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- Betancourt, Lazaro Hiram, et al.
(författare)
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The human melanoma proteome atlas-Defining the molecular pathology
- 2021
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Ingår i: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 11:7, s. 1-20
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Tidskriftsartikel (refereegranskat)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.
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- Bergdahl, Ingvar A, et al.
(författare)
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Lung cancer and exposure to quartz and diesel exhaust in Swedish iron ore miners with concurrent exposure to radon
- 2010
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 67:8, s. 513-518
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Studies of underground miners have documented an increased risk of lung cancer mainly linked to radon exposure but possibly influenced by other concurrent exposures. METHODS: A cohort study was carried out in 8321 iron ore miners with low exposure to radon, employed in 1923-1998 and followed up for lung cancer in 1958-2000. Historical exposures to radon, crystalline silica and diesel exhaust were assessed. Data including exposure to radon, quartz and diesel exhaust from another mine with higher exposure to radon were reanalysed. RESULTS: Miners had increased risk for lung cancer (SIR 1.48 (95% CI 1.22 to 1.78), based on 112 cases during 227,000 person-years). The increased risk could not be explained by exposure to radon or diesel exhaust but was associated with exposure to crystalline silica: SIR 0.96 (0.53 to 1.62), 1.45 (1.10 to 1.87), 1.99 (1.31 to 2.90) and 1.77 (0.92 to 3.10) in groups with exposure to 0, 0-2, 2-5 and >5 mg years/m3, respectively. Reanalysis of data from the other mine indicated that quartz was a possible confounder in the analysis of relationship between radon and lung cancer. In the highest radon exposed group, the point estimate for the RR decreased from 5.65 to 3.90 when adjusting for concurrent exposure to quartz. CONCLUSIONS: Crystalline silica, a known carcinogen, probably affects lung cancer risk in iron ore miners. The main implication of the results is for interpretation of the dose-response curve for radon and lung cancer in underground iron ore miners. Since exposure to radon and quartz is often correlated, quartz exposure can be an important confounder.
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- 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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- 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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- Claesson, Ingvar, et al.
(författare)
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A Multi-DSP implementation of a Broadband Adaptive Beamformer for use in a Hands-free Mobile Radio Telephone
- 1991
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Ingår i: IEEE Transactions on Vehicular Technology. - New York : Institute of electrical and electronics engineers. - 0018-9545. ; 40:1, s. 194-202
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Tidskriftsartikel (refereegranskat)abstract
- An implementation of a broadband adaptive array on a multiprocessor digital signal processing (DSP) system for use in a hands-free mobile radio telephone is described. This implementation of a five-microphone adaptive Griffiths-Jim array can handle FIR filters with up to 128 taps behind each microphone at a sampling rate of 8 kHz. The filter structure makes it possible to combine an adaptive array with a noise canceler. The near-field problem has been solved by using focusing, a speech-controlled adaptive algorithm, and a short hourglass. Preliminary measurements indicate a considerable potential for this technique in hands-free mobile telephony. The array gives a 20-30-dB suppression of a broadband jammer covering 300-1100 Hz, even with three reflecting walls surrounding the microphone.
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