| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 3. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 4. |
- Hellström, Ann, 1959, et al.
(författare)
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Insulin-like growth factor 1 has multisystem effects on foetal and preterm infant development.
- 2016
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 105:6, s. 576-86
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Tidskriftsartikel (refereegranskat)abstract
- Poor postnatal growth after preterm birth does not match the normal rapid growth in utero and is associated with preterm morbidities. Insulin-like growth factor 1 (IGF-1) axis is the major hormonal mediator of growth in utero, and levels of IGF-1 are often very low after preterm birth. We reviewed the role of IGF-1 in foetal development and the corresponding preterm perinatal period to highlight the potential clinical importance of IGF-1 deficiency in preterm morbidities.
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| 5. |
- Lingam, Ingran, et al.
(författare)
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Neonatal outcomes following early fetal growth restriction : a subgroup analysis of the EVERREST study
- 2023
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Ingår i: Archives of disease in childhood. Fetal and neonatal edition. - 1359-2998. ; 108:6, s. 599-606
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To quantify the risks of mortality, morbidity and postnatal characteristics associated with extreme preterm fetal growth restriction (EP-FGR).DESIGN: The EVERREST (Do e s v ascular endothelial growth factor gene therapy saf e ly imp r ove outcome in seve r e e arly-onset fetal growth re st riction?) prospective multicentre study of women diagnosed with EP-FGR (singleton, estimated fetal weight (EFW) <3rd percentile, <600 g, 20+0-26+6 weeks of gestation). The UK subgroup of EP-FGR infants (<36 weeks) were sex-matched and gestation-matched to appropriate for age (AGA) infants born in University College London Hospital (1:2 design, EFW 25th-75th percentile).SETTING: Four tertiary perinatal units (UK, Germany, Spain, Sweden).MAIN OUTCOMES: Antenatal and postnatal mortality, bronchopulmonary dysplasia (BPD), sepsis, surgically treated necrotising enterocolitis (NEC), treated retinopathy of prematurity (ROP).RESULTS: Of 135 mothers recruited with EP-FGR, 42 had a stillbirth or termination of pregnancy (31%) and 93 had live births (69%). Postnatal genetic abnormalities were identified in 7/93 (8%) live births. Mean gestational age at birth was 31.4 weeks (SD 4.6). 54 UK-born preterm EP-FGR infants (<36 weeks) were matched to AGA controls. EP-FGR was associated with increased BPD (43% vs 26%, OR 3.6, 95% CI 1.4 to 9.4, p=0.01), surgical NEC (6% vs 0%, p=0.036) and ROP treatment (11% vs 0%, p=0.001). Mortality was probably higher among FGR infants (9% vs 2%, OR 5.0, 95% CI 1.0 to 25.8, p=0.054). FGR infants more frequently received invasive ventilation (65% vs 50%, OR 2.6, 95% CI 1.1 to 6.1, p=0.03), took longer to achieve full feeds and had longer neonatal stays (median difference 6.1 days, 95% CI 3.8 to 8.9 and 19 days, 95% CI 9 to 30 days, respectively, p<0.0001).CONCLUSIONS: Mortality following diagnosis of EP-FGR is high. Survivors experience increased neonatal morbidity compared with AGA preterm infants.TRIAL REGISTRATION NUMBER: NCT02097667.
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| 6. |
- Agyemang, Alex Adusei, et al.
(författare)
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Cell-free oxidized hemoglobin drives reactive oxygen species production and pro-inflammation in an immature primary rat mixed glial cell culture
- 2021
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Germinal matrix intraventricular hemorrhage (GM-IVH) is associated with deposition of redox active cell-free hemoglobin (Hb), derived from hemorrhagic cerebrospinal fluid (CSF), in the cerebrum and cerebellum. In a recent study, using a preterm rabbit pup model of IVH, intraventricularly administered haptoglobin (Hp), a cell-free Hb scavenger, partially reversed the damaging effects observed following IVH. Together, this suggests that cell-free Hb is central in the pathophysiology of the injury to the immature brain following GM-IVH. An increased understanding of the causal pathways and metabolites involved in eliciting the damaging response following hemorrhage is essential for the continued development and implementation of neuroprotective treatments of GM-IVH in preterm infant.METHODS: We exposed immature primary rat mixed glial cells to hemorrhagic CSF obtained from preterm human infants with IVH (containing a mixture of Hb-metabolites) or to a range of pure Hb-metabolites, incl. oxidized Hb (mainly metHb with iron in Fe3+), oxyHb (mainly Fe2+), or low equivalents of heme, with or without co-administration with human Hp (a mixture of isotype 2-2/2-1). Following exposure, cellular response, reactive oxygen species (ROS) generation, secretion and expression of pro-inflammatory cytokines and oxidative markers were evaluated.RESULTS: Exposure of the glial cells to hemorrhagic CSF as well as oxidized Hb, but not oxyHb, resulted in a significantly increased rate of ROS production that positively correlated with the rate of production of pro-inflammatory and oxidative markers. Congruently, exposure to oxidized Hb caused a disintegration of the polygonal cytoskeletal structure of the glial cells in addition to upregulation of F-actin proteins in microglial cells. Co-administration of Hp partially reversed the damaging response of hemorrhagic CSF and oxidized Hb.CONCLUSION: Exposure of mixed glial cells to oxidized Hb initiates a pro-inflammatory and oxidative response with cytoskeletal disintegration. Early administration of Hp, aiming to minimize the spontaneous autoxidation of cell-free oxyHb and liberation of heme, may provide a therapeutic benefit in preterm infant with GM-IVH.
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| 7. |
- Agyemang, Alex Adusei, et al.
(författare)
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Cerebellar Exposure to Cell-Free Hemoglobin Following Preterm Intraventricular Hemorrhage: Causal in Cerebellar Damage?
- 2017
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Ingår i: Translational Stroke Research. - : Springer Science and Business Media LLC. - 1868-4483 .- 1868-601X. ; 8:5, s. 461-473
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Tidskriftsartikel (refereegranskat)abstract
- Decreased cerebellar volume is associated with intraventricular hemorrhage (IVH) in very preterm infants and may be a principal component in neurodevelopmental impairment. Cerebellar deposition of blood products from the subarachnoid space has been suggested as a causal mechanism in cerebellar underdevelopment following IVH. Using the preterm rabbit pup IVH model, we evaluated the effects of IVH induced at E29 (3 days prior to term) on cerebellar development at term-equivalent postnatal day 0 (P0), term-equivalent postnatal day 2 (P2), and term-equivalent postnatal day 5 (P5). Furthermore, the presence of cell-free hemoglobin (Hb) in cerebellar tissue was characterized, and cell-free Hb was evaluated as a causal factor in the development of cerebellar damage following preterm IVH. IVH was associated with a decreased proliferative (Ki67-positive) portion of the external granular layer (EGL), delayed Purkinje cell maturation, and activated microglia in the cerebellar white matter. In pups with IVH, immunolabeling of the cerebellum at P0 demonstrated a widespread presence of cell-free Hb, primarily distributed in the white matter and the molecular layer. Intraventricular injection of the Hb scavenger haptoglobin (Hp) resulted in a corresponding distribution of immunolabeled Hp in the cerebellum and a partial reversal of the damaging effects observed following IVH. The results suggest that cell-free Hb is causally involved in cerebellar damage following IVH and that blocking cell-free Hb may have protective effects.
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| 8. |
- Amer-Wåhlin, Isis, et al.
(författare)
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Fetal cerebral energy metabolism and electrocardiogram during experimental umbilical cord occlusion and resuscitation.
- 2010
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Ingår i: Journal of Maternal-Fetal & Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 23:2, s. 158-166
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The purpose of this experimental study was to elucidate alterations in fetal energy metabolism in relation to ECG changes during extreme fetal asphyxia, postnatal resuscitation and the immediate post-resuscitatory phase. Study design. Five near-term fetal sheep were subjected to umbilical cord occlusion until cardiac arrest followed by delivery, resuscitation and postnatal pressure-controlled ventilation. Four sheep served as sham controls and were delivered immediately after ligation of the umbilical cord. Fetal ECG was analysed online for changes of the ST segment. Fetal metabolism was monitored by intracerebral and subcutaneous microdialysis catheters. Results. Fetal ECG reacted on cord occlusion with an increase in the T-wave height followed by changes in intracerebral levels of oxidative parameters. Cerebral lactate/pyruvate ratio and glutamate increased to median (range) of 240 (200-744) and 34.0 (22.6-60.5) mmol/l, respectively; both parameters returned to baseline after resuscitation. Cerebral glucose decreased to 0.1 (0.08-0.12) mmol/l after occlusion and increased above baseline upon resuscitation. In subcutaneous tissue as well as blood the increase in lactate occurred with a delay compared to cerebral levels. Conclusion. The fetal ECG changes related to asphyxia preceded the increase in excitotoxicity as determined by increase in cerebral glutamate during asphyxia. Cerebral lactate increase was superior to subcutaneous lactate increase.
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| 9. |
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| 10. |
- Bengtsson, Jörgen, et al.
(författare)
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The influence of age on the distribution of morphine and morphine-3-glucuronide across the blood-brain barrier in sheep
- 2009
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 157:6, s. 1085-1096
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose The effect of age on the distribution of morphine and morphine-3-glucuronide (M3G) across the blood-brain barrier (BBB) was studied in a sheep model utilizing intracerebral microdialysis. The effect of neonatal asphyxia on brain drug distribution was also studied. Experimental approach Microdialysis probes were inserted into the cortex, striatum and blood of 11 lambs (127 gestation days) and six ewes. Morphine, 1 mg.kg(-1), was intravenously administered as a 10 min constant infusion. Microdialysis and blood samples were collected for up to 360 min and analysed using liquid chromatography-tandem mass spectrometry. The half-life, clearance, volume of distribution, unbound drug brain : blood distribution ratio (K(p,uu)) and unbound drug volume of distribution in brain (V(u,brain)) were estimated. Key results Morphine K(p,uu) was 1.19 and 1.89 for the sheep and premature lambs, respectively, indicating that active influx into the brain decreases with age. Induced asphyxia did not affect transport of morphine or M3G across the BBB. Morphine V(u,brain) measurements were higher in sheep than in premature lambs. The M3G K(p,uu) values were 0.27 and 0.17 in sheep and premature lambs, indicating a net efflux from the brain in both groups. Conclusions and implications The morphine K(p,uu) was above unity, indicating active transport into the brain; influx was significantly higher in premature lambs than in adult sheep. These results in sheep differ from those in humans, rats, mice and pigs where a net efflux of morphine from the brain is observed.
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