Rikard Larsson

Case survey methodology: Quantitative analysis of patterns across case studies

Case surveys bridge the gap between nomothetic surveys and idiographic case studies to combine their respective benefits of generalizable, crosssectional analysis and in-depth, processual analysis....

International growth through cooperation: Brand-driven strategies, leadership, and career development in Sweden

Corporate growth is often viewed as being either internally generated or externally achieved through mergers and acquisitions (M&As). During the last decade, strategic alliances have become an ...

The role of PI3K/AKT-related PIP5K1α and the discovery of its selective inhibitor for treatment of advanced prostate cancer

Significance Prostate cancer is the most common malignancy and the third leading cancer-related cause of death among men of the Western world. Treatment options at advanced stages of the disease are scarce, and better therapies are in urgent need. In our study, we show that the clinically relevant lipid kinase phosphatidylinositol-4-phosphate 5-kinase-α (PIP5Kα) plays an important role in cancer cell invasion and survival by regulating the PI3K/AKT/androgen receptor pathways. Elevated levels of PIP5K1α contribute to cancer cell proliferation, survival, and invasion. In this context we introduce a newly developed compound, ISA-2011B, with promising anticancer effects by inhibiting the PIP5K1α-associated AKT pathways. Conclusively, we propose that PIP5K1α may be used as a potential therapeutic target for treatment of advanced prostate cancer. Nitrogen-containing heterocyclic compounds are an important class of molecules that are commonly used for the synthesis of candidate drugs. Phosphatidylinositol-4-phosphate 5-kinase-α (PIP5Kα) is a lipid kinase, similar to PI3K. However, the role of PIP5K1α in oncogenic processes and the development of inhibitors that selectively target PIP5K1α have not been reported. In the present study we report that overexpression of PIP5K1α is associated with poor prognosis in prostate cancer and correlates with an elevated level of the androgen receptor. Overexpression of PIP5K1α in PNT1A nonmalignant cells results in an increased AKT activity and an increased survival, as well as invasive malignant phenotype, whereas siRNA-mediated knockdown of PIP5K1α in aggressive PC-3 cells leads to a reduced AKT activity and an inhibition in tumor growth in xenograft mice. We further report a previously unidentified role for PIP5K1α as a druggable target for our newly developed compound ISA-2011B using a high-throughput KINOMEscan platform. ISA-2011B was discovered during our synthetic studies of C-1 indol-3-yl substituted 1,2,3,4-tetrahydroisoquinolines via a Pictet-Spengler approach. ISA-2011B significantly inhibits growth of tumor cells in xenograft mice, and we show that this is mediated by targeting PIP5K1α-associated PI3K/AKT and the downstream survival, proliferation, and invasion pathways. Further, siRNA-mediated knockdown of PIP5K1α exerts similar effects on PC3 cells as ISA-2011B treatment, significantly inhibiting AKT activity, increasing apoptosis and reducing invasion. Thus, PIP5K1α has high potential as a drug target, and compound ISA-2011B is interesting for further development of targeted cancer therapy.

Biomimetic Synthesis toward the Transtaganolides/Basiliolides.

A concise biomimetic approach toward transtaganolides C and D involving an Ireland-Claisen rearrangement/intramolecular Diels-Alder reaction sequence suggesting the involvement of pericyclic reactions in the biosynthesis of these biologically active plant metabolites is presented. A final coupling reaction establishes the carbon framework of the transtaganolides.

The Handshake between Invisible and Visible Hands

There are different institutional forms for coordinating economic activity. These represent socially established means of ordering action. Whereas economic theory has largely focused on market coordination through the invisible hand of the price mechanism, organization theory has focused on the hierarchical form as a means for coordinating internalized actions within the firm. Markets and hierarchies together can be seen as the two most prominent institutional forms of coordination. Both are included in the

Building motivational capital through career concept and culture fit

Purpose – The purpose of the present paper is to offer a career concept and culture framework for measuring and managing the alignment between people, strategy and culture and especially the motivational capital as the fit between peoples motives and the organizations reward and appraisal systems.Design/methodology/approach – A survey of 312 respondents in a multinational manufacturing firm using two questionnaires about their individual career concepts, motives, and their views about the organizational strategy and culture.Findings – The results suggest that the career‐ and culture‐based motivational capital is positively associated with how effective the people view the strategy, how well‐functioning the structure is experienced, how relevant the performance appraisal is considered, how satisfied the people feel, and how long they stay in the organization.Research limitations/implications – Future research should add more multi‐item‐dependent variables, use more translated questionnaires into the resp...

Clinical Trial Update and Novel Therapeutic Approaches for Metastatic Prostate Cancer

Recurrent prostate cancer (PCa) remains a major clinical challenge. Invasive and metastatic PCa lesions often exhibit a partial and time-limited response to therapy before the cancer progresses and the patient succumbs to the disease. Despite recent advances in early diagnosis and treatment, approximately one-third of treated patients will relapse and become resistant to currently available treatments. In this review we evaluate current treatment practices and recent advances in therapy for localized prostate malignancy and advanced, metastatic prostate cancer. Some of the promising new drugs for PCa treatment include MDV3100, an androgen receptor (AR) antagonist that prevents androgens from binding to the AR and nuclear translocation and co-activator recruitment of the ligand-receptor complex; abiraterone, an orally administered drug that irreversibly inhibits a rate-limiting enzyme in androgen biosynthesis, CYP17; and several newer cytotoxic drugs (epothilones, satraplatin). Key new insights are that cancer stem cells play a role in PCa and that PCa cells are dependent on the AR for proliferation, even in the hormone refractory state of the disease. We also discuss potential molecular targets for new drug candidates for the treatment of metastatic PCa.

Market pull or legislative push: A framework for strategic ecological reorientation

Our understanding of how organizations become reoriented towards more environmentally apt strategies suffers from previously fragmented conceptual approaches and insufficient attention in research to the process and content of such ecological reorientations. This paper develops an orientational framework that systematizes different conceptualizations in the organizational, strategy and marketing literature and adds an ecological orientation. The framework is applied to an exploratory case study of an attempted reorientation towards a greener strategy in a household appliance firm. The minor ecological reorientation that occurred was found to be primarily driven by legislation rather than market pull owing to the dominant production orientation of the firm. Thus it is suggested here that the relative effectiveness of legislative push or market pull in achieving ecological reorientation varies according to the initial orientation of the firms.

Researching Mergers & Acquisitions with the Case Study Method: Idiographic Understanding of Longitudinal Integration Processes

The purpose with this paper is to highlight the comparative advantages of using case study research to contribute to the Mergers and Acquisitions (M&A) field and provide some recommendations how this can be done well. Based on three reviews of the case study methodological literature, influential M&A case studies, and the methodological case survey of 55 M&A cases, we conclude that the case study method is a powerful, yet much underutilized method in M&A research. Even though there seem to be perhaps more than 20 times as many M&A surveys as case studies (Haleblian at al, 2009), we find that especially influential M&A case studies contribute unique value to M&A research in terms of the rich idiographic understanding of the complex combination and especially integration processes where the longitudinal, multi-aspect, and multi-level strengths of the case study method excel.

Swedish Management: Modern Project, Postmodern Implementation

This article begins with a brief characterization of those aspects of the present sociopolitical climate in Sweden that seem of particular relevance in a management context (history will be called in when appropriate). The paper then attempts to describe certain of the important features of organizational life within the two economic sectors: the public (i.e., state, county, and municipal administrations) and the private. Finally, the thesis hinted at in the title is examined that Sweden is a country where organizational design is highly modern and where organizational performance tends to be based on knowledge of a postmodern type.