| 1. |
|
|
| 2. |
- Shungin, Dmitry, et al.
(author)
-
New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
-
Journal article (peer-reviewed)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
|
|
| 3. |
|
|
| 4. |
- Cedervall, Jessica, et al.
(author)
-
Pharmacological targeting of peptidylarginine deiminase 4 prevents cancer-associated kidney injury in mice.
- 2017
-
In: Oncoimmunology. - : Taylor & Francis. - 2162-4011 .- 2162-402X. ; 6:8
-
Journal article (peer-reviewed)abstract
- Renal insufficiency is a frequent cancer-associated problem affecting more than half of all cancer patients at the time of diagnosis. To minimize nephrotoxic effects the dosage of anticancer drugs are reduced in these patients, leading to sub-optimal treatment efficacy. Despite the severity of this cancer-associated pathology, the molecular mechanisms, as well as therapeutic options, are still largely lacking. We here show that formation of intravascular tumor-induced neutrophil extracellular traps (NETs) is a cause of kidney injury in tumor-bearing mice. Analysis of clinical biomarkers for kidney function revealed impaired creatinine clearance and elevated total protein levels in urine from tumor-bearing mice. Electron microscopy analysis of the kidneys from mice with cancer showed reversible pathological signs such as mesangial hypercellularity, while permanent damage such as fibrosis or necrosis was not observed. Removal of NETs by treatment with DNase I, or pharmacological inhibition of the enzyme peptidylarginine deiminase 4 (PAD4), was sufficient to restore renal function in mice with cancer. Tumor-induced systemic inflammation and impaired perfusion of peripheral vessels could be reverted by the PAD4 inhibitor. In conclusion, the current study identifies NETosis as a previously unknown cause of cancer-associated renal dysfunction and describes a novel promising approach to prevent renal failure in individuals with cancer.
|
|
| 5. |
- Magnusson, Lisa U., 1975, et al.
(author)
-
Tasquinimod inhibits prostate cancer growth in bone through alterations in the bone microenvironment.
- 2016
-
In: The Prostate. - : Wiley. - 1097-0045 .- 0270-4137. ; 76:4, s. 383-393
-
Journal article (peer-reviewed)abstract
- Tasquinimod (ABR-215050) is an orally active quinoline-3-carboxamide analog that inhibits occurrence of experimental metastasis and delays disease progression of castration resistant prostate cancer in humans. Its mechanism of action is not fully elucidated, but previous studies show immunomodulatory and anti-angiogenic effects. The aim of the present study was to investigate the tumor inhibiting effect of tasquinimod in bone of castrated mice as well as to elucidate its working mechanism related to bone microenvironment.
|
|
| 6. |
- Nyholm, Tufve, et al.
(author)
-
A national approach for automated collection of standardized and population-based radiation therapy data in Sweden
- 2016
-
In: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 119:2, s. 344-350
-
Journal article (peer-reviewed)abstract
- Purpose: To develop an infrastructure for structured and automated collection of interoperable radiation therapy (RT) data into a national clinical quality registry. Materials and methods: The present study was initiated in 2012 with the participation of seven of the 15 hospital departments delivering RT in Sweden. A national RT nomenclature and a database for structured unified storage of RT data at each site (Medical Information Quality Archive, MIQA) have been developed. Aggregated data from the MIQA databases are sent to a national RT registry located on the same IT platform (INCA) as the national clinical cancer registries. Results: The suggested naming convention has to date been integrated into the clinical workflow at 12 of 15 sites, and MIQA is installed at six of these. Involvement of the remaining 3/15 RT departments is ongoing, and they are expected to be part of the infrastructure by 2016. RT data collection from ARIA (R), Mosaiq (R), Eclipse (TM), and Oncentra (R) is supported. Manual curation of RT-structure information is needed for approximately 10% of target volumes, but rarely for normal tissue structures, demonstrating a good compliance to the RT nomenclature. Aggregated dose/volume descriptors are calculated based on the information in MIQA and sent to INCA using a dedicated service (MIQA2INCA). Correct linkage of data for each patient to the clinical cancer registries on the INCA platform is assured by the unique Swedish personal identity number. Conclusions: An infrastructure for structured and automated prospective collection of syntactically inter operable RT data into a national clinical quality registry for RT data is under implementation. Future developments include adapting MIQA to other treatment modalities (e.g. proton therapy and brachytherapy) and finding strategies to harmonize structure delineations. How the RT registry should comply with domain-specific ontologies such as the Radiation Oncology Ontology (ROO) is under discussion.
|
|
| 7. |
- Svanström, Magdalena, 1969, et al.
(author)
-
Life cycle assessment of sludge management with phosphorus utilisation and improved hygienisation in Sweden
- 2017
-
In: Water Science and Technology. - : IWA Publishing. - 0273-1223 .- 1996-9732. ; 75:9, s. 2013-2024
-
Journal article (peer-reviewed)abstract
- To provide input to sewage sludge management strategies that address expected new regulations in terms of hygienisation and phosphorus recovery in Sweden, an environmental life cycle assessment (LCA) was made. The LCA identified environmental hot spots for methods that may permit sludge or phosphorus from sludge to be applied on agricultural land. In particular, thermophilic digestion, pasteurisation, thermal hydrolysis, urea treatment and mono-incineration with phosphorus recovery were compared. In addition, a sludge management system involving drying of sludge before use in forestry was investigated. The results showed that some major impacts are related to large uncertainties, such as those related to emissions from sludge storage. It also showed that large gains can be achieved when products from the systems replace other products, in particular when biogas is used to replace natural gas in vehicles, but also when sludge is used in agriculture and forestry. In general, there are small differences between the sludge management methods. Retaining the sludge matrix to allow for its utilisation in agriculture may conflict with keeping emissions to air and water from the sludge matrix low. It is recommended that any sludge management option minimises emissions from sludge to air and water and that resources are recovered and used, in line with the principles of a circular economy.
|
|
