Rikshospitalet Radiumhospitalet Medical Center

Norway

Rikshospitalet Radiumhospitalet Medical Center

Norway
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Hannisda R.,University of Bergen | Hannisda R.,National Institute of Nutrition And Seafood Research | Gislefoss R.E.,University of Oslo | Gislefoss R.E.,Rikshospitalet Radiumhospitalet Medical Center | And 6 more authors.
Journal of Nutrition | Year: 2010

Epidemiological studies on folate and chronic diseases often involve the use of frozen serum stored in biorepositories for decades. Folate instability may attenuate associations between folate status and study endpoints. In this cross-sectional study, we retrieved serum samples stored at -25°C for 0, 4, 6, 17, or 29 y in the Janus biobank. Samples were obtained from a total of 650 men aged 40-49 y at the time of blood collection and were evenly distributed according to storage time. Folate was determined by a liquid chromatography tandem MS (LC-MS/MS) assay that measures 5-methyltetrahydrofolate (5mTHF), its oxidation product 4-a-hydroxy-5-methyltetrahydrofolate (hmTHF), and other folate species; by a Lactobacillus rhamnosus microbiological assay; and by LC-MS/MS as p-aminobenzoylglutamate (pABG) equivalents after oxidation and mild acid hydrolysis of the folate species. Concentrations of 5mTHF and microbiologically active folate were lower in samples that had been subjected to long-term storage and the data were consistent with a decrease of 3.2 and 2.8%/y, respectively. hmTHF was detected in all specimens but did not accumulate upon long-term storage (>4 y). Folate measured as pABG declined at a slow rate of 0.98%/y and ≃80% of the folate was recovered after 29 y of storage. B-vitamin status did not differ between individuals delivering samples at different time points, as assessed by measuring total homocysteine, methylmalonic acid, and serum vitamin B-12. In conclusion, folate is substantially degraded in serum frozen for decades but can to a large extent be recovered as pABG equivalents. The pABG assay appears to be the method of choice for the determination of folate status in archival serum samples. © 2010 American Society for Nutrition.


Lagunova Z.,Rikshospitalet Radiumhospitalet Medical Center | Porojnicu A.C.,Rikshospitalet Radiumhospitalet Medical Center | Vieth R.,Mount Sinai Hospital | Lindberg F.A.,Dr. Fedon Lindbergs Clinic | And 3 more authors.
Journal of Nutrition | Year: 2011

Recent research suggests that 1,25-dihydroxyvitamin D [1,25(OH) 2D], a steroid hormone that regulates calcium homeostasis, may also play a role in the development and progression of cancer, multiple sclerosis, cardiovascular, and other diseases. Decreased serum 1,25(OH)2D concentrations are often observed in overweight and obese patients. However, little is known about the factors that may influence 1,25(OH)2D renal synthesis, because it is generally accepted that serum 1,25(OH)2D concentration is strictly regulated by parathyroid hormone and serum concentrations of calcium and phosphorus. In this study, the associations among serum 1,25(OH)2D, serum 25-hydroxyvitamin D [25(OH)D], and body composition were analyzed in 1779 patients with excess body weight registered in aMetabolic and Medical Lifestyle Management Clinic in Oslo, Norway. According to our results, serum 25(OH)D, adiposity, age, season of blood sampling, and gender directly influence serum 1,25(OH)2D (r = 0.33; P < 0.001), with serum 25(OH)D being the strongest predictor for serum 1,25(OH) 2D. The 1,25(OH)2D concentrations were 25.4 pmol/L (95% Cl: 19.3-31.5; P < 0.001) lower in the lowest 25(OH)D quartile to compared with highest quartile. A seasonal variation was observed for both vitamin D metabolites. Thus, our results suggest that in patients with excess body weight, serum 1,25(OH)2D concentrations were associated with 25(OH)D and varied during the year. Therefore, it may also be valuable to measure both serum 25(OH)D\ and 1,25(OH)2D for the evaluation of vitamin D status in overweight and obese persons. © 2011 American Society for Nutrition.


Myrset A.H.,University of Oslo | Fjerdingstad H.B.,University of Oslo | Bendiksen R.,Rikshospitalet Radiumhospitalet Medical Center | Arbo B.E.,Rikshospitalet Radiumhospitalet Medical Center | And 4 more authors.
Ultrasound in Medicine and Biology | Year: 2011

Targeted ultrasound (US) contrast agents represent, because of their size (1 to 5 μm), a unique class of diagnostic imaging agents enabling true vascular imaging of conditions like inflammation and tumor angiogenesis. The objective of this study was to develop technology for preparing targeted microbubbles with binding and acoustic properties compatible with diagnostic use. Phosphatidylcholine (PC) was shown to represent the most favorable wall material. Various thiolated peptide binders were effectively conjugated to PC-based microbubbles containing maleimide functionalized lipids (95:5) without the need for biotin-streptavidin or antibody technology. By optimizing the technology, specific targeting of the inflammatory target E-selectin and the angiogenic target VEGFR2 in the presence of 100% serum was achieved. Increased phospholipid chain length from 18 carbons to 22 carbons improved the stability of the microbubbles during US exposure, without compromising binding or acoustic properties. © 2011 World Federation for Ultrasound in Medicine & Biology.


Hustad S.,University of Bergen | Eussen S.,University of Bergen | Midttun O.,University of Bergen | Ulvik A.,University of Bergen | And 5 more authors.
Clinical Chemistry | Year: 2012

BACKGROUND: Biomarkers and metabolites related to B vitamin function and one-carbon metabolism have been studied as predictors of chronic diseases in studies based on samples stored in biobanks. For most biomarkers, stability data are lacking or fragmentary. METHODS: Degradation and accumulation kinetics of 32 biomarkers were determined at 23 °C in serum and plasma (EDTA, heparin, and citrate) collected from 16 individuals and stored for up to 8 days. In frozen serum (-25 °C), stability was studied crosssectionally in 650 archival samples stored for up to 29 years. Concentration vs time curves were fitted to monoexponential, biexponential, linear, and nonlinear models. RESULTS: For many biomarkers, stability was highest in EDTA plasma. Storage effects were similar at room temperature and at -25 °C; notable exceptions were methionine, which could be recovered as methionine sulfoxide, and cystathionine, which decreased in frozen samples. Cobalamin, betaine, dimethylglycine, sarcosine, total homocysteine, total cysteine, tryptophan, asymetric and symmetric dimethyl argenine, creatinine, and methylmalonic acid were essentially stable under all conditions. Most B vitamins (folate and vitamins B2 and B6) were unstable; choline increased markedly, and some amino acids also increased, particularly in serum. The kynurenines showed variable stability. For many biomarkers, degradation (folate and flavin mononucleotide) or accumulation (pyridoxal, riboflavin, choline, amino acids) kinetics at room temperature were non - first order. CONCLUSIONS: Data on stability and deterioration kinetics for individual biomarkers are required to optimize procedures for handling serum and plasma, and for addressing preanalytical bias in epidemiological and clinical studies. © 2011 American Association for Clinical Chemistry.


Patent
British Columbia Cancer Agency Bcca, Catalan Institute of Nanoscience, Nanotechnology, Rikshospitalet Radiumhospitalet Medical Center, St. Bartholomew's Hospital, Arizona Cancer Center, University of Barcelona, University of Nebraska Medical Center, University of Rochester and Powell | Date: 2011-03-23

Gene expression data provides a basis for more accurate identification and diagnosis of lymphoproliferative disorders. In addition, gene expression data can be used to develop more accurate predictors of survival. The present invention discloses methods for identifying, diagnosing, and predicting survival in a lymphoma or lymphoproliferative disorder on the basis of gene expression patterns. The invention discloses a novel microarray, the Lymph Dx microarray, for obtaining gene expression data from a lymphoma sample. The invention also discloses a variety of methods for utilizing lymphoma gene expression data to determine the identity of a particular lymphoma and to predict survival in a subject diagnosed with a particular lymphoma. This information will be useful in developing the therapeutic approach to be used with a particular subject.


Yamazaki T.,University of Geneva | Yamazaki T.,Tokyo Institute of Technology | Walchli S.,Rikshospitalet Radiumhospitalet Medical Center | Fujita T.,University of Geneva | And 6 more authors.
Cardiovascular Research | Year: 2010

AimsProteins with a PDZ (for PSD-95, DLG, ZO-1) and one to three LIM (for Lin11, Isl-1, Mec-3) domains are scaffolding sarcomeric and cytoskeletal elements that form structured muscle fibres and provide for the link to intracellular signalling by selectively associating protein kinases, ion channels, and transcription factors with the mechanical stress-strain sensors. Enigma homolog (ENH) is a PDZ-LIM protein with four splice variants: ENH1 with an N-terminal PDZ domain and three C-terminal LIM domains and ENH2, ENH3, and ENH4 without LIM domains. We addressed the functional role of ENH alternative splicing.Methods and resultsWe studied the expression of the four ENH isoforms in the heart during development and in a mouse model of heart hypertrophy. All four isoforms are expressed in the heart but the pattern of expression is clearly different between embryonic, neonatal, and adult stages. ENH1 appears as the embryonic isoform, whereas ENH2, ENH3, and ENH4 are predominant in adult heart. Moreover, alternative splicing of ENH was changed following induction of heart hypertrophy, producing an ENH isoform pattern similar to that of neonatal heart. Next, we tested a possible causal role of ENH1 and ENH4 in the development of cardiac hypertrophy. When overexpressed in rat neonatal cardiomyocytes, ENH1 promoted the expression of hypertrophy markers and increased cell volume, whereas, on the contrary, ENH4 overexpression prevented these changes. Conclusion Antagonistic splice variants of ENH may play a central role in the adaptive changes of the link between mechanical stress-sensing and signalling occurring during embryonic development and/or heart hypertrophy. © 2010 The Author.


Sund F.,Uppsala University Hospital | Lidehall A.,Uppsala University Hospital | Claesson K.,Uppsala University Hospital | Foss A.,Rikshospitalet Radiumhospitalet Medical Center | And 3 more authors.
Clinical Transplantation | Year: 2010

Cytomegalovirus (CMV) infection is still the leading opportunistic infection following solid organ transplantation. The aim of this prospective study of renal transplant recipients was to evaluate the dynamics of CMV-specific T-cells, viral load, and clinical symptoms of CMV infection. Methods: Levels of tetramer-selected CD8+ T-cells (TetraCD8), CMV-specific interferon-γ producing CD8+ T-cells (IFNγCD8), and CD4+ T-cells (IFNγCD4), measured using major histocompatibility complex-tetramer and cytokine flow cytometry techniques, and CMV DNA were monitored monthly in 17 CMV-seropositive patients up to one yr (median 12 months, range 3-12) after transplantation and correlated to clinical outcome. Results: CMV DNAemia was detected in 94% of the patients, but only one patient developed CMV disease. CMV DNAemia >1 million copies/mL was seen in asymptomatic patients. CMV-specific T-cells decreased rapidly after transplantation. TetraCD8 and IFNγCD8 regenerated within three months, whereas IFNγCD4 recovery was impaired up to one yr after transplantation. The proportion of IFNγCD4 at two months post-transplantation as compared with baseline, correlated strongly with the magnitude of the CMV DNAemia. Conclusions: Monitoring the reduction of IFNγCD4 compared with baseline during the first months after transplantation could be considered in predicting risk for high-grade CMV DNAemia and in deciding strategic approaches for pre-emptive and prophylactic therapy. © 2009 Wiley Periodicals, Inc.


Bernsdorf M.,Copenhagen University | Ingvar C.,Lund University | Jorgensen L.,Astrazeneca | Tuxen M.K.,Herlev Hospital | And 6 more authors.
Breast Cancer Research and Treatment | Year: 2011

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has shown both anti-proliferative and anti-tumoral activity in breast cancer. This study was designed to determine the effect of adding gefitinib to neoadjuvant epirubicin and cyclophosphamide (EC) on tumor response rates. Women with unilateral, primary operable, estrogen receptor negative invasive breast cancer ≥ 2 cm were eligible for inclusion. Randomized patients were to receive four cycles of neoadjuvant EC plus 12 weeks ofeither gefitinib (250 mg daily) or placebo. Primary endpoint was pathologic complete response (pCR), and secondary endpoints were complete response (CR) and overall objective response (OR). 181 patients were randomized. A pCR was observed in 17% (12/71) of patients treated with gefitinib and in 12% (9/73) of patients treated with placebo (4.57% difference, 95% CI -7.19 to 6.33; P = 0.44). CR was observed in 10% of patients in both the gefitinib (7/71) and the placebo group (7/73) (0.27% difference, 95% CI -9.6 to 10.2; P = 0.96). There was no significant difference in OR (5.96%; 95% CI -9.9 to 21.9; P = 0.45) between the two groups. Post hoc subgroup analysis showed a significant difference in pCR between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups. A significantly higher pCR rate was observed post hoc in TNBC versus non-TNBC independent of treatment. More patients in the gefitinib group discontinued treatment because of AE. © 2011 Springer Science+Business Media, LLC.


Fredriksen L.,Norwegian University of Life Sciences | Mathiesen G.,Norwegian University of Life Sciences | Sioud M.,Rikshospitalet Radiumhospitalet Medical Center | Eijsink V.G.H.,Norwegian University of Life Sciences
Applied and Environmental Microbiology | Year: 2010

The 37-kDa oncofetal antigen (OFA), a tumor immunogen expressed on all mammalian cancers examined to date, was secreted and anchored to the cell wall of Lactobacillus plantarum using homologous signal peptides and LPxTG anchors. Orally administered L. plantarum expressing anchored OFA induced a specific immune response against OFA in mice. Copyright © 2010, American Society for Microbiology.


Dale E.,Rikshospitalet Radiumhospitalet Medical Center
Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al] | Year: 2010

To investigate the lung tissue response measured with computed tomography (CT) after radiotherapy (RT) combined with metoclopramide. Patients with non-small cell lung cancer (tumor stage IIIA and IIIB), included in a multicenter, randomized phase III trial investigating the use of metoclopramide as a radiosensitizing agent, were examined with repetitive post-RT CT scans. The analysis comprised data up to 100 days after RT for a subgroup of 16 patients treated with a total dose of 60 Gy given in 1.82 Gy per fraction. Large radiation doses to subvolumes were associated with denser lung tissue measured with CT (p < 0.001). Opposed to this finding, the volume of lung tissue irradiated with significant doses (V(40Gy)) was negatively correlated with the average increase in lung tissue density (p = 0.003). Patients randomized to metoclopramide injections also experienced less increase in lung tissue density (p = 0.01). There was an increase in the density of irradiated lung tissue with radiation dose and time after RT. Metoclopramide and significant radiation doses to larger lung volumes (V(40Gy)) seemed to protect against fibrosis development.

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