| 1. |
|
|
| 2. |
- Fyrberg, Anna, et al.
(författare)
-
A potential role of fetal hemoglobin in the development of multidrug resistance
- 2012
-
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier. - 0006-291X .- 1090-2104. ; 427:3, s. 456-460
-
Tidskriftsartikel (refereegranskat)abstract
- Our previous data from a human leukemic cell line made resistant to the nucleoside analog (NA) 9-beta-D-arabinofuranosylguanine (AraG) revealed a massive upregulation of fetal hemoglobin (HbF) genes and the ABCB1 gene coding for the multidrug resistance P-glycoprotein (P-gp). The expression of these genes is regulated through the same mechanisms, with activation of the p38-MAPK pathway and inhibition of methylation making transcription factors more accessible to activate these genes. We could show that AraG, as well as other NAs, and P-gp substrates could induce global DNA demethylation and induction of Hb gamma and P-gp both at the mRNA and protein expression level. We speculate that the expression of HbF prior to drug exposure or in drug-resistant cell lines is a strategy of the cancer to gain more oxygen, and thereby survival benefits. We also believe that P-gp may be induced in order to excrete Hb degradation products from the cells that would otherwise be toxic. By using Hb gamma siRNA and pharmacological inhibitors of HbF production we here present a possible relationship between HbF induction and multi-drug resistance in a human leukemia cell line model.
|
|
| 3. |
- Fyrberg, Anna, et al.
(författare)
-
Induction of fetal hemoglobin and ABCB1 gene expression in 9-β-D-arabinofuranosylguanine-resistant MOLT-4 cells
- 2011
-
Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer. - 0344-5704 .- 1432-0843. ; 68:3, s. 583-591
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To characterize resistance mechanisms to the nucleoside analog 9-β-D-arabinofuranosylguanine (AraG) in the T-cell acute lymphoblastic leukemia cell line MOLT-4 and its AraG-resistant variant. METHODS: A gene expression microarray analysis was performed, as well as gene expression and enzyme activity measurements of key enzymes in the activation of AraG. Cytotoxicity of AraG and cross-resistance to other compounds were evaluated using a standard cytotoxicity assay. RESULTS: Gene expression microarray analysis revealed that fetal hemoglobin genes and the multidrug resistance ABCB1 gene, encoding the drug efflux pump P-gp, were the most highly upregulated genes in the resistant cells, while genes traditionally associated with nucleoside analog resistance were not. Fetal hemoglobin and ABCB1 induction can be due to global DNA hypomethylation. This phenomenon was studied using AraG during a period of 4 weeks in MOLT-4 cells and the lung adenocarcinoma cell line A549, leading to up-regulation of hemoglobin gamma and ABCB1 as well as DNA hypomethylation. Inhibiting P-gp in the AraG-resistant MOLT-4 cells led to decreased proliferation, reduced hemoglobin expression, and highly induced ABCB1 expression. CONCLUSIONS: We show that AraG can cause hypomethylation of DNA and induce the expression of the fetal hemoglobin gamma gene and the ABCB1 gene. We speculate that the induction of ABCB1/P-gp may occur in order to help with excretion of hemoglobin degradation products that would otherwise be toxic to the cells, and we present data supporting our theory that P-gp may be linked to the induction of hemoglobin.
|
|
| 4. |
- Fyrberg, Anna, 1981-
(författare)
-
Nucleoside analoge cytotoxicity-focus on enzyme regulation, metabolism, and mechanisms of resistance
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to determine the role of nucleoside analog activating and deactivating enzymes in nucleoside analog metabolism and resistance development. Nucleoside analogs are anti-cancer drogs and are often used to treat different leukemias, attributably to presence of high levels of nucleoside analog activating enzymes in hematopoietic cells. More recently some of the newer analogs have been used successfully to treat solid tumors as well.We have used human leukemic cell lines, and isolated cells from patients with leukemia, to investigate the nucleoside analog activating enzymes deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK) and some of the deactivating enzymes called 5'nucleotidases (5'-NTs). We have measured mRNA expressions and enzymatic activities and correlated them with the cytotoxic response to nuc1eoside analogs and changes in cell cycle progression. We optimized and evaluated a siRNA-transfection method and decreased the activities of dCK and dGK in two different cell lines in order to find out more about their respective contribution to activation of these drogs. An expression microarray analysis of a nucleoside analog resistant cell line was also performed in order to clarify which genes are involved in development of resistance.We found that expressions and activities of dCK and dGK were not correlated. The enzyme activities of activating and deactivating enzymes changed during cell cycle progression, giving actively proliferating cells a more favorable enzymatic profile with regard to nucleoside analog cytotoxicity.The activities of dCK and dGK could be reduced transiently in leukemic and solid tumor cell lines, thereby confer either resistance or increased sensitivity to nucleoside analogs to variable degrees. Expression microarray analysis was used to evaluate the effect of the transfection method and the specificity of siRNA. We concluded that cells tolerated the transfection weIl without major effects on gene expression, and considered the siRNA used to be specific to its target.An expression microarray experiment on a nucleoside analog-induced resistant cell line revealed a hypomethylating capacity of the drog and induction of fetal hemoglobin and a multidrog resistance efflux pump as a result of the hypomethylation. This pump should not be affected by nucleoside analoges since they are not a substrate of it, and upregulation of the pump unfortunately renders the cells highly cross-resistant to different types of drogs. Our preliminary data supports our theory that it may be upregulated in order to help excrete hemoglobin that otherwise would be toxic to the cells.
|
|
| 5. |
- Fyrberg, Anna, et al.
(författare)
-
Optimization and evaluation of electroporation delivery of siRNA in the human leukemic CEM cell line
- 2010
-
Ingår i: CYTOTECHNOLOGY. - : Springer Science Business Media. - 0920-9069 .- 1573-0778. ; 62:6, s. 497-507
-
Tidskriftsartikel (refereegranskat)abstract
- In order to study nucleoside analog activation in the CEM cell line, a transfection protocol had to be optimized in order to silence an enzyme involved in nucleoside analog activation. Hematopoetic cell lines can be difficult to transfect with traditional lipid-based transfection, so the electroporation technique was used. Field strength, pulse length, temperature, electroporation media, siRNA concentration, among other conditions were tested in order to obtain approximately 70-80% mRNA and enzyme activity downregulation of the cytosolic enzyme deoxycytidine kinase (dCK), necessary for nucleoside analog activation. Downregulation was assessed at mRNA and enzyme activity levels. After optimizing the protocol, a microarray analysis was performed in order to investigate whether the downregulation was specific. Additionally two genes were differentially expressed besides the downregulation of dCK. These were however of unknown function. The leakage of intracellular nucleotides was also addressed in the electroporated cells since it can affect the DNA repair mechansism and the efficiency of nucleoside analogs. Three of these pools were increased compared to untreated, unelectroporated cells. The siRNA transfected cells with reduced dCK expression and activity showed reduced sensitivity to several nucleoside analogs as expected. The multidrug resistance to other drugs, as seen in nucleoside analog-induced resistant cells, was not seen with this model.
|
|
| 6. |
|
|
| 7. |
- Fyrberg Yngfalk, Anna, 1980-
(författare)
-
Co-Creating Value : Reframing Interactions in Service Consumption
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- How producers and consumers interact in the market and integrate resources is fundamental for our understanding of how value and value creation develop in contemporary economy. Value co-creation in markets has gained renewed interest in marketing theory. The existing literature has predominantly focused on emphasizing either how co-creation processes are organized from a provider perspective or how consumers create value in their consumption practices. In taking either a service-provider or consumption perspective, previous research disregards the complexity of interactions between two or more actors, and that interactions often are characterized by tensions and conflicts. The aim of this thesis is therefore to analyze how constellations of various actors interact to co-create value, and to demonstrate possible implications for marketing theory and research on value co-creation. This is done by examining different constellations of actors’ interactions, emphasizing organization and consumption of services in sport and tourism, two fruitful contexts for investigating complex actor constellations. In marketing theory, Service Dominant logic (S-D logic) has evolved into a key framework for conceptualizing and organizing value co-creation. The focus on the organization of value co- creation has occurred at the expense of emphasizing actors’ rich and varied competences and the contextual conditions that permeate actors’ interactions. Therefore, as another contribution, the present thesis further bridges S-D logic with socio-cultural oriented consumption theory on meaning creation, and how available recourses are made use of by organizations and consumers. Drawing on these two frameworks, and by conducting 52 interviews with respondents from actor groups, this thesis provides a systematization of interactions, demonstrating that value co-creation is dependent on the constellation of actors, their often contradicting interests and their various competences. The following types of interactions for value co-creation are suggested: converged, diverged, disjointed and fragmented.
|
|
| 8. |
- Fyrberg Yngfalk, Anna, et al.
(författare)
-
Control and Power in Online Consumer Tribes : The Role of Confessions
- 2013
-
Ingår i: Consumer Culture Theory. - : Emerald Group Publishing Limited. - 9781781908105 - 9781781908112 ; 15, s. 325-350
-
Konferensbidrag (refereegranskat)abstract
- Confessions are said to be important for members’ tribal experiences and they are usually ascribed religious meanings in existing research on consumer tribes. This suggests that confessions have a regulative role for tribal life. By employing the Foucauldian notion of pastoral power, the present study explores confession practices and examines how control is manifested.The study is based on a netnographic study and analysis of tribal members’ confessions across three online consumer tribes devoted to opera (Loggionisti, who are opera aficionados of the La Scala theatre in Milan, Italy), sports (football and hockey fans of Djurgården, Sweden), and cars (Alfa Romeo owners).We demonstrate how confessions align consumers with the common tribe ethos and how this constitutes members into various subject positions, which are fundamental social processes for reinforcing the tribe. More specifically, it demonstrates four types of subject positions: the ‘pastor’, ‘regular sheep’, ‘good sheep’ and ‘black sheep’, and how these subject positions regulate the actions of tribe members.The present study theorizes how control is manifested and facilitated in consumer tribes. The study also explicates the confession and its role as a religious regulating practice fundamental for the life of a consumer tribe.Community managers can recognize the different subject positions that emerge within a community and help facilitate the interactions among community members.Previous studies are silent about how confessions reproduce control in consumer tribes. The present study highlights confession practices and the constitution of subject positions, which regulate as well as reinforce consumer tribes.
|
|
| 9. |
- Fyrberg Yngfalk, Anna
(författare)
-
Idrottssponsring och etik
- 2014
-
Ingår i: I gråzonen. - Stockholm : Centrum för idrottsforskning. - 9789198183313 ; , s. 85-97
-
Bokkapitel (populärvet., debatt m.m.)
|
|
| 10. |
- Fyrberg Yngfalk, Anna
(författare)
-
‘It’s not us, it’s them!’– Rethinking value co-creation among multiple actors
- 2013
-
Ingår i: Journal of Marketing Management. - 0267-257X .- 1472-1376. ; 29:9-10, s. 1163-1181
-
Tidskriftsartikel (refereegranskat)abstract
- Marketing theory has conceptualised value co-creation through research on provider and consumer resource integrations. Little attention, however, has been devoted to how companies, consumers, and other stakeholders interact and co-create value in the context of multiple interactions. This study, therefore, explores co-creation by investigating the football experience, which is characterised by often-complex relations of multiple actors involved. Through a sociocultural perspective, actors’ resource integration is understood as being dependent on the shifting and contradicting interests of actors, which renders actors both enabled and also constrained in their interactive processes. This study demonstrates that actors’ contradictory resource integrations and interactions are fundamental for value to be co-created, since they give rise to new interpretations and meaning creations. In conclusion, the study reveals regulations, the media, and the collective strength of consumers to be unbalancing and yet creative mechanisms within the value co-creation process.
|
|
