| 1. |
- Ademuyiwa, Adesoji O., et al.
(författare)
-
Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
-
Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
|
|
| 2. |
- Hudson, Thomas J., et al.
(författare)
-
International network of cancer genome projects
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
-
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.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Bogdanska, Jasna, et al.
(författare)
-
Tissue distribution of (35)S-labelled perfluorooctane sulfonate in adult mice after oral exposure to a low environmentally relevant dose or a high experimental dose
- 2011
-
Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 284:1-3, s. 54-62
-
Tidskriftsartikel (refereegranskat)abstract
- The widespread environmental pollutant perfluorooctane sulfonate (PFOS), detected in most animal species including the general human population, exerts several effects on experimental animals, e.g., hepatotoxicity, immunotoxicity and developmental toxicity. However, detailed information on the tissue distribution of PFOS in mammals is scarce and, in particular, the lack of available information regarding environmentally relevant exposure levels limits our understanding of how mammals (including humans) may be affected. Accordingly, we characterized the tissue distribution of this compound in mice, an important experimental animal for studying PFOS toxicity. Following dietary exposure of adult male C57/BL6 mice for 1-5 days to an environmentally relevant (0.031 mg/kg/day) or a 750-fold higher experimentally relevant dose (23 mg/kg/day) of (35)S-PFOS, most of the radioactivity administered was recovered in liver, bone (bone marrow), blood, skin and muscle, with the highest levels detected in liver, lung, blood, kidney and bone (bone marrow). Following high daily dose exposure, PFOS exhibited a different distribution profile than with low daily dose exposure, which indicated a shift in distribution from the blood to the tissues with increasing dose. Both scintillation counting (with correction for the blood present in the tissues) and whole-body autoradiography revealed the presence of PFOS in all 19 tissues examined, with identification of thymus as a novel site for localization for PFOS and bone (bone marrow), skin and muscle as significant body compartments for PFOS. These findings demonstrate that PFOS leaves the bloodstream and enters most tissues in a dose-dependent manner.
|
|
| 7. |
|
|
| 8. |
- Bogdanska, Jasna, et al.
(författare)
-
Tissue distribution of C-14-labelled perfluorooctanoic acid in adult mice after 1-5 days of dietary exposure to an experimental dose or a lower dose that resulted in blood levels similar to those detected in exposed humans
- 2020
-
Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 239
-
Tidskriftsartikel (refereegranskat)abstract
- Perfluorooctanoic acid (PFOA), a global environmental pollutant detected in both wildlife and human populations, has several pathophysiological effects in experimental animals, including hepatotoxicity, immunotoxicity, and developmental toxicity. However, details concerning the tissue distribution of PFOA, in particular at levels relevant to humans, are lacking, which limits our understanding of how humans, and other mammals, may be affected by this compound. Therefore, we characterized the tissue distribution of C-14-PFOA in mice in the same manner as we earlier examined its analogues perfluorooctanesulfonate (PFOS) and perfluorobutanesulfonate (PFBS) in order to allow direct comparisons. Following dietary exposure of adult male C57/BL6 mice for 1, 3 or 5 days to a low dose (0.06 mg/kg/day) or a higher experimental dose (22 mg/kg/day) of C-14-PFOA, both scintillation counting and whole-body autoradiography revealed the presence of PFOA in most of the 19 different tissues examined, demonstrating its ability to leave the bloodstream and enter tissues. There were no differences in the pattern of tissue distribution with the low and high dose and the tissue-to-blood ratios were similar. At both doses, PFOA levels were highest in the liver, followed by blood, lungs and kidneys. The body compartments estimated to contain the largest amounts of PFOA were the liver, blood, skin and muscle. In comparison with our identical studies on PFOS and PFBS, PFOA reached considerably higher tissue levels than PFBS, but lower than PFOS. Furthermore, the distribution of PFOA differed notably from that of PFOS, with lower tissue-to-blood ratios in the liver, lungs, kidneys and skin.
|
|
| 9. |
- Bogdanska, Jasna, et al.
(författare)
-
Tissue distribution of S-35-labelled perfluorobutanesulfonic acid in adult mice following dietary exposure for 1-5 days
- 2014
-
Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 98, s. 28-36
-
Tidskriftsartikel (refereegranskat)abstract
- Perfluorobutanesulfonyl fluoride (PBSF) has been introduced as a replacement for its eight-carbon homolog perfluorooctanesulfonyl fluoride (POSF) in the manufacturing of fluorochemicals. Fluorochemicals derived from PBSF may give rise to perfluorobutanesulfonic acid (PFBS) as a terminal degradation product. Although basic mammalian toxicokinetic data exist for PFBS, information on its tissue distribution has only been reported in one study focused on rat liver. Therefore, here we characterized the tissue distribution of PFBS in mice in the same manner as we earlier examined its eight-carbon homolog perfluorooctanesulfonate (PFOS) to allow direct comparisons. Following dietary exposure of adult male C57/BL6 mice for 1,3 or 5 d to 16 mg S-35-PFBS kg(-1) d(-1), both scintillation counting and whole-body autoradiography (WBA) revealed the presence of PFBS in all of the 20 different tissues examined, demonstrating its ability to leave the bloodstream and enter tissues. After 5 d of treatment the highest levels were detected in liver, gastrointestinal tract, blood, kidney, cartilage, whole bone, lungs and thyroid gland. WBA revealed relatively high levels of PFBS in male genital organs as well, with the exception of the testis. The tissue levels increased from 1 to 3 d of exposure but appeared thereafter to level-off in most cases. The estimated major body compartments were whole bone, liver, blood, skin and muscle. This exposure to PFBS resulted in 5-40-fold lower tissue levels than did similar exposure to PFOS, as well as in a different pattern of tissue distribution, including lower levels in liver and lungs relative to blood.
|
|
| 10. |
- Borg, Daniel, et al.
(författare)
-
Perinatal tissue distribution of perfluorooctane sulphonate (PFOS) in mice.
- 2009
-
Ingår i: Abstracts of the 46th Congress of the European Societies of Toxicology. - : Elsevier BV. ; 189:SI, s. S147-S147
-
Konferensbidrag (refereegranskat)abstract
- Perfluorooctane sulfonate (PFOS) is an industrial chemical that has been used as a surfactant and surface protector for more than fifty years. It has during the last decade emerged as an environmental contaminant due to its widespread presence in humans and wildlife and its persistant, bioaccumulative and toxic properties. PFOS is developmentally toxic and late in utero exposure in rodents affects neonatal survival and growth. Observed symptoms suggest impaired pulmonary function, but the cause of the mortality has not been clarified. The purpose of this study was to determine the perinatal tissue distribution of S35-labelled PFOS in mice using whole-body autoradiography (WBA) combined with liquid scintillation counting (LSC). Pregnant C57Bl/6 mice were dosed orally on gestation day (GD) 16 and sampled on GD18, GD20 and postnatal day (PND) 1 (dams + pups). The results from the WBA and the LSC were unequivocal. In dams, PFOS accumulated primarily in the liver, but also the lungs contained levels higher than the blood. PFOS was readily transferred to the fetus. At GD18 general PFOS levels were higher in the fetus than in the blood of the corresponding dam with accumulation in the liver. At GD20, general PFOS levels remained higher in the fetus than in the dam, with substantial accumulation also in the lung. The accumulation in the lung persisted at PND1. Our results show that the fetus is exposed to higher levels of PFOS than the dam and point towards the lung being the main perinatal target organ of PFOS.
|
|
| 11. |
- Cope, Henry, et al.
(författare)
-
Routine omics collection is a golden opportunity for European human research in space and analog environments
- 2022
-
Ingår i: PATTERNS. - : Elsevier BV. - 2666-3899. ; 3:10, s. 100550-
-
Tidskriftsartikel (refereegranskat)abstract
- Widespread generation and analysis of omics data have revolutionized molecular medicine on Earth, yet its power to yield new mechanistic insights and improve occupational health during spaceflight is still to be fully realized in humans. Nevertheless, rapid technological advancements and ever-regular spaceflight programs mean that longitudinal, standardized, and cost-effective collection of human space omics data are firmly within reach. Here, we consider the practicality and scientific return of different sampling methods and omic types in the context of human spaceflight, We also appraise ethical and legal considerations pertinent to omics data derived from European astronauts and spaceflight participants (SFPs). Ultimately, we propose that a routine omics collection program in spaceflight and analog environments presents a golden opportunity. Unlocking this bright future of artificial intelligence (AI)-driven analyses and personalized medicine approaches will require further investigation into best practices, including policy design and standardization of omics data, metadata, and sampling methods.
|
|
| 12. |
|
|
| 13. |
- Ferreira, MA, et al.
(författare)
-
Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1741-
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
|
|
| 14. |
- Gaudet, Mia M., et al.
(författare)
-
Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer
- 2010
-
Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
-
Tidskriftsartikel (refereegranskat)abstract
- The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.
|
|
| 15. |
|
|
| 16. |
- Malander, Susanne, et al.
(författare)
-
Ovarialcancer är på många sätt en heterogen sjukdom
- 2015
-
Ingår i: Läkartidningen. - 1652-7518. ; 112
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Ovarian cancer develops due to a complex interplay between hereditary and environmental factors. Although often described as one disease, ovarian cancer is actually a group of distinct tumor types. Recent research has indicated that a large percentage of ovarian cancers may originate from the fallopian tube epithelium. Although most cancers develop in patients without a known hereditary syndrome, it is clear that the number of familial cancers is larger than previously supposed. The two most common hereditary syndromes where ovarian cancer can develop are hereditary breast ovarian cancer syndrome (HBOC) and Lynch syndrome.
|
|
| 17. |
- Manzano, Aránzazu, et al.
(författare)
-
Enhancing European capabilities for application of multi-omics studies in biology and biomedicine space research
- 2023
-
Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 26:9
-
Forskningsöversikt (refereegranskat)abstract
- Following on from the NASA twins’ study, there has been a tremendous interest in the use of omics techniques in spaceflight. Individual space agencies, NASA's GeneLab, JAXA's ibSLS, and the ESA-funded Space Omics Topical Team and the International Standards for Space Omics Processing (ISSOP) groups have established several initiatives to support this growth. Here, we present recommendations from the Space Omics Topical Team to promote standard application of space omics in Europe. We focus on four main themes: i) continued participation in and coordination with international omics endeavors, ii) strengthening of the European space omics infrastructure including workforce and facilities, iii) capitalizing on the emerging opportunities in the commercial space sector, and iv) capitalizing on the emerging opportunities in human subjects research.
|
|
| 18. |
- Overbey, Eliah G., et al.
(författare)
-
Challenges and considerations for single-cell and spatially resolved transcriptomics sample collection during spaceflight
- 2022
-
Ingår i: CELL REPORTS METHODS. - : Elsevier BV. - 2667-2375. ; 2:11
-
Forskningsöversikt (refereegranskat)abstract
- Single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (SRT) have experienced rapid development in recent years. The findings of spaceflight-based scRNA-seq and SRT investigations are likely to improve our understanding of life in space and our comprehension of gene expression in various cell systems and tissue dynamics. However, compared to their Earth-based counterparts, gene expression experiments conducted in spaceflight have not experienced the same pace of development. Out of the hundreds of spaceflight gene expression datasets available, only a few used scRNA-seq and SRT. In this perspective piece, we explore the growing importance of scRNA-seq and SRT in space biology and discuss the challenges and considerations relevant to robust experimental design to enable growth of these methods in the field.
|
|
| 19. |
- Rao, P. M, et al.
(författare)
-
The Information and Communication Technologies and Enforcement of Intellectual Property Rights : a Relationship Perspective
- 2008
-
Ingår i: The Journal of World Intellectual Property. - : Wiley. - 1422-2213 .- 1747-1796. ; 11:2, s. 105-119
-
Tidskriftsartikel (refereegranskat)abstract
- Intellectual capital represents an increasingly important area in the world economy. Information and communication technologies (ICTs) have played an essential role in the globalization of the economy. The protection of intellectual property rights (IPRs) is an essential factor in international economic affairs. This article discusses the legal issues concerning proprietary and open software licensing and suggests alternatives to legally enforcing IPRs. Global technology networking and outsourcing have involved the use of open source software (OSS), and have implications for the enforcement of IPRs. Propriety and OSS licensing are analyzed in this article. Companies may adopt alternative strategies to the strict enforcement of IPRs. A relationship view of IPRs is presented, a perspective that adopts relationship marketing as a means of gaining profits from IPRs in the ICT sector. By establishing a relationship to customers, software producers may gain customer loyalty and commitment from users of their software and, in the long run, retain a position as a chosen supplier of software.
|
|
| 20. |
- Semb, Anne Grete, et al.
(författare)
-
Diabetes mellitus and cardiovascular risk management in patients with rheumatoid arthritis: An international audit
- 2021
-
Ingår i: RMD Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 7:2
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: The objective was to examine the prevalence of atherosclerotic cardiovascular disease (ASCVD) and its risk factors among patients with RA with diabetes mellitus (RA-DM) and patients with RA without diabetes mellitus (RAwoDM), and to evaluate lipid and blood pressure (BP) goal attainment in RA-DM and RAwoDM in primary and secondary prevention.Methods: The cohort was derived from the Survey of Cardiovascular Disease Risk Factors in Patients with Rheumatoid Arthritis from 53 centres/19 countries/3 continents during 2014-2019. We evaluated the prevalence of cardiovascular disease (CVD) among RA-DM and RAwoDM. The study population was divided into those with and without ASCVD, and within these groups we compared risk factors and CVD preventive treatment between RA-DM and RAwoDM.Results: The study population comprised of 10 543 patients with RA, of whom 1381 (13%) had DM. ASCVD was present in 26.7% in RA-DM compared with 11.6% RAwoDM (p<0.001). The proportion of patients with a diagnosis of hypertension, hyperlipidaemia and use of lipid-lowering or antihypertensive agents was higher among RA-DM than RAwoDM (p<0.001 for all). The majority of patients with ASCVD did not reach the lipid goal of low-density lipoprotein cholesterol <1.8 mmol/L. The lipid goal attainment was statistically and clinically significantly higher in RA-DM compared with RAwoDM both for patients with and without ASCVD. The systolic BP target of <140 mm Hg was reached by the majority of patients, and there were no statistically nor clinically significant differences in attainment of BP targets between RA-DM and RAwoDM.Conclusion: CVD preventive medication use and prevalence of ASCVD were higher in RA-DM than in RAwoDM, and lipid goals were also more frequently obtained in RA-DM. Lessons may be learnt from CVD prevention programmes in DM to clinically benefit patients with RA.
|
|
| 21. |
- Smith, Roger O., et al.
(författare)
-
Assistive technology products : a position paper from the first global research, innovation, and education on assistive technology (GREAT) summit
- 2018
-
Ingår i: Disability and Rehabilitation. - : Informa Healthcare. - 1748-3107 .- 1748-3115. ; 13:5, s. 473-485
-
Tidskriftsartikel (refereegranskat)abstract
- This paper is based on work from the Global Research, Innovation, and Education on Assistive Technology (GREAT) Summit that was coordinated by WHO's Global Cooperation on Assistive Technology (GATE). The purpose of this paper is to describe the needs and opportunities embedded in the assistive product lifecycle as well as issues relating to the various stages of assistive product mobilization worldwide. The paper discusses assistive technology product terminology and the dangers of focusing on products outside the context and rolling out products without a plan. Additionally, the paper reviews concepts and issues around technology transfer, particularly in relation to meeting global needs and among countries with limited resources. Several opportunities are highlighted including technology advancement and the world nearing a state of readiness through a developing capacity of nations across the world to successfully adopt and support the assistive technology products and applications. The paper is optimistic about the future of assistive technology products reaching the people that can use it the most and the excitement across large and small nations in increasing their own capacities for implementing assistive technology. This is expressed as hope in future students as they innovate and in modern engineering that will enable assistive technology to pervade all corners of current and potential marketplaces. Importantly, the paper poses numerous topics where discussions are just superficially opened. The hope is that a set of sequels will follow to continue this critical dialog.Implications for RehabilitationSuccessful assistive technology product interventions are complex and include much more than the simple selection of the right product.Assistive technology product use is highly context sensitive in terms of an individual user's environment.The development of assistive technology products is tricky as it must be contextually sensitive to the development environment and market as well.As a field we have much to study and develop around assistive technology product interventions from a global perspective.
|
|
| 22. |
|
|
| 23. |
- Vickovic, Sanja, et al.
(författare)
-
High-definition spatial transcriptomics for in situ tissue profiling
- 2019
-
Ingår i: Nature Methods. - : NATURE PUBLISHING GROUP. - 1548-7091 .- 1548-7105. ; 16:10, s. 987-
-
Tidskriftsartikel (refereegranskat)abstract
- Spatial and molecular characteristics determine tissue function, yet high-resolution methods to capture both concurrently are lacking. Here, we developed high-definition spatial transcriptomics, which captures RNA from histological tissue sections on a dense, spatially barcoded bead array. Each experiment recovers several hundred thousand transcriptcoupled spatial barcodes at 2-mu m resolution, as demonstrated in mouse brain and primary breast cancer. This opens the way to high-resolution spatial analysis of cells and tissues.
|
|
| 24. |
- Wall, Anders, et al.
(författare)
-
E-Cigarette Aerosol Deposition and Disposition of [C-11]Nicotine Using Positron Emission Tomography : A Comparison of Nicotine Uptake in Lungs and Brain Using Two Different Nicotine Formulations
- 2022
-
Ingår i: Pharmaceuticals. - : MDPI. - 1424-8247. ; 15:3
-
Tidskriftsartikel (refereegranskat)abstract
- Smoking is a cause of serious disease in smokers. Electronic cigarettes, delivering aerosolized nicotine, offer adult smokers a potentially less harmful alternative to combustible cigarettes. This explorative PET/CT study investigated the distribution and deposition of inhaled [C-11]nicotine using the myblu (TM) e-cigarette with two nicotine formulations, freebase and lactate salt. Fifteen healthy adult smokers participated in the two-part study to assess the distribution and accumulation of [C-11]nicotine in the respiratory pathways and brain. Time-activity data for the respiratory pathways, lungs, oesophagus and brain were derived. 31-36% of both inhaled tracer formulations accumulated in the lung within 15-35 s. [C-11]Nicotine(freebase) exhibited higher uptake and deposition in the upper respiratory pathways. For [C-11]nicotine(lactate), brain deposition peaked at 4-5%, with an earlier peak and a steeper decline. A different kinetic profile was obtained for [C-11]nicotine(lactate) with lower tracer uptake and accumulation in the upper respiratory pathways and an earlier peak and a steeper decline in lung and brain. Using nicotine lactate formulations in e-cigarettes may thus contribute to greater adult smoker acceptance and satisfaction compared to freebase formulations, potentially aiding a transition from combustible cigarettes and an acceleration of tobacco harm reduction initiatives.
|
|
| 25. |
- Wessman, Sandra, et al.
(författare)
-
Precision oncology of high-grade ovarian cancer defined through targeted sequencing
- 2021
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:20
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We examined whether molecular characterization of high-grade epithelial ovarian cancer can inform the diagnosis and/or identify potential actionable targets. Methods: All of the consecutively sequenced high-grade ovarian tumours with consent between 2014 until 2019 were included. A total of 274 tumours underwent next generation sequencing using a targeted panel. Results: Patients with high-grade ovarian epithelial cancer were consented to prospective molecular characterization. Clinical information was extracted from their medical record. Tumour DNA was subjected to sequencing, and selected patients received PARP inhibitor therapy. Conclu-sions: Tumours from 274 women were sequenced, including high-grade serous carcinoma (n = 252), clear cell carcinoma (n = 4), carcinosarcoma (n = 9), endometrioid carcinoma (n = 3), undifferentiated carcinoma (n = 1), and mixed tumours (n = 5). Genomic profiling did not influence histologic diag-nosis. Mutations were identified in TP53, BRCA1, BRCA2, as well as additional homologous recombination repair pathway genes BARD1, ATR, CHEK2, PALB2, RAD51D, RAD50, SLX4, FANCA, RAD51C, and RAD54L. In addition, mutations in PTEN and CDKN2A were identified. Several so-matic mutations with implications for germline testing were identified, including RMI1, STK11, and CDH1. Germline testing identified 16 previously unknown BRCA1/2 carriers. Finally, 20 patients were treated with the PARP inhibitor olaparib based on the sequencing results.
|
|
| 26. |
|
|
