204 results on '"Jensen KE"'
Search Results
2. Physico-chemical findings related to the resilience of different soils in the semi-arid parts of Tanzania and their implications on sustainable agriculture
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Moberg, JP, Szilas, C, Jensen, KE, and Midtgaard, T
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As part of an interdisciplinary study on Sustainable Agriculture in semiarid Areas (SASA) in south-central Tanzania, soils from five different locations were investigated for their mineralogical composition and physico-chemical characteristics in order to determine their resilience in relation to land use. The results of the investigation show that soils developed in such areas on sediments of Holocene age to a certain extent are capable of retaining their chemical fertility as long as low intensity agriculture is being practised. The content of weatherable minerals in the quite silt-rich soils is so large that the weathering taking place, seems sufficient under the prevailing semiarid conditions to ensure adequate supply of plant nutrients for low intensity crop production with the exception of N, P and S. The sand and silt fractions contained substantial amounts of mica and plagioclase and smaller amounts of hornblende/pyroxene. In addition to kaolinite and iron oxides, the clay fraction contains illite and smaller amounts of other 2:1 layer silicate clay minerals. The extractable amount of P is low, although the P-retention is expected to be limited, as the content of P-fixing components is limited. In contrast, the soils in the area formed in situs on metamorphic rocks contain only quartz and very small amounts of microcline and muscovite in the sand fraction. The silt fraction is high in quartz too besides having some kaolinite and gibbsite, The clay fraction of these soils is composed mainly of kaolinite with smaller amounts of Fe-oxides and illite, Chemically, the capacity of these soils is so low that they will not to any degree release any plant nutrients by weathering. The extractable P is also low in these soils, as the P present may be considered to be strongly retained due to the mineralogical composition of these soils. Due to their content of stable micropeds the strongly weathered soils developed in situs are more porous than the less strongly weathered soils developed on the Holocene sediments. However, their available water holding capacity may be expected to be lower than that of the soils developed on the sediments, as such soils normally have a limited number of pores in which plant available water is stored.Keywords: different soils, semi arid putsTanzania J. Agrlc. Sc. (1999) Vol. 2 No.1, 37-52
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- 2015
3. Fast and robust analysis of dynamic contrast enhanced MRI datasets
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Kubassova, O, Boesen, M, Boyle, Rd, Cimmino, MARCO AMEDEO, Jensen, Ke, Bliddal, H, and Radjenovic, A.
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- 2007
4. Cervical vertebral column morphology in patients with obstructive sleep apnoea assessed using lateral cephalograms and cone beam CT. A comparative study
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Sonnesen, L, primary, Jensen, KE, additional, Petersson, AR, additional, Petri, N, additional, Berg, S, additional, and Svanholt, P, additional
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- 2013
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5. The venereological profile in Godthab District Venereal Clinic, Nuuk, Grønland. A 3-month study in 1991
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Møller, B R, From, E, Christensen, RB, Heilmann, B, Jensen, KE, and Thorsen, P
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Male ,Gonorrhea ,Greenland ,Sexually Transmitted Diseases ,Humans ,Female ,Vaginosis, Bacterial ,Chlamydia Infections - Abstract
A total of 803 patients participated in a consecutive review of the disease pattern concerning venereal diseases. The investigation took place in the Clinic for Venereal Diseases in Nuuk/Godthåb during a period of three months. Less than half of the contacts were on account of symptoms of genital infection. One fifth of the patients had been summoned for partner control. A corresponding proportion felt well and had not been exposed to any known risk of infection. Chlamydia trachomatis was demonstrated in 19% and gonorrhoea in 10%. Among the asymptomatic persons, 16% were found to be Chlamydia positive and 0.6% gonococcal positive. Syphilis was demonstrated in one man and one woman. One man was known to be HIV-positive and two contacts of this patient were found to be negative but seroconversion occurred subsequently in both cases. Vaginitis and bacterial vaginosis were found in 38% of the women. In over one third (39%), no clinical or microbiological evidence of genital infection was found. Early diagnosis, treatment, information and tracing of contacts are still the cardinal principles in the combat of venereal diseases in Greenland. Udgivelsesdato: 1992-May-18
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- 1992
6. SAT0202 Short-term erosive progression on magnetic resonance images is highly correlated with long-term radiographic progression in rheumatoid arthritis wrists
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Østergaard, M, primary, Hansen, M, additional, Stoltenberg, M, additional, Jensen, KE, additional, Szkudlarek, M, additional, Klarlund, M, additional, Gideon, P, additional, Pedersen-Zbinden, B, additional, and Lorenzen, I, additional
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- 2001
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7. Reflection on EPO
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Stenver D, Jensen Ke, and Nielsen B
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Biomaterials ,Optics ,business.industry ,Biomedical Engineering ,Medicine (miscellaneous) ,Medicine ,Bioengineering ,General Medicine ,business ,Reflection (computer graphics) - Published
- 1990
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8. Social inequality and incidence of and survival from cancer of the female genital organs in a population-based study in Denmark, 1994-2003.
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Jensen KE, Hannibal CG, Nielsen A, Jensen A, Nøhr B, Munk C, and Kjaer SK
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We investigated the effects of socioeconomic, demographic and health-related indicators on the incidence of and survival from cancers of the cervix, endometrium and ovary diagnosed in 1994-2003 with follow-up through 2006 in Denmark using information from nationwide registers. The analyses were based on the data on 3007 patients with cervical cancer, 3826 with endometrial cancer and 3855 with ovarian cancer in a cohort of 3.22 million persons born between 1925 and 1973 and aged >or=30 years. The incidence of cervical cancer increased with decreasing socioeconomic position; the incidences of endometrial and ovarian cancer were mostly associated with higher disposable income. Relative survival from cervical cancer was the highest among women of high socioeconomic position; increased excess mortality rates from endometrial and ovarian cancer were associated with low educational level, mainly during the first year after diagnosis. Socioeconomic position seemed to affect both the incidence of and the survival from cancers of the female genital organs. [ABSTRACT FROM AUTHOR]
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- 2008
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9. Biomarkers of inflammation in patients with unclassified polyarthritis and early rheumatoid arthritis. Relationship to disease activity and radiographic outcome.
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Knudsen LS, Klarlund M, Skjødt H, Jensen T, Østergaard M, Jensen KE, Hansen MS, Hetland ML, Nielsen HJ, Johansen JS, Knudsen, Lene S, Klarlund, Mette, Skjødt, Henrik, Jensen, Trine, Ostergaard, Mikkel, Jensen, Karl Erik, Hansen, Michael S, Hetland, Merete L, Nielsen, Hans J, and Johansen, Julia S
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- 2008
10. Clinical outcome and imaging changes after intraarticular (IA) application of etanercept or methylprednisolone in rheumatoid arthritis: magnetic resonance imaging and ultrasound-Doppler show no effect of IA injections in the wrist after 4 weeks.
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Boesen M, Boesen L, Jensen KE, Cimmino MA, Torp-Pedersen S, Terslev L, Koenig M, Danneskiold-Samsøe B, Røgind H, and Bliddal H
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- 2008
11. Outcome of isolated tibial polyethylene insert exchange after uncemented total knee arthroplasty: 27 patients followed for 8-71 months.
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Jensen CL, Petersen MM, Jensen KE, Therbo M, and Schrøder HM
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Background The outcome of performing isolated tibial polyethylene insert exchange (ITPIE) after total knee arthroplasty (TKA) is under debate. We evaluated the survival probability of ITPE after uncemented TKA. Method 27 patients (27 knees) with an ITPIE performed mean 9 (0.9-17) years after the initial TKA were included in the study (22 patients also had the patellar component replaced simultaneously). All patients had their exchange performed at our department between 1997 and 2001 and had their latest follow-up examination mean 40 (8-71) months after the exchange. Results During the follow-up, 2 patients had total knee revision because of aseptic loosening and 2 patients had isolated patella component exchange (in 1 of the patients, combined with a new ITPIE). Kaplan-Meier survival analysis gave a survival probability of 80% at 34 months of follow-up. Interpretation The short-term survival after an ITPIE was similar to that of a total knee revision with exchange of all components. Since the ITPIE is a much smaller operation with fast rehabilitation, we recommend it in elderly patients with a well-fixed and wellaligned prosthesis without surface damage of the components. [ABSTRACT FROM AUTHOR]
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- 2006
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12. New radiographic bone erosions in the wrists of patients with rheumatoid arthritis are detectable with magnetic resonance imaging a median of two years earlier.
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Østergaard M, Hansen M, Stoltenberg M, Jensen KE, Szkudlarek M, Pedersen-Zbinden B, and Lorenzen I
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OBJECTIVE: In a 5-year followup study, we investigated the temporal relationship between development of wrist joint erosions as visualized by magnetic resonance imaging (MRI) versus conventional radiography (CR), in patients with rheumatoid arthritis. We also evaluated the risk of erosive progression on CR associated with the presence of MRI erosions. METHODS: In 10 patients with rheumatoid arthritis, MRI and CR of the dominant wrist were performed annually for 5 years. In each image set, each wrist bone (metacarpal bases, carpal bones, radius, and ulna) was assessed for the absence or presence of bone erosions. RESULTS: Nine bones showed radiographic erosions at baseline. Twenty-seven new radiographic erosions developed during the 5-year followup period. Of these 27 new erosions, 21 were detected 1-5 years earlier by MRI than by CR, 3 were simultaneously detected by both methods, 2 were detected 1-2 years later by MRI than by CR, and 1 erosion (radiographically detected at 5-year followup) was not visualized with MRI. MRI detection of new radiographic erosions preceded CR detection by a median of 2 years. In bones with MRI erosions at baseline, the relative risk of radiographic erosions at 5-year followup was 4.5 (95% confidence interval [95% CI] 2.6-7.6), compared with bones without baseline MRI erosions. If bones with baseline radiographic erosions were excluded from the analysis, the relative risk was 4.1 (95% CI 2.2-7.5). CONCLUSION: Most new radiographic bone erosions (78%) were visualized at least 1 year earlier by MRI than by CR. This illustrates that the information on joint destruction provided by CR is considerably delayed compared with that provided by MRI. A significantly increased risk of progression of radiographic erosion in bones with baseline MRI erosions was observed, demonstrating a prognostic value of MRI with respect to long-term radiographic outcome. [ABSTRACT FROM AUTHOR]
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- 2003
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13. Carbon black nanoparticle instillation induces sustained inflammation and genotoxicity in mouse lung and liver
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Bourdon Julie A, Saber Anne T, Jacobsen Nicklas R, Jensen Keld A, Madsen Anne M, Lamson Jacob S, Wallin Håkan, Møller Peter, Loft Steffen, Yauk Carole L, and Vogel Ulla B
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Oxidative stress ,Genotoxicity ,DNA strand breaks ,Inflammation ,Nanoparticles ,Carbon Black ,Toxicology. Poisons ,RA1190-1270 ,Industrial hygiene. Industrial welfare ,HD7260-7780.8 - Abstract
Abstract Background Widespread occupational exposure to carbon black nanoparticles (CBNPs) raises concerns over their safety. CBNPs are genotoxic in vitro but less is known about their genotoxicity in various organs in vivo. Methods We investigated inflammatory and acute phase responses, DNA strand breaks (SB) and oxidatively damaged DNA in C57BL/6 mice 1, 3 and 28 days after a single instillation of 0.018, 0.054 or 0.162 mg Printex 90 CBNPs, alongside sham controls. Bronchoalveolar lavage (BAL) fluid was analyzed for cellular composition. SB in BAL cells, whole lung and liver were assessed using the alkaline comet assay. Formamidopyrimidine DNA glycosylase (FPG) sensitive sites were assessed as an indicator of oxidatively damaged DNA. Pulmonary and hepatic acute phase response was evaluated by Saa3 mRNA real-time quantitative PCR. Results Inflammation was strongest 1 and 3 days post-exposure, and remained elevated for the two highest doses (i.e., 0.054 and 0.162 mg) 28 days post-exposure (P < 0.001). SB were detected in lung at all doses on post-exposure day 1 (P < 0.001) and remained elevated at the two highest doses until day 28 (P < 0.05). BAL cell DNA SB were elevated relative to controls at least at the highest dose on all post-exposure days (P < 0.05). The level of FPG sensitive sites in lung was increased throughout with significant increases occurring on post-exposure days 1 and 3, in comparison to controls (P < 0.001-0.05). SB in liver were detected on post-exposure days 1 (P < 0.001) and 28 (P < 0.001). Polymorphonuclear (PMN) cell counts in BAL correlated strongly with FPG sensitive sites in lung (r = 0.88, P < 0.001), whereas no such correlation was observed with SB (r = 0.52, P = 0.08). CBNP increased the expression of Saa3 mRNA in lung tissue on day 1 (all doses), 3 (all doses) and 28 (0.054 and 0.162 mg), but not in liver. Conclusions Deposition of CBNPs in lung induces inflammatory and genotoxic effects in mouse lung that persist considerably after the initial exposure. Our results demonstrate that CBNPs may cause genotoxicity both in the primary exposed tissue, lung and BAL cells, and in a secondary tissue, the liver.
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- 2012
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14. Nanotitanium dioxide toxicity in mouse lung is reduced in sanding dust from paint
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Saber Anne, Jacobsen Nicklas, Mortensen Alicia, Szarek Józef, Jackson Petra, Madsen Anne, Jensen Keld, Koponen Ismo K, Brunborg Gunnar, Gützkow Kristine, Vogel Ulla, and Wallin Håkan
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Nanoparticles ,Nano titanium dioxide ,UV-Titan L181 ,sanding dusts ,paint matrix ,inflammation ,DNA damage ,liver histology ,Toxicology. Poisons ,RA1190-1270 ,Industrial hygiene. Industrial welfare ,HD7260-7780.8 - Abstract
Abstract Background Little is known of how the toxicity of nanoparticles is affected by the incorporation in complex matrices. We compared the toxic effects of the titanium dioxide nanoparticle UV-Titan L181 (NanoTiO2), pure or embedded in a paint matrix. We also compared the effects of the same paint with and without NanoTiO2. Methods Mice received a single intratracheal instillation of 18, 54 and 162 μg of NanoTiO2 or 54, 162 and 486 μg of the sanding dust from paint with and without NanoTiO2. DNA damage in broncheoalveolar lavage cells and liver, lung inflammation and liver histology were evaluated 1, 3 and 28 days after intratracheal instillation. Printex 90 was included as positive control. Results There was no additive effect of adding NanoTiO2 to paints: Therefore the toxicity of NanoTiO2 was reduced by inclusion into a paint matrix. NanoTiO2 induced inflammation in mice with severity similar to Printex 90. The inflammatory response of NanoTiO2 and Printex 90 correlated with the instilled surface area. None of the materials, except of Printex 90, induced DNA damage in lung lining fluid cells. The highest dose of NanoTiO2 caused DNA damage in hepatic tissue 1 day after intratracheal instillation. Exposure of mice to the dust from paints with and without TiO2 was not associated with hepatic histopathological changes. Exposure to NanoTiO2 or to Printex 90 caused slight histopathological changes in the liver in some of the mice at different time points. Conclusions Pulmonary inflammation and DNA damage and hepatic histopathology were not changed in mice instilled with sanding dust from NanoTiO2 paint compared to paint without NanoTiO2. However, pure NanoTiO2 caused greater inflammation than NanoTiO2 embedded in the paint matrix.
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- 2012
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15. Modest effect on plaque progression and vasodilatory function in atherosclerosis-prone mice exposed to nanosized TiO2
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Mikkelsen Lone, Sheykhzade Majid, Jensen Keld A, Saber Anne T, Jacobsen Nicklas R, Vogel Ulla, Wallin Håkan, Loft Steffen, and Møller Peter
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Toxicology. Poisons ,RA1190-1270 ,Industrial hygiene. Industrial welfare ,HD7260-7780.8 - Abstract
Abstract Background There is growing evidence that exposure to small size particulate matter increases the risk of developing cardiovascular disease. Methods We investigated plaque progression and vasodilatory function in apolipoprotein E knockout (ApoE-/-) mice exposed to TiO2. ApoE-/- mice were intratracheally instilled (0.5 mg/kg bodyweight) with rutile fine TiO2 (fTiO2, 288 nm), photocatalytic 92/8 anatase/rutile TiO2 (pTiO2, 12 nm), or rutile nano TiO2 (nTiO2, 21.6 nm) at 26 and 2 hours before measurement of vasodilatory function in aorta segments mounted in myographs. The progression of atherosclerotic plaques in aorta was assessed in mice exposed to nanosized TiO2 (0.5 mg/kg bodyweight) once a week for 4 weeks. We measured mRNA levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue to assess pulmonary inflammation and vascular function. TiO2-induced alterations in nitric oxide (NO) production were assessed in human umbilical vein endothelial cells (HUVECs). Results The exposure to nTiO2 was associated with a modest increase in plaque progression in aorta, whereas there were unaltered vasodilatory function and expression levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue. The ApoE-/- mice exposed to fine and photocatalytic TiO2 had unaltered vasodilatory function and lung tissue inflammatory gene expression. The unaltered NO-dependent vasodilatory function was supported by observations in HUVECs where the NO production was only increased by exposure to nTiO2. Conclusion Repeated exposure to nanosized TiO2 particles was associated with modest plaque progression in ApoE-/- mice. There were no associations between the pulmonary TiO2 exposure and inflammation or vasodilatory dysfunction.
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- 2011
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16. Correction: Effects of prenatal exposure to surface-coated nanosized titanium dioxide (UV-Titan). A study in mice
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Vibenholt Anni, Birkedal Renie K, Larsen Erik H, Löschner Katrin, Sloth Jens J, Jensen Keld A, Jackson Petra, Hougaard Karin S, Boisen Anne-Mette Z, Wallin Håkan, and Vogel Ulla
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Toxicology. Poisons ,RA1190-1270 ,Industrial hygiene. Industrial welfare ,HD7260-7780.8 - Published
- 2011
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17. Effects of prenatal exposure to surface-coated nanosized titanium dioxide (UV-Titan). A study in mice
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Vibenholt Anni, Birkedal Renie K, Larsen Erik H, Löschner Katrin, Sloth Jens J, Jensen Keld A, Jackson Petra, Hougaard Karin S, Boisen Anne-Mette Z, Wallin Håkan, and Vogel Ulla
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Toxicology. Poisons ,RA1190-1270 ,Industrial hygiene. Industrial welfare ,HD7260-7780.8 - Abstract
Abstract Background Engineered nanoparticles are smaller than 100 nm and designed to improve or achieve new physico-chemical properties. Consequently, also toxicological properties may change compared to the parent compound. We examined developmental and neurobehavioral effects following maternal exposure to a nanoparticulate UV-filter (UV-titan L181). Methods Time-mated mice (C57BL/6BomTac) were exposed by inhalation 1h/day to 42 mg/m3 aerosolized powder (1.7·106 n/cm3; peak-size: 97 nm) on gestation days 8-18. Endpoints included: maternal lung inflammation; gestational and litter parameters; offspring neurofunction and fertility. Physicochemical particle properties were determined to provide information on specific exposure and deposition. Results Particles consisted of mainly elongated rutile titanium dioxide (TiO2) with an average crystallite size of 21 nm, modified with Al, Si and Zr, and coated with polyalcohols. In exposed adult mice, 38 mg Ti/kg was detected in the lungs on day 5 and differential cell counts of bronchoalveolar lavage fluid revealed lung inflammation 5 and 26-27 days following exposure termination, relative to control mice. As young adults, prenatally exposed offspring tended to avoid the central zone of the open field and exposed female offspring displayed enhanced prepulse inhibition. Cognitive function was unaffected (Morris water maze test). Conclusion Inhalation exposure to nano-sized UV Titan dusts induced long term lung inflammation in time-mated adult female mice. Gestationally exposed offspring displayed moderate neurobehavioral alterations. The results are discussed in the light of the observed particle size distribution in the exposure atmosphere and the potential pathways by which nanoparticles may impart changes in fetal development.
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- 2010
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18. Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice
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Ladefoged Ole, Vogel Ulla, Jensen Keld, Møller Peter, Jacobsen Nicklas, Loft Steffen, and Wallin Håkan
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Toxicology. Poisons ,RA1190-1270 ,Industrial hygiene. Industrial welfare ,HD7260-7780.8 - Abstract
Abstract Background The toxic and inflammatory potential of 5 different types of nanoparticles were studied in a sensitive model for pulmonary effects in apolipoprotein E knockout mice (ApoE-/-). We studied the effects instillation or inhalation Printex 90 of carbon black (CB) and compared CB instillation in ApoE-/- and C57 mice. Three and 24 h after pulmonary exposure, inflammation was assessed by mRNA levels of cytokines in lung tissue, cell composition, genotoxicity, protein and lactate dehydrogenase activity in broncho-alveolar lavage (BAL) fluid. Results Firstly, we found that intratracheal instillation of CB caused far more pulmonary toxicity in ApoE-/- mice than in C57 mice. Secondly, we showed that instillation of CB was more toxic than inhalation of a presumed similar dose with respect to inflammation in the lungs of ApoE-/- mice. Thirdly, we compared effects of instillation in ApoE-/- mice of three carbonaceous particles; CB, fullerenes C60 (C60) and single walled carbon nanotubes (SWCNT) as well as gold particles and quantum dots (QDs). Characterization of the instillation media revealed that all particles were delivered as agglomerates and aggregates. Significant increases in Il-6, Mip-2 and Mcp-1 mRNA were detected in lung tissue, 3 h and 24 h following instillation of SWCNT, CB and QDs. DNA damage in BAL cells, the fraction of neutrophils in BAL cells and protein in BAL fluid increased statistically significantly. Gold and C60 particles caused much weaker inflammatory responses. Conclusion Our data suggest that ApoE-/- model is sensitive for evaluating particle induced inflammation. Overall QDs had greatest effects followed by CB and SWCNT with C60 and gold being least inflammatory and DNA-damaging. However the gold was used at a much lower mass dose than the other particles. The strong effects of QDs were likely due to Cd release. The surface area of the instilled dose correlated well the inflammatory response for low toxicity particles.
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- 2009
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19. Effects of prenatal exposure to diesel exhaust particles on postnatal development, behavior, genotoxicity and inflammation in mice
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Vogel Ulla, Taxvig Camilla, Nordly Pernille, Jensen Keld A, Hougaard Karin S, Saber Anne T, and Wallin Håkan
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Toxicology. Poisons ,RA1190-1270 ,Industrial hygiene. Industrial welfare ,HD7260-7780.8 - Abstract
Abstract Background Results from epidemiological studies indicate that particulate air pollution constitutes a hazard for human health. Recent studies suggest that diesel exhaust possesses endocrine activity and therefore may affect reproductive outcome. This study in mice aimed to investigate whether exposure to diesel exhaust particles (DEP; NIST 2975) would affect gestation, postnatal development, activity, learning and memory, and biomarkers of transplacental toxicity. Pregnant mice (C57BL/6; BomTac) were exposed to 19 mg/m3 DEP (~1·106 particles/cm3; mass median diameter ≅ 240 nm) on gestational days 9–19, for 1 h/day. Results Gestational parameters were similar in control and diesel groups. Shortly after birth, body weights of DEP offspring were slightly lower than in controls. This difference increased during lactation, so by weaning the DEP exposed offspring weighed significantly less than the control progeny. Only slight effects of exposure were observed on cognitive function in female DEP offspring and on biomarkers of exposure to particles or genotoxic substances. Conclusion In utero exposure to DEP decreased weight gain during lactation. Cognitive function and levels of biomarkers of exposure to particles or to genotoxic substances were generally similar in exposed and control offspring. The particle size and chemical composition of the DEP and differences in exposure methods (fresh, whole exhaust versus aged, resuspended DEP) may play a significant role on the biological effects observed in this compared to other studies.
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- 2008
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20. CHEK2 Founder Variants and Thyroid Cancer Risk.
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Brock P, Liynarachchi S, Nieminen TT, Chan C, Kohlmann W, Stout LA, Yao S, La Greca A, Jensen KE, Kolesar JM, Salhia B, Gulhati P, Hicks JK, and Ringel MD
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- Humans, Case-Control Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Germ-Line Mutation, Checkpoint Kinase 2 genetics, Thyroid Cancer, Papillary, Thyroid Neoplasms genetics
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Background: Germline pathogenic variants in CHEK2 are associated with a moderate increase in the lifetime risk for breast cancer. Increased risk for other cancers, including non-medullary thyroid cancer (NMTC), has also been suggested. To date, data implicating CHEK2 variants in NMTC predisposition primarily derive from studies within Poland, driven by a splice site variant (c.444 + 1G>A) that is uncommon in other populations. In contrast, the predominant CHEK2 variants in non-Polish populations are c.1100del and c.470T>C/p.I157T, representing 61.1% and 63.8%, respectively, of all CHEK2 pathogenic variants in two large U.S.-based commercial laboratory datasets. To further delineate the impact of common CHEK2 variants on thyroid cancer, we aimed to investigate the association of three CHEK2 founder variants (c.444 + 1G>A, c.1100del, and c.470T>C/p.Ile157Thr) on NMTC susceptibility in three groups of unselected NMTC patients. Methods: The presence of three CHEK2 founder variants was assessed within three groups: (1) 1544 NMTC patients (and 1593 controls) from previously published genome-wide association study (GWAS) analyses, (2) 789 NMTC patients with germline exome sequencing (Oncology Research Information Exchange Network [ORIEN] Avatar), and (3) 499 NMTC patients with germline sequence data available in The Cancer Genome Atlas (TCGA). A case-control study design was utilized with odds ratios (ORs) calculated by comparison of all three groups with the Ohio State University GWAS control group. Results: The predominant Polish variant (c.444 + 1G>A) was present in only one case. The proportion of patients with c.1100del was 0.92% in the GWAS group, 1.65% in the ORIEN Avatar group, and 0.80% in the TCGA group. The ORs (with 95% confidence intervals [CIs]) for NMTC associated with c.1100del were 1.71 (0.73-4.29), 2.64 (0.95-7.63), and 2.5 (0.63-8.46), respectively. The proportion of patients with c.470T>C/p.I157T was 0.91% in the GWAS group, 0.76% in the ORIEN Avatar group, and 0.80% in the TCGA group, respectively. The ORs (with CIs) for NMTC associated with c.470T>C/p.I157T were 1.75 (0.74-4.39), 1.52 (0.42-4.96), and 2.31 (0.58-7.90), respectively. Conclusions: Our analyses of unselected patients with NMTC suggest that CHEK2 variants c.1100del and c.470T>C/p.I157T have only a modest impact on thyroid cancer risk. These results provide important information for providers regarding the relatively low magnitude of thyroid cancer risk associated with these CHEK2 variants.
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- 2024
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21. A 3D-printed flow-cell for on-grid purification of electron microscopy samples directly from lysate.
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Ramlaul K, Feng Z, Canavan C, de Martín Garrido N, Carreño D, Crone M, Jensen KE, Li B, Barnett H, Riglar DT, Freemont PS, Miller D, and Aylett CHS
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- Cryoelectron Microscopy methods, Microscopy, Electron, Proteins, Printing, Three-Dimensional
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While recent advances in cryo-EM, coupled with single particle analysis, have the potential to allow structure determination in a near-native state from vanishingly few individual particles, this vision has yet to be realised in practise. Requirements for particle numbers that currently far exceed the theoretical lower limits, challenges with the practicalities of achieving high concentrations for difficult-to-produce samples, and inadequate sample-dependent imaging conditions, all result in significant bottlenecks preventing routine structure determination using cryo-EM. Therefore, considerable efforts are being made to circumvent these bottlenecks by developing affinity purification of samples on-grid; at once obviating the need to produce large amounts of protein, as well as more directly controlling the variable, and sample-dependent, process of grid preparation. In this proof-of-concept study, we demonstrate a further practical step towards this paradigm, developing a 3D-printable flow-cell device to allow on-grid affinity purification from raw inputs such as whole cell lysates, using graphene oxide-based affinity grids. Our flow-cell device can be interfaced directly with routinely-used laboratory equipment such as liquid chromatographs, or peristaltic pumps, fitted with standard chromatographic (1/16") connectors, and can be used to allow binding of samples to affinity grids in a controlled environment prior to the extensive washing required to remove impurities. Furthermore, by designing a device which can be 3D printed and coupled to routinely used laboratory equipment, we hope to increase the accessibility of the techniques presented herein to researchers working towards single-particle macromolecular structures., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2023
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22. Editorial: Translational research in thyroid cancer, Volume II.
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Cheng SY, Vasko V, and Jensen KE
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- Humans, Translational Research, Biomedical, Thyroid Neoplasms genetics, Thyroid Neoplasms therapy
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Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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- 2023
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23. Non-metabolic functions of phosphofructokinase-1 orchestrate tumor cellular invasion and genome maintenance under bevacizumab therapy.
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Lim YC, Jensen KE, Aguilar-Morante D, Vardouli L, Vitting-Seerup K, Gimple RC, Wu Q, Pedersen H, Elbaek KJ, Gromova I, Ihnatko R, Kristensen BW, Petersen JK, Skjoth-Rasmussen J, Flavahan W, Rich JN, and Hamerlik P
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- Humans, Bevacizumab pharmacology, Bevacizumab therapeutic use, Phosphofructokinase-1, Glioblastoma drug therapy, Glioblastoma genetics, Glioblastoma metabolism, Brain Neoplasms drug therapy, Brain Neoplasms genetics, Brain Neoplasms metabolism
- Abstract
Background: Glioblastoma (GBM) is a highly lethal malignancy for which neoangiogenesis serves as a defining hallmark. The anti-VEGF antibody, bevacizumab, has been approved for the treatment of recurrent GBM, but resistance is universal., Methods: We analyzed expression data of GBM patients treated with bevacizumab to discover potential resistance mechanisms. Patient-derived xenografts (PDXs) and cultures were interrogated for effects of phosphofructokinase-1, muscle isoform (PFKM) loss on tumor cell motility, migration, and invasion through genetic and pharmacologic targeting., Results: We identified PFKM as a driver of bevacizumab resistance. PFKM functions dichotomize based on subcellular location: cytosolic PFKM interacted with KIF11, a tubular motor protein, to promote tumor invasion, whereas nuclear PFKM safeguarded genomic stability of tumor cells through interaction with NBS1. Leveraging differential transcriptional profiling, bupivacaine phenocopied genetic targeting of PFKM, and enhanced efficacy of bevacizumab in preclinical GBM models in vivo., Conclusion: PFKM drives novel molecular pathways in GBM, offering a translational path to a novel therapeutic paradigm., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
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24. Geometrical frustration of phase-separated domains in Coscinodiscus diatom frustules.
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Feofilova M, Schüepp S, Schmid R, Hacker F, Spanke HT, Bain N, Jensen KE, and Dufresne ER
- Subjects
- Nanostructures, Porosity, Cell Wall chemistry, Diatoms chemistry, Silicon Dioxide
- Abstract
Diatoms are single-celled organisms with a cell wall made of silica, called the frustule. Even though their elaborate patterns have fascinated scientists for years, little is known about the biological and physical mechanisms underlying their organization. In this work, we take a top-down approach and examine the micrometer-scale organization of diatoms from the Coscinodiscus family. We find two competing tendencies of organization, which appear to be controlled by distinct biological pathways. On one hand, micrometer-scale pores organize locally on a triangular lattice. On the other hand, lattice vectors tend to point globally toward a center of symmetry. This competition results in a frustrated triangular lattice, populated with geometrically necessary defects whose density increases near the center.
- Published
- 2022
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25. A discrete parasubthalamic nucleus subpopulation plays a critical role in appetite suppression.
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Kim JH, Kromm GH, Barnhill OK, Sperber J, Heuer LB, Loomis S, Newman MC, Han K, Gulamali FF, Legan TB, Jensen KE, Funderburk SC, Krashes MJ, and Carter ME
- Subjects
- Animals, Corticotropin-Releasing Hormone metabolism, Eating physiology, Mice, Neurons physiology, Optogenetics, Appetite, Appetite Regulation
- Abstract
Food intake behavior is regulated by a network of appetite-inducing and appetite-suppressing neuronal populations throughout the brain. The parasubthalamic nucleus (PSTN), a relatively unexplored population of neurons in the posterior hypothalamus, has been hypothesized to regulate appetite due to its connectivity with other anorexigenic neuronal populations and because these neurons express Fos, a marker of neuronal activation, following a meal. However, the individual cell types that make up the PSTN are not well characterized, nor are their functional roles in food intake behavior. Here, we identify and distinguish between two discrete PSTN subpopulations, those that express tachykinin-1 (PSTN
Tac1 neurons) and those that express corticotropin-releasing hormone (PSTNCRH neurons), and use a panel of genetically encoded tools in mice to show that PSTNTac1 neurons play an important role in appetite suppression. Both subpopulations increase activity following a meal and in response to administration of the anorexigenic hormones amylin, cholecystokinin (CCK), and peptide YY (PYY). Interestingly, chemogenetic inhibition of PSTNTac1 , but not PSTNCRH neurons, reduces the appetite-suppressing effects of these hormones. Consistently, optogenetic and chemogenetic stimulation of PSTNTac1 neurons, but not PSTNCRH neurons, reduces food intake in hungry mice. PSTNTac1 and PSTNCRH neurons project to distinct downstream brain regions, and stimulation of PSTNTac1 projections to individual anorexigenic populations reduces food consumption. Taken together, these results reveal the functional properties and projection patterns of distinct PSTN cell types and demonstrate an anorexigenic role for PSTNTac1 neurons in the hormonal and central regulation of appetite., Competing Interests: JK, GK, OB, JS, LH, SL, MN, KH, FG, TL, KJ, SF, MK, MC No competing interests declared- Published
- 2022
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26. Development of a highly sensitive chemiluminescence immunoassay for quantification of aggrecanase-generated ARGS aggrecan fragments in serum.
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He Y, Jensen KE, Siebuhr AS, Karsdal MA, Larkin J, and Bay-Jensen AC
- Abstract
Objective: Cartilage degradation is a hallmark of osteoarthritis (OA). Aggrecan, a major proteoglycan of articular cartilage extracellular matrix (ECM), is degraded by ADAMTS-5 resulting in the release of ARGS-G2 fragments to synovial fluid and circulation. The aim was to quantify ARGS-G2 in the serum of OA patients using the huARGS immunoassay., Methods: The immunoassay was produced under GMP conditions and the technical performance was assessed. The biological relevance of the immunoassay was assessed in the conditioned media from a bovine full-depth cartilage explant (BEX) model. The diurnal and inter-day variations of ARGS levels were evaluated in OA patients' serum. Post-hoc analysis of huARGS was conducted in a sub-cohort of a phase III OA trial testing the safety and efficacy of oral salmon calcitonin., Results: Technical performance : huARGS demonstrated good technical performance. Biological relevance : ARGS release was induced by inflamatory facotrs stimulation compared to the vehicle group, reaching a peak at day 3 and gradually decreasing to base level at day 12. The ARGS release was suppressed by the addition of the ADAMTS-4/-5 activation inhibitor. Biological variation : No significant diurnal or inter-day effect was found. Phase III clinical trial: The participants in the lowest group (Q1) of baseline huARGS levels were more likely to progress radiographically than the highest group (Q4): OR 3.38[0.81-14.02]., Conclusions: The huARGS shows good technical performance and low biological variation. It has the potential to aid drug development in various stages, both as a PD biomarker and identifying progressors who might be likely to respond to an OA drug., Competing Interests: MAK, ACBJ are full-time employees and shareholders of Nordic Bioscience A/S. YH, KEJ and ASS are full-time employees at Nordic Bioscience A/S. JLA is a full-time employee and shareholder of GlaxoSmithKline., (© 2021 The Author(s).)
- Published
- 2021
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27. Perspective: targeting VEGF-A and YKL-40 in glioblastoma - matter matters.
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Holst CB, Pedersen H, Obara EAA, Vitting-Seerup K, Jensen KE, Skjøth-Rasmussen J, Lund EL, Poulsen HS, Johansen JS, and Hamerlik P
- Subjects
- Animals, Antineoplastic Agents, Immunological administration & dosage, Brain Neoplasms metabolism, Chitinase-3-Like Protein 1 metabolism, Drug Resistance, Neoplasm drug effects, Drug Resistance, Neoplasm physiology, Glioblastoma metabolism, Humans, Mice, Mice, Inbred NOD, Tumor Microenvironment drug effects, Tumor Microenvironment physiology, Vascular Endothelial Growth Factor A metabolism, Xenograft Model Antitumor Assays methods, Bevacizumab administration & dosage, Brain Neoplasms drug therapy, Chitinase-3-Like Protein 1 antagonists & inhibitors, Drug Delivery Systems methods, Glioblastoma drug therapy, Vascular Endothelial Growth Factor A antagonists & inhibitors
- Abstract
Glioblastomas (GBM) are heterogeneous highly vascular brain tumors exploiting the unique microenvironment in the brain to resist treatment and anti-tumor responses. Anti-angiogenic agents, immunotherapy, and targeted therapy have been studied extensively in GBM patients over a number of decades with minimal success. Despite maximal efforts, prognosis remains dismal with an overall survival of approximately 15 months.Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, underwent accelerated approval by the U.S. Food and Drug Administration in 2009 for the treatment of recurrent GBM based on promising preclinical and early clinical studies. Unfortunately, subsequent clinical trials did not find overall survival benefit. Pursuing pleiotropic targets and leaning toward multitarget strategies may be a key to more effective therapeutic intervention in GBM, but preclinical evaluation requires careful consideration of model choices. In this study, we discuss bevacizumab resistance, dual targeting of pro-angiogenic modulators VEGF and YKL-40 in the context of brain tumor microenvironment, and how model choice impacts study conclusions and its translational significance.
- Published
- 2021
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28. Feed Intake as an Estimation of Attractability in Pacific White Shrimp Litopenaeus vannamei .
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Yuan Y, Chehade SB, Jensen KE, Barry RJ, Fowler LA, Makowsky R, Powell ML, Lawrence AL, and Watts SA
- Abstract
A simple bioassay that quantifies feed intake as an estimation of relative attractability of feeds containing different ingredients in the Pacific white shrimp Litopenaeus vannamei is described. Fish meal (FM), fish protein hydrolysate (FPH), squid meal (SqM) and casein (CN) were assessed at the same dietary level for their relative influence on feed intake rates of Litopenaeus vannamei . A bland diet containing 92% whole wheat grain meal, 6% diatomaceous earth and 2% alginate with a known low attractability was used as the standard control or base diet. Ingredients were added to the bland base control diet at a level of 3% as fed. Shrimp were stocked into 80 L glass tanks (n= 20 per tank) in a recirculating aquaculture system. Tanks were randomly assigned to one of five diet treatments (3tanks/treatment). Experiments measuring the attractability of each feed were conducted twice daily at 0900 hours and 1330 hours over a five day period. For each experiment, 40 feed pellets (ca. 1 g) corresponding to the assigned treatment were provided to each tank. To calculate the rate of feed intake, pellets remaining in each tank were counted at six minute intervals for a seventy-two minute period. Differences in rate of feed intake among diets were evaluated using Cox Regression Analysis. This attractability assay required only small amounts of ingredients and incorporated ingredients into a bland feed, which significantly reduces the influence from other ingredients or compound in the pellets. All of the test protein ingredients, especially SqM, in the feeds significantly increased the feed consumption rate. The diet containing SqM was consumed at a significantly higher rate than those containing casein and FM but not FPH. FPH and CN containing diets were not significantly different but consumed at a higher rate than the diet containing FM. Results of these trials indicate that the presence of certain ingredients can increase feed intake, thereby increasing nutrient availability of the diets. This reported method to determine consumption of diets containing certain ingredients can be considered as a valid method to estimate attractability., Competing Interests: Conflict of Interest: The authors have no conflict of interest. DECLARATIONS OF COMPETING INTEREST The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
- Published
- 2021
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29. A High-Affinity Peptide Ligand Targeting Syntenin Inhibits Glioblastoma.
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Haugaard-Kedström LM, Clemmensen LS, Sereikaite V, Jin Z, Fernandes EFA, Wind B, Abalde-Gil F, Daberger J, Vistrup-Parry M, Aguilar-Morante D, Leblanc R, Egea-Jimenez AL, Albrigtsen M, Jensen KE, Jensen TMT, Ivarsson Y, Vincentelli R, Hamerlik P, Andersen JH, Zimmermann P, Lee W, and Strømgaard K
- Subjects
- Animals, Cell Line, Tumor, Drug Delivery Systems, High-Throughput Screening Assays, Humans, Ligands, Mice, Microsomes metabolism, Models, Molecular, Mutation, Protein Binding, X-Ray Diffraction, Xenograft Model Antitumor Assays, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Brain Neoplasms drug therapy, Glioblastoma drug therapy, Peptides chemistry, Peptides pharmacology, Syntenins drug effects
- Abstract
Despite the recent advances in cancer therapeutics, highly aggressive cancer forms, such as glioblastoma (GBM), still have very low survival rates. The intracellular scaffold protein syntenin, comprising two postsynaptic density protein-95/discs-large/zona occludens-1 (PDZ) domains, has emerged as a novel therapeutic target in highly malignant phenotypes including GBM. Here, we report the development of a novel, highly potent, and metabolically stable peptide inhibitor of syntenin, KSL-128114, which binds the PDZ1 domain of syntenin with nanomolar affinity. KSL-128114 is resistant toward degradation in human plasma and mouse hepatic microsomes and displays a global PDZ domain selectivity for syntenin. An X-ray crystal structure reveals that KSL-128114 interacts with syntenin PDZ1 in an extended noncanonical binding mode. Treatment with KSL-128114 shows an inhibitory effect on primary GBM cell viability and significantly extends survival time in a patient-derived xenograft mouse model. Thus, KSL-128114 is a novel promising candidate with therapeutic potential for highly aggressive tumors, such as GBM.
- Published
- 2021
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30. Viscoelastic and Poroelastic Relaxations of Soft Solid Surfaces.
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Xu Q, Wilen LA, Jensen KE, Style RW, and Dufresne ER
- Abstract
Understanding surface mechanics of soft solids, such as soft polymeric gels, is crucial in many engineering processes, such as dynamic wetting and adhesive failure. In these situations, a combination of capillary and elastic forces drives the motion, which is balanced by dissipative mechanisms to determine the rate. While shear rheology (i.e., viscoelasticity) has long been assumed to dominate the dissipation, recent works have suggested that compressibility effects (i.e., poroelasticity) could play roles in swollen networks. We use fast interferometric imaging to quantify the relaxation of surface deformations due to a displaced contact line. By systematically measuring the profiles at different time and length scales, we experimentally observe a crossover from viscoelastic to poroelastic surface relaxations.
- Published
- 2020
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31. SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells.
- Author
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Obara EAA, Aguilar-Morante D, Rasmussen RD, Frias A, Vitting-Serup K, Lim YC, Elbæk KJ, Pedersen H, Vardouli L, Jensen KE, Skjoth-Rasmussen J, Brennum J, Tuckova L, Strauss R, Dinant C, Bartek J, and Hamerlik P
- Subjects
- Animals, Apoptosis, BRCA1 Protein, Brain Neoplasms genetics, Cell Cycle Checkpoints, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Gene Silencing, Glioblastoma pathology, HEK293 Cells, Heterografts, Humans, Mice, Mice, Inbred BALB C, RNA, Small Interfering genetics, Radiation Tolerance, Radiation, Ionizing, Transcriptome, DNA Repair, Genomic Instability, Glioblastoma genetics, Neoplastic Stem Cells pathology, Transcription Factors genetics, Transcription Factors metabolism
- Abstract
Glioblastoma cancer-stem like cells (GSCs) display marked resistance to ionizing radiation (IR), a standard of care for glioblastoma patients. Mechanisms underpinning radio-resistance of GSCs remain largely unknown. Chromatin state and the accessibility of DNA lesions to DNA repair machineries are crucial for the maintenance of genomic stability. Understanding the functional impact of chromatin remodeling on DNA repair in GSCs may lay the foundation for advancing the efficacy of radio-sensitizing therapies. Here, we present the results of a high-content siRNA microscopy screen, revealing the transcriptional elongation factor SPT6 to be critical for the genomic stability and self-renewal of GSCs. Mechanistically, SPT6 transcriptionally up-regulates BRCA1 and thereby drives an error-free DNA repair in GSCs. SPT6 loss impairs the self-renewal, genomic stability and tumor initiating capacity of GSCs. Collectively, our results provide mechanistic insights into how SPT6 regulates DNA repair and identify SPT6 as a putative therapeutic target in glioblastoma.
- Published
- 2020
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32. Editorial: Translational Research in Thyroid Cancer.
- Author
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Vasko V, Kebebew E, Cheng SY, and Jensen KE
- Subjects
- Humans, Thyroid Neoplasms diagnosis, Thyroid Neoplasms therapy, Translational Research, Biomedical
- Published
- 2020
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33. 3D Printing of Reservoir Devices for Oral Drug Delivery: From Concept to Functionality through Design Improvement for Enhanced Mucoadhesion.
- Author
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Vaut L, Juszczyk JJ, Kamguyan K, Jensen KE, Tosello G, and Boisen A
- Subjects
- Microtechnology, Printing, Three-Dimensional, Drug Delivery Systems, Pharmaceutical Preparations
- Abstract
So far, microdevices for oral drug delivery have been fabricated as square or cylindrical reservoir structures with a localized and unidirectional release. The fabrication is usually carried out using sophisticated and costly microfabrication techniques. Here, 3D printing of microreservoirs on sacrificial substrates is presented. This approach allows the devices to be accurately arranged in predetermined patterns, enabling implementation into batch production schemes in which the fabrication of the devices is linked to processing steps such as automated drug loading and sealing. Moreover, design and 3D printing of alternative geometries of minireservoirs featuring anchor-like surface structures for improved mucoadhesion and intestinal retention is demonstrated. Surface texturing of minireservoirs increases mucoadhesion of the devices up to two-fold compared to a nonstructured control. The structuring also leads to a strong bias in mucoadhesion in different orientations, which can facilitate a correct orientation of the devices and thus lead to unidirectional release of drugs toward the intestinal mucosa for increased drug uptake.
- Published
- 2020
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34. Comparison of hippocampal volume measurement by autopsy and post-mortem magnetic resonance imaging.
- Author
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Lundemose S, Busch JR, Møller M, Jensen KE, Lynnerup N, Banner J, and Jacobsen C
- Subjects
- Algorithms, Anatomic Landmarks, Autopsy, Humans, Image Processing, Computer-Assisted, Imaging, Three-Dimensional, Tomography, X-Ray Computed, Hippocampus diagnostic imaging, Hippocampus pathology, Magnetic Resonance Imaging
- Abstract
We present an autopsy-validated, non-invasive, magnetic resonance imaging (MRI) based segmentation algorithm, for determining hippocampal volume. A segmentation algorithm was developed to assess the volume of the hippocampus. Deceased individuals with severe mental illness were used to evaluate the use of MRI imaging to determine hippocampal volume as this group has previously been associated with altered hippocampal volume diagnosed on MRI. The accuracy of the MR- scanning protocol for volume measurement was tested on a water filled phantom control with a known volume of 500 ml, and a difference of 0.08% was found. Thus the scanning protocol was deemed to have produced acceptable results when comparing volume measures of a pair of segmented hippocampi obtained at the 1 T MR scanner and a 3 T MR scanner using the software program Mimics®. The segmentation algorithm was tested by a volume comparison obtained using anterior and posterior landmarks (in situ) and the exact volume of the dissected hippocampus (ex situ). The in situ and ex situ hippocampal volumes were highly correlated; R
2 was 96%, with a mean difference of 4-5%. Cases were also examined for intra- and inter-observer agreement. This study presents a validated segmentation algorithm that can be used to determine the hippocampal volume using post-mortem MR and anatomical landmarks.- Published
- 2020
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35. Effects of strain-dependent surface stress on the adhesive contact of a rigid sphere to a compliant substrate.
- Author
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Liu Z, Jensen KE, Xu Q, Style RW, Dufresne ER, Jagota A, and Hui CY
- Abstract
Recent experiments have reported that the surface stress of soft elastic solids can increase rapidly with surface strain. For example, when a small hard sphere in adhesive contact with a soft silicone gel is slowly retracted from its rest position, it was found that the retraction force versus displacement relation cannot be explained either by the Johnson-Kendall-Roberts (JKR) theory or a recent indentation theory based on an isotropic surface stress that is independent of surface strain. In this paper, we address this problem using a finite element method to simulate the retraction process. Our numerical model does not have the restrictions of the aforementioned theories; that is, it can handle large nonlinear elastic deformation as well as a surface-strain-dependent surface stress. Our simulation is in good agreement with experimental force versus displacement data with no fitting parameters. Therefore, our results lend further support to the claim that significant strain-dependent surface stresses can occur in simple soft elastic gels. However, significant challenges remain in the reconciliation of theory and experiments, particularly regarding the geometry of the contact and substrate deformation.
- Published
- 2019
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36. Singular dynamics in the failure of soft adhesive contacts.
- Author
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Berman JD, Randeria M, Style RW, Xu Q, Nichols JR, Duncan AJ, Loewenberg M, Dufresne ER, and Jensen KE
- Abstract
We characterize the mechanical recovery of compliant silicone gels following adhesive contact failure. We establish broad, stable adhesive contacts between rigid microspheres and soft gels, then stretch the gels to large deformations by pulling quasi-statically on the contact. Eventually, the adhesive contact begins to fail, and ultimately slides to a final contact point on the bottom of the sphere. Immediately after detachment, the gel recoils quickly with a self-similar surface profile that evolves as a power law in time, suggesting that the adhesive detachment point is singular. The singular dynamics we observe are consistent with a relaxation process driven by surface stress and slowed by viscous flow through the porous, elastic network of the gel. Our results emphasize the importance of accounting for both the liquid and solid phases of gels in understanding their mechanics, especially under extreme deformation.
- Published
- 2019
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37. Author Correction: BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity.
- Author
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Rasmussen RD, Gajjar MK, Tuckova L, Jensen KE, Maya-Mendoza A, Holst CB, Møllgård K, Rasmussen JS, Brennum J, Bartek J Jr, Syrucek M, Sedlakova E, Andersen KK, Frederiksen MH, Bartek J, and Hamerlik P
- Abstract
This Article contains an error in the spelling of the author Kjeld Møllgård, which is incorrectly given as Kjeld Møllgaard. The error has not been fixed in the original PDF and HTML versions of the Article.
- Published
- 2018
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38. VEGF-C sustains VEGFR2 activation under bevacizumab therapy and promotes glioblastoma maintenance.
- Author
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Michaelsen SR, Staberg M, Pedersen H, Jensen KE, Majewski W, Broholm H, Nedergaard MK, Meulengracht C, Urup T, Villingshøj M, Lukacova S, Skjøth-Rasmussen J, Brennum J, Kjær A, Lassen U, Stockhausen MT, Poulsen HS, and Hamerlik P
- Subjects
- Angiogenesis Inhibitors pharmacology, Animals, Apoptosis, Autocrine Communication, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Cell Cycle, Cell Proliferation, Female, Gene Expression Regulation, Neoplastic, Glioblastoma drug therapy, Glioblastoma metabolism, Humans, Mice, Mice, Nude, Signal Transduction, Tumor Cells, Cultured, Vascular Endothelial Growth Factor C genetics, Vascular Endothelial Growth Factor Receptor-2 genetics, Xenograft Model Antitumor Assays, Bevacizumab pharmacology, Glioblastoma pathology, Vascular Endothelial Growth Factor C metabolism, Vascular Endothelial Growth Factor Receptor-2 metabolism
- Abstract
Background: Glioblastoma ranks among the most lethal cancers, with current therapies offering only palliation. Paracrine vascular endothelial growth factor (VEGF) signaling has been targeted using anti-angiogenic agents, whereas autocrine VEGF/VEGF receptor 2 (VEGFR2) signaling is poorly understood. Bevacizumab resistance of VEGFR2-expressing glioblastoma cells prompted interrogation of autocrine VEGF-C/VEGFR2 signaling in glioblastoma., Methods: Autocrine VEGF-C/VEGFR2 signaling was functionally investigated using RNA interference and exogenous ligands in patient-derived xenograft lines and primary glioblastoma cell cultures in vitro and in vivo. VEGF-C expression and interaction with VEGFR2 in a matched pre- and post-bevacizumab treatment cohort were analyzed by immunohistochemistry and proximity ligation assay., Results: VEGF-C was expressed by patient-derived xenograft glioblastoma lines, primary cells, and matched surgical specimens before and after bevacizumab treatment. VEGF-C activated autocrine VEGFR2 signaling to promote cell survival, whereas targeting VEGF-C expression reprogrammed cellular transcription to attenuate survival and cell cycle progression. Supporting potential translational significance, targeting VEGF-C impaired tumor growth in vivo, with superiority to bevacizumab treatment., Conclusions: Our results demonstrate VEGF-C serves as both a paracrine and an autocrine pro-survival cytokine in glioblastoma, promoting tumor cell survival and tumorigenesis. VEGF-C permits sustained VEGFR2 activation and tumor growth, where its inhibition appears superior to bevacizumab therapy in improving tumor control.
- Published
- 2018
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39. The contact mechanics challenge: tribology meets soft matter.
- Author
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Style RW, Krick BA, Jensen KE, and Sawyer WG
- Abstract
In the fall of 2015, Martin Müser suggested a Contact Mechanics Challenge for the Tribology community. The challenge was an ambitious effort to compare a wide variety of theoretical and computational contact-mechanics approaches, and involved researchers voluntarily tackling the same hypothetical contact problem. The result is an impressive collection of innovative approaches - including a surprise experimental effort - that highlight the continuing importance of surface contact mechanics and the challenges of solving these large-scale problems. Here, we describe how the Contact Mechanics Challenge also reveals exciting opportunities for the Soft Matter community to engage intensely with classical and emerging problems in tribology, surface science, and contact mechanics.
- Published
- 2018
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40. The Impact of Road Construction on Subjective Well-Being in Communities in Madre de Dios, Peru.
- Author
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Riley-Powell AR, Lee GO, Naik NS, Jensen KE, O'Neal C, Salmón-Mulanovich G, Hartinger SM, Bausch DG, and Paz-Soldan VA
- Subjects
- Adult, Cross-Sectional Studies, Female, Health Surveys, Humans, Male, Middle Aged, Peru, Qualitative Research, Construction Industry, Environmental Health, Health Status, Transportation
- Abstract
The interoceanic highway (IOH) in Madre de Dios, Peru has driven dramatic change in the Peruvian Amazon basin. We conducted a mixed methods study to examine the impact of these changes on the subjective well-being (SWB) of four communities on the IOH. Themes that emerged qualitatively included changing health threats, environmental degradation, and the impact of increased migration. To achieve a higher level of SWB, respondents emphasized the need for higher incomes, opportunities to learn new skills, and a better education for their children. Potential threats to SWB included marital problems and poorer health. Quantitative analyses suggested that social support and a sense of security impacted reported SWB scores based on life satisfaction, and the impact of income on life satisfaction was mediated by food security. Although long-term residents felt that specific determinants of SWB had both increased (food variety, transport and access to work) and decreased (access to natural resources and hunting), the majority reported that their lives had improved overall. Health had been affected by the IOH in both negative ways (increased dengue and road accidents) and positive ways (improved access to health services). Our results suggest that the rapidly-changing communities near the IOH link well-being to health, income, community, and the environment.
- Published
- 2018
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41. Targeting glioma stem-like cell survival and chemoresistance through inhibition of lysine-specific histone demethylase KDM2B.
- Author
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Staberg M, Rasmussen RD, Michaelsen SR, Pedersen H, Jensen KE, Villingshøj M, Skjoth-Rasmussen J, Brennum J, Vitting-Seerup K, Poulsen HS, and Hamerlik P
- Subjects
- Apoptosis drug effects, Astrocytes metabolism, Brain Neoplasms pathology, Cell Line, DNA Damage drug effects, Etoposide administration & dosage, F-Box Proteins genetics, Glioblastoma pathology, Histones metabolism, Humans, Jumonji Domain-Containing Histone Demethylases genetics, Lomustine administration & dosage, Lysine metabolism, Primary Cell Culture, Antineoplastic Agents administration & dosage, Brain Neoplasms drug therapy, Drug Resistance, Neoplasm, F-Box Proteins metabolism, Glioblastoma drug therapy, Jumonji Domain-Containing Histone Demethylases metabolism, Neoplastic Stem Cells metabolism
- Abstract
Glioblastoma (GBM) ranks among the most lethal cancers, with current therapies offering only palliation. Inter- and intrapatient heterogeneity is a hallmark of GBM, with epigenetically distinct cancer stem-like cells (CSCs) at the apex. Targeting GSCs remains a challenging task because of their unique biology, resemblance to normal neural stem/progenitor cells, and resistance to standard cytotoxic therapy. Here, we find that the chromatin regulator, JmjC domain histone H3K36me2/me1 demethylase KDM2B, is highly expressed in glioblastoma surgical specimens compared to normal brain. Targeting KDM2B function genetically or pharmacologically impaired the survival of patient-derived primary glioblastoma cells through the induction of DNA damage and apoptosis, sensitizing them to chemotherapy. KDM2B loss decreased the GSC pool, which was potentiated by coadministration of chemotherapy. Collectively, our results demonstrate KDM2B is crucial for glioblastoma maintenance, with inhibition causing loss of GSC survival, genomic stability, and chemoresistance., (© 2018 Danish Cancer Society. Published by FEBS Press and John Wiley & Sons Ltd.)
- Published
- 2018
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42. Small scale migration along the interoceanic highway in Madre de Dios, Peru: an exploration of community perceptions and dynamics due to migration.
- Author
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Jensen KE, Naik NN, O'Neal C, Salmón-Mulanovich G, Riley-Powell AR, Lee GO, Hartinger SM, Bausch DG, and Paz-Soldan VA
- Subjects
- Female, Focus Groups, Humans, Male, Peru, Rural Population, Surveys and Questionnaires, Demography, Economic Development, Perception, Transients and Migrants psychology
- Abstract
Background: Madre de Dios, a southern state in the Peruvian Amazon basin, has experienced rapid development as well as an influx of migrants since the construction of the Interoceanic Highway (IOH) connecting Brazil, Bolivia, and the Peruvian coast. We explored perceptions of migration and development in up to eight communities along the IOH in Madre de Dios following construction of the highway., Methods: We conducted a multiple methods study involving focus group (FG) discussions and interviews with key informants (KIs) in eight communities in Madre de Dios. The data was used to develop and apply a survey on demographics, financial, personal, social, human, and physical capital in four communities between February 2014 and March 2015., Results: We conducted 12 FGs and 34 KI interviews. A total of 522 people participated in the survey. Comparing migrants (those who had moved to the area after construction of the IOH) and non-migrants, we found no difference in food security or access to health services. The majority (67.6%) of respondents from both groups reported that illness was their primary threat to well-being. Non-migrants owned more land than migrants (p < 0.001), were more likely to have piped water directly in their home (p = 0.046), and were more likely to participate in community groups (p = 0.012). Looking at perceptions about migrants, KIs and FGs discussed both positive perceptions of migrants (increased cultural exchange and new technology) and negative perceptions (increased drugs and alcohol in their communities and a lack of investment in the community). Both migrants and non-migrants reported trusting the local government more than the national government., Conclusions: Although we hypothesized that migrants would have decreased access to food, water, health services, and land relative to non-migrants, our results show that the only significant differences were in land ownership and water access. Efforts to improve community infrastructure should be carried out at the local level and focus on improving issues reported by both groups, such as potable water, sewage, and increased access to health services. Furthermore, an emphasis on community cohesion, ensuring land rights, and increasing long-term job opportunities should help ease tensions between migrants and non-migrants.
- Published
- 2018
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43. Side Effects Associated with the Use of Intensity-Modulated Radiation Therapy in Breast Cancer Patients Undergoing Adjuvant Radiation Therapy: A Systematic Review and Meta-Analysis.
- Author
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Jensen KE, Soril LJJ, Stelfox HT, Clement FM, Lin Y, and Marshall DA
- Subjects
- Female, Humans, Radiotherapy, Adjuvant, Treatment Outcome, Breast Neoplasms radiotherapy, Radiotherapy, Intensity-Modulated adverse effects
- Abstract
Purpose: The purpose of the study was to establish the efficacy and safety of breast intensity-modulated radiation therapy (IMRT) compared with non-IMRT standard wedge radiation therapy (RT) for the treatment of adjuvant breast cancer., Methods: A systematic review and meta-analysis were completed using STATA and a random effects model. A total of 1,499 citations were identified from the literature search. Of those, 1,475 were excluded based on abstract review. Full texts of 24 remaining articles were reviewed and 11 articles were included in the final analysis. Side effects were analysed as the primary outcomes of interest. We calculated individual odds ratios and 95% confidence intervals for 17 classifications of side effects reported. The data for eight classifications of side effects were then pooled for meta-analyses to obtain more precise estimates of the relationships between adjuvant RT and a particular side effect., Results: The pooled analyses revealed potential protective associations between adjuvant IMRT and two acute side effects: dermatitis and moist desquamation. The remaining pooled estimates suggest that the odds of developing edema, hyperpigmentation, fat necrosis, pain, induration were no worse, nor better among those treated with IMRT compared with those treated with non-IMRT standard wedge RT., Conclusion: The pooled estimates from this meta-analysis are in line with the existing evidence. When the outcome of interest is reduction of the acute side effects: dermatitis and moist desquamation IMRT is a viable treatment option for women undergoing external beam RT after breast-conserving surgery., (Copyright © 2017 Canadian Association of Medical Radiation Technologists. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
44. A Prospective Study Comparing 99m Tc-Hydroxyethylene-Diphosphonate Planar Bone Scintigraphy and Whole-Body SPECT/CT with 18 F-Fluoride PET/CT and 18 F-Fluoride PET/MRI for Diagnosing Bone Metastases.
- Author
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Löfgren J, Mortensen J, Rasmussen SH, Madsen C, Loft A, Hansen AE, Oturai P, Jensen KE, Mørk ML, Reichkendler M, Højgaard L, and Fischer BM
- Subjects
- Adult, Aged, Female, Fluorine Radioisotopes, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multimodal Imaging, Positron-Emission Tomography methods, Predictive Value of Tests, Prospective Studies, Radionuclide Imaging, Reproducibility of Results, Tomography, Emission-Computed, Single-Photon methods, Bone Neoplasms diagnostic imaging, Bone Neoplasms secondary, Bone and Bones diagnostic imaging, Diphosphonates, Organotechnetium Compounds, Radiopharmaceuticals, Sodium Fluoride, Whole Body Imaging methods
- Abstract
We prospectively evaluated and compared the diagnostic performance of
99m Tc-hydroxyethylene-diphosphonate (99m Tc-HDP) planar bone scintigraphy (pBS),99m Tc-HDP SPECT/CT,18 F-NaF PET/CT, and18 F-NaF PET/MRI for the detection of bone metastases. Methods: One hundred seventeen patients with histologically proven malignancy referred for clinical pBS were prospectively enrolled. pBS and whole-body SPECT/CT were performed followed by18 F-NaF PET/CT within 9 d.18 F-NaF PET/MRI was also performed in 46 patients. Results: Bone metastases were confirmed in 16 patients and excluded in 101, which was lower than expected. The number of equivocal scans was significantly higher for pBS than for SPECT/CT and PET/CT (18 vs. 5 and 6, respectively; P = 0.004 and 0.01, respectively). When equivocal readings were excluded, no statistically significant difference in sensitivity, specificity, positive predictive value, negative predictive value, or overall accuracy were found when comparing the different imaging techniques. In the per-patient analysis, equivocal scans were either assumed positive for metastases ("pessimistic analysis") or assumed negative for metastases ("optimistic analysis"). The percentages of misdiagnosed patients for the pessimistic analysis were 21%, 15%, 9%, and 7% for pBS, SPECT/CT, PET/CT, and PET/MRI, respectively. Corresponding figures for the optimistic analysis were 9%, 12%, 5%, and 7%. In those patients identified as having bone metastases according to the reference standard, SPECT/CT,18 F-NaF PET/CT, and PET/MRI detected additional lesions compared with pBS in 31%, 63%, and 71%, respectively. Conclusion:18 F-NaF PET/CT and whole-body SPECT/CT resulted in a significant reduction of equivocal readings compared with pBS, which implies an improved diagnostic confidence. However, the clinical benefit of using, for example,18 F-NaF PET/CT or PET/MRI as compared with SPECT/CT and pBS in this patient population with a relatively low prevalence of bone metastases (14%) is likely limited. This conclusion is influenced by the low prevalence of patients with osseous metastases. There may well be significant differences in the sensitivity of SPECT/CT, PET/CT, and PET/MRI compared with pBS, but a larger patient population or a patient population with a higher prevalence of bone metastases would have to be studied to demonstrate this., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2017
- Full Text
- View/download PDF
45. Direct measurement of strain-dependent solid surface stress.
- Author
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Xu Q, Jensen KE, Boltyanskiy R, Sarfati R, Style RW, and Dufresne ER
- Abstract
Surface stress, also known as surface tension, is a fundamental material property of any interface. However, measurements of solid surface stress in traditional engineering materials, such as metals and oxides, have proven to be very challenging. Consequently, our understanding relies heavily on untested theories, especially regarding the strain dependence of this property. Here, we take advantage of the high compliance and large elastic deformability of a soft polymer gel to directly measure solid surface stress as a function of strain. As anticipated by theoretical work for metals, we find that the surface stress depends on the strain via a surface modulus. Remarkably, the surface modulus of our soft gels is many times larger than the zero-strain surface tension. This suggests that surface stresses can play a dominant role in solid mechanics at larger length scales than previously anticipated.Solid surface stress is a fundamental property of solid interfaces. Here authors measure the solid surface stress of a gel, and show its dependence on surface strain through a surface modulus.
- Published
- 2017
- Full Text
- View/download PDF
46. The collagen receptor uPARAP/Endo180 as a novel target for antibody-drug conjugate mediated treatment of mesenchymal and leukemic cancers.
- Author
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Nielsen CF, van Putten SM, Lund IK, Melander MC, Nørregaard KS, Jürgensen HJ, Reckzeh K, Christensen KR, Ingvarsen SZ, Gårdsvoll H, Jensen KE, Hamerlik P, Engelholm LH, and Behrendt N
- Subjects
- Animals, Cell Cycle drug effects, Cell Cycle genetics, Cell Survival, Disease Models, Animal, Endocytosis, Gene Expression, Humans, Leukemia drug therapy, Leukemia metabolism, Leukemia mortality, Leukemia pathology, Mannose-Binding Lectins genetics, Mannose-Binding Lectins metabolism, Membrane Glycoproteins genetics, Membrane Glycoproteins metabolism, Mice, Molecular Targeted Therapy, Receptors, Cell Surface genetics, Receptors, Cell Surface metabolism, Receptors, Mitogen genetics, Receptors, Mitogen metabolism, Sarcoma drug therapy, Sarcoma metabolism, Sarcoma mortality, Sarcoma pathology, Tumor Burden drug effects, Tumor Burden genetics, Xenograft Model Antitumor Assays, Antineoplastic Agents, Immunological pharmacology, Immunoconjugates pharmacology, Mannose-Binding Lectins antagonists & inhibitors, Membrane Glycoproteins antagonists & inhibitors, Receptors, Cell Surface antagonists & inhibitors, Receptors, Mitogen antagonists & inhibitors
- Abstract
A key task in developing the field of personalized cancer therapy is the identification of novel molecular targets that enable treatment of cancers not susceptible to other means of specific therapy. The collagen receptor uPARAP/Endo180 is overexpressed by malignant cells in several non-epithelial cancers, notably including sarcomas, glioblastomas and subsets of acute myeloid leukemia. In contrast, in healthy adult individuals, expression is restricted to minor subsets of mesenchymal cells. Functionally, uPARAP/Endo180 is a rapidly recycling endocytic receptor that delivers its cargo directly into the endosomal-lysosomal system, thus opening a potential route of entry into receptor-positive cells. This combination of specific expression and endocytic function appears well suited for targeting of uPARAP/Endo180-positive cancers by antibody-drug conjugate (ADC) mediated drug delivery. Therefore, we utilized a specific monoclonal antibody against uPARAP/Endo180, raised through immunization of a uPARAP/Endo180 knock-out mouse, which reacts with both the human and the murine receptor, to construct a uPARAP-directed ADC. This antibody was coupled to the highly toxic dolastatin derivative, monomethyl auristatin E, via a cathepsin-labile valine-citrulline linker. With this ADC, we show strong and receptor-dependent cytotoxicity in vitro in uPARAP/Endo180-positive cancer cell lines of sarcoma, glioblastoma and leukemic origin. Furthermore, we demonstrate the potency of the ADC in vivo in a xenograft mouse model with human uPARAP/Endo180-positive leukemic cells, obtaining a complete cure of all tested mice following intravenous ADC treatment with no sign of adverse effects. Our study identifies uPARAP/Endo180 as a promising target for novel therapy against several highly malignant cancer types.
- Published
- 2017
- Full Text
- View/download PDF
47. Osseous osteoarthritic-like changes and joint mobility of the temporomandibular joints and upper cervical spine: is there a relation?
- Author
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Sonnesen L, Petersson A, Wiese M, Jensen KE, Svanholt P, and Bakke M
- Subjects
- Adult, Aged, Cervical Vertebrae diagnostic imaging, Cone-Beam Computed Tomography, Female, Humans, Male, Middle Aged, Osteoarthritis diagnostic imaging, Range of Motion, Articular, Temporomandibular Joint diagnostic imaging, Cervical Vertebrae physiopathology, Osteoarthritis physiopathology, Temporomandibular Joint physiopathology
- Abstract
Objectives: To compare 1) temporomandibular joint (TMJ) mobility between patients with and without reduced upper cervical spine (UCS) mobility and with and without TMJ osseous osteoarthritic-like changes, and 2) UCS osseous changes between patients with and without TMJ osseous osteoarthritic-like changes and with and without reduced UCS mobility., Study Design: The study comprised 39 patients without pain from TMJ or UCS and with obstructive sleep apnea, 15 women (age range 26-72 years, mean 56.0) and 24 men (age range 27-71 years, mean 49.8). The range of motion (ROM) of the mandible and UCS was assessed clinically. Osseous changes of the TMJ and UCS were assessed by cone beam computed tomography. Differences were tested and adjusted for age and gender by multiple linear and logistic regression analyses., Results: The mandibular ROM was within normal range (45-64 mm) but the UCS ROM was reduced in 15 patients. Osseous TMJ and UCS changes were both found in 38.5% of the patients. Osseous UCS changes were found more frequently in patients with than without TMJ changes (P = .0003; odds ratio 21.9). No other significant results were found., Conclusions: The present findings of comorbid osseous changes in patients with obstructive sleep apnea support a possible biomechanical relationship between the TMJ and the UCS., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
48. BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity.
- Author
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Rasmussen RD, Gajjar MK, Tuckova L, Jensen KE, Maya-Mendoza A, Holst CB, Møllgaard K, Rasmussen JS, Brennum J, Bartek J Jr, Syrucek M, Sedlakova E, Andersen KK, Frederiksen MH, Bartek J, and Hamerlik P
- Subjects
- Animals, BRCA1 Protein metabolism, Brain Neoplasms metabolism, Brain Neoplasms pathology, Carcinogenesis genetics, Cell Line, Tumor, DNA Replication genetics, Glioblastoma metabolism, Glioblastoma pathology, Humans, Mice, Inbred BALB C, Mice, Nude, RNA Interference, Retrospective Studies, Ribonucleoside Diphosphate Reductase metabolism, Survival Analysis, Transplantation, Heterologous, Tumor Cells, Cultured, BRCA1 Protein genetics, Brain Neoplasms genetics, Gene Expression Regulation, Neoplastic, Glioblastoma genetics, Ribonucleoside Diphosphate Reductase genetics
- Abstract
Oncogene-evoked replication stress (RS) fuels genomic instability in diverse cancer types. Here we report that BRCA1, traditionally regarded a tumour suppressor, plays an unexpected tumour-promoting role in glioblastoma (GBM), safeguarding a protective response to supraphysiological RS levels. Higher BRCA1 positivity is associated with shorter survival of glioma patients and the abrogation of BRCA1 function in GBM enhances RS, DNA damage (DD) accumulation and impairs tumour growth. Mechanistically, we identify a novel role of BRCA1 as a transcriptional co-activator of RRM2 (catalytic subunit of ribonucleotide reductase), whereby BRCA1-mediated RRM2 expression protects GBM cells from endogenous RS, DD and apoptosis. Notably, we show that treatment with a RRM2 inhibitor triapine reproduces the BRCA1-depletion GBM-repressive phenotypes and sensitizes GBM cells to PARP inhibition. We propose that GBM cells are addicted to the RS-protective role of the BRCA1-RRM2 axis, targeting of which may represent a novel paradigm for therapeutic intervention in GBM.
- Published
- 2016
- Full Text
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49. Combinatorial Strategies for Synthesis and Characterization of Alloy Microstructures over Large Compositional Ranges.
- Author
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Li Y, Jensen KE, Liu Y, Liu J, Gong P, Scanley BE, Broadbridge CC, and Schroers J
- Subjects
- High-Throughput Screening Assays, Materials Testing, Physical Phenomena, Alloys chemistry, Combinatorial Chemistry Techniques methods, Copper chemistry, Gold chemistry, Silicon chemistry
- Abstract
The exploration of new alloys with desirable properties has been a long-standing challenge in materials science because of the complex relationship between composition and microstructure. In this Research Article, we demonstrate a combinatorial strategy for the exploration of composition dependence of microstructure. This strategy is comprised of alloy library synthesis followed by high-throughput microstructure characterization. As an example, we synthesized a ternary Au-Cu-Si composition library containing over 1000 individual alloys using combinatorial sputtering. We subsequently melted and resolidified the entire library at controlled cooling rates. We used scanning optical microscopy and X-ray diffraction mapping to explore trends in phase formation and microstructural length scale with composition across the library. The integration of combinatorial synthesis with parallelizable analysis methods provides a efficient method for examining vast compositional ranges. The availability of microstructures from this vast composition space not only facilitates design of new alloys by controlling effects of composition on phase selection, phase sequence, length scale, and overall morphology, but also will be instrumental in understanding the complex process of microstructure formation in alloys.
- Published
- 2016
- Full Text
- View/download PDF
50. PET/MR Imaging in Musculoskeletal Disorders.
- Author
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Andersen KF, Jensen KE, and Loft A
- Subjects
- Humans, Muscle, Skeletal diagnostic imaging, Magnetic Resonance Imaging methods, Multimodal Imaging methods, Musculoskeletal Diseases diagnostic imaging, Positron-Emission Tomography methods
- Abstract
There is emerging evidence suggesting that PET/MR imaging will have a role in many aspects of musculoskeletal imaging. The synergistic potential of hybrid PET/MR imaging in terms of acquiring anatomic, molecular, and functional data simultaneously seems advantageous in the diagnostic workup, treatment planning and monitoring, and follow-up of patients with musculoskeletal malignancies, and may also prove helpful in assessment of musculoskeletal infectious and inflammatory disorders. The application of more sophisticated MR imaging sequences and PET radiotracers other than FDG in the diagnostic workup and follow-up of patients with musculoskeletal disorders should be explored., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
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