| 1. |
- Baldetorp, Bo, et al.
(author)
-
Analysis of protein expression in pure cell nuclei populations isolated from human breast cancer tissue by DNA flow cytometric sorting.
- 2010
-
In: Journal of Proteomics. - : Elsevier BV. - 1874-3919. ; 73, s. 1111-1116
-
Journal article (peer-reviewed)abstract
- In this study, cell nuclei from aneuploid breast cancer samples were sorted with respect to DNA content into pure diploid and aneuploid fractions using flow cytometry. The nuclear proteins were then separated by one-dimensional gel electrophoresis (1D-PAGE) and differences in protein expression patterns, between diploid and aneuploid nuclei from the same tumours, were compared. Using a combination of peptide finger printing and peptide identification by MALDI-TOF mass spectrometry, we identified proteins and confirmed that the proteins were of nuclear origins. The results in this study add further information to the knowledge about the breast cancer disease complexity and heterogeneity at molecular level. For some of the tumours studied different nuclei protein patterns were obtained, in the diploid respective aneuploid nuclei populations, whilst other tumours did not show these differences.
|
|
| 2. |
- Betancourt, Lazaro Hiram, et al.
(author)
-
Improved survival prognostication of node-positive malignant melanoma patients utilizing shotgun proteomics guided by histopathological characterization and genomic data
- 2019
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
-
Journal article (peer-reviewed)abstract
- Metastatic melanoma is one of the most common deadly cancers, and robust biomarkers are still needed, e.g. to predict survival and treatment efficiency. Here, protein expression analysis of one hundred eleven melanoma lymph node metastases using high resolution mass spectrometry is coupled with in-depth histopathology analysis, clinical data and genomics profiles. This broad view of protein expression allowed to identify novel candidate protein markers that improved prediction of survival in melanoma patients. Some of the prognostic proteins have not been reported in the context of melanoma before, and few of them exhibit unexpected relationship to survival, which likely reflects the limitations of current knowledge on melanoma and shows the potential of proteomics in clinical cancer research.
|
|
| 3. |
- Betancourt, Lazaro Hiram, et al.
(author)
-
The hidden story of heterogeneous B-raf V600E mutation quantitative protein expression in metastatic melanoma—association with clinical outcome and tumor phenotypes
- 2019
-
In: Cancers. - : MDPI AG. - 2072-6694. ; 11:12
-
Journal article (peer-reviewed)abstract
- In comparison to other human cancer types, malignant melanoma exhibits the greatest amount of heterogeneity. After DNA-based detection of the BRAF V600E mutation in melanoma patients, targeted inhibitor treatment is the current recommendation. This approach, however, does not take the abundance of the therapeutic target, i.e., the B-raf V600E protein, into consideration. As shown by immunohistochemistry, the protein expression profiles of metastatic melanomas clearly reveal the existence of inter-and intra-tumor variability. Nevertheless, the technique is only semi-quantitative. To quantitate the mutant protein there is a fundamental need for more precise techniques that are aimed at defining the currently non-existent link between the levels of the target protein and subsequent drug efficacy. Using cutting-edge mass spectrometry combined with DNA and mRNA sequencing, the mutated B-raf protein within metastatic tumors was quantitated for the first time. B-raf V600E protein analysis revealed a subjacent layer of heterogeneity for mutation-positive metastatic melanomas. These were characterized into two distinct groups with different tumor morphologies, protein profiles and patient clinical outcomes. This study provides evidence that a higher level of expression in the mutated protein is associated with a more aggressive tumor progression. Our study design, comprised of surgical isolation of tumors, histopathological characterization, tissue biobanking, and protein analysis, may enable the eventual delineation of patient responders/non-responders and subsequent therapy for malignant melanoma.
|
|
| 4. |
|
|
| 5. |
- Betancourt, Lazaro Hiram, et al.
(author)
-
The human melanoma proteome atlas-Defining the molecular pathology
- 2021
-
In: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 11:7, s. 1-20
-
Journal article (peer-reviewed)abstract
- The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in-depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients.
|
|
| 6. |
- Bonnier, Gaga, et al.
(author)
-
Kirunas Framtid - Kan man flytta en stad? : restaureringskonst på sin spets
- 2010
-
Reports (pop. science, debate, etc.)abstract
- Ar 2004 konstaterade gruvbolaget LKAB att en på världsmarknaden ökad efterfrågan på järnmalm innebär att marken ovanför brytningsområdet i Kiruna spricker i takt med att malmen bryts. Detta deformationsområde kommer att omfatta större delen av den gamla staden inklusive kyrkan och stadshuset. Osäkerheten är stor om hur man skall gå till väga och de konkreta frågorna är ännu obesvarade. Diskussionen handlar om vart man skall flytta och den pendlar mellan ytterligheterna att helt avstå från det gamla och bygga helt nytt eller skapa ett nytt område med de gamla husen musealt återuppbyggda i ett landskapssammanhang som så långt möjligt påminner om det gamla. Den avgörande frågan är, menar vi, hur staden och dess invånare kan behålla sin identitet och sitt minne - framtiden för kulturmiljön i vidaste bemärkelse.Omvandlingen och den successiva flytten av Kirunas centrala delar är en av de riktigt stora samhällsbyggnads- och bevarandefrågorna i vår samtid, en samhällsförändring med global räckvidd - restaureringskonst på sin spets.
|
|
| 7. |
|
|
| 8. |
- Cirenajwis, Helena, et al.
(author)
-
Molecular stratification of metastatic melanoma using gene expression profiling: prediction of survival outcome and benefit from molecular targeted therapy.
- 2015
-
In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:14, s. 12297-12309
-
Journal article (peer-reviewed)abstract
- Melanoma is currently divided on a genetic level according to mutational status. However, this classification does not optimally predict prognosis. In prior studies, we have defined gene expression phenotypes (high-immune, pigmentation, proliferative and normal-like), which are predictive of survival outcome as well as informative of biology. Herein, we employed a population-based metastatic melanoma cohort and external cohorts to determine the prognostic and predictive significance of the gene expression phenotypes. We performed expression profiling on 214 cutaneous melanoma tumors and found an increased risk of developing distant metastases in the pigmentation (HR, 1.9; 95% CI, 1.05-3.28; P=0.03) and proliferative (HR, 2.8; 95% CI, 1.43-5.57; P=0.003) groups as compared to the high-immune response group. Further genetic characterization of melanomas using targeted deep-sequencing revealed similar mutational patterns across these phenotypes. We also used publicly available expression profiling data from melanoma patients treated with targeted or vaccine therapy in order to determine if our signatures predicted therapeutic response. In patients receiving targeted therapy, melanomas resistant to targeted therapy were enriched in the MITF-low proliferative subtype as compared to pre-treatment biopsies (P=0.02). In summary, the melanoma gene expression phenotypes are highly predictive of survival outcome and can further help to discriminate patients responding to targeted therapy.
|
|
| 9. |
|
|
| 10. |
- Gil, Jeovanis, et al.
(author)
-
Clinical protein science in translational medicine targeting malignant melanoma
- 2019
-
In: Cell Biology and Toxicology. - : Springer Science and Business Media LLC. - 0742-2091 .- 1573-6822. ; 35:4, s. 293-332
-
Journal article (peer-reviewed)abstract
- Melanoma of the skin is the sixth most common type of cancer in Europe and accounts for 3.4% of all diagnosed cancers. More alarming is the degree of recurrence that occurs with approximately 20% of patients lethally relapsing following treatment. Malignant melanoma is a highly aggressive skin cancer and metastases rapidly extend to the regional lymph nodes (stage 3) and to distal organs (stage 4). Targeted oncotherapy is one of the standard treatment for progressive stage 4 melanoma, and BRAF inhibitors (e.g. vemurafenib, dabrafenib) combined with MEK inhibitor (e.g. trametinib) can effectively counter BRAFV600E-mutated melanomas. Compared to conventional chemotherapy, targeted BRAFV600E inhibition achieves a significantly higher response rate. After a period of cancer control, however, most responsive patients develop resistance to the therapy and lethal progression. The many underlying factors potentially causing resistance to BRAF inhibitors have been extensively studied. Nevertheless, the remaining unsolved clinical questions necessitate alternative research approaches to address the molecular mechanisms underlying metastatic and treatment-resistant melanoma. In broader terms, proteomics can address clinical questions far beyond the reach of genomics, by measuring, i.e. the relative abundance of protein products, post-translational modifications (PTMs), protein localisation, turnover, protein interactions and protein function. More specifically, proteomic analysis of body fluids and tissues in a given medical and clinical setting can aid in the identification of cancer biomarkers and novel therapeutic targets. Achieving this goal requires the development of a robust and reproducible clinical proteomic platform that encompasses automated biobanking of patient samples, tissue sectioning and histological examination, efficient protein extraction, enzymatic digestion, mass spectrometry–based quantitative protein analysis by label-free or labelling technologies and/or enrichment of peptides with specific PTMs. By combining data from, e.g. phosphoproteomics and acetylomics, the protein expression profiles of different melanoma stages can provide a solid framework for understanding the biology and progression of the disease. When complemented by proteogenomics, customised protein sequence databases generated from patient-specific genomic and transcriptomic data aid in interpreting clinical proteomic biomarker data to provide a deeper and more comprehensive molecular characterisation of cellular functions underlying disease progression. In parallel to a streamlined, patient-centric, clinical proteomic pipeline, mass spectrometry–based imaging can aid in interrogating the spatial distribution of drugs and drug metabolites within tissues at single-cell resolution. These developments are an important advancement in studying drug action and efficacy in vivo and will aid in the development of more effective and safer strategies for the treatment of melanoma. A collaborative effort of gargantuan proportions between academia and healthcare professionals has led to the initiation, establishment and development of a cutting-edge cancer research centre with a specialisation in melanoma and lung cancer. The primary research focus of the European Cancer Moonshot Lund Center is to understand the impact that drugs have on cancer at an individualised and personalised level. Simultaneously, the centre increases awareness of the relentless battle against cancer and attracts global interest in the exceptional research performed at the centre.
|
|
| 11. |
- Giniewska, Ewa, et al.
(author)
-
Högskolebibliotekets roll i en inkluderande lärandemiljö : slutrapport
- 2012
-
Reports (other academic/artistic)abstract
- Slutrapport från projektet "Högskolebibliotekets roll i en inkluderande lärandemiljö" vars syfte var att förtydliga vilken roll högskolebiblioteket spelar för breddad rekrytering och retention, samt att öka kunskapen och medvetenheten om detta bland bibliotekspersonalen. I rapporten ges exempel på arbetsformer för att utveckla bibliotekets bemötande och pedagogiska verksamhet gentemot en heterogen studentgrupp.
|
|
| 12. |
- Harbst, Katja, et al.
(author)
-
Molecular and genetic diversity in the metastatic process of melanoma.
- 2014
-
In: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 233:1, s. 39-50
-
Journal article (peer-reviewed)abstract
- Diversity between metastatic melanoma tumours in individual patients is known; however, the molecular and genetic differences remain unclear. To examine the molecular and genetic differences between metastatic tumours, we performed gene-expression profiling of 63 melanoma tumours obtained from 28 patients (two or three tumours/patient), followed by analysis of their mutational landscape, using targeted deep sequencing of 1697 cancer genes and DNA copy number analysis. Gene-expression signatures revealed discordant phenotypes between tumour lesions within a patient in 50% of the cases. In 18 of 22 patients (where matched normal tissue was available), we found that the multiple lesions within a patient were genetically divergent, with one or more melanoma tumours harbouring 'private' somatic mutations. In one case, the distant subcutaneous metastasis of one patient occurring 3 months after an earlier regional lymph node metastasis had acquired 37 new coding sequence mutations, including mutations in PTEN and CDH1. However, BRAF and NRAS mutations, when present in the first metastasis, were always preserved in subsequent metastases. The patterns of nucleotide substitutions found in this study indicate an influence of UV radiation but possibly also DNA alkylating agents. Our results clearly demonstrate that metastatic melanoma is a molecularly highly heterogeneous disease that continues to progress throughout its clinical course. The private aberrations observed on a background of shared aberrations within a patient provide evidence of continued evolution of individual tumours following divergence from a common parental clone, and might have implications for personalized medicine strategies in melanoma treatment. Published by John Wiley & Sons, Ltd. www.pathsoc.org.uk.
|
|
| 13. |
- Harbst, Katja, et al.
(author)
-
Molecular profiling reveals low- and high-grade forms of primary melanoma.
- 2012
-
In: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1557-3265. ; 18:15, s. 4026-4036
-
Journal article (peer-reviewed)abstract
- For primary melanomas, tumor thickness, mitotic rate, and ulceration are well-laid cornerstones of prognostication. However, a molecular exposition of melanoma aggressiveness is critically missing. We recently uncovered a four-class structure in metastatic melanoma, which predicts outcome and informs biology. This raises the possibility that a molecular structure exists even in the early stages of melanoma and that molecular determinants could underlie histophenotype and eventual patient outcome.We subjected 223 archival primary melanomas to a horizontally integrated analysis of RNA expression, oncogenic mutations at 238 lesions, histomorphometry, and survival data.Our previously described four-class structure that was elucidated in metastatic lesions was evident within the expression space of primary melanomas. Because these subclasses converged into two larger prognostic and phenotypic groups, we used the metastatic lesions to develop a binary subtype-based signature capable of distinguishing between "high" and "low" grade forms of the disease. The two-grade signature was subsequently applied to the primary melanomas. Compared with low-grade tumors, high-grade primary melanomas were significantly associated with increased tumor thickness, mitotic rate, ulceration (all P < 0.01), and poorer relapse-free (HR = 4.94; 95% CI, 2.84-8.59), and overall (HR = 3.66; 95% CI, 2.40-5.58) survival. High-grade melanomas exhibited elevated levels of proliferation and BRCA1/DNA damage signaling genes, whereas low-grade lesions harbored higher expression of immune genes. Importantly, the molecular-grade signature was validated in two external gene expression data sets.We provide evidence for a molecular organization within melanomas, which is preserved across all stages of disease.
|
|
| 14. |
- Hellström, Ann, 1959, et al.
(author)
-
Association of Docosahexaenoic Acid and Arachidonic Acid Serum Levels With Retinopathy of Prematurity in Preterm Infants
- 2021
-
In: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:10
-
Journal article (peer-reviewed)abstract
- IMPORTANCE Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) has been inconsistent in reducing the severity and incidence of retinopathy of prematurity (ROP). Furthermore, few studies have measured the long-term serum lipid levels after supplementation. OBJECTIVE To assess whether ROP severity is associated with serum levels of LC-PUFA, especially docosahexaenoic acid (DHA) and arachidonic acid (AA), during the first 28 postnatal days. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed the Mega Donna Mega study, a randomized clinical trial that provided enteral fatty acid supplementation at 3 neonatal intensive care units in Sweden. Infants included in this cohort study were born at a gestational age of less than 28 weeks between December 20, 2016, and August 6, 2019. MAIN OUTCOMES AND MEASURES Severity of ROP was classified as no ROP, mild or moderate ROP (stage 1-2), or severe ROP (stage 3 and type 1). Serum phospholipid fatty acids were measured through gas chromatography-mass spectrometry. Ordinal logistic regression, with a description of unadjusted odds ratio (OR) as well as gestational age- and birth weight-adjusted ORs and 95% CIs, was used. Areas under the curve were used to calculate mean daily levels of fatty acids during postnatal days 1 to 28. Blood samples were obtained at the postnatal ages of 1, 3, 7, 14, and 28 days. RESULTS A total of 175 infants were included in analysis. Of these infants, 99 were boys (56.6%); the median (IQR) gestational age was 25 weeks 5 days (24 weeks 3 days to 26 weeks 6 days), and the median (IQR) birth weight was 785 (650-945) grams. A higher DHA proportion was seen in infants with no ROP compared with those with mild or moderate ROP or severe ROP (OR per 0.5-molar percentage increase, 0.49 [95% CI, 0.36-0.68]; gestational age- and birth weight-adjusted OR, 0.66 [95% CI, 0.46-0.93]). The corresponding adjusted OR for AA levels per 1-molar percentage increase was 0.83 (95% CI, 0.66-1.05). The association between DHA levels and ROP severity appeared only in infants with sufficient AA levels, suggesting that a mean daily minimum level of 7.8 to 8.3 molar percentage of AA was necessary for a detectable association between DHA level and less severe ROP. CONCLUSIONS AND RELEVANCE This cohort study found that higher mean daily serum levels of DHA during the first 28 postnatal days were associated with less severe ROP even after adjustment for known risk factors, but only in infants with sufficiently high AA levels. Further studies are needed to identify LC-PUFA supplementation strategies that may prevent ROP and other morbidities.
|
|
| 15. |
- Hellström, Ann, 1959, et al.
(author)
-
Retrospective evaluation of ophthalmological and neurological outcomes for infants born before 24 weeks gestational age in a Swedish cohort
- 2022
-
In: Bmj Open. - : BMJ. - 2044-6055. ; 12:8
-
Journal article (peer-reviewed)abstract
- Objectives To retrospectively evaluate ophthalmological and neurological outcomes in a Swedish cohort of infants born before 24 weeks gestational age (GA) and explore risk factors for visual impairment. Setting Eye and paediatric clinics in Sweden. Participants Infants screened for retinopathy of prematurity (ROP) (n=399), born before 24 weeks GA, 2007-2018. Cases were excluded if ophthalmological follow-up records could not be traced. Primary and secondary outcome measures Primary outcomes were ophthalmological, including visual acuity (VA), refractive error, strabismus, nystagmus and cerebral visual impairment (CVI). Secondary outcomes comprised neonatal and neurological morbidities. Data were retrospectively retrieved from medical records. Results The 355 assessed children had a median GA of 23 weeks and 2 days and a median birth weight of 565 g. At the last available ophthalmological examination, the median age was 4.8 years (range 0.5-13.2 years). Nystagmus was recorded in 21.1%, strabismus in 34.8%, and 51.0% wore spectacles. Seventy-three of 333 (21.9%) were visually impaired, defined as being referred to a low vision clinic and/or having a VA less than 20/60 at 3.5 years of age or older. ROP treatment was a significant risk factor for visual impairment (OR 2.244, p=0.003). Visually impaired children, compared with children without visual impairment, more often had neurological deficits such as intellectual disability 63.8% versus 33.3% (p<0.001), epilepsy 21.1% versus 7.5% (p=0.001) and autism spectrum disorders 32.8% versus 20.9% (p=0.043). Nine of the 355 children had been diagnosed with CVI. Conclusions Children born before 24 weeks GA frequently had visual impairment in association with neurological deficits. CVI was rarely diagnosed. A multidisciplinary approach for the evaluation and habilitation of these vulnerable infants is warranted. National follow-up guidelines need to be developed and implemented.
|
|
| 16. |
|
|
| 17. |
- Jakobsson, Lotta, 1967, et al.
(author)
-
Evaluation criteria for AIS 1 neck injuries in frontal impacts - A parameter study combining field data and Madymo modelling
- 2004
-
In: Traffic Injury Prevention. - : Informa UK Limited. - 1538-957X .- 1538-9588. ; 5:4, s. 374-381
-
Journal article (peer-reviewed)abstract
- Two situations with an expected higher AIS 1 neck injury rate in frontal impact were compared to a reference situation using a Madymo human body model in three different sitting postures and four different crash pulses. The two situations were reduced occupant weight and occupant with initial forward arm resistance, respectively. Occupant neck motion phases were identified and corresponding possible evaluation criteria were evaluated within the phases. Typical neck kinematics was seen for the two different situations. Occupants of lower weight had a more extended neck in the initial protraction phase and also a generally more pronounced upper neck link angle. Occupants with initial arm resistance had generally greater lower neck link angle at the time when the upper neck link angle was straight. No evaluation criteria reflected the anticipated AIS 1 neck injury rate consistently. In the initial protraction phase, NICmincorrelated to expected injury outcome in almost half of the cases. In the protractionflexion shift phase, Nkm, Nij, upper neck shear force and neck tension force reflected anticipated severity outcome to some extent. In the flexion phase, upper and lower neck extension correlated to anticipated AIS 1 neck injury rate only to a minor extent. The different sitting postures were more influential than the different crash pulses, emphasizing the importance of not only considering the spectra of impact severity but also differences in sitting postures in safety system development and evaluation.
|
|
| 18. |
|
|
| 19. |
- Joensuu, Heikki, et al.
(author)
-
Effect of Adjuvant Trastuzumab for a Duration of 9 Weeks vs 1 Year With Concomitant Chemotherapy for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer The SOLD Randomized Clinical Trial
- 2018
-
In: JAMA Oncology. - : AMER MEDICAL ASSOC. - 2374-2437 .- 2374-2445. ; 4:9, s. 1199-1206
-
Journal article (peer-reviewed)abstract
- Importance: Trastuzumab plus chemotherapy is the standard adjuvant treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. While the standard duration of trastuzumab treatment is 12 months, the benefits and harms of trastuzumab continued beyond the chemotherapy are unclear.Objective: To evaluate the efficacy and safety of adjuvant trastuzumab continued beyond chemotherapy in women treated with up-front chemotherapy containing a taxane and trastuzumab.Design, Setting, and Participants: Open-label, randomized (1:1) clinical trial including women with HER2-positive breast cancer. Chemotherapy was identical in the 2 groups, consisting of 3 cycles of 3-weekly docetaxel (either 80 or 100 mg/m2) plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide. Thereafter, no trastuzumab was administered in the 9-week group, whereas controls received trastuzumab to complete 1 year of administration. Disease-free survival (DFS) was compared between the groups using a Cox model and the noninferiority approach. The estimated sample size was 2168 patients (1-sided testing, with a relative noninferiority margin of 1.3). From January 3, 2008, to December 16, 2014, 2176 patients were accrued from 7 countries.Intervention: Docetaxel plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide in both groups. Controls continued trastuzumab to 1 year.Main Outcomes and Measures: The primary objective was DFS; secondary objectives included distant disease–free survival, overall survival, cardiac DFS, and safety.Results: In the 2174 women analyzed, median age was 56 (interquartile range [IQR], 48-64) years. The median follow-up was 5.2 (IQR, 3.8-6.7) years. Noninferiority of the 9-week treatment could not be demonstrated for DFS (hazard ratio, 1.39; 2-sided 90% CI, 1.12-1.72). Distant disease–free survival and overall survival did not differ substantially between the groups. Thirty-six (3%) and 21 (2%) patients in the 1-year and the 9-week groups, respectively, had cardiac failure; the left ventricle ejection fraction was better maintained in the 9-week group. An interaction was detected between the docetaxel dose and DFS; patients in the 9-week group treated with 80 mg/m2 had inferior and those treated with 100 mg/m2 had similar DFS as patients in the 1-year group.Conclusions and Relevance: Nine weeks of trastuzumab was not noninferior to 1 year of trastuzumab when given with similar chemotherapy. Cardiac safety was better in the 9-week group. The docetaxel dosing with trastuzumab requires further study.Trial Registration: ClinicalTrials.gov Identifier: NCT00593697
|
|
| 20. |
- Kim, Yonghyo, et al.
(author)
-
Protein Expression in Metastatic Melanoma and the Link to Disease Presentation in a Range of Tumor Phenotypes
- 2020
-
In: Cancers. - : MDPI AG. - 2072-6694. ; 12:3
-
Research review (peer-reviewed)abstract
- Malignant melanoma is among the most aggressive skin cancers and it has among the highest metastatic potentials. Although surgery to remove the primary tumor is the gold standard treatment, once melanoma progresses and metastasizes to the lymph nodes and distal organs, i.e., metastatic melanoma (MM), the usual outcome is decreased survival. To improve survival rates and life span, advanced treatments have focused on the success of targeted therapies in the MAPK pathway that are based on BRAF (BRAF V600E) and MEK. The majority of patients with tumors that have higher expression of BRAF V600E show poorer prognosis than patients with a lower level of the mutated protein. Based on the molecular basis of melanoma, these findings are supported by distinct tumor phenotypes determined from differences in tumor heterogeneity and protein expression profiles. With these aspects in mind, continued challenges are to: (1) deconvolute the complexity and heterogeneity of MM; (2) identify the signaling pathways involved; and (3) determine protein expression to develop targeted therapies. Here, we provide an overview of the results from protein expression in MM and the link to disease presentation in a variety of tumor phenotypes and how these will overcome the challenges of clinical problems and suggest new promising approaches in metastatic melanoma and cancer therapy.
|
|
| 21. |
- Larsson, Anna Maria, et al.
(author)
-
Longitudinal enumeration and cluster evaluation of circulating tumor cells improve prognostication for patients with newly diagnosed metastatic breast cancer in a prospective observational trial
- 2018
-
In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 20:1, s. 1-14
-
Journal article (peer-reviewed)abstract
- Background: Circulating tumor cells (CTCs) carry independent prognostic information in patients with metastatic breast cancer (MBC) on different lines of therapy. Moreover, CTC clusters are suggested to add prognostic information to CTC enumeration alone but their significance is unknown in patients with newly diagnosed MBC. We aimed to evaluate whether longitudinal enumeration of circulating tumor cells (CTCs) and CTC clusters could improve prognostication and monitoring of patients with metastatic breast cancer (MBC) starting first-line therapy. Methods: This prospective study included 156 women with newly diagnosed MBC. CTCs and CTC clusters were detected using CellSearch technology at baseline (BL) and after 1, 3, and 6months of systemic therapy. The primary end point was progression-free survival (PFS) and the secondary end point overall survival (OS). Median follow-up time was 25 (7-69) months. Results: There were 79 (52%) and 30 (20%) patients with ≥5 CTCs and≥1 CTC cluster at baseline, respectively; both factors were significantly associated with impaired survival. Landmark analyses based on follow-up measurements revealed increasing prognostic hazard ratios for ≥5 CTCs and CTC clusters during treatment, predicting worse PFS and OS. Both factors added value to a prognostic model based on clinicopathological variables at all time points and ≥5 CTCs and presence of CTC clusters enhanced the model's C-index to >0.80 at 1, 3, and 6months. Importantly, changes in CTCs during treatment were significantly correlated with survival and patients with a decline from ≥5 CTCs at BL to <5 CTCs at 1month had a similar odds ratio for progression to patients with <5 CTCs at BL and 1month. Stratification of patients based on CTC count and CTC clusters into four groups (0 CTCs, 1-4 CTCs, ≥5 CTCs, and ≥1 CTC+CTC clusters) demonstrated that patients with CTC clusters had significantly worse survival compared to patients without clusters. Conclusions: Longitudinal evaluation of CTC and CTC clusters improves prognostication and monitoring in patients with MBC starting first-line systemic therapy. The prognostic value increases over time, suggesting that changes in CTC count are clinically relevant. The presence of CTC clusters adds significant prognostic value to CTC enumeration alone.
|
|
| 22. |
- Larsson, Eva, 1961-, et al.
(author)
-
Ophthalmological outcome of 6.5 years children treated for retinopathy of prematurity: a Swedish register study
- 2024
-
In: British Journal of Ophthalmology. - : BMJ. - 0007-1161 .- 1468-2079. ; 108:1, s. 137-142
-
Journal article (peer-reviewed)abstract
- AimsTo determine the ophthalmological outcome at 6.5 years of age in children treated for retinopathy of prematurity (ROP), and registered in the national Swedish National Register for ROP register. MethodsData on ROP, treatment and ophthalmological outcome were retrieved from the register. Visual acuity (VA), refractive errors and strabismus, together with visual impairment (VI) and any significant eye problem, defined as VA >0.5 logarithm of the minimal angle of resolution (logMAR) and/or strabismus and/or any refractive error were analysed. Risk factors such as sex, gestational age (GA), birth weight SD score, number of treatments and retreatments, postnatal age and postmenstrual age at first treatment were analysed. ResultsFollow-up data were available in 232 of 270 children born between 2007 and 2014 who had been treated for ROP. VI (VA >0.5 logMAR) was found in 32 (14%), strabismus in 82 (38%), refractive errors in 114 (52%) and significant eye problem in 143 (65%) children. Retreatment was a risk factor for VI and refractive errors. Male sex and neonatal brain lesion were risk factors for strabismus. An additional week of GA at birth reduced the risk for refractive errors, strabismus and significant eye problems. ConclusionThe results of the present study revealed a high number of eye problems in children treated for ROP, emphasising the need for long-term follow-up. Retreatment of ROP was a risk factor for VI, and emphasises the importance of an accurate first treatment for the long-term ophthalmological outcome.
|
|
| 23. |
- Lundeheim, Nils, et al.
(author)
-
Shoulder ulcers in sows are genetically correlated to leanness of young pigs and to litter weight
- 2014
-
In: Acta Agriculturae Scandinavica, Section A - Animal Science. - : Informa UK Limited. - 0906-4702 .- 1651-1972. ; 64, s. 67-72
-
Journal article (peer-reviewed)abstract
- The aim of this study was to estimate the heritability for shoulder ulcers (SU) and sows' body condition at weaning (BCw), and the genetic correlations between these traits and some production and reproduction traits included in the current breeding goal of sow lines. The analyses were based on data on Swedish purebred Yorkshire from nucleus as well as multiplier herds. The estimated heritabilities were for BCw 0.21, and for SU 0.13. Significant genetic correlations were found between sidefat thickness (at 100 kg) and BCw (thicker fat layer at 100 kg - better condition at weaning), between sidefat thickness and SU (thicker fat layer - less SU), between litter weight at 3 weeks and BCw (heavier litter - lower body condition) and between litter weight at 3 weeks and SU (heavier litter - more SU). The genetic correlation between BCw and SU was also significant (lower body condition - more SU).
|
|
| 24. |
- Lundgren, Helena, et al.
(author)
-
Genetic analysis of reproductive performance in Landrace sows and its correlation to piglet growth
- 2010
-
In: Livestock Science. - : Elsevier BV. - 1871-1413 .- 1878-0490. ; 128, s. 173-178
-
Journal article (peer-reviewed)abstract
- The aim of this study was to investigate the reproductive performance of sows, including the interval from weaning to service after 1st litter and litter size in the following (2nd) parity, as well as the direct and maternal genetic effects of piglet growth on these reproduction traits. Data on 15 946 Norwegian Landrace sows' 1st and 2nd parity, and on 106,962 piglets born in 11,323 1st parity litters were included in the analyses, in total, five traits were analysed. Weaning-to-service interval was based on a 1- to 7-day interval (WS17) or a transformed 1- to 50-day interval (WS150). A third reproduction trait was total number of piglets born in 2nd parity (NBTnext). Piglet weight was included in the analyses, either as average piglet weight in the litter at 3 weeks of age (meanW3) or as individual piglet weight gain during the first 3 weeks of life (IWG03). Genetic parameters were estimated with animal models, including both direct and maternal effects for IWG03. Heritability estimates for WS17, WS150 and NBTnext were 0.08, 0.03 and 0.09 respectively. For meanW3. the heritability estimate was 0.21. For IWG03, the direct and maternal heritability estimates were 0.15 and 0.10 respectively. Negative and unfavourable genetic correlations were estimated between meanW3 and NBTnext (r(g) = -0.37), and between IWG03(maternal) and NBTnext (r(g) = -0.39). The ability to raise fast growing, heavy piglets seems to have an unfavorable effect on total number born in next litter but not on the weaning-to-service interval. (C) 2009 Elsevier B.V. All rights reserved.
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
- Lundgren, Helena, et al.
(author)
-
Genetic parameters for feed intake, litter weight, body condition and rebreeding success in primiparous Norwegian Landrace sows
- 2014
-
In: Animal. - 1751-7311 .- 1751-732X. ; 8, s. 175-183
-
Journal article (peer-reviewed)abstract
- The aim of this study was to estimate genetic parameters for feed intake recorded as farmers' perception of young sows' appetite for the first 3 weeks of lactation (APP) and feed intake recorded for one day in the 3rd week of lactation (FEED), litter weight (LW) at 3 weeks, sow body condition at weaning (BC) and the following five reproduction traits: weaning-to-service interval of 1 to 7 days (WSI7), weaning-to-service interval of 1 to 50 days (WSI50), delayed service or not (DELAYED), pregnant on first service or not (PREGNANT) and litter size in 2nd parity (NBT2). The analyses included data on 4606 Norwegian Landrace 1st-parity sows and their litters. The Gibbs sampling method was used. The traits DELAYED and PREGNANT were analysed as threshold traits and APP, FEED, LW, BC, WSI7, WSI50 and NBT2 were analysed as linear traits. The heritability estimates for APP and FEED were low (<0.1), whereas the estimates for DELAYED and PREGNANT were rather high (0.4 and 0.3). The heritability estimate for BC was 0.2. The genetic correlations confirmed the complexity of breeding for sow performance; selection for heavy 1st litters may lead to lower body condition at weaning, which in turn leads to lower reproductive performance and smaller litters in 2nd parity. Selection for higher sow feed intake would improve body condition, but the simple way of measuring feed intake tested in this study (APP and FEED) cannot be recommended because of the low heritability obtained for these traits.
|
|
| 28. |
- Lundgren, Helena, et al.
(author)
-
Genetics of growth in piglets and the association with homogeneity of body weight within litters
- 2010
-
In: Journal of Animal Science. - : Oxford University Press (OUP). - 0021-8812 .- 1525-3163. ; 88, s. 1240-1247
-
Journal article (peer-reviewed)abstract
- The objective of this study was to examine the genetic basis of homogeneity in piglets and the genetic correlations with litter size and growth during lactation. Genetic parameters for variation in piglet BW within litters at birth and at 3 wk of age, and in the BW of individual piglets at 3 wk (BW3) were estimated from the Norwegian Landrace nucleus population. Data on BW3 were collected from 146,572 piglets from 14,045 litters in 58 herds. Body weight at birth and at 3 wk of age was recorded for 13,318 piglets from 5 nucleus herds. Litter data were evaluated using multivariate trait models. The heritability estimates for the SD of BW at birth and at 3 wk (SDBW3) were in agreement with the literature (0.10 and 0.08, respectively). The genetic correlation for the number of piglets born alive and the mean BW at 3 wk was negative (-0.40 +/- 0.07), and the correlation of number of piglets born alive with SDBW3 was close to zero (-0.03 +/- 0.11). The genetic correlation between the SD of BW at birth and SDBW3 was moderate (0.51 +/- 0.31). The mean BW at birth was genetically correlated with mean BW at 3 wk (0.59 +/- 0.16) but was independent of SDBW3 (0.08 +/- 0.27). The estimates of direct and maternal heritability for BW3 were 0.03 and 0.07, respectively, and the genetic correlation between the 2 components was negative (-0.43 +/- 0.10). The genetic correlation of SDBW3 with the maternal effect on BW3 was positive and strong (0.66 +/- 0.08), whereas a negative correlation was found with the direct effect on BW3 (-0.18 +/- 0.14). These results suggest that it is possible to select for mean BW at birth without an increase in within-litter heterogeneity at 3 wk of age. A more efficient strategy would be to consider both the direct and the maternal effects on BW3 in the genetic evaluation, together with SDBW3. Thus, it is possible to avoid the increase in within- litter heterogeneity that would occur as a result of selection performed at 3 wk on a litter trait such as mean BW.
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
- Lundgren, Ib, et al.
(author)
-
Högskolebibliotekets roll i en inkluderande lärandemiljö : erfarenheter från ett pågående projekt
- 2010
-
Conference paper (other academic/artistic)abstract
- Mot bakgrund av frågor som rör bibliotekets roll i vidgat deltagande och retention, startade Malmö högskolas bibliotek i januari 2010 ett tvåårigt projekt för att få kunskap och idéer om hur bibliotekets bemötande och pedagogiska verksamhet kan utvecklas. Genom att lära mer om breddad rekrytering och nya studentgruppers väg in i, genom och ut ur högskolan, vill vi bidra till att skapa en mer inkluderande lärandemiljö i högskolan. Vi har valt att presentera detta på Mötesplats inför framtiden innan avslutat projekt, eftersom vi tycker att konferensen är ett bra forum för en diskussion om bibliotekens roll i en bred rekrytering och i högskolornas arbete med inkludering. Vi ser detta som ett bra tillfälle att knyta kontakter och ta del av andras arbete med likabehandling och inkludering, på såväl högskole- som folkbibliotek. Detta paper och vår presentation på konferensen, är alltså en del av projektet och en inbjudan till dialog med andra bibliotek med erfarenhet av mångfaldsarbete.
|
|
| 32. |
- Lundgren, Ib, et al.
(author)
-
Högskolebibliotekets roll i en inkluderande lärandemiljö
- 2010
-
Conference paper (other academic/artistic)abstract
- Beskriver projektet "Högskolebibliotekets roll i en inkluderande lärandemiljö" vars syfte är att förtydliga vilken roll högskolebiblioteket spelar för breddad rekrytering och retention, samt att öka kunskapen och medvetenheten om detta bland bibliotekspersonalen. Projektet syftar också till att ge en tydligare bild av hur studenternas informationssökningsprocess ser ut. Hur möter vi en heterogen studentgrupp på bästa sätt? Hur bör bibliotekets tjänster och lokaler utformas för att tilltala studenter med olika behov? I detta paper diskuteras ovanstående. Det ges också förslag på verktyg och arbetsformer som kan användas när biblioteket ska utvärdera och beforska sin praktik i syfte att utveckla densamma.
|
|
| 33. |
- Lundgren, Pia, et al.
(author)
-
High rate and large intercentre variability in retreatment of retinopathy of prematurity in infants born < 24 gestational weeks
- 2021
-
In: BMJ Open Ophthalmology. - : BMJ Publishing Group Ltd. - 2397-3269. ; 6:1
-
Journal article (peer-reviewed)abstract
- Objective Prematurity is a major risk factor for retinopathy of prematurity (ROP). We aimed to elucidate ROP prevalence, treatment and retreatment in infants born before 24 gestational age (GA) weeks in a Swedish cohort. Methods and analysis Infants with completed ROP screening, born at <24 GA weeks, 2007-2018 in Sweden were included. Data of GA, birth weight (BW), sex, neonatal morbidities, maximal ROP stage, aggressive posterior ROP (APROP), ROP treatments, treatment modality and treatment centre were retrieved. Results In total, 399 infants, with a mean GA of 23.2 weeks (range 21.9-23.9) and a mean BW of 567 g (range 340-874), were included. ROP was detected in 365 (91.5%) infants, 173 (43.4%) were treated for ROP and 68 of 173 (39.3%) were treated more than once. As the first treatment, 142 (82.0%) received laser and 29 (16.1%) received intravitreal injection of antivascular endothelial growth factor (anti-VEGF). Retreatment was performed after first laser in 46 of 142 (32.4%) and in 20 of 29 (69.0%) after first anti-VEGF treatment. Retreatment rate was not associated with GA, BW or sex but with APROP, treatment method (anti-VEGF) and treatment centre where the laser was performed (p<0.001). Twenty eyes progressed to retinal detachment, and two infants developed unilateral endophthalmitis after anti-VEGF treatment. Conclusion Infants, born at <24 weeks GA, had high rates of treatment-warranting ROP and retreatments. Treatment centre highly influenced the retreatment rate after laser indicating that laser treatment could be improved in some settings.
|
|
| 34. |
- Lundgren, Pia, 1967, et al.
(author)
-
Visual outcome at 2.5 years of age in ω-3 and ω-6 long-chain polyunsaturated fatty acid supplemented preterm infants: a follow-up of a randomized controlled trial
- 2023
-
In: Lancet Regional Health-Europe. - 2666-7762. ; 32
-
Journal article (peer-reviewed)abstract
- Background We investigated ophthalmological outcomes at 2.5 years of corrected age in children born extremely preterm (EPT) to evaluate the effects of postnatal enteral supplementation with omega-3 and omega-6 long-chain polyunsaturated fatty acids.Methods In the Mega Donna Mega clinical trial, EPT infants born at less than 28 weeks of gestation were randomized to receive an enteral supplementation of docosahexaenoic acid (DHA) and arachidonic acid (AA) from birth to 40 weeks postmenstrual age. In this exploratory follow-up at 2.5 years of corrected age, we assessed visual acuity (VA), refraction, manifest strabismus, and nystagmus. Satisfactory VA was defined as >= 20/63. Multiple imputation (MI) was used to address the issue of missing data.Findings Of 178 children in the trial, 115 (with median gestational age (GA) of 25 + 4/7 weeks and median birth weights of 790 g) were ophthalmologically assessed at a median corrected age of 2.7 years (range 2.0-3.9 years). VA assessment was missing in 42.1% (75/178), in 41.7% (35/84) of the AA/DHA supplemented infants, and in 42.6% (40/94) of the control infants. After MI and adjustments for GA, study center, plurality, and corrected age at VA exam, no significant effect of AA/DHA supplementation was detected in VA outcome (>= 20/63) (odds ratio 2.16, confidence interval 95% 0.99-4.69, p = 0.053).Interpretation In this randomized controlled trial follow-up, postnatal supplementation with enteral AA/DHA to EPT children did not significantly alter VA at 2.5 years of corrected age. Due to the high loss to follow-up rate and the limited statistical power, additional studies are needed.
|
|
| 35. |
|
|
| 36. |
- O'Day, S. J., et al.
(author)
-
Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study
- 2010
-
In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 21:8, s. 1712-1717
-
Journal article (peer-reviewed)abstract
- Background: This phase II study evaluated the safety and activity of ipilimumab, a fully human mAb that blocks cytotoxic T-lymphocyte antigen-4, in patients with advanced melanoma. Patients and methods: Patients with previously treated, unresectable stage III/stage IV melanoma received 10 mg/kg ipilimumab every 3 weeks for four cycles (induction) followed by maintenance therapy every 3 months. The primary end point was best overall response rate (BORR) using modified World Health Organization (WHO) criteria. We also carried out an exploratory analysis of proposed immune-related response criteria (irRC). Results: BORR was 5.8% with a disease control rate (DCR) of 27% (N = 155). One-and 2-year survival rates (95% confidence interval) were 47.2% (39.5% to 55.1%) and 32.8% (25.4% to 40.5%), respectively, with a median overall survival of 10.2 months (7.6-16.3). Of 43 patients with disease progression by modified WHO criteria, 12 had disease control by irRC (8% of all treated patients), resulting in a total DCR of 35%. Adverse events (AEs) were largely immune related, occurring mainly in the skin and gastrointestinal tract, with 19% grade 3 and 3.2% grade 4. Immune-related AEs were manageable and generally reversible with corticosteroids. Conclusion: Ipilimumab demonstrated clinical activity with encouraging long-term survival in a previously treated advanced melanoma population.
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
- Olofsson, Roger, 1978, et al.
(author)
-
Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial) : study protocol for a randomized controlled trial
- 2014
-
In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 15, s. 317-
-
Journal article (peer-reviewed)abstract
- Background: Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in approximately 50% of patients, with the liver being the most common site for metastases. The median survival for patients with liver metastases is between 6 and 12 months, and no treatment has in randomized trials ever been shown to prolong survival. A previous phase II trial using isolated hepatic perfusion (IHP) has suggested a 14-month increase in overall survival compared with a historic control group consisting of the longest surviving patients in Sweden during the same time period (26 versus 12 months). Methods/Design: This is the protocol for a multicenter phase III trial randomizing patients with isolated liver metastases of uveal melanoma to IHP or best alternative care (BAC). Inclusion criteria include liver metastases (verified by biopsy) and no evidence of extra-hepatic tumor manifestations by positron emission tomography-computed tomography (PET-CT). The primary endpoint is overall survival at 24 months, with secondary endpoints including response rate, progression-free survival, and quality of life. The planned sample size is 78 patients throughout five years. Discussion: Patients with isolated liver metastases of uveal melanoma origin have a short expected survival and no standard treatment option exists. This is the first randomized clinical trial to evaluate IHP as a treatment option with overall survival being the primary endpoint.
|
|
| 40. |
- Pearson, Kevin, et al.
(author)
-
Childhood tuberous sclerosis complex in southern Sweden: A paradigm shift in diagnosis and treatment.
- 2023
-
In: BMC Pediatrics. - 1471-2431. ; 23:1
-
Journal article (peer-reviewed)abstract
- AimTo investigate the complete clinical spectrum of individuals with paediatric tuberous sclerosis complex in southern Sweden and explore changes over time.MethodsIn this retrospective observational study, 52 individuals aged up to 18 years at the study start were followed-up at regional hospitals and centres for habilitation from 2000 to 2020.ResultsCardiac rhabdomyoma was detected prenatally/neonatally in 69.2% of the subjects born during the latest ten years of the study period. Epilepsy was diagnosed in 82.7% of subjects, and 10 (19%) were treated with everolimus, mainly (80%) for a neurological indication. Renal cysts were detected in 53%, angiomyolipomas in 47%, astrocytic hamartomas in 28% of the individuals. There was a paucity of standardized follow-up of cardiac, renal, and ophthalmological manifestations and no structured transition to adult care.ConclusionOur in-depth analysis shows a clear shift towards an earlier diagnosis of tuberous sclerosis complex in the latter part of the study period, where more than 60% of cases showed evidence of this condition already in utero due to the presence of a cardiac rhabdomyoma. This allows for preventive treatment of epilepsy with vigabatrin and early intervention with everolimus for potential mitigation of other symptoms of tuberous sclerosis complex.
|
|
| 41. |
- Pivodic, Aldina, 1978, et al.
(author)
-
Development and validation of a new clinical decision support tool to optimize screening for retinopathy of prematurity
- 2022
-
In: British Journal of Ophthalmology. - : BMJ Publishing Group Ltd. - 0007-1161 .- 1468-2079. ; 106:11, s. 1573-1580
-
Journal article (peer-reviewed)abstract
- BACKGROUND/AIMS: Prematurely born infants undergo costly, stressful eye examinations to uncover the small fraction with retinopathy of prematurity (ROP) that needs treatment to prevent blindness. The aim was to develop a prediction tool (DIGIROP-Screen) with 100% sensitivity and high specificity to safely reduce screening of those infants not needing treatment. DIGIROP-Screen was compared with four other ROP models based on longitudinal weights.METHODS: Data, including infants born at 24-30 weeks of gestational age (GA), for DIGIROP-Screen development (DevGroup, N=6991) originate from the Swedish National Registry for ROP. Three international cohorts comprised the external validation groups (ValGroups, N=1241). Multivariable logistic regressions, over postnatal ages (PNAs) 6-14 weeks, were validated. Predictors were birth characteristics, status and age at first diagnosed ROP and essential interactions.RESULTS: ROP treatment was required in 287 (4.1%)/6991 infants in DevGroup and 49 (3.9%)/1241 in ValGroups. To allow 100% sensitivity in DevGroup, specificity at birth was 53.1% and cumulatively 60.5% at PNA 8 weeks. Applying the same cut-offs in ValGroups, specificities were similar (46.3% and 53.5%). One infant with severe malformations in ValGroups was incorrectly classified as not needing screening. For all other infants, at PNA 6-14 weeks, sensitivity was 100%. In other published models, sensitivity ranged from 88.5% to 100% and specificity ranged from 9.6% to 45.2%.CONCLUSIONS: DIGIROP-Screen, a clinical decision support tool using readily available birth and ROP screening data for infants born GA 24-30 weeks, in the European and North American populations tested can safely identify infants not needing ROP screening. DIGIROP-Screen had equal or higher sensitivity and specificity compared with other models. DIGIROP-Screen should be tested in any new cohort for validation and if not validated it can be modified using the same statistical approaches applied to a specific clinical setting.
|
|
| 42. |
- Pivodic, Aldina, et al.
(author)
-
Prognostic Value of Parenteral Nutrition Duration on Risk of Retinopathy of Prematurity
- 2023
-
In: JAMA ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 141:8, s. 716-716
-
Journal article (peer-reviewed)abstract
- Importance The prognostic impact of parenteral nutrition duration (PND) on retinopathy of prematurity (ROP) is not well studied. Safe prediction models can help optimize ROP screening by effectively discriminating high-risk from low-risk infants.Objective To evaluate the prognostic value of PND on ROP; to update and validate the Digital ROP (DIGIROP) 2.0 birth into prescreen and screen prediction models to include all ROP-screened infants regardless of gestational age (GA) and incorporate PND; and to compare the DIGIROP model with the Weight, IGF-1, Neonatal, and ROP (WINROP) and Postnatal Growth and ROP (G-ROP) models.Design, Setting, and Participants This retrospective study included 11 139 prematurely born infants from 2007 to 2020 from the Swedish National Registry for ROP. Extended Poisson and logistic models were applied. Data were analyzed from August 2022 to February 2023.Main Outcomes and Measures Any ROP and ROP requiring treatment were studied in relation to PND. ROP treatment was the outcome in DIGIROP models. Sensitivity, specificity, area under the receiver operating characteristic curve, and adjusted OR (aOR) with 95% CI were the main measures. Internal and external validations were performed.Results Of 11 139 screened infants, 5071 (45.5%) were girls, and the mean (SD) gestational age was 28.5 (2.4) weeks. ROP developed in 3179 infants (29%), treatment was given in 599 (5%), 7228 (65%) had PND less than 14 days, 2308 (21%) had PND for 14 days or more, and 1603 (14%) had unknown PND. PND was significantly correlated with ROP severity (Spearman r = 0.45; P < .001). Infants with 14 days or more of PND vs less than 14 days had faster progression from any ROP to ROP treatment (adjusted mean difference, −0.9 weeks; 95% CI, −1.5 to −0.3; P = .004). Infants with PND for 14 days or more vs less than 14 days had higher odds of any ROP (aOR, 1.84; 95% CI, 1.62-2.10; P < .001) and of severe ROP requiring treatment (aOR, 2.20; 95% CI, 1.73-2.80; P < .001). Among all 11 139 infants, the DIGIROP 2.0 models had 100% sensitivity (95% CI, 99.4-100). The specificity was 46.6% (95% CI, 45.6-47.5) for the prescreen model and 76.9% (95% CI, 76.1-77.7) for the screen model. G-ROP as well as the DIGIROP 2.0 prescreen and screen models showed 100% sensitivity on a validation subset (G-ROP: sensitivity, 100%; 95% CI, 93-100; DIGIROP prescreen: sensitivity, 100%; 95% CI, 93-100; DIGIROP screen: sensitivity, 100%; 95% CI, 93-100), whereas WINROP showed 89% sensitivity (95% CI, 77-96). Specificity for each prediction model was 29% (95% CI, 22-36) for G-ROP, 38% (95% CI, 32-46) for DIGIROP prescreen, 53% (95% CI, 46-60) for DIGIROP screen at 10 weeks, and 46% (95% CI, 39-53) for WINROP.Conclusion and Relevance Based on more than 11 000 ROP-screened infants born in Sweden, PND of 14 days or more corresponded to a significantly higher risk of having any ROP and receiving ROP treatment. These findings provide evidence to support consideration of using the updated DIGIROP 2.0 models instead of the WINROP or G-ROP models in the management of ROP.
|
|
| 43. |
- Pivodic, Aldina, 1978, et al.
(author)
-
Prognostic Value of Parenteral Nutrition Duration on Risk of Retinopathy of Prematurity Development and Validation of the Revised DIGIROP Clinical Decision Support Tool
- 2023
-
In: JAMA ophthalmology. - : AMER MEDICAL ASSOC. - 2168-6165 .- 2168-6173. ; 141:8, s. 716-724
-
Journal article (peer-reviewed)abstract
- IMPORTANCE The prognostic impact of parenteral nutrition duration (PND) on retinopathy of prematurity (ROP) is not well studied. Safe prediction models can help optimize ROP screening by effectively discriminating high-risk from low-risk infants. OBJECTIVE To evaluate the prognostic value of PND on ROP; to update and validate the Digital ROP (DIGIROP) 2.0 birth into prescreen and screen prediction models to include all ROP-screened infants regardless of gestational age (GA) and incorporate PND; and to compare the DIGIROP model with the Weight, IGF-1, Neonatal, and ROP (WINROP) and Postnatal Growth and ROP (G-ROP) models. DESIGN, SETTING, AND PARTICIPANTS This retrospective study included 11 139 prematurely born infants from 2007 to 2020 from the Swedish National Registry for ROP. Extended Poisson and logistic models were applied. Data were analyzed from August 2022 to February 2023. MAIN OUTCOMES AND MEASURES Any ROP and ROP requiring treatment were studied in relation to PND. ROP treatment was the outcome in DIGIROP models. Sensitivity, specificity, area under the receiver operating characteristic curve, and adjusted OR (aOR) with 95% CI were the main measures. Internal and external validations were performed. RESULTS Of 11 139 screened infants, 5071 (45.5%) were girls, and the mean (SD) gestational age was 28.5 (2.4) weeks. ROP developed in 3179 infants (29%), treatment was given in 599 (5%), 7228 (65%) had PND less than 14 days, 2308 (21%) had PND for 14 days or more, and 1603 (14%) had unknown PND. PND was significantly correlated with ROP severity (Spearman r = 0.45; P < .001). Infants with 14 days or more of PND vs less than 14 days had faster progression from any ROP to ROP treatment (adjusted mean difference, -0.9 weeks; 95% CI, -1.5 to -0.3; P = .004). Infants with PND for 14 days or more vs less than 14 days had higher odds of any ROP (aOR, 1.84; 95% CI, 1.62-2.10; P < .001) and of severe ROP requiring treatment (aOR, 2.20; 95% CI, 1.73-2.80; P < .001). Among all 11 139 infants, the DIGIROP 2.0 models had 100% sensitivity (95% CI, 99.4-100). The specificity was 46.6%(95% CI, 45.6-47.5) for the prescreen model and 76.9%(95% CI, 76.1-77.7) for the screen model. G-ROP as well as the DIGIROP 2.0 prescreen and screen models showed 100% sensitivity on a validation subset (G-ROP: sensitivity, 100%; 95% CI, 93-100; DIGIROP prescreen: sensitivity, 100%; 95% CI, 93-100; DIGIROP screen: sensitivity, 100%; 95% CI, 93-100), whereas WINROP showed 89% sensitivity (95% CI, 77-96). Specificity for each prediction model was 29% (95% CI, 22-36) for G-ROP, 38%(95% CI, 32-46) for DIGIROP prescreen, 53%(95% CI, 46-60) for DIGIROP screen at 10 weeks, and 46%(95% CI, 39-53) for WINROP. CONCLUSION AND RELEVANCE Based on more than 11 000 ROP-screened infants born in Sweden, PND of 14 days or more corresponded to a significantly higher risk of having any ROP and receiving ROP treatment. These findings provide evidence to support consideration of using the updated DIGIROP 2.0 models instead of the WINROP or G-ROP models in the management of ROP.
|
|
| 44. |
- Pivodic, Aldina, 1978, et al.
(author)
-
Validation of DIGIROP models and decision support tool for prediction of treatment for retinopathy of prematurity on a contemporary Swedish cohort
- 2023
-
In: British Journal of Ophthalmology. - : BMJ. - 0007-1161 .- 1468-2079. ; 107:8, s. 1132-1138
-
Journal article (peer-reviewed)abstract
- Background/Aims Retinopathy of prematurity (ROP) is currently diagnosed through repeated eye examinations to find the low percentage of infants that fulfil treatment criteria to reduce vision loss. A prediction model for severe ROP requiring treatment that might sensitively and specifically identify infants that develop severe ROP, DIGIROP-Birth, was developed using birth characteristics. DIGIROP-Screen additionally incorporates first signs of ROP in different models over time. The aim was to validate DIGIROP-Birth, DIGIROP-Screen and their decision support tool on a contemporary Swedish cohort. Methods Data were retrieved from the Swedish national registry for ROP (2018-2019) and two Swedish regions (2020), including 1082 infants born at gestational age (GA) 24 to <31 weeks. The predictors were GA at birth, sex, standardised birth weight and age at the first sign of ROP. The outcome was ROP treatment. Sensitivity, specificity and area under the receiver operating characteristic curve (AUC) with 95% CI were described. Results For DIGIROP-Birth, the AUC was 0.93 (95% CI 0.90 to 0.95); for DIGIROP-Screen, it ranged between 0.93 and 0.97. The specificity was 49.9% (95% CI 46.7 to 53.0) and the sensitivity was 96.5% (95% CI 87.9 to 99.6) for the tool applied at birth. For DIGIROP-Screen, the cumulative specificity ranged between 50.0% and 78.7%. One infant with Beckwith-Wiedemann syndrome who fulfilled criteria for ROP treatment and had no missed/incomplete examinations was incorrectly flagged as not needing screening. Conclusions DIGIROP-Birth and DIGIROP-Screen showed high predictive ability in a contemporary Swedish cohort. At birth, 50% of the infants born at 24 to <31 weeks of gestation were predicted to have low risk of severe ROP and could potentially be released from ROP screening examinations. All routinely screened treated infants, excluding those screened for clinical indications of severe illness, were correctly flagged as needing ROP screening.
|
|
| 45. |
- Robert, Caroline, et al.
(author)
-
Nivolumab in Previously Untreated Melanoma without BRAF Mutation
- 2015
-
In: New England Journal of Medicine. - 0028-4793. ; 372:4, s. 320-330
-
Journal article (peer-reviewed)abstract
- BACKGROUND Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma. The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study. METHODS We randomly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive nivolumab (at a dose of 3 mg per kilogram of body weight every 2 weeks and dacarbazine-matched placebo every 3 weeks) or dacarbazine (at a dose of 1000 mg per square meter of body-surface area every 3 weeks and nivolumab-matched placebo every 2 weeks). The primary end point was overall survival. RESULTS At 1 year, the overall rate of survival was 72.9% (95% confidence interval [CI], 65.5 to 78.9) in the nivolumab group, as compared with 42.1% (95% CI, 33.0 to 50.9) in the dacarbazine group (hazard ratio for death, 0.42; 99.79% CI, 0.25 to 0.73; P < 0.001). The median progression-free survival was 5.1 months in the nivolumab group versus 2.2 months in the dacarbazine group (hazard ratio for death or progression of disease, 0.43; 95% CI, 0.34 to 0.56; P < 0.001). The objective response rate was 40.0% (95% CI, 33.3 to 47.0) in the nivolumab group versus 13.9% (95% CI, 9.5 to 19.4) in the dacarbazine group (odds ratio, 4.06; P < 0.001). The survival benefit with nivolumab versus dacarbazine was observed across prespecified subgroups, including subgroups defined by status regarding the programmed death ligand 1 (PD-L1). Common adverse events associated with nivolumab included fatigue, pruritus, and nausea. Drug-related adverse events of grade 3 or 4 occurred in 11.7% of the patients treated with nivolumab and 17.6% of those treated with dacarbazine. CONCLUSIONS Nivolumab was associated with significant improvements in overall survival and progression-free survival, as compared with dacarbazine, among previously untreated patients who had metastatic melanoma without a BRAF mutation.
|
|
| 46. |
- Sanchez, Aniel, et al.
(author)
-
Novel functional proteins coded by the human genome discovered in metastases of melanoma patients
- 2020
-
In: Cell Biology and Toxicology. - : Springer Science and Business Media LLC. - 0742-2091 .- 1573-6822. ; 36:3, s. 261-272
-
Journal article (peer-reviewed)abstract
- In the advanced stages, malignant melanoma (MM) has a very poor prognosis. Due to tremendous efforts in cancer research over the last 10 years, and the introduction of novel therapies such as targeted therapies and immunomodulators, the rather dark horizon of the median survival has dramatically changed from under 1 year to several years. With the advent of proteomics, deep-mining studies can reach low-abundant expression levels. The complexity of the proteome, however, still surpasses the dynamic range capabilities of current analytical techniques. Consequently, many predicted protein products with potential biological functions have not yet been verified in experimental proteomic data. This category of ‘missing proteins’ (MP) is comprised of all proteins that have been predicted but are currently unverified. As part of the initiative launched in 2016 in the USA, the European Cancer Moonshot Center has performed numerous deep proteomics analyses on samples from MM patients. In this study, nine MPs were clearly identified by mass spectrometry in MM metastases. Some MPs significantly correlated with proteins that possess identical PFAM structural domains; and other MPs were significantly associated with cancer-related proteins. This is the first study to our knowledge, where unknown and novel proteins have been annotated in metastatic melanoma tumour tissue.
|
|
| 47. |
- Smedje, Greta, et al.
(author)
-
Hearing status among aircraft maintenance personnel in a commercial airline company
- 2011
-
In: Noise & Health. - : Medknow. - 1463-1741 .- 1998-4030. ; 13:54, s. 364-370
-
Journal article (peer-reviewed)abstract
- The aim was to study subjective and objective hearing loss in a population of aircraft maintenance workers and identify predictors. A total of 327 aircraft maintenance personnel answered a self-administered work environment questionnaire (response rate 76) and underwent audiometric test. The mean values for the hearing threshold at 3, 4, and 6 kHz for the ear with the most hearing loss were compared with a Swedish population database of persons not occupationally exposed to noise. Equivalent noise exposure during a working day was measured. Relationships between subjective and objective hearing loss and possible predictors (age, years of employment, self-reported exposure to solvents, blood pressure, and psycho-social factors) were analyzed by multiple logistic regression. At younger ages (< 40 years), aircraft maintenance workers had higher hearing thresholds (1-3 dB) compared to the reference group, but such a difference was not found in older employees. Relationships were found between age and objective hearing loss, and between exposure to solvents and reported subjective hearing loss. Equivalent noise exposure during working days were 70-91 dB(A) with a maximal noise level of 119 dB(A). Aircraft maintenance workers are exposed to equivalent noise levels above the Swedish occupational standard, including some very high peak exposures. Younger employees have a higher age-matched hearing threshold level compared with a reference group. Thus, there is a need for further preventive measures.
|
|
| 48. |
- Steiner, Ann, et al.
(author)
-
Sexualitet i ord och bild
- 2010
-
In: Sexologi. - : Liber. - 9789147015450 ; , s. 155-160
-
Book chapter (other academic/artistic)
|
|
| 49. |
- Sugihara, Yutaka, et al.
(author)
-
A New Look at Drugs Targeting Malignant Melanoma – An Application for Mass Spectrometry Imaging
- 2014
-
In: Proteomics. - : Wiley. - 1615-9861 .- 1615-9853. ; 14:17-18, s. 1963-1970
-
Research review (peer-reviewed)abstract
- Malignant melanoma (MM) patients are being treated with an increasing number of personalized medicine (PM) drugs, several of which are small molecule drugs developed to treat patients with specific disease genotypes and phenotypes. In particular, the clinical application of protein kinase inhibitors (PKI) has been highly effective for certain subsets of MM patients. Vemurafenib, a PKI targeting BRAF mutated protein, has shown significant efficacy in slowing disease progression. In this paper we provide an overview of this new generation of targeted drugs, and demonstrate the first data on localization of personalized medicine drugs within tumor compartments. In this study, we have introduced matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to provide new information on one of the drugs currently used in the PM treatment of MM, vemurafenib. In a proof-of-concept in vitro study, MALDI-MSI was used to identify vemurafenib applied to metastatic lymph nodes tumors of subjects attending the regional hospital network of Southern Sweden. The paper provides evidence of BRAF overexpression in tumors isolated from MM patients and localization of the specific drug targeting BRAF, vemurafenib, using mass spectrometry fragment ion signatures. Our ability to determine drug uptake at the target sites of directed therapy provides important opportunity for increasing our understanding about the mode of action of drug activity within the disease environment.
|
|
| 50. |
- Welinder, Charlotte, et al.
(author)
-
A protein deep sequencing evaluation of metastatic melanoma tissues.
- 2015
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
-
Journal article (peer-reviewed)abstract
- Malignant melanoma has the highest increase of incidence of malignancies in the western world. In early stages, front line therapy is surgical excision of the primary tumor. Metastatic disease has very limited possibilities for cure. Recently, several protein kinase inhibitors and immune modifiers have shown promising clinical results but drug resistance in metastasized melanoma remains a major problem. The need for routine clinical biomarkers to follow disease progression and treatment efficacy is high. The aim of the present study was to build a protein sequence database in metastatic melanoma, searching for novel, relevant biomarkers. Ten lymph node metastases (South-Swedish Malignant Melanoma Biobank) were subjected to global protein expression analysis using two proteomics approaches (with/without orthogonal fractionation). Fractionation produced higher numbers of protein identifications (4284). Combining both methods, 5326 unique proteins were identified (2641 proteins overlapping). Deep mining proteomics may contribute to the discovery of novel biomarkers for metastatic melanoma, for example dividing the samples into two metastatic melanoma "genomic subtypes", ("pigmentation" and "high immune") revealed several proteins showing differential levels of expression. In conclusion, the present study provides an initial version of a metastatic melanoma protein sequence database producing a total of more than 5000 unique protein identifications. The raw data have been deposited to the ProteomeXchange with identifiers PXD001724 and PXD001725.
|
|
