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1.	Sjöberg, Trygve, et al. (författare) Kamp om sjukvårdsresurser kräver stark patientgrupp. 2009 Ingår i: Njurvårdens framtid. ; , s. 16-17 Bokkapitel (övrigt vetenskapligt/konstnärligt)
2.	Abdullah Nasir, Ahmad, et al. (författare) Ligand-specific regulation of transforming growth factor beta superfamily factors by leucine-rich repeats and immunoglobulin-like domains proteins 2023 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:8 Tidskriftsartikel (refereegranskat)abstract Leucine-rich repeats and immunoglobulin-like domains (LRIG) are transmembrane proteins shown to promote bone morphogenetic protein (BMP) signaling in Caenorhabditis elegans, Drosophila melanogaster, and mammals. BMPs comprise a subfamily of the transforming growth factor beta (TGFβ) superfamily, or TGFβ family, of ligands. In mammals, LRIG1 and LRIG3 promote BMP4 signaling. BMP6 signaling, but not BMP9 signaling, is also regulated by LRIG proteins, although the specific contributions of LRIG1, LRIG2, and LRIG3 have not been investigated, nor is it known whether other mammalian TGFβ family members are regulated by LRIG proteins. To address these questions, we took advantage of Lrig-null mouse embryonic fibroblasts (MEFs) with doxycycline-inducible LRIG1, LRIG2, and LRIG3 alleles, which were stimulated with ligands representing all the major TGFβ family subgroups. By analyzing the signal mediators pSmad1/5 and pSmad3, as well as the induction of Id1 expression, we showed that LRIG1 promoted BMP2, BMP4, and BMP6 signaling and suppressed GDF7 signaling; LRIG2 promoted BMP2 and BMP4 signaling; and LRIG3 promoted BMP2, BMP4, BMP6, and GDF7 signaling. BMP9 and BMP10 signaling was not regulated by individual LRIG proteins, however, it was enhanced in Lrig-null cells. LRIG proteins did not regulate TGFβ1-induced pSmad1/5 signaling, or GDF11- or TGFβ1-induced pSmad3 signaling. Taken together, our results show that some, but not all, TGFβ family ligands are regulated by LRIG proteins and that the three LRIG proteins display differential regulatory effects. LRIG proteins thereby provide regulatory means for the cell to further diversify the signaling outcomes generated by a limited number of TGFβ family ligands and receptors.
3.	Abdullah Nasir, Ahmad, et al. (författare) Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling 2021 Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1 Tidskriftsartikel (refereegranskat)abstract Netrin-1 is a secreted protein that is well known for its involvement in axonal guidance during embryonic development and as an enhancer of cancer cell metastasis. Despite extensive efforts, the molecular mechanisms behind many of the physiological functions of netrin-1 have remained elusive. Here, we show that netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling in various cellular systems, including a mutually inhibitory interaction with the BMP-promoting function of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins. The BMP inhibitory function of netrin-1 in mouse embryonic fibroblasts was dependent on the netrin receptor neogenin, with the expression level regulated by both netrin-1 and LRIG proteins. Our results reveal a previously unrecognized function of netrin-1 that may help to explain several of the developmental, physiological, and cancer-promoting functions of netrins at the signal transduction level.
4.	Andersson, Magnus, et al. (författare) Model System for in Situ Investigation of Binding Strengths of Integrin Mediated Cellular Adhesion 2003 Ingår i: World congress on medical physics and biomedical engineering. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
5.	Andersson, Ulrika, et al. (författare) Epidermal growth factor receptor family (EGFR, ErbB2-4) in gliomas and meningiomas 2004 Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 108:2, s. 135-142 Tidskriftsartikel (refereegranskat)abstract Overexpression of epidermal growth factor receptor (EGFR, ErbB1) correlates with enhanced malignant potential of many human tumor types including glioblastoma multiforme. The significance of EGFR expression in meningiomas is, however, unclear. Reports regarding the other EGFR family members, ErbB2-4, in brain tumors are sparse. In this study, the expression of the EGFR family members was analyzed in relation to various parameters for the clinical importance of these receptors in 44 gliomas and 26 meningiomas. In gliomas, quantitative real-time reverse transcription (RT)-PCR revealed the highest EGFR mRNA expression in high-grade gliomas, while ErbB2 and ErbB3 mRNA were detected only in a few high-grade gliomas. In contrast, ErbB4 expression was most pronounced in low-grade gliomas. Immunohistochemistry showed significantly higher EGFR protein expression in high-grade gliomas compared to low-grade gliomas (P= 0.004). ErbB2 protein expression was mainly seen in high-grade gliomas. ErbB3 protein expression was low in all gliomas analyzed. ErbB4 protein expression was significantly higher in low-grade gliomas than in high-grade gliomas (P= 0.007). In meningiomas, quantitative real-time RT-PCR revealed expression of EGFR, ErbB2, and ErbB4 mRNA in the majority of the tumors. ErbB3 was detected in only one of the meningiomas analyzed. Immunohistochemistry demonstrated high ErbB2 protein expression in meningiomas. An intriguing observation in astrocytomas and oligodendrogliomas grade II, was a significantly decreased overall survival for patients with high EGFR protein expression (P= 0.04). The high ErbB4 expression in low-grade compared to high-grade gliomas might suggest that ErbB4 acts as a suppressor of malignant transformation in brain tumors, which is in line with previous studies in other tumor types.
6.	Andersson, Ulrika, et al. (författare) Rapid induction of long-lasting drug efflux activity in brain vascular endothelial cells but not malignant glioma following irradiation 2002 Ingår i: Medical Oncology. - 1357-0560 .- 1559-131X. ; 19:1, s. 1-9 Tidskriftsartikel (refereegranskat)abstract The influence of radiotherapy on malignant glioma multidrug resistance to chemotherapy was evaluated because patients with glioma often are treated with a combination of radiotherapy and chemotherapy. Multidrug resistance gene (MDR1, mdr1a, and mdr1b) transcripts were found in human and rat glioma cell lines. P-Glycoprotein (Pgp) was immunohistochemically detected in glioma cell lines and in the rat brain vascular endothelial cell line (RBE4). A multidrug resistance pump efflux activity assay demonstrated increased calcein efflux of RBE4 endothelial cells, but not glioma cells, 2 h after irradiation and still increased 14 d after irradiation. The increased efflux was equally inhibited by verapamil with or without irradiation. In the rat intracranial glioma model (BT4C), Pgp was demonstrated in capillary endothelial cells of the tumor tissue and surrounding normal brain, but not in tumor cells. The expression of gene transcripts or Pgp was not affected by irradiation. The results indicate that long-lasting verapamil-resistant drug efflux mechanisms are activated in brain endothelial cells after irradiation. The results might explain the poor efficacy of chemotherapy following radiotherapy and contribute to consideration of new treatment strategies in the management of malignant glioma.
7.	Andrén, Ulla, 1955-, et al. (författare) Utveckling av ett nytt yrke inom socialpsykiatrisk vård 2019 Rapport (övrigt vetenskapligt/konstnärligt)abstract The program in Social Psychiatric Care is a three-year program at the university level leading to a vocational qualification in social psychiatric care and a bachelor's degree in the field of Health Sciences. Until the spring of 2018, six litters have graduated. Students in the social psychiatric care program often have personal interest, previous professional experience from the business areas or inspiration from related friends working in the field of activity. Personal experiences of problems in the fields of activity are also prominent among the students. Students believe that personal experience, willingness and ability is important in order to work within the profession. Characteristics of the students are also an interest and a clear empathetic willingness to work with people and they consider that the profession primarily requires characteristics such as altruism, empathy, social skills and deeper knowledge and understanding in the field. Upon completion of education, students want a career role where they can help other people, feel motivated, or they aim for specific positions or areas of activity. Both managers and alumni from the Social Psychiatric Care program value the broad professional competence that the program leads to. Psychiatric competence is emphasized as particularly valuable by both alumni and managers. This competence means that they also complement the other professions in the activities. Students consider themselves possessed a professional identity that involves introducing psychiatric and custody skills to organizations that previously lacked these perspectives. Something that also brings new approaches to patients, users and clients. Being able to use knowledge from several disciplines are considered to be a strength and competence that are well-needed in environments where people with mental ill health are cared for. The alumni perceive their knowledge as both interdisciplinary and interprofessional.
8.	Asklund, Thomas, et al. (författare) Synergistic Killing of Glioblastoma Stem-like Cells by Bortezomib and HADC Inhibitors. 2012 Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:7, s. 2407-2413 Tidskriftsartikel (refereegranskat)abstract Background: The malignant brain tumour glioblastoma is a devastating disease that remains a therapeutic challenge. Materials and Methods: Effects of combinations of the US Food and Drug Administation (FDA) approved proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors vorinostat, valproic acid and sodium phenylbutyrate were studied on primary glioblastoma stem cell lines and conventional glioblastoma cell lines. Cell survival, proliferation and death were analyzed by fluorometric microculture cytotoxicity assay (FMCA), propidium iodide labeling and flow cytometry, and cell cloning through limiting dilution and live-cell bright-field microscopy. Results: Bortezomib and the HDAC inhibitors showed synergistic cell killing at clinically relevant drug concentrations, while the conventional cell lines cultured in serum-containing medium were relatively resistant to the same treatments. Conclusion: These findings of synergistic glioblastoma stem cell killing by bortezomib and three different FDA-approved HDAC inhibitors confirm and expand previous observations on co-operative effects between these classes of drugs.
9.	Berg, Charlotte, et al. (författare) Utegående nötkreatur och får 2020 Rapport (övrigt vetenskapligt/konstnärligt)
10.	Bernesson, Sven, et al. (författare) Glycerin från omförestring av vegetabiliska oljor som tillsatsmedel : praktiska försök med pelletering och eldning av några biobränslen 2011 Rapport (övrigt vetenskapligt/konstnärligt)abstract During transesterification of vegetable oils in particular, but also animal fats and used frying oils, glycerine is obtained as a by-product. It is important for transesterification economics that the glycerine by-product can be sold for the best possible price. In Sweden today, glycerine is often sold to biogas production for a few Swedish crowns per kilo. If other markets where glycerine replaces a more expensive product can be found, the willingness to pay for glycerine will increase. This project examined whether glycerine can be used as an additive in pelleting some biofuel types, and the value it would have in this use. The project investigated admixtures of appropriate amounts of glycerine of varying quality during pelleting of some types of fuel (straw, reed canary grass and pine wood). To determine how these affect pellet quality, the function of the pellet press, pellet storage properties, the risk of harmful emission levels of carbon monoxide (CO), nitrogen oxides (NOx), sulphur oxides (SO2) and aldehydes during incineration of the pellets, the risk of ash sintering and the risk of corrosive deposits in flue gas channels were examined. In addition, the commercial value of the glycerine when added to pellets was estimated. Pelleting trials were conducted using 1% and 5% admixtures of four types of glycerine in three types of fuel. Two of the glycerine products were alkaline, originating from alkaline transesterification of rapeseed oil, and two were acidic, originating from acid esterification/transesterification followed by alkaline transesterification, of rapeseed oil in one case and used frying oil in the other. The fuel types were pine wood, reed canary grass and straw. After pelleting, pellet durability, the amount of fine fraction and bulk density were measured. Chemical analyses were performed of glycerine types, fuel types and glycerine/fuel mixtures to evaluate ash melting behaviour and the risk of corrosion associated with alkali chlorides. Pellets from the trials were stored for 6 months, during which time moisture uptake and the incidence of mould were studied. After the storage experiments, pellet durability was measured again. Wherever possible, the experimental design was evaluated statistically using multivariate data analysis. About half the samples were incinerated and emissions of CO, NOx, SO2, particulate matter, acrolein and formaldehyde were measured. In addition, the average temperature and maximum temperature during incineration were measured and the amount of combustion residues and their content of unburned and sintered material were determined. Some ash samples from the combustion of glycerine/pine wood mixes were sent for chemical analysis. The admixture of glycerine in the fuel types generally resulted in pellets with lower durability, higher proportion of fines (fine fraction) and significantly lower bulk density. However, pellets with the same or slightly better durability and the same or lower proportion of fines were obtained by admixture of 1% acidic glycerine to the fuel types. The specific energy consumption for pelleting the fuels containing glycerine was generally lowered, which may have been due to the lubricating properties of the glycerine. The addition of glycerine in all cases resulted in a decrease in pellet bulk density. Reed canary grass had the best durability, least share of fines and highest bulk density, while straw usually had the worst durability, highest share of fines and lowest bulk density. During the storage experiments the pellets took up some water, but never to such a level that the storability was compromised. Pellets with glycerine took up more water, often an increasing amount with increasing glycerine content. Mould was not found in any pellets from any experiment. Durability deteriorated more frequently with higher glycerine content, and thus low durability in the pellets at the outset. The initial moisture content and thus the type of fuel were also of great importance for moisture absorption. Straw contained most moisture from the start and took up the most water. In addition, durability decreased most for straw during storage. During incineration, the main problem with an increasing admixture of glycerine in the fuels was an increasing amount of particles in the flue gas. Calculations of potassium (K) losses with the flue gases, based on analysis of fuels and their ash composition, suggested that this increased sharply with increasing admixture of glycerine. For example, incineration of pine wood with about 1% added glycerine increased the amount of K leaving with the flue gases to the level observed with straw incineration. There seemed to be a close link between the amount of particles in the flue gas and the amount of K released. It is therefore likely that addition of glycerine will cause problems with corrosive deposits in the flues for fuels that normally do not present such problems. However, with fuels that normally give rise to such problems, e.g. straw, it is likely that there will be little obvious difference. Glycerine (acid) containing sulphur can probably prevent particle release and thus lower the risk of corrosion associated with alkali chlorides in the flue gas. The emissions of acrolein and formaldehyde did not increase as might be expected in experiments with glycerine admixture. The levels of acrolein were below the detection limit, and the levels of formaldehyde were very low. Emissions of CO, NOx and SO2 varied widely between experiments in a more or less random way. However, CO emissions may have increased with lower pellet quality. Sulphur dioxide should be produced during incineration of pellets with high sulphur levels. Ash melting point declined in pine wood in particular on addition of glycerine, but also in reed canary grass. The ash melting point for straw was not affected at all by glycerine admixture. The reason why pine wood ash was more sensitive is that the amounts produced from pine are so small that properties of the glycerine ash can have an impact even at small admixture rates. The K content of reed canary grass is so low that very little glycerine with high K content is required before its properties start to become apparent. However, straw has a high initial content of an ash that is already high in K, so the K content of glycerine ash is les obvious even at rather high admixture rates. Calculations using key numbers showed that the ash melting point of reed canary grass in particular should be lowered by the admixture of glycerine, but also that of pine wood to a lesser degree, from an initially high level. Straw ash should scarcely be affected at all. High losses of K in the flue gases can suppress the problem of ash melting point depression in bottom ash. Some of the glycerine types initially had high contents of methanol. It is important that this can be removed, as it constitutes a fire hazard during pelleting and also during transport and handling of the glycerine. High methanol concentrations are also a human health risk, as methanol is toxic. The commercial value of the glycerine is at one of three different levels depending on how it functions when mixed in different fuels. A) If glycerine admixture degrades a good fuel such as wood in terms of the risk of acid deposits in the flue so much that it is similar to straw as a fuel, glycerine value has a negative value. B) On admixture of glycerine in a poor fuel, such as straw, the properties of the glycerine are not evident and its value based on the energy is therefore the same as for the pure fuel. This is currently approximately SEK 0.6-0.9/kg glycerine, which can be compared with the current price of SEK 1/kg for glycerine in biodigestion applications. These factors combined make it difficult to find a profitable use for glycerine as an additive in pelleting or when used as fuel. Glycerine would therefore not be of commercial interest for use in these applications. C) If the glycerine acts as an additive in very small amounts at pelleting, most likely as a lubricant, the value would then be about SEK 3/kg. However, only small amounts would be used in this application, probably just a few hundred tonnes per annum. The advice to the industry is that glycerine should not be used in pelleting as it probably does not work well for this application. If glycerine is incinerated, it should be co-fired with a poor fuel, so as not to impair the properties of the fuel. Glycerine is probably more profitable in applications other than fuel to produce heat. At low addition rates glycerine could probably act as a lubricant during pelleting of certain fuels. However, more research is required to determine whether glycerine can act as a lubricant along with some cheap binding agent in pelleting of fuels
11.	Billing, Ola, 1981-, et al. (författare) LRIG1 is a conserved EGFR regulator involved in melanoma development, survival and treatment resistance 2021 Ingår i: Oncogene. - : Springer Nature. - 0950-9232 .- 1476-5594. ; 40, s. 3707-3718 Tidskriftsartikel (refereegranskat)abstract Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a pan-negative regulator of receptor tyrosine kinase (RTK) signaling and a tumor suppressor in several cancers, but its involvement in melanoma is largely unexplored. Here, we aim to determine the role of LRIG1 in melanoma tumorigenesis, RTK signaling, and BRAF inhibitor resistance. We find that LRIG1 is downregulated during early tumorigenesis and that LRIG1 affects activation of the epidermal growth factor receptor (EGFR) in melanoma cells. LRIG1-dependent regulation of EGFR signaling is evolutionary conserved to the roundworm C. elegans, where negative regulation of the EGFR-Ras-Raf pathway by sma-10/LRIG completely depends on presence of the receptor let-23/EGFR. In a cohort of metastatic melanoma patients, we observe an association between LRIG1 and survival in the triple wild-type subtype and in tumors with high EGFR expression. During in vitro development of BRAF inhibitor resistance, LRIG1 expression decreases; and mimics LRIG1 knockout cells for increased EGFR expression. Treating resistant cells with recombinant LRIG1 suppresses AKT activation and proliferation. Together, our results show that sma-10/LRIG is a conserved regulator of RTK signaling, add to our understanding of LRIG1 in melanoma and identifies recombinant LRIG1 as a potential therapeutic against BRAF inhibitor-resistant melanoma.
12.	Britten, Nicky, et al. (författare) Learning from Gothenburg model of person centred healthcare. 2020 Ingår i: BMJ. - : BMJ. - 0959-8138 .- 1756-1833. ; 370 Tidskriftsartikel (refereegranskat)abstract Systematik och en tydlig struktur – det är faktorer som är avgörande i omställningen till personcentrerad vård. I en studie från Göteborgs universitet, publicerad i tidskriften BMJ, speglas nu ett decennium av erfarenheter och forskning i fältet. Förväntningarna växer sig allt starkare på att hälso- och sjukvården ska vara personcentrerad, och därmed ta avstamp i ett partnerskap mellan personal, patient och anhöriga. Samtidigt är det på många håll trögt att införa och upprätthålla detta arbetssätt. Att personcentrerad vård kan minska antalet vårddagar på sjukhus och skapa ökad tilltro till vården är redan känt. Nu gäller det istället att fokusera på hur man går tillväga, menar författarna bakom den övergripande artikeln i BMJ. Studien ger tips och verktyg för fortsatt forskning och utveckling av personcentrering i hälso- och sjukvården. Korresponderande författare är Axel Wolf, docent i vårdvetenskap vid institutionen för vårdvetenskap och hälsa på Sahlgrenska akademin, Göteborgs universitet, och verksam vid Centrum för personcentrerad vård, GPCC. Hela organisationen ska med – Ett av de viktigaste råden är att personcentrerad etik måste praktiseras på ett systematiskt sätt i vardagen. Det innebär att skapa organisatoriska och individuella förutsättningar för utvecklingen av ett partnerskap mellan patient, anhöriga om det är aktuellt, och personal vid varje möte, inte bara när det passar i schemat, säger han, och fortsätter: – För att få bästa kliniska effekt är det viktigt att frågan om personcentrering inte enbart blir något mellan patienten och den enskilde yrkesföreträdaren, utan återfinns i hela organisationen. Det ligger också en stor utmaning i att öka förståelsen för hur personcentrerad vård skiljer sig från nuvarande vårdpraktik. Grundläggande är att representanter från hälso- och sjukvården tar sig tid att lyssna in patientens erfarenheter och mål, som kan handla om att till exempel återgå i arbete eller kunna ta en promenad, och låter dessa mål vara vägledande i den gemensamt överenskomna hälsoplanen. Patientens prioriteringar ska speglas i planen som också ska utvärderas kontinuerligt. Dokumentationen ska sedan följa patienten, även vid övergång från exempelvis sjukhusvård till primärvård eller kommunal omsorg. Hierarkier och låsta roller Sedan starten för tio år sedan har den nationella centrumbildningen GPCC varit ledande aktör i att utveckla, testa, utvärdera och implementera personcentrerad vård i många olika hälso- och sjukvårdssammanhang, nationellt och internationellt. Tillsammans med kollegan Nicky Britten, professor vid University of Exeter, England, har Axel Wolf lett en internationell forskargrupp som har undersökt förutsättningar och hinder som forskare, kliniker och patienter upplevt under kliniska studier inom ramen för GPCC, och vid implementering av forskningsresultat i vardagen. Bland de hinder som beskrivs i den aktuella studien finns hierarkiska vårdstrukturer, låsta yrkesroller och övertygelsen om att man redan jobbar personcentrerat. – I och med omställningen till nära vård, som genomsyras av ett personcentrerat arbetssätt, måste den personcentrerade etiken praktiseras konstant för att få optimala förutsättningar. Det kräver en systematik gällande utbildning, livslångt lärande och verktyg som underlättar partnerskapet, avslutar Axel Wolf.
13.	Cruz Alsina, Fernando, et al. (författare) Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling 2016 Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 17:4, s. 601-616 Tidskriftsartikel (refereegranskat)abstract Even though many extracellular factors have been identified as promoters of general dendritic growth and branching, little is known about the cell-intrinsic modulators that allow neurons to sculpt distinctive patterns of dendrite arborization. Here, we identify Lrig1, a nervous system-enriched LRR protein, as a key physiological regulator of dendrite complexity of hippocampal pyramidal neurons. Lrig1-deficient mice display morphological changes in proximal dendrite arborization and defects in social interaction. Specifically, knockdown of Lrig1 enhances both primary dendrite formation and proximal dendritic branching of hippocampal neurons, two phenotypes that resemble the effect of BDNF on these neurons. In addition, we show that Lrig1 physically interacts with TrkB and attenuates BDNF signaling. Gain and loss of function assays indicate that Lrig1 restricts BDNF-induced dendrite morphology. Together, our findings reveal a novel and essential role of Lrig1 in regulating morphogenic events that shape the hippocampal circuits and establish that the assembly of TrkB with Lrig1 represents a key mechanism for understanding how specific neuronal populations expand the repertoire of responses to BDNF during brain development.
14.	Dahlqvist Jönsson, Patrik, 1974-, et al. (författare) Problematization of perspectives on health promotion and empowerment in mental health nursing : within the research network "MeHNuRse" and the Horatio conference, 2012 2014 Ingår i: International Journal of Qualitative Studies on Health and Well-being. - Abingdon : Informa UK Limited. - 1748-2623 .- 1748-2631. ; 9, s. 22945- Tidskriftsartikel (refereegranskat)abstract Mental illness is increasing worldwide, while society's response seems to be a trend toward narrower and more specialized mental health care. This development is creating great demands on mental health nurses to include a health promotion perspective in care and support of persons with mental illness. A health promotion perspective emphasizes cooperation and communication with people who suffer from long-term mental illness, focusing on their independence and health. From a health perspective, every human being is an actor in his/her own life, with an inherent ability to make his/her own choices. However, persons who suffer from long-term mental illness are at risk of losing power and control over areas of their lives and their health. Mental health nurses are in a position to support these individuals in promoting health and in maintaining or regaining control over their lives. The emphasis of this paper is to problematize mental health nurses' responsibility to provide health-promoting nursing care in relation to empowerment by means of emancipation, self-efficacy, and self-management. We argue that mental health nurses can work from a health-promoting perspective by using these concepts and that this challenges some of the traditional ideas of health promotion in mental health nursing. The theoretical background discussions in this paper have their origin in the research network ''Mental Health Nursing Research in Scandinavia'' (MeHNuRse) and from the professional discussions developed during a 2012 workshop that included mental health nurses and researchers at the European Horatio Festival in Stockholm.
15.	De Vincenti, Ana Paula, et al. (författare) Lrig1 and Lrig3 cooperate to control Ret receptor signaling, sensory axonal growth and epidermal innervation 2021 Ingår i: Development. - : The Dompany of Biologists. - 0950-1991 .- 1477-9129. ; 148:16 Tidskriftsartikel (refereegranskat)abstract Negative feedback loops represent a regulatory mechanism that guarantees that signaling thresholds are compatible with a physiological response. Previously, we established that Lrig1 acts through this mechanism to inhibit Ret activity. However, it is unclear whether other Lrig family members play similar roles. Here, we show that Lrig1 and Lrig3 are co-expressed in Ret-positive mouse dorsal root ganglion (DRG) neurons. Lrig3, like Lrig1, interacts with Ret and inhibits GDNF/Ret signaling. Treatment of DRG neurons with GDNF ligands induces a significant increase in the expression of Lrig1 and Lrig3. Our findings show that, whereas a single deletion of either Lrig1 or Lrig3 fails to promote Ret-mediated axonal growth, haploinsufficiency of Lrig1 in Lrig3 mutants significantly potentiates Ret signaling and axonal growth of DRG neurons in response to GDNF ligands. We observe that Lrig1 and Lrig3 act redundantly to ensure proper cutaneous innervation of nonpeptidergic axons and behavioral sensitivity to cold, which correlates with a significant increase in the expression of the cold-responsive channel TrpA1. Together, our findings provide insights into the in vivo functions through which Lrig genes control morphology, connectivity and function in sensory neurons.
16.	Ekman, Inger, 1952, et al. (författare) The person-centred approach to an ageing society 2013 Ingår i: European Journal for Person Centered Healthcare. - : University of Buckingham Press. - 2052-5656 .- 2052-5648. ; 1:1, s. 132-137 Tidskriftsartikel (refereegranskat)abstract Modern care is often based on investigations such as laboratory markers and imaging - for example, x-ray or ultrasound. The results contribute to a diagnosis and, if judged necessary, treatment is initiated. This diseased-oriented approach is the prevailing mode of management in modern medicine. In contrast, person-centered care (PCC) takes the point of departure from each person´s subjective experience of illness and its impact on daily life. A patient is considered as a person with emotions and feelings. PCC is considered present within clinical care according to a definition articulated by the Centre for Person Centred Care at the University of Gothenburg (GPCC) when three core components are present: elicitation of a detailed patient narrative; formulated partnership between caregiver and patient and documentation of the partnership in the patient record. Accordingly, when there is an illness requiring care and the person is attended using these components, PCC is being applied. In most situations today, PCC is not applied as the narrative is not fully elicited or the partnership and/or the documentation are not included. It is proposed that the challenge to Society arising from changing demographics can be addressed by implementing PCC and creating an alternative to existing healthcare. The importance and benefits of such an approach on a wider scale is not yet clear as research has been limited to date. Studies in selected patient populations (heart failure and hip fractures), however, have shown promising results. As the population ages, there will be a dramatic increase in healthcare consumption. Even with technological developments, there will be a need for tremendous resources to be dedicated to care. A new organization and attitude from healthcare policymakers and providers above and beyond the present model appears required in order to respond to this demand. As part of such change, person-centred care, with the interaction between healthcare providers and the person of the patient, can facilitate, compensate and develop more effective healthcare services for the future.
17.	Faraz, Mahmood, et al. (författare) A protein interaction network centered on leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) regulates growth factor receptors 2018 Ingår i: Journal of Biological Chemistry. - : The American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 293:9, s. 3421-3435 Tidskriftsartikel (refereegranskat)abstract Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a tumor suppressor and a negative regulator of several receptor tyrosine kinases. The molecular mechanisms by which LRIG1 mediates its tumor suppressor effects and regulates receptor tyrosine kinases remain incompletely understood. Here, we performed a yeast two-hybrid screen to identify novel LRIG1-interacting proteins and mined data from the BioPlex (biophysical interactions of ORFeome-based complexes) protein interaction data repository. The putative LRIG1 interactors identified in the screen were functionally evaluated using a triple co-transfection system in which HEK293 cells were co-transfected with platelet-derived growth factor receptor α, LRIG1, and shRNAs against the identified LRIG1 interactors. The effects of the shRNAs on the ability of LRIG1 to down-regulate platelet-derived growth factor receptor α expression were evaluated. On the basis of these results, we present an LRIG1 protein interaction network with many newly identified components. The network contains the apparently functionally important LRIG1-interacting proteins RAB4A, PON2, GAL3ST1, ZBTB16, LRIG2, CNPY3, HLA-DRA, GML, CNPY4, LRRC40, and LRIG3, together with GLRX3, PTPRK, and other proteins. In silico analyses of The Cancer Genome Atlas data sets revealed consistent correlations between the expression of the transcripts encoding LRIG1 and its interactors ZBTB16 and PTPRK and inverse correlations between the transcripts encoding LRIG1 and GLRX3. We further studied the LRIG1 function–promoting paraoxonase PON2 and found that it co-localized with LRIG1 in LRIG1-transfected cells. The proposed LRIG1 protein interaction network will provide leads for future studies aiming to understand the molecular functions of LRIG1 and the regulation of growth factor signaling.
18.	Faraz, Mahmood, 1978- (författare) Investigations of Leucine-rich repeats and immunoglobulin-like domain-proteins 1 and 2 (LRIG1 and LRIG2) and their genes in cancer 2018 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The mammalian leucine-rich repeats and immunoglobulin-like domains (LRIG) gene family consists of three different members, LRIG1, LRIG2, and LRIG3. These genes are expressed in all human and mouse tissues analyzed to date. All LRIG proteins share similar and evolutionary conserved structural domains including a leucine-rich repeat domain, three immunoglobulin-like domains, a transmembrane domain, and a cytosolic tail. Since the discovery of this family, around 20 years ago, various research groups have shown the importance of this family in cancer biology and prognosis. The aim of this thesis was to further investigate the role of LRIG1 and LRIG2 in cancer.To investigate the roles of LRIG1 and LRIG2 in physiology and gliomagenesis, we generated Lrig1- and Lrig2-deficient mice and induced platelet-derived growth factor B (PDGFB)-driven gliomagenesis. We studied the effects of Lrig2 ablation on mouse development and survival and investigated if the ablation of Lrig1 or Lrig2 affects the incidence or malignancy of induced gliomas. We also investigated if Lrig2 ablation affects Pdgfr signaling in mouse embryonic fibroblasts (MEFs). Additionally, we analyzed the effects of ectopic LRIG1 expression in human primary glioblastoma cell lines TB101 and TB107, in vivo and in vitro. We reported no macroscopic anatomical defect but reduced growth and increased spontaneous mortality rate in Lrig2-deficient mice. However, the Lrig2-deficient mice were protected against the induced gliomagenesis. Lrig2-deficient MEFs showed faster kinetics of induction of immediate-early genes in response to PDGFB stimulation, whereas the phosphorylations of Pdgfra, Pdgfrb, Erk1/2, and Akt1 appeared unaltered. Lrig1-heterozygote mice showed a higher incidence of high-grade tumors (grade IV) compared to wildtype mice, demonstrating a haploinsufficient function of Lrig1. LRIG1 overexpression suppressed TB107 cell invasion in vivo and in vitro, which was partially mediated through the suppression of the MET receptor tyrosine kinase.To identify LRIG1-interacting proteins, we used the yeast-two hybrid system and data-mined the Bio-Plex network of high throughput protein-protein interaction database. To study the function of interactors, we used a triple co-transfection system to overexpress LRIG1 and PDGFRA and downregulate endogenous levels of interactors by short hairpin RNAs (shRNAs), simultaneously. This analysis demonstrated that CNPY3, CNPY4, GAL3ST1, GML, HLA-DRA, LRIG2, LRIG3, LRRC40, PON2, RAB4A, and ZBTB16 were important for the PDGFRA-downregulating function of LRIG1.To investigate the clinical significance of LRIG1 copy number alterations (CNAs) in breast cancer, we used droplet digital PCR (ddPCR) to analyze 423 breast cancer tumors. We found that LRIG1 CNAs were significantly different in steroid-receptor-positive vs steroid-receptor-negative tumors and in ERBB2-amplified vs ERBB2-non-amplified tumors. In the whole cohort, patients with LRIG1 loss or gain had a worse metastasis-free survival than patients with normal LRIG1 copy numbers, however, among the early-stage breast cancer subgroup, this difference was not significant. In summary, Lrig1 behaved like a haploinsufficient tumor suppressor gene in malignant glioma, whereas Lrig2 appeared to promote malignant glioma. Our functional analysis of LRIG1 interactome uncovered several unanticipated and novel proteins that might be important for the regulation of receptor tyrosine kinases by LRIG1. LRIG1 CNAs predicted metastasis-free survival time in breast cancer. Hopefully, our findings might lead to a better understanding of the regulation of growth factor signaling and its importance in cancer biology and prognosis.
19.	Faraz, Mahmood, et al. (författare) LRIG1 gene copy number analysis by ddPCR and correlations to clinical factors in breast cancer 2020 Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407. ; 20:1 Tidskriftsartikel (refereegranskat)abstract Background: Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) copy number alterations and unbalanced gene recombination events have been reported to occur in breast cancer. Importantly, LRIG1 loss was recently shown to predict early and late relapse in stage I-II breast cancer.Methods: We developed droplet digital PCR (ddPCR) assays for the determination of relative LRIG1 copy numbers and used these assays to analyze LRIG1 in twelve healthy individuals, 34 breast tumor samples previously analyzed by fluorescence in situ hybridization (FISH), and 423 breast tumor cytosols.Results: Four of the LRIG1/reference gene assays were found to be precise and robust, showing copy number ratios close to 1 (mean, 0.984; standard deviation, +/-0.031) among the healthy control population. The correlation between the ddPCR assays and previous FISH results was low, possibly because of the different normalization strategies used. One in 34 breast tumors (2.9%) showed an unbalanced LRIG1 recombination event. LRIG1 copy number ratios were associated with the breast cancer subtype, steroid receptor status, ERBB2 status, tumor grade, and nodal status. Both LRIG1 loss and gain were associated with unfavorable metastasis-free survival; however, they did not remain significant prognostic factors after adjustment for common risk factors in the Cox regression analysis. Furthermore, LRIG1 loss was not significantly associated with survival in stage I and II cases.Conclusions: Although LRIG1 gene aberrations may be important determinants of breast cancer biology, and prognostic markers, the results of this study do not verify an important role for LRIG1 copy number analyses in predicting the risk of relapse in early-stage breast cancer.
20.	Farnebäck, Malin, 1972- (författare) Quantitative analysis of melanoma transcripts : with emphasis on methodological and biological variation 2004 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The introduction of RT-PCR made it possible to detect circulating tumor cells in melanoma patients by analysis of melanoma-associated transcripts, especially tyrosinase. Since the development of the first PCR method for tyrosinase mRNA, several studies have presented varying results. In the present thesis I have developed and used quantitative PCR methods in order to evaluate methodological and biological factors which may explain the disparity in the literature.Two methods were developed for tyrosinase, one competitive PCR and one real-time PCR method. With the real-time PCR technique, quantitative methods were also developed for tyrosinase related protein (TRP)-1, TRP-2, MART-1/Melan-A, S-100, GD2 synthase, MAGE-A3 and MAGE-A12. Methodological studies on the RNA extraction showed that the silica based RNA extraction method QIAamp gave considerably higher yields compared with the phenol-chloroform based extraction methods Ultraspec and FastRNA. Further studies showed that yields comparable with the QIAamp method could be obtained with the mRNA extraction method GenoPrep. Optimization of the cDNA synthesis procedure revealed that the reverse transcriptase and factors in the RNA sample inhibited the following PCR. This was avoided by diluting the cDNA sample before PCR.The stability of the tumor cell RNA in the samples is of great concern when it comes to transporting samples from distant hospitals to the laboratory. It was found that blood collected in ACD was best, although insufficiently, stabilized when stored at +4 °C compared with room temperature. Similar stability was also obtained for PAXgene tubes stored at room temperature, however the stability of RNA was much improved when the PAXgene tubes were frozen.Studies on the biological variation in cultured melanoma cell lines and tissue sections from melanoma metastases showed that the expression of melanoma associated transcripts varied widely. In melanoma cell lines the expression of the transcripts tyrosinase, TRP-1, TRP-2 and MART-1/Melan-A was related to the pigmentation of the cell lines. The pigment-related transcripts and S-100 were expressed at higher levels than GD2 synthase, MAGE-A3 and MAGE-A12 in the melanoma metastases. The expressions of TRP-2 and GD2 synthase appeared to be influenced by therapy. In metastases from patients treated with a combination of cisplatinum, DTIC and interferon-α2b, TRP-2 was expressed at higher levels and GD2 synthase at lower levels compared with untreated patients.
21.	Ghasimi, Soma, et al. (författare) Immunohistochemical analysis of LRIG proteins in meningiomas: correlation between estrogen receptor status and LRIG expression 2012 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 108:3, s. 435-441 Tidskriftsartikel (refereegranskat)abstract The leucine-rich repeats and immunoglobulin-like domains (LRIG) protein family is comprised of three integral membrane proteins: LRIG1, LRIG2, and LRIG3. LRIG1 is a negative regulator of growth factor signaling. The expression and subcellular localization of LRIG proteins have prognostic implications in primary brain tumors, such as oligodendrogliomas and astrocytomas. The expression of LRIG proteins has not previously been studied in meningiomas. In this study, the expression of LRIG1, LRIG2, and LRIG3 was analyzed in 409 meningiomas by immunohistochemistry, and potential associations between LRIG protein expression and tumor grade, gender, progesterone receptor status, and estrogen receptor (ER) status were investigated. The LRIG proteins were most often expressed in the cytoplasm, though LRIG1 also showed prominent nuclear expression. Cytoplasmic expression of LRIG1 and LRIG2 correlated with histological subtypes of meningiomas (p = 0.038 and 0.013, respectively). Nuclear and cytoplasmic expression of LRIG1 was correlated with ER status (p = 0.003 and 0.004, respectively), as was cytoplasmic expression of LRIG2 (p = 0.006). This study is the first to examine the expression of LRIG proteins in meningiomas, and it shows a correlation between ER status and the expression of LRIG1 and LRIG2, which suggests a possible role for LRIG proteins in meningioma pathogenesis.
22.	Ghasimi, Soma, et al. (författare) Immunohistochemical analysis of LRIG proteins in meningiomas : correlation between estrogen receptor status and LRIG expression 2012 Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 14:Suppl 3, s. 69-69 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
23.	Guo, Dongsheng, et al. (författare) Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors 2006 Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 111:3, s. 238-346 Tidskriftsartikel (refereegranskat)abstract We have previously characterized three human leucine-rich repeats and immunoglobulin-like domains (LRIG) genes and proteins, named LRIG1-3 and proposed that they may act as suppressors of tumor growth. The LRIG1 transmembrane protein antagonizes the activity of epidermal growth factor receptor family receptor tyrosine kinases. In this study, we evaluated the mRNA expression level of LRIG1-3 in human glioma cell lines and control-matched glioma tissues, characterized the sub-cellular localization of an LRIG3–GFP fusion protein, and analyzed the relationship between sub-cellular localization of LRIG1-3 and clinical parameters in 404 astrocytic tumors by immunohistochemistry. LRIG1-3 mRNA was detected in all human glioma cell lines and matched glioma samples, with large differences in the expression levels. Ectopically expressed LRIG3–GFP localized to perinuclear and cytoplasmic compartments, and to the cell surface of transfected glioma cells. Perinuclear staining of LRIG1-3 was associated with low WHO grade and better survival of the patients. Perinuclear staining of LRIG3 was associated with a lower proliferation index and was in addition to tumor grade, an independent prognostic factor. Furthermore, within the groups of grade III and grade IV tumors, perinuclear staining of LRIG3 significantly correlated with better survival. These results indicate that expression and sub-cellular localization of LRIG1-3 might be of importance in the pathogenesis and prognosis of astrocytic tumors.
24.	Guo, Dongsheng, et al. (författare) The LRIG gene family has three vertebrate paralogs widely expressed in human and mouse tissues and a homolog in ascidiacea 2004 Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 84:1, s. 157-165 Tidskriftsartikel (refereegranskat)abstract Human LRIG1 (formerly LIG1), human LRIG2, and mouse Lrig1 (also known as Lig-1) encode integral membrane proteins. The human genes are located at chromosomes 3p14 and 1p13, which are regions frequently deleted in human cancers. We have searched for additional members of the LRIG family and by molecular cloning identified human LRIG3 and its mouse ortholog Lrig3. Human LRIG3 is located at chromosome 12q13. In silico analysis of public databases revealed a mouse Lrig2 mRNA, three LRIG homologs in the puffer fish Fugu rubripes, and one LRIG homolog in the ascidian tunicate Ciona intestinalis. The human and mouse LRIG polypeptides have the same predicted domain organization: a signal peptide, 15 tandem leucine-rich repeats with cysteine-rich N- and C-flanking domains, three immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tail. The extracellular part—especially the IgC2.2 domain, the transmembrane domain, and the membrane-proximal part of the cytoplasmic tail—are the most conserved regions. Northern blot analysis and real-time RT-PCR revealed that the three LRIG paralogs are widely expressed in human and mouse tissues. In conclusion, the LRIG gene family was found to have three widely expressed mammalian paralogs, corresponding orthologs in fish, and a homolog in Ascidiacea.
25.	Gur, Gal, et al. (författare) LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation 2004 Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 23:16, s. 3270-3281 Tidskriftsartikel (refereegranskat)
26.	Göstring, Lovisa, 1970- (författare) Cellular Studies of HER-family Specific Affibody Molecules 2011 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The human epidermal growth-factor like receptor (HER) family of receptor tyrosine kinases are important targets for cancer therapy. The family consists of four members - EGFR, HER2, HER3 and HER4 - that normally transfer stimulatory signals from extracellular growth factors to the intracellular signalling network. Over-activation of these receptors leads to uncontrolled cell proliferation and is seen in several types of tumours. The aim of the studies reported in this thesis was to study the uptake and effects of affibody molecules against EGFR, HER2 and HER3 in cultured cells. Affibody molecules are affinity proteins originally derived from one of the domains of protein A, and their small size and robust structure make them suitable agents for tumour targeting and therapy.Papers I and II of this thesis concern EGFR-specific affibody molecules, which were shown to be more similar to the antibody cetuximab than the natural ligand EGF in terms of cellular uptake, binding site and internalisation rate. In addition, fluorescence-based methods for the quantification of internalisation were evaluated.In the studies reported in papers III and IV, HER2-specific affibody molecules were utilised as carriers of radionuclides. Paper III reports that different cell lines exhibit different radiosensitivities to 211At-labelled affibody molecules; radiosensitivity was found to correlate with cell geometry and the rate of internalisation. Paper IV discusses the use of 17-AAG, an agent that induces HER2 internalisation and degradation, to force the internalisation of 211At- and 111In-labelled affibody molecules.Papers V and VI describe the selection and maturation of HER3-specific affibody molecules, which were found to compete with the receptor’s natural ligand, heregulin, for receptor binding. These affibody molecules were demonstrated to inhibit heregulin-induced HER3 activation and cell proliferation.The studies summarised in this paper will hopefully contribute to a better understanding of these affibody molecules and bring them one step closer to being helpful tools in the diagnosis and treatment of cancer.
27.	Hedman, Anna, et al. (författare) Fitts’ law to the rescue: A comparison of graph tables 2011 Ingår i: Open Computer Science. - : Walter de Gruyter GmbH. - 2299-1093. ; 1:3, s. 280-293 Tidskriftsartikel (refereegranskat)abstract In this paper we investigate image browsing as an interactive method for visualizing line graphs. We have compared two interfaces that both presented exactly identically looking tables, but while one version was an overview+detail interface, the other one was a distortion-oriented interface of bifocal type. We expected there to be no difference in task completion times, and found none in our first statistical evaluation. Users preferred the static overview+detail interface to the distortion-oriented, which was motivated by complaints about the changed appearance of the distortion-oriented table. The empirical results were compared to theoretical results obtained using Fitts’ law, which showed a difference in task completion time for a certain task type. A second statistical analysis included only data from task type for which a difference could be expected. The new results supported the theoretical model, saying that users were faster with the overview+detail interface. In this paper we discuss problems with image browsing tests, and suggest some ideas for future research topics and designs.
28.	Hedman, Anna, et al. (författare) Multiple diagrams for efficient reading of line graphs 2011 Ingår i: ISAST Transactions on Computers and Intelligent Systems. - 1798-2448. ; 3:3, s. 15-19 Tidskriftsartikel (refereegranskat)
29.	Hedman, Anna, et al. (författare) Testing image browsers : an analysis of layout and presentation factors that affect usability 2009 Ingår i: ISAST Transactions on Computers and Intelligent Systems. - 1798-2448. ; 1:2, s. 23-28 Tidskriftsartikel (refereegranskat)abstract Digital cameras are replacing analogue ones, and electronic photo albums are everywhere on the Internet. Image browsing is used for searching the contents of such albums, but also for a variety of other tasks. Results from image browser studies are sometimes either unexpected or in conflict with previous results. Based on observations made during such experiments, we have identified and analysed a number of visual factors that seem to be relevant for the outcome of the test. This analysis identifies research gaps that need to be filled in order to support choice of appropriate browsing technique in interface design. Some suggestions for future user tests are also given.
30.	Hedman, Björn, et al. (författare) Enhancing fuel qualities of cassava crop residues by washing 2015 Ingår i: Fuel processing technology. - : Elsevier BV. - 0378-3820 .- 1873-7188. ; 139, s. 127-134 Tidskriftsartikel (refereegranskat)abstract Cassava (Manihot esculenta Crantz) stems, being waste residues after harvesting starchy roots, are a potential bio-fuel resource. However high concentrations of ash and elements Cl, K, etc. in the stems may cause severe deposition, corrosion and particle emissions, in addition to slagging during combustion. This study tests washing by water as a pretreatment to reduce the problems. A 3-level full factorial designed experiment was conducted with washing time (<1800 s) and temperature (20-40 degrees C) as factors and fuel characteristics as responses. The effect of milling particle size was also examined in a supplementary experiment. After washing, the net calorific value of the biomass tended to be higher, though not significant. Both washing time and temperature increased C but decreased H, while N and S content decreased with time only. A short washing of 50s decreased the ash content by approximately 50% and Cl around 75%, followed by K and P that decreased to 50% after 5 min. Smaller milling size resulted in a larger amount of starch washed away, but no significant change in content of total ash and individual elements, except for Cl which was significantly higher in the smaller particles. The effect of washing on the ash composition is visualized in a ternary diagram, showing that the risk for slagging and fine particle emissions is reduced. A reduction in the risk of corrosion is also predicted as indicated by a relatively higher ratio of S/Cl and lower Cl/(K + Na). Thus, in addition to extraction of starch, the washing can also improve fuel quality of the residual biomass.
31.	Hedman, Håkan, et al. (författare) Is LRIG1 a tumour suppressor gene at chromosome 3p14.3? 2002 Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 41:4, s. 352-354 Tidskriftsartikel (refereegranskat)abstract The LRIG1 gene (formerly LIG-1), recently cloned by us, displays structural similarities to the Drosophila Kek I gene. Kek I encodes a cell surface protein, Kekkon-1, which inhibits epidermal growth factor receptor-mediated signalling. We localized the LRIG1 gene to chromosome band 3p14.3, a region known to be deleted in various human cancers. In the present study LRIG1 gene expression was examined in different tumour cell lines and corresponding normal tissues by real-time RT-PCR. In many tumour cell lines, LRIG1 expression appeared absent or was down regulated compared to corresponding normal tissues. The results are consistent with LRIG1 being a tumour suppressor gene in humans. However, further studies are justified to elucidate the explicit role of LRIG1 as a negative regulator of oncogenesis.
32.	Hedman, Håkan, et al. (författare) LRIG inhibitors of growth factor signalling - double-edged swords in human cancer? 2007 Ingår i: Eur J Cancer. - : Elsevier BV. - 0959-8049. ; 43:4, s. 676-682 Tidskriftsartikel (refereegranskat)
33.	Hedman, Håkan, et al. (författare) LRIG2 in contrast to LRIG1 predicts poor survival in early-stage squamous cell carcinoma of the uterine cervix 2010 Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 49:6, s. 812-815 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The human leucine-rich repeats and immunoglobulin-like domains (LRIG) protein family comprises LRIG1, 2, and 3. LRIG1 negatively regulates growth factor signaling and is a proposed tumor suppressor. In early stage uterine cervical carcinoma, expression of LRIG1 is associated with good survival. Less is known about the function and expression of LRIG2; it has not been studied in cervical carcinoma, previously. MATERIALS AND METHODS: LRIG2 expression was studied by immunohistochemistry in 129 uterine cervical squamous cell carcinomas and 36 uterine cervical adenocarcinomas. Possible associations between LRIG2 immunoreactivity and patient survival were evaluated. RESULTS: In early-stage squamous cell carcinoma (stages IB-IIB), high expression of LRIG2 was associated with poor survival (Kaplan-Meier, log-rank, p=0.02). The 10-year survival rate for patients with high expression of LRIG2 was 60%, compared to 87% in patients with low expression (odds ratio 0.22, 95% CI 0.07-0.64). In multivariate analysis including the previously studied tumor suppressor LRIG1 and clinical stage, LRIG2 emerged as an independent prognostic factor (odds ratio 0.22, 95% CI 0.09-0.50). For patients with both high expression of LRIG2 and low expression of LRIG1, the 10-year survival rate was only 26% compared to 66% for the remaining study population. There was no correlation between LRIG2 expression and prognosis in the limited adenocarcinoma series. DISCUSSION AND CONCLUSION: LRIG2 appears to be a significant predictor of poor prognosis in early-stage squamous cell carcinoma of the uterine cervix. A combination of high LRIG2 expression and low LRIG1 expression identified women with a very poor prognosis.
34.	Hedman, Håkan, 1961- (författare) Regulation of leukocyte integrin adhesiveness 1995 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
35.	Hedman, Lowe, et al. (författare) Medieutveckling-ett forskningsområde med många ingångar 2005 Ingår i: Nordicom Information. - : Nordicom, Göteborg. ; 27:4, s. 25-41 Bokkapitel (refereegranskat)
36.	Hellström, Martin, et al. (författare) Cardiac hypertrophy and decreased high-density lipoprotein cholesterol in Lrig3-deficient mice 2016 Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 310:11, s. R1045-R1052 Tidskriftsartikel (refereegranskat)abstract Genetic factors confer risk for cardiovascular disease. Recently, large genome-wide population studies have shown associations between genomic loci close to LRIG3 and heart failure and plasma high-density lipoprotein (HDL) cholesterol level. Here, we ablated Lrig3 in mice and investigated the importance of Lrig3 for heart function and plasma lipid levels. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze Lrig3 expression in the hearts of wild-type and Lrig3-deficient mice. In addition, molecular, physiological, and functional parameters such as organ weights, heart rate, blood pressure, heart structure and function, gene expression in the heart, and plasma insulin, glucose, and lipid levels were evaluated. The Lrig3-deficient mice were smaller than the wild-type mice but otherwise appeared grossly normal. Lrig3 was expressed at detectable but relatively low levels in adult mouse hearts. At 9 mo of age, ad libitum-fed Lrig3-deficient mice had lower insulin levels than wildtype mice. At 12 mo of age, Lrig3-deficient mice exhibited increased blood pressure, and the Lrig3-deficient female mice displayed signs of cardiac hypertrophy as assessed by echocardiography, heart-to-body weight ratio, and expression of the cardiac hypertrophy marker gene Nppa. Additionally, Lrig3-deficient mice had reduced plasma HDL cholesterol and free glycerol. These findings in mice complement the human epidemiological results and suggest that Lrig3 may influence heart function and plasma lipid levels in mice and humans.
37.	Herdenberg, Carl, et al. (författare) Hypothesis : Do LRIG proteins regulate stem cell quiescence by promoting BMP signaling? 2023 Ingår i: Stem Cell Reviews and Reports. - : Springer. - 2629-3269 .- 2629-3277. ; 19:1, s. 59-66 Forskningsöversikt (refereegranskat)abstract Leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins are evolutionarily conserved integral membrane proteins. Mammalian LRIG1 regulates stem cell quiescence in various tissue compartments, including compartments in the epidermis, oral mucosa, intestines, neural system, and incisors. The planarian LRIG1 homolog regulates the quiescence of multipotent neoblasts. The mechanism through which LRIG proteins regulate stem cell quiescence has not been well documented, although it is generally assumed that LRIG1 regulates the epidermal growth factor receptor (EGFR) or other receptor tyrosine kinases. However, Lrig-null (Lrig1-/-;Lrig2-/-; and Lrig3-/-) mouse embryonic fibroblasts (MEFs) have been recently found to exhibit apparently normal receptor tyrosine kinase functions. Moreover, bone morphogenetic protein (BMP) signaling has been shown to depend on LRIG1 and LRIG3 expression. BMPs are well-known regulators of stem cell quiescence. Here, we hypothesize that LRIG1 might regulate stem cell quiescence by promoting BMP signaling.HYPOTHESIS: Based on recent findings, it is hypothesized that LRIG1 regulates stem cell quiescence in mammalian tissues as well as in planarian neoblasts by promoting BMP signaling.
38.	Herdenberg, Carl, et al. (författare) LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes 2021 Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4 Tidskriftsartikel (refereegranskat)abstract Leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins have been implicated as regulators of growth factor signaling; however, the possible redundancy among mammalian LRIG1, LRIG2, and LRIG3 has hindered detailed elucidation of their physiological functions. Here, we show that Lrig-null mouse embryonic fibroblasts (MEFs) are deficient in adipogenesis and bone morphogenetic protein (BMP) signaling. In contrast, transforming growth factor-beta (TGF-β) and receptor tyrosine kinase (RTK) signaling appeared unaltered in Lrig-null cells. The BMP signaling defect was rescued by ectopic expression of LRIG1 or LRIG3 but not by expression of LRIG2. Caenorhabditis elegans with mutant LRIG/sma-10 variants also exhibited a lipid storage defect. Human LRIG1 variants were strongly associated with increased body mass index (BMI) yet protected against type 2 diabetes; these effects were likely mediated by altered adipocyte morphology. These results demonstrate that LRIG proteins function as evolutionarily conserved regulators of lipid metabolism and BMP signaling and have implications for human disease.
39.	Herdenberg, Carl, et al. (författare) Lrig3 affects liver fat accumulation in female mice Annan publikation (övrigt vetenskapligt/konstnärligt)
40.	Herdenberg, Carl, 1982- (författare) Molecular and physiological functions of LRIG proteins and netrin-1 in health and disease 2021 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The leucine-rich repeats and immunoglobulin-like domains (LRIG) gene family has three members, LRIG1, LRIG2, and LRIG3, that encode three structurally similar transmembrane proteins. LRIG1 is a receptor tyrosine kinase regulator, tumor suppressor, and stem cell marker in the skin, intestine, and brain. LRIG2 and LRIG3 have been less studied but shown to interact with LRIG1. The different roles and mechanisms of action of LRIG proteins have not yet been fully elucidated. In Caenorhabditis elegans (C. elegans), the LRIG homolog SMA-10 regulates bone morphogenetic protein (BMP) signaling; however, this function has not been demonstrated for mammalian LRIG proteins. In mice, the gene encoding the neurodevelopmental guidance cue netrin-1, Ntn1, interacts with Lrig3 in inner ear development. The physical interactions between LRIG proteins and other proteins are mostly unknown. Here, we describe an LRIG1-centered protein interaction network that regulates growth factor receptor levels. The LRIG1 interactome comprised LRIG2 and LRIG3 as well as many unanticipated proteins. An unbiased pathological examination of female mice with different Lrig3 genotypes (homozygous, heterozygous, or knockout) revealed a reduced incidence of spontaneous fatty liver and lymphocytic hyperplasia of the spleen in Lrig3-null mice. Female Lrig3-null mice also had a lower incidence of microvesicular cytoplasm in the liver after eight weeks on a high-fat diet. To further explore the molecular and physiological functions of LRIG proteins, we generated Lrig-null (Lrig1-/-;Lrig2-/-;Lrig3-/-) mouse embryonic fibroblasts (MEFs), which displayed a deficiency in adipogenesis caused by impaired BMP signaling. LRIG1 and LRIG3, but not LRIG2, sensitized cells to BMP and rescued the adipogenesis deficiency in Lrig-null MEFs. In C. elegans, the LRIG homolog sma-10 was needed for proper lipid accumulation. By analyzing data from the UK Biobank and GENiAL cohort, we found that certain LRIG1 gene variants were associated with a higher body mass index (BMI) yet protected against type 2 diabetes. This effect was probably mediated by altered adipocyte morphology. CRISPR/Cas9-mediated ablation of Ntn1 revealed that the BMP-promoting function of LRIG1 and LRIG3 was opposed by netrin-1, which functioned as an inhibitor of BMP signaling via its receptor neogenin.In summary, the present thesis describes a novel LRIG protein interaction network, the regulation of BMP signaling by LRIG proteins and netrin-1, and an important function of LRIG proteins in regulating fat metabolism with implications for human metabolic health.
41.	Holmlund, Camilla, 1969-, et al. (författare) Characterization and tissue-specific expression of human LRIG2 2004 Ingår i: Gene. - : Elsevier BV. - 0378-1119 .- 1879-0038. ; 332, s. 35-43 Tidskriftsartikel (refereegranskat)abstract We have recently identified and cloned the human LRIG1 gene (formerly LIG1). LRIG1 is a predicted integral membrane protein with a domain organization reminiscent of the Drosophila epidermal growth factor (EGF)-receptor antagonist Kekkon-1. We have searched for additional members of the human LRIG family and identified LRIG2 (KIAA0806). The LRIG2 gene was localized to chromosome 1p13 and had an open reading frame of 1065 amino acids. The LRIG2 protein was predicted to have the same domain organization as LRIG1 with a signal peptide, an extracellular part containing15 leucine-rich repeats and three immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tail. The LRIG2 amino acid sequence was 47% identical to human LRIG1 and mouse Lrig1 (also known as Lig-1). Northern blotting and RT-PCR revealed LRIG2 transcripts in all tissues analyzed. Quantitative real-time RT-PCR showed the most prominent RNA expression in skin, uterus, ovary, kidney, brain, small intestine, adrenal gland, and stomach. Immunoblotting of COS-7 cell lysates demonstrated that heterologously expressed human LRIG2 had an apparent molecular weight of 132 kDa under reducing gel-running conditions. N-glycosidase F treatment resulted in a reduction of the apparent molecular weight to 107 kDa, showing that LRIG2 was a glycoprotein carrying N-linked oligosaccharides. Cell surface biotinylation experiments and confocal fluorescence laser microscopy demonstrated expression of LRIG2 both at the cell surface and in the cytoplasm. LRIG2 was detected in tissue lysates from stomach, prostate, lung, and fetal brain by immunoblotting. In conclusion, LRIG2 was found to be a glycoprotein which was encoded by a gene on human chromosome 1p13 and its mRNA was present in all tissues analyzed.
42.	Holmlund, Camilla, 1969-, et al. (författare) Cytoplasmic LRIG2 expression is associated with poor oligodendroglioma patient survival. 2009 Ingår i: Neuropathology (Kyoto. 1993). - : Wiley. - 0919-6544 .- 1440-1789. ; 29:3, s. 242-247 Tidskriftsartikel (refereegranskat)abstract The three leucine-rich repeats and immunoglobulin-like domains (LRIG) genes encode integral membrane proteins. Of these, LRIG1 negatively regulates growth factor signaling and is implicated as a tumor suppressor in certain malignancies. In astrocytic tumors, the subcellular distribution of LRIG proteins is associated with specific clinicopathological features and patient survival. The role of LRIG proteins in oligodendroglioma has not previously been studied. Here we used immunohistochemistry to analyze the expression of the LRIG proteins in 63 oligodendroglial tumors, and evaluated possible associations between LRIG protein expression and clinicopathological parameters. Notably, cytoplasmic LRIG2 expression was found to be an independent prognostic factor associated with poor oligodendroglioma patient survival. This is the first report of an LRIG protein showing a negative effect on survival, suggesting that LRIG2 might have a function different from that of LRIG1, and possibly contributing to the etiology of oligodendroglioma.
43.	Holmlund, Camilla, 1969- (författare) Identification and investigations of leucine-rich repeats and immunoglobulin-like domains protein 2 (LRIG2) 2010 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Receptor tyrosine kinases (RTKs) constitute a family of proteins controlling cell growth and proliferation and whose activities are tightly controlled in normal cells. LRIG1 is a negative regulator of RTK signaling and is a proposed tumor suppressor. The aim of this thesis was to identify and study possible paralogs of LRIG1. By using the basic local alignment search tool and cDNA cloning, a human mRNA sequence with similarity to LRIG1 was identified and named LRIG2. By fluorescence in situ hybridization analysis, LRIG2 was found to reside on chromosome 1p13. The LRIG2 amino acid sequence was 47% identical to LRIG1, and the predicted protein domain organization was the same as that of LRIG1. Antibodies against LRIG2 were developed and the apparent molecular weight of the protein was determined to be 132 kDa by SDS-polyacrylamide gel electrophoresis and Western blot analysis. The sub-cellular localization was studied by cell surface biotinylation experiments and confocal fluorescence laser microscopy, which revealed that LRIG2 resided at the cell surface and in the cytoplasm. The expression patterns of LRIG2 mRNA, during development and in adult tissues, were evaluated using whole-mount in situ hybridization and quantitative real-time RT-PCR, respectively. In E10.5, E11.5 and E12.5 mouse embryos, the Lrig2 expression domains were both overlapping and unique as compared to the expression domains of Lrig1 and the third family member, Lrig3. In adult human tissues, the most prominent LRIG2 mRNA expression was found in skin, uterus and ovary. To study the developmental and physiological role of LRIG2, Lrig2 knock-out mice were generated. The knock-out mice were born at Mendelian frequencies without any apparent morphological abnormalities. However, Lrig2 knock-out mice showed reduced body weight between 5 days and 12-15 weeks of age, increased mortality, and impaired reproductive capacity. To study the role of LRIG2 as a prognostic factor in oligodendroglioma, LRIG2 expression was analyzed in 65 human oligodendrogliomas by immunohistochemistry. Cytoplasmic LRIG2 expression was an independent prognostic factor associated with poor oligodendroglioma patient survival. The possible functional role of LRIG2 in oligodendroglioma biology was further investigated using the RCAS/tv-a mouse model. Tumors resembling human oligodendroglioma were induced by intracranial injection of PDGFB carrying RCAS retroviruses into newborn Ntv-a mice. Lrig2 wild-type animals developed tumors at a higher frequency and of higher malignancy than the Lrig2 knock-out mice. This result supports the notion that LRIG2 promotes PDGF-induced oligodendroglioma genesis. A possible molecular mechanism was revealed as LRIG2 overexpression increased PDGFRa levels in transfected cells. In summary, we identified a new gene named LRIG2, showed that it is expressed in a variety of tissues during development and in adulthood, knocked it out and found that it was required for proper animal growth, health, and reproduction. We also found that Lrig2 expression promoted PDGF-induced oligodendroglioma genesis and was associated with poor oligodendroglioma patient survival, possibly via a PDGFRa stabilizing function.
44.	Holmlund, Camilla, 1969-, et al. (författare) LRIG2 promotes PDGF induced experimental glioma Annan publikation (övrigt vetenskapligt/konstnärligt)
45.	Janson, V, et al. (författare) Lrig2 knock-out mice have increased mortality, impaired fertility and transiently reduced body weight Annan publikation (övrigt vetenskapligt/konstnärligt)
46.	Jerevall, Piiha-Lotta, 1980- (författare) Homeobox B13 in breast cancer : Prediction of tamoxifen benefit 2011 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract A major issue in the management of breast cancer is to identify patients who are less likely to be cured after primary treatment and would benefit from adjuvant chemotherapy. Of great importance is also identification of patients with only local disease who traditionally would be given chemotherapy but would survive without. In this thesis we have validated the utility of the two-gene ratio HOXB13:IL17BR, which previously has been demonstrated to predict disease-free survival in tamoxifen-treated breast cancer patients. We have also studied the prognostic and predictive utility of a single gene as a biomarker in breast cancer medicine.We could confirm that HOXB13:IL17BR may classify patients with different treatment benefit; only patients with a low value showed benefit from prolonged duration of tamoxifen therapy, whereas for the group with high ratios, the long-term recurrence rate did not improve with longer treatment duration.The combination of HOXB13:IL17BR and the molecular grade index (MGI), another prognostic marker, has been shown to outperform either alone in predicting risk of breast cancer recurrence. We validated the prognostic utility of HOXB13:IL17BR+MGI in a large randomized patient cohort and found that this risk classification identified more than 50% of the tamoxifen-treated lymph node-negative patients as having a less than 3% risk of distant recurrence and breast cancer death. Furthermore, we developed and tested a continuous risk model of HOXB13:IL17BR+MGI called Breast Cancer Index (BCI), for estimation of recurrence risk at the individual level. Our study shows that BCI has the ability to identify more than 50% of patients with a low risk of recurrence more accurately than using traditional risk assessment. These results suggest that BCI may help clinicians to make better informed treatment decisions and spare toxic chemotherapy for a large group of breast cancer patients.The protein expression of HOXB13 was also shown to be a valuable predictor in postmenopausal patients. High expression was associated with worse outcome after tamoxifen therapy. In a premenopausal cohort, patients with hormone receptor-positive tumors showed benefit from tamoxifen regardless of HOXB13 expression. Further analysis indicated that estrogen receptor β (ERβ) modified the performance of HOXB13 as a predictor of treatment effect and should be taken into account when identifying patients less likely to respond to the therapy given.In conclusion, BCI identifies patients with a very low risk of distant recurrence. It may be utilized in the management of breast cancer patients to optimize the use of chemotherapy. HOXB13 protein expression may be used as a marker for tamoxifen benefit, but its performance in premenopausal patients might be modified by ERβ.
47.	Johansson, Mikael, et al. (författare) The soluble form of the tumor suppressor Lrig1 potently inhibits in vivo glioma growth irrespective of EGF receptor status 2013 Ingår i: Neuro-Oncology. - : Oxford University Press (OUP). - 1522-8517 .- 1523-5866. ; 15:9, s. 1200-1211 Tidskriftsartikel (refereegranskat)abstract Deregulated growth factor signaling is a major driving force in the initiation and progression of glioblastoma. The tumor suppressor and stem cell marker Lrig1 is a negative regulator of the epidermal growth factor receptor (EGFR) family. Here, we addressed the therapeutic potential of the soluble form of Lrig1 (sLrig1) in glioblastoma treatment and the mechanism of sLrig1-induced growth inhibition. With use of encapsulated cells, recombinant sLrig1 was locally delivered in orthotopic glioblastoma xenografts generated from freshly isolated patient tumors. Tumor growth and mouse survival were evaluated. The efficacy of sLrig1 and the affected downstream signaling was studied in vitro and in vivo in glioma cells displaying variable expression of wild-type and/or a constitutively active EGFR mutant (EGFRvIII). Continuous interstitial delivery of sLrig1 in genetically diverse patient-derived glioma xenografts led to strong tumor growth inhibition. Glioma cell proliferation in vitro and tumor growth in vivo were potently inhibited by sLrig1, irrespective of EGFR expression levels. Of importance, tumor growth was also suppressed in EGFRvIII-driven glioma. sLrig1 induced cell cycle arrest without changing total receptor level or phosphorylation. Affected downstream effectors included MAP kinase but not AKT signaling. Of importance, local delivery of sLrig1 into established tumors led to a 32 survival advantage in treated mice. To our knowledge, this is the first report demonstrating that sLrig1 is a potent inhibitor of glioblastoma growth in clinically relevant experimental glioma models and that this effect is largely independent of EGFR status. The potent anti-tumor effect of sLrig1, in combination with cell encapsulation technology for in situ delivery, holds promise for future treatment of glioblastoma.
48.	Johansson, Mikael, et al. (författare) The soluble form of the tumor suppressor Lrig1 potently inhibits in vivo glioma growth irrespective of EGF receptor status 2012 Ingår i: Neuro-Oncology. - Oxford : Oxford University Press. - 1522-8517 .- 1523-5866. ; 14:Suppl. 3, s. 15-16 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
49.	Karlsson, Emelie, et al. (författare) Get Back, a person-centred digital programme targeting physical activity for patients undergoing spinal stenosis surgery-a study protocol of a randomized feasibility study 2024 Ingår i: PILOT AND FEASIBILITY STUDIES. - 2055-5784. ; 10:1 Tidskriftsartikel (refereegranskat)abstract BackgroundSpinal stenosis is the most common reason for elective spine surgery, and the cardinal symptom is leg pain and discomfort when walking. Patients with spinal stenosis have a decreased level of physical activity and thereby an increased risk of poor health. Get Back is a person-centred digital programme that strives to support patients being physically active after surgery. The aim is to explore if Get Back, in its present format (referred to as Get Backfeasibility), is feasible and contributes to detectable change in variables related to intervention content.MethodsThirty patients planned for decompression surgery due to central lumbar spinal stenosis who present with low physical activity, pain catastrophizing or fear of movement, will be included in a randomized feasibility study. All patients will be randomly allocated to either Get Backfeasibility or usual physical therapy. Get Backfeasibility aims to increase the patient's physical activity level by combining a person-centred and cognitive behavioural approach. It comprises 10 video and telephone sessions led by a physical therapist over 12 weeks (pre/postoperatively). Outcomes are treatment fidelity (treatment dose, adherence, and content), process feasibility (recruitment, intervention use, and acceptability of measurements and intervention), and variables related to the intervention content (steps per day, physical activity level, pain catastrophizing, fear of movement, and general self-efficacy). Treatment fidelity and feasibility data will be assessed during the full study period (12 weeks). Physical activity, physical capacity, and patient-reported outcomes will be assessed digitally at baseline (2 weeks preoperatively) and 11-12 weeks postoperatively. Variables related to the intervention content will be monitored weekly through a digital application. Feasibility data will be analysed descriptively and inferentially using a nonparametric approach, data from repeated measures will be displayed graphically and data from telephone interviews will be analysed using content analysis with a descriptive manifest approach.DiscussionThe results will provide information on whether Get Back in its present format is feasible and can be evaluated for effectiveness in a larger randomized controlled trial, for patients with a low physical activity level and a high fear of movement who are undergoing decompression surgery.Trial registrationRegistered at ClinicalTrails.gov 04/08/2023, registration no. NCT05806593.
50.	Karlsson, Terese, et al. (författare) Induction of apoptosis in resistant glioma cells by synthetic caspase-activation 2004 Ingår i: J Neurooncol. - 0167-594X. ; 66:1-2, s. 71-79 Tidskriftsartikel (refereegranskat)

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