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- Almqvist, Roland, et al.
(författare)
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Management control of health - the Swedish example
- 2007
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Ingår i: Work Health and Management Control. - Stockholm : Thomson Fakta AB. - 9789176102725 ; , s. 291-318
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Management control practices have spread to areas other than formerly occupied by traditional management accounting techniques. In this chapter, results from a number of development projects regarding management control of health are presented. The purpose of the chapter is to assess the proposed health statement models in Sweden as leading or lagging management control systems: (1) How are health statements used in the organizations? (2) Could health statements be an effective device to develop management control practices with the aim of improving health? The research has been performed through longitudinal studies including in-depth interviews and observations made over a three-year period. The empirical findings are analyzed using a two-dimensional matrix comprising diagnostic reporting routines and interactive management control functions. Tentative conclusions indicate that the proposed health statement models are mainly based on diagnostic control with a focus on lagging indicators, but there are examples of the successful integration of health statement models with management control models when certain criteria of change are fulfilled.
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| 4. |
- Bruzzese, Francesca, et al.
(författare)
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Local and Systemic Protumorigenic Effects of Cancer-Associated Fibroblast-Derived GDF15
- 2014
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 74:13, s. 3408-3417
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Tidskriftsartikel (refereegranskat)abstract
- The tumor stroma is vital to tumor development, progression, and metastasis. Cancer-associated fibroblasts (CAF) are among the abundant cell types in the tumor stroma, but the range of their contributions to cancer pathogenicity has yet to be fully understood. Here, we report a critical role for upregulation of the TGF beta/BMP family member GDF15 (MIC-1) in tumor stroma. GDF15 was found upregulated in situ and in primary cultures of CAF from prostate cancer. Ectopic expression of GDF15 in fibroblasts produced prominent paracrine effects on prostate cancer cell migration, invasion, and tumor growth. Notably, GDF15-expressing fibroblasts exerted systemic in vivo effects on the outgrowth of distant and otherwise indolent prostate cancer cells. Our findings identify tumor stromal cells as a novel source of GDF15 in human prostate cancer and illustrate a systemic mechanism of cancer progression driven by the tumor microenvironment. Further, they provide a functional basis to understand GDF15 as a biomarker of poor prognosis and a candidate therapeutic target in prostate cancer.
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| 5. |
- Dussauge, Isabelle, 1978-, et al.
(författare)
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Precursors of the IT Nation : Computer use and control in swedish society, 1955–1985
- 2011
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Ingår i: 3rd IFIP WG 9.7 Conference on History of Nordic Computing, HiNC 2010. - Berlin, Heidelberg : Springer-Verlag New York. - 9783642233142 - 9783642233159 - 9783642270192 ; , s. 425-432, s. 425-432
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Konferensbidrag (refereegranskat)abstract
- This paper is a presentation of a research project that aims at writing the history of computing in Sweden in the mainframe age from a user perspective. Rather than beginning with the history of hardware, this project takes as its point of departure the way in which actors in different sectors of society used computer technology in order to achieve a higher degree of control over crucial processes, whether through electronic data processing systems, process control or technical/scientific computation.
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| 8. |
- Furuhashi, Masao, et al.
(författare)
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Platelet-derived growth factor production by B16 melanoma cells leads to increased pericyte abundance in tumors and an associated increase in tumor growth rate
- 2004
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Ingår i: Cancer Research. - : American Association for Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 64:8, s. 2725-2733
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor (PDGF) receptor signaling participates in different processes in solid tumors, including autocrine stimulation of tumor cell growth, recruitment of tumor stroma fibroblasts, and stimulation of tumor angiogenesis. In the present study, the B16 mouse melanoma tumor model was used to investigate the functional consequences of paracrine PDGF stimulation of host-derived cells. Production of PDGF-BB or PDGF-DD by tumor cells was associated with an increased tumor growth rate. Characterization of tumors revealed an increase in pericyte abundance in tumors derived from B16 cells producing PDGF-BB or PDGF-DD. The increased tumor growth rate associated with PDGF-DD production was not seen in mice expressing an attenuated PDGF beta-receptor and was thus dependent on host PDGF beta-receptor signaling. The increased pericyte abundance was not associated with an increased tumor vessel density. However, tumor cell apoptosis, but not proliferation, was reduced in tumors displaying PDGF-induced increased pericyte coverage. Our findings thus demonstrate that paracrine PDGF production stimulates pericyte recruitment to tumor vessels and suggest that pericyte abundance influences tumor cell apoptosis and tumor growth.
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| 9. |
- Gazit, Aviv, et al.
(författare)
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Tricyclic quinoxalines as potent kinase inhibitors of PDGFR kinase, Flt3 and Kit
- 2003
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Ingår i: Bioorganic & Medicinal Chemistry. - 0968-0896 .- 1464-3391. ; 11:9, s. 2007-2018
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Tidskriftsartikel (refereegranskat)abstract
- Here we report on novel quinoxalines as highly potent and selective inhibitors of the type III receptor tyrosine kinases PDGFR, FLT3, and KIT. These compounds, tricyclic quinoxalines, were generated in order to improve bioavailability over the highly hydrophobic bicyclic quinoxalines. Four of the highly active compounds were characterized in detail and are shown to inhibit PDGFR kinase activity of the isolated receptor as well as in intact cells in the sub-micromolar concentration range. We show that the most active inhibitor (compound 13, AGL 2043) is approximately 15-20 times more potent than its isomer (compound 14, AGL 2044). We therefore compared the three dimensional structures of the two compounds by X-ray crystallography. These compounds are also highly effective in blocking the kinase activity of FLT3, KIT, and the oncogenic protein Tel-PDGFR in intact cells. These compounds are potent inhibitors of the proliferation of pig heart smooth muscle cells. They fully arrest the growth of these cells and the effect is fully reversible. The chemical, biochemical and cellular properties of these compounds as well as the solubility properties make them suitable for development as anti-restenosis and anti-cancer agents.
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| 10. |
- Herrera, Mercedes, et al.
(författare)
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Prognostic Interactions between FAP plus Fibroblasts and CD8a+T Cells in Colon Cancer
- 2020
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary In addition to malignant cells, tumors are composed also of other cell types including immune cells and fibroblasts. These cell types interact with each other and with the malignant cells. Prognosis associations have previously been demonstrated for CD8-positive immune cells. Recent studies suggest that fibroblasts can affect the function of immune cells. The aim of this study was to investigate if the fibroblast composition of tumors affected the prognosis association of CD8 immune cells. This study demonstrated that in colon cancer, CD8 prognosis associations was restricted to the group of tumors with high expression the FAP fibroblast marker. Our findings suggest continued mechanistic studies regarding crosstalk between FAP-positive fibroblasts and the different immune cell types; and also support the investigation of fibroblast/T-cell interactions for therapeutic purposes. Inter-case variations in immune cell and fibroblast composition are associated with prognosis in solid tumors, including colon cancer. A series of experimental studies suggest immune-modulatory roles of marker-defined fibroblast populations, including FAP-positive fibroblasts. These studies imply that the fibroblast status of tumors might affect the prognostic significance of immune-related features. Analyses of a population-based colon cancer cohort demonstrated good prognosis associations of FAP intensity and CD8a density. Notably, a significant prognostic interaction was detected between these markers (p = 0.013 in nonadjusted analyses and p = 0.003 in analyses adjusted for cofounding factors) in a manner where the good prognosis association of CD8 density was restricted to the FAP intensity-high group. This prognostic interaction was also detected in an independent randomized trial-derived colon cancer cohort (p = 0.048 in nonadjusted analyses). In the CD8-high group, FAP intensity was significantly associated with a higher total tumor density of FoxP3-positive immune cells and a higher ratio of epithelial-to-stromal density of CD8a T cells. The study presents findings relevant for the ongoing efforts to improve the prognostic performance of CD8-related markers and should be followed by additional validation studies. Furthermore, findings support, in general, earlier model-derived studies implying fibroblast subsets as clinically relevant modulators of immune surveillance. Finally, the associations between FAP intensity and specific immune features suggest mechanisms of fibroblast-immune crosstalk with therapeutic potential.
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