for planned systemic anti-HER2 nuclide-based treatment. MATERIALS AND METHODS: HER2 expression was evaluated with two different immunohistochemical methods in 90 patients with primary urinary bladder cancer tumours and corresponding metastases. Sections were first stained with the commercially available breast cancer test kit (HercepTest, Dako, Glostrup, Denmark). Parallel sections were then stained with a modified HercepTest procedure. Two different evaluation criteria were compared; the HercepTest score that requires > or = 10% stained tumour cells (as for breast cancer) and a proposed 'Target score' that requires > 67% stained tumour cells. The latter score is assumed to be preferable for HER2-targeted radionuclide therapy. RESULTS: Using the HercepTest kit, the Target score gave lower fractions of positive primary tumours and metastases than the HercepTest score. The modified HercepTest staining procedure and Target score gave high HER2 values in 80% of primary tumours and 62% of metastases, which is considerably more than that obtained with the HercepTest staining and score. There was a significant decrease in HER2 positivity with increasing distance from the primary tumour. In nine sentinel-node metastases assessed, all but one were HER2-positive. Considering all regional metastases, 74% were positive, and of distant metastases, 47%; 72% of the patients with positive primary tumours also expressed HER2 in their metastases. CONCLUSIONS: When combining the modified HercepTest with customised evaluation criteria, more HER2-positive tumours were diagnosed. The degree of HER2 down-regulation was significantly higher in distant than in regional metastases. HER2-targeted therapy may be an alternative or complementary to other methods in the future treatment of metastatic urinary bladder carcinoma.
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| 15. |
- Hassan, Saadia Bashir, et al.
(author)
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A hollow fiber model for in vitro studies of cytotoxic compounds : Activity of the cyanoguanidine CHS 828
- 2001
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In: Anti-Cancer Drugs. - 0959-4973 .- 1473-5741. ; 12:1, s. 33-42
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Journal article (peer-reviewed)abstract
- The hollow fiber assay is currently used as an in vivo model for anticancer drug screening in nude mice, but it can also be used as an in vitro model. In the current study, an in vitro hollow fiber model was used to study the effect and mode of induced cell death of a new cyanoguanidine, CHS 828. Human leukemia, adenocarcinoma and lymphoma cell lines as well as primary cultures of human tumor cells from patients with chronic lymphocytic leukemia (CLL) and ovarian cancer (OC) and normal human lymphocytes were cultured in semipermeable hollow fibers. The fibers were incubated for 3 or 14 days prior to CHS 828 exposure for 72 h, followed by determination of living cell density by MTT staining. For cell morphology, using harvested cultures on cytospin slides had technical advantages compared to using paraffin sections of the formalin-fixed fibers. CHS 828 showed higher antitumor activity on CLL and normal human lymphocyte cultures compared to OC cultures, and cell lines cultured 3 days were more sensitive than those cultured 14 days. Morphological examination of CHS 828-treated cultures revealed a mixture of apoptosis and necrosis.
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| 16. |
- Hemdan, Tammer, et al.
(author)
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Stathmin-1 is a promising prognostic factor and potential therapeutic target in urinary bladder cancer
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Other publication (other academic/artistic)abstract
- Aim: The oncoprotein 18/stathmin 1 (STMN1), involved in cell cycle progression and cell migration, has been reported to be expressed in several types of cancer, and is associated with clinical outcome in e.g. breast and liver cancer. The aims in this study were to investigate the clinical significance of STMN1 and to examine if STMN1 might be a possible therapeutic target in urinary bladder cancer.Experimental design: Immunohistochemical analyses of STMN1 protein expression were performed in a wide-range tissue microarray (115 Ta-, 115 T1-, 112 T2-4-tumors) and in a metastatic primary tumor/matched metastasis-material (90 patients). In the T24 cell line, the effect of STMN1 on cell proliferation was evaluated by inhibiting the cellular expression of STMN using STMN1-siRNA.Results: Patients with T1- or muscle-invasive disease exhibiting high expression of the STMN1 protein had a poorer overall survival (OS) and disease specific survival (DSS). In a multivariate analysis adjusting for stage, age and gender the results were for T2-T4 patients: OS (HR=1.77 95% CI 1.02-3.07; p=0.04) and DSS (HR=2.04 95% CI 1.13-3.68; p=0.02); for T1-4 patients: DSS (HR=1.83 95% CI 1.09-3.08; p=0.02). In the metastatic bladder cancer material, the majority of the patients with one metastasis (69%) and with several matched metastases (70%) were STMN1-positive in both the primary tumor and the matched metastases. Moreover, the ability of the urinary bladder cancer cell line to grow was significantly reduced after 72 hours (p<0.0001) when transfecting the cells with a siRNA targeting STMN1.Conclusion: Our results suggest that STMN1 protein-expression has a potential both as a prognostic marker and a novel treatment target in urinary bladder cancer.
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| 17. |
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| 18. |
- Kivipelto, Miia, et al.
(author)
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World-Wide FINGERS Network : A global approach to risk reduction and prevention of dementia
- 2020
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In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:7, s. 1078-1094
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Journal article (peer-reviewed)abstract
- Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.
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| 19. |
- Kloos, Jacob L., et al.
(author)
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The First Martian Year of Cloud Activity from Mars Science Laboratory (Sol 0 - 800)
- 2016
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In: Advances in Space Research. - : Elsevier BV. - 0273-1177 .- 1879-1948. ; 57:5, s. 1223-1240
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Journal article (peer-reviewed)abstract
- Using images from the Navigation Cameras onboard the Mars Science Laboratory rover Curiosity, atmospheric movies were created to monitor the cloud activity over Gale Crater. Over the course of the first 800 sols of the mission, 133 Zenith Movies and 152 Supra-Horizon Movies were acquired which use a mean frame subtraction technique to observe tenuous cloud movement. Moores et al. (2015a) reported on the first 360 sols of observations, representing LS = 150° to 5°, and found that movies up to LS = 184° showed visible cloud features with good contrast while subsequent movies were relatively featureless. With the extension of the observations to a full Martian year, more pronounced seasonal changes were observed. Within the Zenith Movie data set, clouds are observed primarily during LS = 3° - 170°, when the solar flux is diminished and the aphelion cloud belt is present at equatorial latitudes. Clouds observed in the Supra-Horizon Movie data set also exhibit seasonality, with clouds predominantly observed during LS = 72° - 108°. The seasonal occurrence of clouds detected in the atmospheric movies is well correlated with orbital observations of water-ice clouds at similar times from the MCS and MARCI instruments on the MRO spacecraft. The observed clouds are tenuous and on average only make up a few-hundredths of an optical depth, although more opaque clouds are observed in some of the movies. Additionally, estimates of the phase function calculated using water-ice opacity retrievals from MCS are provided to show how Martian clouds scatter sunlight, and thus provide insight into the types of ice crystals that comprise the clouds.
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| 20. |
- Koliadi, Anthoula, et al.
(author)
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Cyclin B is an immunohistochemical proliferation marker which can predict for breast cancer death in low-risk node negative breast cancer
- 2010
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 49:6, s. 816-820
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Journal article (peer-reviewed)abstract
- Patients with low-risk node negative breast cancer have an excellent prognosis with 5% breast cancer mortality at 10 years. However, prognostic factors are needed to identify poor prognostic patients who might benefit from adjuvant systemic therapy. Proliferation has been identified as the most important component of gene expression profiles. Cyclin B is a proliferative marker easily assessed by immunohistochemistry. We wanted to examine cyclin B as a prognostic factor in low-risk breast cancer patients. Patients and methods. Using an experimental study design, we compared women dying early from their breast cancer (n=17) with women free from relapse more than eight years after initial diagnosis (n=24). All women had stage I, node negative and hormone receptor positive disease. None had received adjuvant chemotherapy. Tumor samples were immunostained for cyclin B using commercial antibodies. Results. The mean percentage of cyclin B (12%) was significantly higher (p=0.001) in women dying from their breast cancer compared with women free from relapse ( 5%). High cyclin B (>= 9%) identified 11/17 patients dying from breast cancer and low cyclin B identified 22/24 patients free from relapse. The sensitivity and specificity of cyclin B was 65% and 92%, respectively. Discussion. We found that low-risk node negative patients with high expression of cylin B had a significantly worse outcome than patients with low expression of cyclin B. Cyclin B could separate patients with poor survival from those with good survival with 80% accuracy. We suggest that cyclin B might be a potent prognostic factor in this low-risk patient group.
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| 21. |
- Lindén, Mårten, et al.
(author)
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Galectin-1, a potential therapeutic target, in primary tumors and metastases of urinary bladder carcinomas
- 2013
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Other publication (other academic/artistic)abstract
- Urinary bladder cancer would gain from new protein biomarkers due to the heterogeneity of disease. The beta-galactoside-binding protein (GAL1) is one such candidate and in present study its prognostic value and expression at protein level in metastatic bladder cancer-disease, have been evaluated. The protein expression of GAL1 was investigated by immunohistochemistry in two tumor cohorts, one with primary tumors of different stage and grade (n=344) and another with primary tumors matched with metastases (n=90). The expression in the actual cancer cells as well as in stroma and blood vessels were considered since the presence of GAL1 in different tissue compartments has shown cancer relevance. The cellular expression increased with increased tumor stage and grade (p<0.001). For the majority of the patients, cells from both primary tumor and metastasis showed a positive immunoreactivity for GAL1 (91% (n=64) for primary tumors with single metastasis (n=70) and 100% (n=20) for primary tumors with multiple metastasis (n=20). Further, strong immunoreactivity in T1 tumor cells correlated with lower risk of recurrence (p<0.05). Both tumors and metastasis exhibited strong stromal-GAL1 staining that could not be correlated with clinical parameters. The expression in vessels showed that T1 tumors surrounded by GAL1 negative blood vessels had a higher risk of progression (p<0.0001) into muscle invasive T2-4 stages. The results show that GAL1 is an important bladder cancer-protein from several aspects. Further, GAL1 is a promising therapeutic target in bladder cancer due to the general expression in advanced disease.
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| 22. |
- Loskog, Angelica, et al.
(author)
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Human bladder carcinoma is dominated by T-regulatory cells and Th1 inhibitory cytokines
- 2007
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In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 177:1, s. 353-358
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Journal article (peer-reviewed)abstract
- Purpose: Immunotherapy has faced limited success, although many solutions have been proposed. Recently regulatory T cells have made a comeback in the immunological arena and the role of these cells in patients with cancer is in focus. It is under evaluation whether the immunological status of patients with cancer may affect their sensitivity to immunotherapy. We are developing immunostimulating gene therapy for treating bladder cancer. In this study we constructed an immunological profile of patients with bladder carcinoma to understand which obstacles must be circumvented. Materials and Methods: Biopsies and blood were used to identify immune cell populations by FACS®, histochemistry and proliferation assays, and cytokine production by polymerase chain reaction. Results: Results indicate that bladder carcinoma is a Tri dominated tumor, as shown by the infiltration of T-regulatory cells expressing FOXP3, and the presence of tumor necrosis factor-β and interleukin-10 mRNA copies. We further noted that circulating patient T cells were unresponsive to polyclonal T-cell activation compared to healthy donor cells. Moreover, CD4+CD25+ T cells were increased in patient blood and could suppress the expansion of allogeneic T cells from healthy donors. Conclusions: Patients with bladder carcinoma show an immunosuppressive regulatory profile, including nonresponsive T cells. Clinical protocols able to effectively counteract these mechanisms are warranted.
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| 23. |
- Loskog, Angelica, et al.
(author)
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Human urinary bladder carcinomas express adenovirus attachment and internalization receptors
- 2002
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In: Gene Therapy. - : Springer Science and Business Media LLC. - 0969-7128 .- 1476-5462. ; 9:9, s. 547-553
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Journal article (peer-reviewed)abstract
- The use of adenoviral vectors as potent gene delivery systems requires expression of the Coxsackievirus/adenovirus receptor (CVADR) on the target cell surface. This receptor is important for virus attachment to the cell surface. For effective internalization of the vector into the target cell the integrins alpha(v)beta(3) and/or alpha(v)beta(5) are needed. Since there have been reports of loss of CVADR in bladder cancer cell lines, we wanted to investigate the expression of this receptor in bladder carcinoma biopsies. Surgical biopsies, as well as five human bladder cancer cell lines, were analyzed for expression of CVADR, the integrins alpha(v)beta(3) and alpha(v)beta(5) and MHC class I. Further, we studied the ability to transduce these cell lines using adenoviral vectors. Immunohistochemistry revealed that all biopsies (27/27) were positive for CVADR. Some variation in expression was evident, and superficially growing tumors stained more strongly than invasive ones. Most human tumors expressed the integrin alpha(v)beta(5) (14/24), whereas integrin alpha(v)beta(3) was less frequently seen (3/20). The established cell lines were efficiently transduced with adenoviral vectors, and transduction could be reduced with anti-CVADR antibodies. The abundance of appropriate viral receptors on tumor biopsy cells is a further argument for using adenoviral vectors in gene therapy of bladder cancer.
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| 24. |
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| 25. |
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| 26. |
- Moores, John E., et al.
(author)
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Atmospheric movies acquired at the Mars Science Laboratory landing site : Cloud Morphology, Frequency and Significance to the Gale Crater Water Cycle and Phoenix Mission Results
- 2015
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In: Advances in Space Research. - : Elsevier BV. - 0273-1177 .- 1879-1948. ; 55:9, s. 2217-2238
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Journal article (peer-reviewed)abstract
- We report on the first 360 sols (LS 150° to 5°), representing just over half a Martian year, of atmospheric monitoring movies acquired using the NavCam imager from the Mars Science Laboratory (MSL) Rover Curiosity. Such movies reveal faint clouds that are difficult to discern in single images. The data set acquired was divided into two different classifications depending upon the orientation and intent of the observation. Up to sol 360, 73 Zenith Movies and 79 Supra-Horizon Movies have been acquired and time-variable features could be discerned in 25 of each. The data set from MSL is compared to similar observations made by the Surface Stereo Imager (SSI) onboard the Phoenix Lander and suggests a much drier environment at Gale Crater (4.6°S) during this season than was observed in Green Valley (68.2°N) as would be expected based on latitude and the global water cycle. The optical depth of the variable component of clouds seen in images with features are up to 0.047 ± 0.009 with a granularity to the features observed which averages 3.8 degrees. MCS also observes clouds during the same period of comparable optical depth at 30 and 50 km that would suggest a cloud spacing of 2.0 to 3.3 km. Multiple motions visible in atmospheric movies support the presence of two distinct layers of clouds. At Gale Crater, these clouds are likely caused by atmospheric waves given the regular spacing of features observed in many Zenith movies and decreased spacing towards the horizon in sunset movies consistent with clouds forming at a constant elevation. Reanalysis of Phoenix data in the light of the NavCam equatorial dataset suggests that clouds may have been more frequent in the earlier portion of the Phoenix mission than was previously thought.
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| 27. |
- Moores, John E., et al.
(author)
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Observational evidence of a suppressed planetary boundary layer in northern Gale Crater, Mars as seen by the Navcam instrument onboard the Mars Science Laboratory rover
- 2015
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In: Icarus. - : Elsevier BV. - 0019-1035 .- 1090-2643. ; 249, s. 129-142
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Journal article (peer-reviewed)abstract
- The Navigation Cameras (Navcam) of the Mars Science Laboratory rover, Curiosity, have been used to examine two aspects of the planetary boundary layer: vertical dust distribution and dust devil frequency. The vertical distribution of dust may be obtained by using observations of the distant crater rim to derive a line-of-sight optical depth within Gale Crater and comparing this optical depth to column optical depths obtained using Mastcam observations of the solar disc. The line of sight method consistently produces lower extinctions within the crater compared to the bulk atmosphere. This suggests a relatively stable atmosphere in which dust may settle out leaving the air within the crater clearer than air above and explains the correlation in observed column opacity between the floor of Gale Crater and the higher elevation Meridiani Planum. In the case of dust devils, despite an extensive campaign only one optically thick vortex (τ=1.5±0.5×10-3) was observed compared to 149 pressure events > 0.5Pa observed in REMS pressure data. Correcting for temporal coverage by REMS and geographic coverage by Navcam still suggests 104 vortices should have been viewable, suggesting that most vortices are dustless. Additionally, the most intense pressure excursions observed on other landing sites (pressure drop >2.5Pa) are lacking from the observations by the REMS instrument. Taken together, these observations are consistent with pre-landing circulation modeling of the crater showing a suppressed, shallow boundary layer. They are further consistent with geological observations of dust that suggests the northern portion of the crater is a sink for dust in the current era.
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| 28. |
- Nishi, Stephanie K., et al.
(author)
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Mediterranean, DASH, and MIND Dietary Patterns and Cognitive Function : The 2-Year Longitudinal Changes in an Older Spanish Cohort
- 2021
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In: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13
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Journal article (peer-reviewed)abstract
- Background and Aims: Plant-forward dietary patterns have been associated with cardiometabolic health benefits, which, in turn, have been related to cognitive performance with inconsistent findings. The objective of this study was to examine the relationship between baseline adherence to three a priori dietary patterns (Mediterranean, DASH, and MIND diets) with 2-year changes in cognitive performance in older adults with overweight or obesity and high cardiovascular disease risk. Methods: A prospective cohort analysis was conducted within the PREDIMED-Plus trial, involving 6,647 men and women aged 55–75 years with overweight or obesity and metabolic syndrome. Using a validated, semiquantitative 143-item food frequency questionnaire completed at baseline, the dietary pattern adherence scores were calculated. An extensive neuropsychological test battery was administered at baseline and 2-year follow-up. Multivariable-adjusted linear regression models were used to assess associations between 2-year changes in cognitive function z-scores across tertiles of baseline adherence to the a priori dietary patterns. Results: Adherence to the Mediterranean diet at baseline was associated with 2-year changes in the general cognitive screening Mini-Mental State Examination (MMSE, β: 0.070; 95% CI: 0.014, 0.175, P-trend = 0.011), and two executive function-related assessments: the Trail Making Tests Part A (TMT-A, β: −0.054; 95% CI: −0.110, − 0.002, P-trend = 0.047) and Part B (TMT-B, β: −0.079; 95% CI: −0.134, −0.024, P-trend = 0.004). Adherence to the MIND diet was associated with the backward recall Digit Span Test assessment of working memory (DST-B, β: 0.058; 95% CI: 0.002, 0.114, P-trend = 0.045). However, higher adherence to the DASH dietary pattern was not associated with better cognitive function over a period of 2 years. Conclusion: In older Spanish individuals with overweight or obesity and at high cardiovascular disease risk, higher baseline adherence to the Mediterranean dietary pattern may be associated with better cognitive performance than lower adherence over a period of 2 years.
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| 29. |
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| 30. |
- Rubio, Carlos A., et al.
(author)
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Reliability of the reported size of removed colorectal polyps
- 2006
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 26:6C, s. 4895-4899
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Journal article (peer-reviewed)abstract
- Background: The size of colorectal polyps is important in the clinical management of these lesions. Aim: To audit the accuracy in calculating the size of polyps by various specialists. Materials and Methods: Eighteen pathologists and four surgeons measured, with a conventional millimetre ruler, the largest diameter of 12 polyp phantoms. The results of two independent measurements (two weeks apart) were compared with the gold standard-size assessed at The Royal Institute of Technology, Sweden. Results: Thirty-one percent (83/264-trial 1) and 33% (88/264-trial 2) of the measurements underestimated or overestimated the gold standard size by > 1 mm. Of the 22 experienced participants, 95% (21/22-trial 1) and 91% (20/22-trial 2) misjudged by > 1 mm the size of one or more polyps. Values given by 13 participants (4.9%) in trial I and by 15 participants (5.7%) in trial 2, differed by ! 4 mm from the gold standard size. In addition, a big difference between the highest and the lowest values was recorded in some polyps (up to 11.4 mm). Those disparate values were regarded as a human error in reading the scale on the ruler. Conclusion: Using a conventional ruler (the tool of pathologists worldwide) unacceptably high intra-observer and inter-observer variations in assessing the size of polyp-phantoms was found. The volume and the shape of devices, as well as human error in reading the scale of the ruler were confounding factors in size assessment. In praxis, the size is crucial in the management of colorectal polyps. Considering the clinical implications of the results obtained, the possibility of developing a method that will allow assessment of the true size of removed clinical polyps is being explored.
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| 31. |
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| 32. |
- Segersten, M. Ulrika, et al.
(author)
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A novel strategy based on histological protein profiling in-silico for identifying potential biomarkers in urinary bladder cancer
- 2009
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In: BJU International. - 1464-4096 .- 1464-410X. ; 104:11, s. 1780-1785
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To screen a publicly available immunohistochemistry (IHC) based web-atlas, to identify key proteins in bladder cancer that might serve as potential biomarkers. MATERIALS AND METHODS: The first version of the Human Protein Atlas (HPA 1.0), with 660 proteins, was visually examined to identify proteins with a variable staining pattern among the 12 tissue samples representing bladder cancer. None or limited previous characterization in bladder cancer, as well as a supportive Western blot, were also required. The selected proteins were then evaluated in an independent set of patient samples (106 tumour samples of differing stage and grade) represented in a tissue microarray (TMAi). The IHC expression of the identified proteins in the TMAi was scored and related to tumour stage and grade. RESULTS: The expression profiles of the 13 proteins selected from the web-atlas were confirmed in the TMAi. Expression patterns for seven proteins were significantly altered (P < 0.05) with higher stage and/or grade. Three of those (CN130, DSG3, PHF6) lack characterization in bladder cancer, whereas the remaining four proteins have previously been suggested as key proteins/potential biomarkers in cancer, some of them also in bladder cancer. CONCLUSION: New candidate proteins for urinary bladder cancer were identified through screening of the publicly available HPA 1.0. Although further evaluation is necessary, this strategy is promising in the search for new biomarkers, with potential to improve the management of patients with this disease.
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| 33. |
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| 34. |
- Tamai, Anna, et al.
(author)
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High-Resolution Photoemission on Sr2RuO4 Reveals Correlation-Enhanced Effective Spin-Orbit Coupling and Dominantly Local Self-Energies
- 2019
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In: Physical Review X. - New York : American Physical Society. - 2160-3308. ; 9:2
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Journal article (peer-reviewed)abstract
- We explore the interplay of electron-electron correlations and spin-orbit coupling in the model Fermi liquid Sr2RuO4 using laser-based angle-resolved photoemission spectroscopy. Our precise measurement of the Fermi surface confirms the importance of spin-orbit coupling in this material and reveals that its effective value is enhanced by a factor of about 2, due to electronic correlations. The self-energies for the β and γ sheets are found to display significant angular dependence. By taking into account the multi-orbital composition of quasiparticle states, we determine self-energies associated with each orbital component directly from the experimental data. This analysis demonstrates that the perceived angular dependence does not imply momentum-dependent many-body effects but arises from a substantial orbital mixing induced by spin-orbit coupling. A comparison to single-site dynamical mean-field theory further supports the notion of dominantly local orbital self-energies and provides strong evidence for an electronic origin of the observed nonlinear frequency dependence of the self-energies, leading to “kinks” in the quasiparticle dispersion of Sr2RuO4.
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| 35. |
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| 36. |
- Vikman, Sofia, et al.
(author)
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Gene expression in midgut carcinoid tumors : potential targets for immunotherapy
- 2005
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:1, s. 32-40
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Journal article (peer-reviewed)abstract
- Classical midgut carcinoids are serotonin-secreting tumors derived from enterochromaffin cells in the gut. Metastatic disease represents a therapeutic challenge and immunotherapy implies a novel approach for treatment. In order to define antigens suitable for T-cell therapy with a preferential expression in midgut carcinoid tissue a broad screening of genes with preferential neuroendocrine restriction, genes described as over-expressed in various malignancies, and genes encoding cancer-testis associated antigens was performed. The expression of 32 genes was analyzed by reverse transcription polymerase chain reaction (RT-PCR) in 28 midgut carcinoid specimens, in the cell line BON and in normal tissues. Immunohistochemistry (IHC) was used to evaluate protein expression. Expression is shown of genes that have previously not been observed in midgut carcinoid tumors, such as Survivin and GAGEs. Also the expression is confirmed of genes that encode pivotal proteins in enterochromaffin cells, such as TPH1 and VMAT1, and their tissue-restricted expression is indicated. In addition, gene expression of IA-2 and CDX-2 in normal gastrointestinal (GI) tract and in tumor is shown. Protein expression of TPH, VMAT1, and Survivin was detected in tumor tissue. This study elucidates that TPH1, VMAT1, and Survivin should be further investigated as potential target antigens for T cell-mediated immunotherapy of midgut carcinoids.
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| 37. |
- Vikman, Sofia, et al.
(author)
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Midgut carcinoid patients display increased numbers of regulatory T cells in peripheral blood with infiltration into tumor tissue
- 2009
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 48:3, s. 391-400
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Our aim was to investigate the immune status of midgut carcinoid patients. Cancer patients generally display suppressed Th1-type immunity that disables mounting of an efficient anti-tumor response. However, little is known about patients with neuroendocrine midgut carcinoids. MATERIAL AND METHODS: Circulating regulatory T cells were determined in patient blood by staining for CD4, CD25 and FoxP3 in flow cytometric analysis. T cell proliferation was measured by Alamar Blue in response to polyclonal activation and the regulatory phenotype of patient CD25+ cells was validated by allogeneic stimulation of CFSE labelled responders. Cytokine levels in patient peripheral blood were measured by ELISA and CBA. Tumor infiltrating T cells were analyzed by immunohistochemistry and immunofluorescence. RESULTS: The results demonstrate that midgut carcinoid patients exhibit increased frequencies of circulating Tregs and patient T cells have a decreased proliferative capacity compared to healthy donors. Systemic Th1-promoting cytokines are reduced. Midgut carcinoid tumors display CD4+ and CD8+ T cell infiltration, always in the presence of regulatory CD4+FoxP3+ cells. DISCUSSION: Midgut carcinoid patients display elevated T regulatory cell numbers and T cell dysfunction. Therapeutic strategies to overcome tumor-induced Th1 immunosuppression are required in combination with anti-tumor vaccinations.
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| 38. |
- Wester, Kenneth, et al.
(author)
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HER-2 : A possible target for therapy of metastatic urinary bladder carcinoma
- 2002
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 41:3, s. 282-288
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Journal article (peer-reviewed)abstract
- Human epidermal growth factor receptor 2, HER-2, is overexpressed in various tumours, e.g. breast- and bladder tumours. The aim of this study was to predict the potential use of HER-2 receptors as targets in systemic treatment of disseminated bladder tumours. HER-2 expression was assessed in bladder carcinoma metastases and the corresponding primary tumours, and subsequently compared with the EGFR expression. HER-2 and EGFR expression was analysed by immunohistochemistry in formalin-fixed, paraffin-embedded tissues from 21 patients with metastatic bladder carcinoma. HER-2 was overexpressed in 81% of the primary tumours and in 67% of the metastases. All HER-2-positive metastases were from HER-2-positive primary tumours. The results for EG FR were 71% of both primary and metastases-positive tumours. In 90% of the primary tumours and 86% of the metastases, at least one of the receptors was overexpressed. These results suggest that HER-2 targeted therapy can be considered as an alternative or a complement to other modalities in the treatment of metastatic urinary bladder carcinoma.
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| 39. |
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