| 1. |
- Baldetorp, Bo, et al.
(author)
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Analysis of protein expression in pure cell nuclei populations isolated from human breast cancer tissue by DNA flow cytometric sorting.
- 2010
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In: Journal of Proteomics. - : Elsevier BV. - 1874-3919. ; 73, s. 1111-1116
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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.
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| 2. |
- Bonnier, Gaga, et al.
(author)
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Kirunas Framtid - Kan man flytta en stad? : restaureringskonst på sin spets
- 2010
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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.
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| 3. |
- Giniewska, Ewa, et al.
(author)
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Högskolebibliotekets roll i en inkluderande lärandemiljö : slutrapport
- 2012
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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.
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| 4. |
- Harbst, Katja, et al.
(author)
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Molecular and genetic diversity in the metastatic process of melanoma.
- 2014
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In: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 233:1, s. 39-50
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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.
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| 5. |
- Harbst, Katja, et al.
(author)
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Molecular profiling reveals low- and high-grade forms of primary melanoma.
- 2012
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In: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1557-3265. ; 18:15, s. 4026-4036
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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.
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| 6. |
- Lundeheim, Nils, et al.
(author)
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Shoulder ulcers in sows are genetically correlated to leanness of young pigs and to litter weight
- 2014
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In: Acta Agriculturae Scandinavica, Section A - Animal Science. - : Informa UK Limited. - 0906-4702 .- 1651-1972. ; 64, s. 67-72
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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).
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| 7. |
- Lundgren, Helena, et al.
(author)
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Genetic analysis of reproductive performance in Landrace sows and its correlation to piglet growth
- 2010
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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.
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| 8. |
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| 9. |
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| 10. |
- Lundgren, Helena, et al.
(author)
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Genetic parameters for feed intake, litter weight, body condition and rebreeding success in primiparous Norwegian Landrace sows
- 2014
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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.
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| 11. |
- Lundgren, Helena, et al.
(author)
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Genetics of growth in piglets and the association with homogeneity of body weight within litters
- 2010
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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.
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| 12. |
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| 13. |
- Lundgren, Ib, et al.
(author)
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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.
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| 14. |
- Lundgren, Ib, et al.
(author)
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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.
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| 15. |
- O'Day, S. J., et al.
(author)
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Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study
- 2010
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In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 21:8, s. 1712-1717
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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.
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| 16. |
- Olofsson, Roger, 1978, et al.
(author)
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Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial) : study protocol for a randomized controlled trial
- 2014
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In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 15, s. 317-
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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.
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| 17. |
- Smedje, Greta, et al.
(author)
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Hearing status among aircraft maintenance personnel in a commercial airline company
- 2011
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In: Noise & Health. - : Medknow. - 1463-1741 .- 1998-4030. ; 13:54, s. 364-370
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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.
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| 18. |
- Steiner, Ann, et al.
(author)
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Sexualitet i ord och bild
- 2010
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In: Sexologi. - : Liber. - 9789147015450 ; , s. 155-160
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Book chapter (other academic/artistic)
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| 19. |
- Sugihara, Yutaka, et al.
(author)
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A New Look at Drugs Targeting Malignant Melanoma – An Application for Mass Spectrometry Imaging
- 2014
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In: Proteomics. - : Wiley. - 1615-9861 .- 1615-9853. ; 14:17-18, s. 1963-1970
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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.
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| 20. |
- Welinder, Charlotte, et al.
(author)
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Analysis of Alpha-Synuclein in Malignant Melanoma - Development of a SRM Quantification Assay.
- 2014
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:10
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Journal article (peer-reviewed)abstract
- Globally, malignant melanoma shows a steady increase in the incidence among cancer diseases. Malignant melanoma represents a cancer type where currently no biomarker or diagnostics is available to identify disease stage, progression of disease or personalized medicine treatment. The aim of this study was to assess the tissue expression of alpha-synuclein, a protein implicated in several disease processes, in metastatic tissues from malignant melanoma patients. A targeted Selected Reaction Monitoring (SRM) assay was developed and utilized together with stable isotope labeling for the relative quantification of two target peptides of alpha-synuclein. Analysis of alpha-synuclein protein was then performed in ten metastatic tissue samples from the Lund Melanoma Biobank. The calibration curve using peak area ratio (heavy/light) versus concentration ratios showed linear regression over three orders of magnitude, for both of the selected target peptide sequences. In support of the measurements of specific protein expression levels, we also observed significant correlation between the protein and mRNA levels of alpha-synuclein in these tissues. Investigating levels of tissue alpha-synuclein may add novel aspect to biomarker development in melanoma, help to understand disease mechanisms and ultimately contribute to discriminate melanoma patients with different prognosis.
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| 21. |
- Welinder, Charlotte, et al.
(author)
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Establishing a Southern Swedish Malignant Melanoma OMICS and Biobank Clinical Capability
- 2013
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In: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 2:1
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Journal article (peer-reviewed)abstract
- Background: The Southern Swedish Malignant Melanoma (SSMM) research team is a truly cross functional group with members from oncology, clinical, surgery, bioinformatics, proteomics, and genomics initiatives. The SSMM’s objectives and goals are to develop, build and utilize cutting edge biobanks and OMICS platforms to better understand disease pathology and drug mechanisms. Within the research team there are members who daily diagnose patients with suspect melanomas, do follow-ups on malignant melanoma patients and remove primary or metastatic lesions by surgery. This inter-disciplinary clinical patient care ensures a competence build as well as a best practice procedure where the patient benefits. The science output in these resulting study outcomes further strengthens the build of healthcare benefit in the complex challenges of malignant melanoma pathophysiology that is addressed by the novel personalized medicines entering the market. These patient biobank archives will be fully automated with novel ultralow temperature biobank storage units and used as a clinical resource. Methods: Clinical materials from patients before, during and after treatments, with clinical end points are being collected. Tissue samples as well as bio-fluid samples such as blood fractions, plasma, serum and whole blood will be archived in 384-high density sample tube formats. We are developing standardized approaches for patient selections, patient sampling, sample-processing and analysis platforms with dedicated protein assays and genomics platforms that will hold value for the research community. Results: An IT-infrastructure using a laboratory information management system (LIMS) has been established, that will be the key interface for the research teams in order to share and explore data generated within the project. The cross-site data repository in Lund will form the basis for sample processing, together with biological samples in southern Sweden, including blood fractions and tumor tissues. Clinical registries are being associated with the biobank materials, including pathology reports on disease diagnosis on the MM patients. Conclusions: We provide data on the developments of protein profiling and targeted protein target assays on isolated melanoma tumors, as well as reference blood standards that is used by the team members in the respective laboratories. These pilot data show biobank access and feasibility of performing quantitative proteomics in MM biobank repositories collected in southern Sweden.
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| 22. |
- Welinder, Charlotte, et al.
(author)
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Feasibility Study on Measuring Selected Proteins in Malignant Melanoma Tissue by SRM Quantification.
- 2014
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 13:3, s. 1315-1326
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Journal article (peer-reviewed)abstract
- Currently there are no clinically recognized molecular biomarkers for malignant melanoma (MM) for either diagnosing disease stage or measuring response to therapy. The aim of this feasibility study was to develop targeted selected reaction monitoring (SRM) assays for identifying candidate protein biomarkers in metastatic melanoma tissue lysate. In a pilot study applying the SRM assay, the tissue expression of nine selected proteins [complement 3 (C3), T-cell surface glycoprotein CD3 epsilon chain E (CD3E), dermatopontin, minichromosome maintenance complex component (MCM4), premelanosome protein (PMEL), S100 calcium binding protein A8 (S100A8), S100 calcium binding protein A13 (S100A13), transgelin-2 and S100B] was quantified in a small cohort of metastatic malignant melanoma patients. The SRM assay was developed using a TSQ Vantage triple quadrupole mass spectrometer that generated highly accurate peptide quantification. Repeated injection of internal standards spiked into matrix showed relative standard deviation (RSD) from 6% to 15%. All nine target proteins were identified in tumor lysate digests spiked with heavy peptide standards. The multiplex SRM peptide assay panel was then measured and quantified on a set of frozen MM tissue samples obtained from the Malignant Melanoma Biobank collected in Lund, Sweden. All nine proteins could be accurately quantified using the new SRM assay format. This study provides preliminary data on the heterogeneity of biomarker expression within MM patients. The S100B protein, which is clinically used as the pathology identifier of MM, was identified in 9 out of 10 MM tissue lysates. The use of the targeted SRM assay provides potential advancements in the diagnosis of MM that can aid in future assessments of disease in melanoma patients.
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