| 1. |
- Andersson, Claes, et al.
(författare)
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Mebendazole is unique among tubulin-active drugs in activating the MEK-ERK pathway
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity in monocyte/macrophage models and induces ERK signalling. In the present study we investigated whether MBZ induced ERK activation is shared by other tubulin binding agents (TBAs) and if it is observable also in other human cell types. Curated gene signatures for a panel of TBAs in the LINCS Connectivity Map (CMap) database showed a unique strong negative correlation of MBZ with MEK/ERK inhibitors indicating ERK activation also in non-haematological cell lines. L1000 gene expression signatures for MBZ treated THP-1 monocytes also connected negatively to MEK inhibitors. MEK/ERK phosphoprotein activity testing of a number of TBAs showed that only MBZ increased the activity in both THP-1 monocytes and PMA differentiated macrophages. Distal effects on ERK phosphorylation of the substrate P90RSK and release of IL1B followed the same pattern. The effect of MBZ on MEK/ERK phosphorylation was inhibited by RAF/MEK/ERK inhibitors in THP-1 models, CD3/IL2 stimulated PBMCs and a MAPK reporter HEK-293 cell line. MBZ was also shown to increase ERK activity in CD4+ T-cells from lupus patients with known defective ERK signalling. Given these mechanistic features MBZ is suggested suitable for treatment of diseases characterized by defective ERK signalling, notably difficult to treat autoimmune diseases.
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| 2. |
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| 3. |
- Blom, Angelica, et al.
(författare)
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Omnichannel-based promotions' effects on purchase behavior and brand image
- 2017
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Ingår i: Journal of Retailing and Consumer Services. - : Elsevier. - 0969-6989. ; 39:4, s. 286-295
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Tidskriftsartikel (refereegranskat)abstract
- This paper examines the effects of utilizing consumers’ digital shopping traces when designing in-store promotions on purchase behavior and brand image. In two experimental studies with 526 and 550 espondents, the authors examine the effects of omnichannel-based promotions (e.g. using digital shopping trace to offer a promotion when the consumer enters the physical store) in two different product categories (utilitarian vs. hedonic), spontaneous/planned purchases and two different retail industries (durable good vs. travel). The results show that retailers benefit from using digital shopping traces as it increases purchases and enhances brand imagery. The effects are moderated by product category and type of purchase.
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| 4. |
- Blom, Angelica
(författare)
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One size fits all? Understanding shopper responses towards integration activtites in omnichannel retailing
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Contemporary shopper journeys often entail myriad interactions, including online or offline stores, smartphone applications, social media platforms and mass communication. Shoppers typically expect to shop seamlessly across interactions, leading retailers to develop omnichannel strategies focused on integrating such interactions. This thesis investigates shopper responses, linked to sales- and brand-related outcomes, towards these integration attempts, seeking to determine if these responses are dependent on four distinct aspects in the shopping situation: type of purchase made by the shopper, how well-planned the purchase is, the shopper’s smartphone shopping expertise and the location of the shopper. The shopping behavior literature suggests that shoppers respond differently towards marketing, depending on their shopping situation. However, a common belief in both omnichannel research and practice is that integration across interactions is preferable in all situations. This thesis contributes to research and practice by examining if and when shopper responses towards retailers’ integration activities can be dependent upon the shopping situation. The empirical results from five articles consisting of eight experimental studies indicate that a one-size-fits-all integration strategy is not universally applicable. The overall patterns demonstrate that retailers will gain more by focusing on integration activities targeted towards shoppers who purchase utilitarian products, make planned purchases, have less experience in using their smartphone while shopping, and are located outside the store. The findings can be used as a guide for retailers in the design of their integration activities.
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| 5. |
- Blom, Angelica, et al.
(författare)
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Promises and Pitfalls of Targeted Communication Encouraging Sustainable Purchase Decisions in Grocery Retailing
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In this working paper we set out to investigate whether retailers can use targeted communication to encourage sustainable consumer behavior in online grocery retailing. More specifically, in two scenario-based experiments we explore if targeted communication can increase purchase intentions of sustainable food, if this effect can be explained by perceived relevance of the communication, as well as be moderated by customer sustainability knowledge and product category. The results from the two studies indicate that targeted communication might be more effective in encouraging sustainable purchase decisions for some product categories than others. However, the results from the two studies raise several questions. These can be seen as guidance for retailers and researchers interested in exploring targeted communication and its effects on sustainable consumer behavior further.
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| 6. |
- Blom, Angelica, et al.
(författare)
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Towards a better understanding of sustainability gaps in retail organizations
- 2023
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Ingår i: International Review of Retail, Distribution and Consumer Research. - : Taylor & Francis. - 1466-4402 .- 0959-3969. ; 33:5, s. 539-557
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Tidskriftsartikel (refereegranskat)abstract
- Retailers have been identified as important actors in driving sustainable change, due to their vital role in connecting production and consumption. In this paper, we explore what retailers do to enable consumers to act more sustainable. Whereas there is ample research focusing either on sustainability on the production and sourcing side or on sustainable consumer behaviors, we bridge the two by focusing specifically on consumer-facing sustainability work in grocery retail organizations. Through workshops, interviews, and secondary data, we find a clear ambition among retailers to help consumers behave sustainably. However, our findings also point to several barriers to sustainability work within the organization. The paper concludes by outlining a model of different sustainability ambition-action gaps within retail organizations and possible solutions for closing them. ARTICLE HISTORY
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| 7. |
- Blom, Kristin, et al.
(författare)
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Mebendazole-induced M1 polarisation of THP-1 macrophages may involve DYRK1B inhibition
- 2019
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Ingår i: BMC Research Notes. - : Springer Nature. - 1756-0500. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity by inducing a M2 to M1 phenotype switch in monocyte/macrophage models. In the present study we investigated the potential role of protein kinases in mediating this effect.Results: MBZ potently binds and inhibits Dual specificity tyrosine-phosphorylation-regulated kinase 1B (DYRK1B) with a Kd and an IC50 of 7 and 360 nM, respectively. The specific DYRK1B inhibitor AZ191 did not mimic the cytokine release profile of MBZ in untreated THP-1 monocytes. However, in THP-1 cells differentiated into macrophages, AZ191 strongly induced a pro-inflammatory cytokine release pattern similar to MBZ and LPS/IFNγ. Furthermore, like MBZ, AZ191 increased the expression of the M1 marker CD80 and decreased the M2 marker CD163 in THP-1 macrophages. In this model, AZ191 also increased phospho-ERK activity although to a lesser extent compared to MBZ. Taken together, the results demonstrate that DYRK1B inhibition could, at least partly, recapitulate immune responses induced by MBZ. Hence, DYRK1B inhibition induced by MBZ may be part of the mechanism of action to switch M2 to M1 macrophages.
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| 8. |
- Blom, Kristin, et al.
(författare)
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The anticancer effect of mebendazole may be due to M1 monocyte/macrophage activation via ERK1/2 and TLR8-dependent inflammasome activation
- 2017
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Ingår i: Immunopharmacology and immunotoxicology. - : Informa UK Limited. - 0892-3973 .- 1532-2513. ; 39:4, s. 199-210
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Tidskriftsartikel (refereegranskat)abstract
- Mebendazole (MBZ), a drug commonly used for helminitic infections, has recently gained substantial attention as a repositioning candidate for cancer treatment. However, the mechanism of action behind its anticancer activity remains unclear. To address this problem, we took advantage of the curated MBZ-induced gene expression signatures in the LINCS Connectivity Map (CMap) database. The analysis revealed strong negative correlation with MEK/ERK1/2 inhibitors. Moreover, several of the most upregulated genes in response to MBZ exposure were related to monocyte/macrophage activation. The MBZ-induced gene expression signature in the promyeloblastic HL-60 cell line was strongly enriched in genes involved in monocyte/macrophage pro-inflammatory (M1) activation. This was subsequently validated using MBZ-treated THP-1 monocytoid cells that demonstrated gene expression, surface markers and cytokine release characteristic of the M1 phenotype. At high concentrations MBZ substantially induced the release of IL-1 beta and this was further potentiated by lipopolysaccharide (LPS). At low MBZ concentrations, cotreatment with LPS was required for MBZ-stimulated IL-1 beta secretion to occur. Furthermore, we show that the activation of protein kinase C, ERK1/2 and NF-kappaB were required for MBZ-induced IL-1 release. MBZ-induced IL-1 release was found to be dependent on NLRP3 inflammasome activation and to involve TLR8 stimulation. Finally, MBZ induced tumor-suppressive effects in a coculture model with differentiated THP-1 macrophages and HT29 colon cancer cells. In summary, we report that MBZ induced a pro-inflammatory (M1) phenotype of monocytoid cells, which may, at least partly, explain MBZ's anticancer activity observed in animal tumor models and in the clinic.
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