| 1. |
- Betancourt, Lazaro Hiram, et al.
(författare)
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Improved survival prognostication of node-positive malignant melanoma patients utilizing shotgun proteomics guided by histopathological characterization and genomic data
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Betancourt, Lazaro Hiram, et al.
(författare)
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The hidden story of heterogeneous B-raf V600E mutation quantitative protein expression in metastatic melanoma—association with clinical outcome and tumor phenotypes
- 2019
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 11:12
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Tidskriftsartikel (refereegranskat)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.
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| 3. |
- Carlsson, Bo, et al.
(författare)
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Introduction : the blend of science and sport
- 2019
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Ingår i: Sport in Society. - Oxon : Taylor & Francis. - 1743-0437 .- 1743-0445. ; 22:9, s. 1497-1500
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- An introduction to a theme issue of the journal Sport in Society, in which the relationship between science and sports are being scrutinized from different perspectives.
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| 4. |
- Gil, Jeovanis, et al.
(författare)
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Clinical protein science in translational medicine targeting malignant melanoma
- 2019
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Ingår i: Cell Biology and Toxicology. - : Springer Science and Business Media LLC. - 0742-2091 .- 1573-6822. ; 35:4, s. 293-332
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Tidskriftsartikel (refereegranskat)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.
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| 5. |
- Shu, Huan, 1980-, et al.
(författare)
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PVC flooring at home and uptake of phthalates in pregnant women
- 2019
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Ingår i: Indoor Air. - : John Wiley & Sons. - 0905-6947 .- 1600-0668. ; 29:1, s. 43-54
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Tidskriftsartikel (refereegranskat)abstract
- Phthalates are used as plasticizers in polyvinyl chloride (PVC) materials and it is known that phthalates may migrate into the surrounding environment and then become a source for human uptake. The aim of the study was to investigate whether residential PVC flooring was related to the urinary levels of phthalate metabolites determined in pregnant women. The data were from the Swedish SELMA study where sampling was conducted during the time period 2007-2010. Spot urine samples from 1674 women at the end of the first trimester were analyzed for 14 metabolites from seven phthalates and one phthalate alternative. Data on flooring material in the kitchen and the parents' bedrooms as well as potential confounders were collected by postal questionnaires at the same time as the urine samples were taken. Multiple regression modeling by least square geometric mean and weighted quantile sum regression was applied to log-transformed and creatinine-adjusted phthalate metabolite concentrations adjusted for potential confounders from questionnaire data. This study has found significantly higher urinary levels of the BBzP metabolite (MBzP) in pregnant women living in homes with PVC flooring as compared to homes with other flooring materials
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| 6. |
- Strömqvist, Fredrik, et al.
(författare)
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Incidental durotomy in degenerative lumbar spine surgery – a register study of 64,431 operations
- 2019
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Ingår i: Spine Journal. - : Elsevier BV. - 1529-9430 .- 1878-1632. ; 19:4, s. 624-630
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Incidental durotomy (ID) is one of the most common intraoperative complications seen in spine surgery. Conflicting evidence has been presented regarding whether or not outcomes are affected by the presence of an ID. PURPOSE: To evaluate whether outcomes following degenerative spine surgery are affected by ID and the incidence of ID with different diagnoses and different surgical procedures. MATERIALS: By using SweSpine, the national Swedish Spine Surgery Register, preoperative, surgical and postoperative 1-year follow-up data were obtained for 64,431 surgeries. All patients were surgically treated due to lumbar spinal stenosis (LSS) without or with concomitant degenerative spondylolisthesis (DS) or lumbar disc herniation (LDH) between 2000 and 2015. Gender, age, smoking habits, walking distance, consumption of analgesics, back and leg pain (Visual Analogue Scale [VAS]), quality of life (EuroQol [EQ5D] and Short Form 36 [SF-36]), and disability (Oswestry Disability Index [ODI]) were recorded. RESULTS: Overall, incidence of ID during the study period was 5.0%. For the LDH, LSS, and DS subgroups, it was 2.8%, 6.5%, and 6.5%, respectively. Laminectomy was associated with a higher incidence of ID than discectomy (p<.001). ID was more common in all three subgroups if the patient had previously been subjected to spine surgery and with increasing age of the patients (p<.001). LDH patients with an ID reported a higher degree of residual leg pain, inferior mental quality of life (SF-36 MCS), and higher disability (ODI) than LDH patients without ID (all p<.001) 1-year after surgery. LSS patients with an ID reported inferior SF-36 MCS (p<.001) and DS patients with an ID had inferior SF-36 MCS and higher ODI compared to patients with the same diagnosis but without an ID (p<.001). However, these numerical differences are well below references for MCID, for all three subgroups. ID was associated with a higher frequency of patients being dissatisfied with the surgical outcome at 1-year follow-up. In patients who did not improve in back and leg pain following surgery (delta-value), ID was less common than in patients reporting improved back and leg pain from before as compared to following surgery. CONCLUSIONS: The overall occurrence of ID in the present study was 5%, with higher figures in LSS and DS and lower figures in LDH. Higher age of the patient and previous surgery were associated with higher frequencies of ID. The outcome at 1 year following surgery was not affected to a clinically relevant extent when an ID was obtained. However, ID was associated with a higher degree of patient dissatisfaction and a longer hospital length of stay.
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