| 1. |
- Bernsen, MR, et al.
(författare)
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On the biological relevance of MHC class II and B7 expression by tumour cells in melanoma metastases
- 2003
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 88:3, s. 424-431
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Tidskriftsartikel (refereegranskat)abstract
- A large number of studies have indicated that specific immune reactivity plays a crucial role in the control of malignant melanoma. In this context, expression of MHC I, MHC II and B7 molecules by melanoma cells is seen as relevant for the immune response against the tumour. For a better understanding of the biological relevance of MHC II and B7 expression by tumour cells in metastatic melanoma, we studied the expression of these molecules in melanoma metastases in relation to the inflammatory response, regression of the tumour and survival from 27 patients treated with biochemotherapy (30 mg m-2 Cisplatin and 250 mg m-2 decarbazine (dimethyl-triazene-imidazole-carboxamide, DTIC) on days 1-3 i.v., and 107 IU IFN-a2b 3 days a week s.c., q. 28d). In 19 out of 27 lesions studied, we found expression of MHC II by the tumour cells, while only in one out of II tumour biopsies obtained from untreated metastatic melanoma patients, MHC II expression was detected. Expression of B7.1 and B7.2 by tumour cells was found in nine out of 24 and 19 out of 24 lesions, respectively. In all cases where B7.1 expression was found, expression of B7.2 by the tumour cells was also seen. In general, no or only few inflammatory cells positive for B7 were found. Expression of MHC II by tumour cells was positively correlated with the presence of tumour-infiltrating lymphocytes, regression of the lesion, and with time to progression (TTP) and overall survival (OS) of the patient. However, no significant correlation between B7.1 or B7.2 expression and regression of the tumour, TTP or OS was found. In light of other recent findings, these data altogether do support a role as biomarker for MHC II expression by tumour cells, however, its exact immunological pathomechanism(s) remain to be established. ⌐ 2003 Cancer Research UK.
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| 2. |
- Bernsen, Monique R, et al.
(författare)
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Heparan sulphate epitope-expression is associated with the inflammatory response in metastatic malignant melanoma
- 2003
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Ingår i: Cancer Immunology and Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 52:12, s. 780-783
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulphate (HS) represents a heterogeneous class of molecules on cell membranes and extracellular matrices. These molecules are involved in a variety of biological processes, including immune responses, through their binding and functional modulation of proteins. Recently a panel of HS-epitope-specific, human single chain antibodies have been generated by phage display, facilitating analysis of the structural heterogeneity of HS in relation to pathological conditions. In a pilot study a heterogeneous staining pattern in melanoma metastases was observed with one of the clones (EW4G1). Using a double-staining technique, the expression of this epitope was studied in 12 metastatic melanoma lesions in relation to the presence of a CD3 + cell infiltrate. Different staining patterns with EW4G1 were observed in the different lesions. The different staining patterns were associated with the presence and pattern of inflammation with CD3+ cells. A pronounced staining pattern of blood vessels with EW4G1 was associated with a more or less brisk presence of CD3+ cells, while a pronounced staining of tumour cells or tumour cell matrix or absence of staining with EW4G1 was associated with absence of CD3+ cells. These results suggest a dualistic role for HS in the recruitment and intratumoural migration of CD3+ cells, depending on the location of expression of its epitope recognized by EW4G1. Further characterization of the structural diversity of HS and its function in T-cell recruitment and migration is therefore warranted, since detailed understanding of this relation may provide new targets for therapeutic intervention, such that better homing and migration of T cells (in)to tumours might be achieved in immunologically based treatment strategies.
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| 3. |
- Clinchy, Birgitta, 1957-, et al.
(författare)
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Preoperative interleukin-6 production by mononuclear blood cells predicts survival after radical surgery for colorectal carcinoma
- 2007
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 109:9, s. 1742-1749
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Colorectal cancer is one of the most common forms of cancer in the Western world. Staging based on histopathology is currently the most accurate predictor of outcome after surgery. Colorectal cancer is curable if treated at an early stage (stage I-III). However, for tumors in stages II and III there is a great need for tests giving more accurate prognostic information defining the patient population in need of closer follow-up and/or adjuvant therapy. Furthermore, tests that provide prognostic information preoperatively could provide a guide both for preoperative oncologic treatment and the surgical procedure. METHODS. Peripheral blood mononuclear cells (PBMCs) were isolated preoperatively, within a week before primary surgery, from 39 patients undergoing surgery for colorectal cancer. The PBMCs were cultured in vitro for 24 hours in the presence of autologous serum and lipopolysaccharide (LPS). Interleukin-6 (IL-6) production was measured with enzyme-linked immunosorbent assay (ELISA). Staging based on histopathology was performed in all patients. Patients were followed for at least 54 months. RESULTS. A production of >5000 pg/mL of IL-6 identified colorectal cancer patients with a poor prognosis. Eight out of 13 patients with >5000 pg/mL IL-6 died from cancer within the follow-up period, whereas no cancer-related deaths were recorded among 21 patients with 5000 pg/mL IL-6 or less. A multivariate Cox regression analysis, stratified for T- and N-stage, identified IL-6 production as an independent prognostic factor. CONCLUSIONS. IL-6 production in vitro by PBMC can predict survival after radical surgery for colorectal cancer. © 2007 American Cancer Society.
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| 4. |
- Clinchy, Birgitta, et al.
(författare)
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Production of IL-1Ra by human mononuclear blood cells in vitro : Influence of serum factors
- 2006
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Ingår i: Cytokine. - : Elsevier BV. - 1043-4666 .- 1096-0023. ; 34:5-6, s. 320-330
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Tidskriftsartikel (refereegranskat)abstract
- In vitro cell culture models that measure cytokine production can be of great value when analyzing regulatory mechanisms underlying various pathological conditions. However, testing the function of peripheral blood cells has to take into consideration that serum factors are likely to be of importance in maintaining their function. Interleukin-1 receptor antagonist (IL-1Ra) is a cytokine of key importance in immune regulation and is believed to be involved in numerous pathological processes, such as autoimmunity and cancer. We investigated the influence of normal, human serum on spontaneous production of IL-1Ra by human peripheral blood mononuclear cells (PBMC) in vitro. IL-1Ra production in vitro spanned over a wide range of concentrations, which could be attributed to a combined effect of both cellular parameters and properties of the serum used. The production of IL-1Ra in vitro could be correlated to the level of immobilized IgG, especially IgG1 and IgG3, which is adsorbed from the serum and bound to the tissue culture wells during culture. However, the amount of serum IgG adsorbed to the tissue culture wells could not necessarily be predicted based on the serum concentration of IgG. © 2006 Elsevier Ltd. All rights reserved.
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| 5. |
- Håkansson, Annika, 1962-, et al.
(författare)
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Bcl-2 expression in metastatic malignant melanoma. Importance for the therapeutic efficacy of biochemotherapy
- 2003
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Ingår i: Cancer Immunology and Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 52:4, s. 249-254
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Tidskriftsartikel (refereegranskat)abstract
- For the majority of patients with metastatic malignant melanoma the prognosis is poor. Immunotherapy and biochemotherapy have shown promise with a subset of durable responses, but there is still a great need for a better understanding of the mechanisms of action during treatment to optimize future treatment schedules. In the present study Bcl-2 expression was studied in biopsies from ten patients with metastatic malignant melanoma (five with regional disease and five with systemic disease) treated with biochemotherapy, (cisplatinum 30 mg/m2 days 1-3, DTIC 250 mg/m2 days 1-3 i.v. and Interferon-a2b 10 MIU s.c. 3 days a week, on a 28-day cycle). The expression of Bcl-2 by the tumour cells was separately recorded in areas of histopathological regressive changes and in areas of unaffected tumour growth. Comparisons were made with biopsies from 14 untreated patients. In 10 of 10 treated patients a high expression of Bcl-2 by the tumour cells was found in areas of unaffected tumour growth. In contrast, only in 5 of 13 untreated patients was a high expression of Bcl-2 by the tumour cells found in these areas (P = 0.008). A significant difference was also found in the expression of Bcl-2 by the tumour cells between areas of unaffected tumour growth and areas of histopathological regressive changes (P=0.03). The significantly higher expression of Bcl-2 by the tumour cells in areas of unaffected tumour growth in treated patients compared to untreated patients indicates that clones with a high expression of Bcl-2 may be present after therapy, preventing apoptosis and eventually in many patients resulting in progressive disease. Supporting this concept, a difference was also found between the expression of Bcl-2 in areas of unaffected tumour growth, i.e. in areas of treatment failure, and the expression in areas of histopathological regressive changes. Thus immunohistochemical analysis of tumour biopsies shortly after therapy seems to be a good surrogate endpoint that allows a detailed analysis of Bcl-2 expression. The high expression of Bcl-2 shown in unaffected tumour areas after therapy suggests the need for additional treatment, e.g. Bcl-2 antisense therapy.
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| 6. |
- Håkansson, Annika, 1962-, et al.
(författare)
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Bcl-2 monitoring in malignant melanoma
- 2004
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Ingår i: Hospital Pharmacy. - 0018-5787 .- 1945-1253. ; , s. 46-47
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Håkansson, Annika, 1962-, et al.
(författare)
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Biochemotherapy of metastatic malignant melanoma. On down-regulation of CD28
- 2002
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Ingår i: Cancer Immunology and Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 51:9, s. 499-504
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Tidskriftsartikel (refereegranskat)abstract
- Immunotherapy and combination treatments such as biochemotherapy have shown promise, with higher response rates and a subset of durable responses, however, as the majority of responses are still of short duration, they do not provide any survival benefit. There is therefore a great need to better understand the mechanisms whereby tumours escape immune surveillance. The present study examines the expression of CD28 in patients with untreated and treated melanoma metastases. Twenty-eight patients with metastatic malignant melanoma were treated by biochemotherapy (cisplatinum 30 mg/m2 days 1-3, DTIC 250 mg/m2 days1-3 i.v., and IFN-a2b 10 million IU s.c. three days a week for 28 days treatment cycle). Tumours were resected post-biochemotherapy and analysed for the expression of CD28 in CD4+ and CD8+ lymphocytes in areas where histopathological regressive changes had occurred, and close to tumour cells in areas of unaffected tumour growth using a double-staining technique. A high percentage of the lymphocytes in areas with regressive changes were found to be CD4+ CD28-. In contrast, the vast majority of CD4+ lymphocytes migrating close to the tumour cells were found to be CD28+ (P<0.001). A similar difference in the expression of CD28 was also found for the CD8+ subset (P=0.004). A difference in down-regulation of the expression of CD28 was found between CD4+ and CD8+ lymphocytes both in the areas of regressive changes and in the unaffected tumour areas. The present study demonstrates that extensive down-regulation of the co-stimulatory factor CD28 is found in metastases following biochemotherapy. These results indicate that parameters of importance for the immune function have already undergone modification after one or two treatment cycles and that this down-regulation occurs in particular in areas with regressive tumour changes.
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| 8. |
- Håkansson, Annika, 1962-, et al.
(författare)
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Biochemotherapy of metastatic malignant melanoma. Predictive value of tumour-infiltrating lymphocytes
- 2001
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 85:12, s. 1871-1877
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Tidskriftsartikel (refereegranskat)abstract
- The therapeutic efficacy of biochemotherapy in metastatic malignant melanoma still carries a low remission rate, but with some durable responses. It would therefore be of considerable importance if patients with a high probability of responding could be identified using predictive tests. The response to interferon-alpha (IFN-a) correlates with the occurrence of CD4+ lymphocytes identified by fine-needle aspirates from melanoma metastases (Hσkansson et al, 1996). The present investigation studies a possible correlation between tumour-infiltrating CD4+ lymphocytes in malignant melanoma metastases and the therapeutic effect of biochemotherapy. A total of 25 patients with systemic and 16 with regional metastatic melanoma were analysed before initiation of biochemotherapy (cis-platinum 30 mg/m2 d.1-3, DTIC 250 mg/m2 d.1-3 i.v. and IFN-a2b 10 million IU s.c. 3 days a week, q. 28d.). A monoclonal antibody, anti-CD4, was used to identify tumour-infiltrating lymphocytes in fine-needle aspirates before start of treatment. The presence of these lymphocytes was correlated to response, time to progression and overall survival. A statistically significant correlation (P = 0.01) was found between the occurrence of CD4+ lymphocytes and tumour regression during biochemotherapy in patients with systemic disease. Out of 14 patients with moderate to high numbers of infiltrating CD4+ lymphocytes, 12 achieved tumour regression. In contrast, among patients with low numbers of these cells in metastatic lesions, 8 out of 11 had progressive disease. We also found a significantly longer time to progression (P < 0.003) and overall survival (P < 0.01) among patients with moderate to high numbers of these cells compared to patients with low numbers of these cells before initiation of biochemotherapy. Furthermore, in patients with regional disease, we found a significantly longer time to progression (P = 0.01) and a trend toward a longer overall survival time (P = 0.09). Based on these results and as previously shown with IFN-a therapy alone, there seems to be a need for CD4+ lymphocytes infiltrating the tumours before the start of biochemotherapy to make the treatment successful. Determination of these cells in fine-needle aspirates seems to be a method to predict responders to biochemotherapy, thus increasing the cost-benefit of this treatment strategy considerably, both in terms of patient adverse reactions and health care costs. ⌐ 2001 Cancer Research Campaign.
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| 9. |
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| 10. |
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| 11. |
- Håkansson, Annika, 1962-, et al.
(författare)
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On the effect of biochemotherapy in metastatic malignant melanoma : An immunopathological evaluation
- 2003
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Ingår i: Melanoma research. - : Ovid Technologies (Wolters Kluwer Health). - 0960-8931 .- 1473-5636. ; 13:4, s. 401-407
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Tidskriftsartikel (refereegranskat)abstract
- Although immunotherapy and biochemotherapy have shown promise, producing a subset of durable responses, for the majority of patients with metastatic melanoma the prognosis is still poor. Therefore there is a great need for predictive tests to identify patients with a high probability of responding. Furthermore, there is also a need for a better understanding of the mechanisms of action during treatment in order to be able to monitor the relevant antitumour reactivity during treatment and to optimize the efficacy of future immunotherapy and biochemotherapy. In the present study histopathological regression criteria were used to study the efficacy of biochemotherapy. Thirty-two patients with metastatic malignant melanoma (18 with regional disease and 14 with systemic disease) were treated with biochemotherapy (cisplatin 30 mg/m2 intravenously on days 1-3, dacarbazine 250 mg/m2 intravenously on days 1-3 and interferon-a2b 10 million IU subcutaneously 3 days a week, every 28 days). Pre-treatment fine needle aspirates were obtained from metastases to analyse the number of tumour-infiltrating CD4+ lymphocytes. Therapeutic efficacy was evaluated in metastases resected after treatment using histopathological criteria of tumour regression. Comparisons were also made with metastases from 17 untreated patients, all with regional disease. Regressive changes of 25% or more (of the section area) were found in two of the 17 untreated patients with regional disease compared with 13 of the 18 patients with regional disease and 10 of the 14 patients with systemic disease after biochemotherapy. Fifty per cent of the patients with regional disease showed a high degree of regressive changes (75-100% of the section area) after biochemotherapy. These results demonstrate the occurrence of an antitumour reactivity in the majority of patients. Patients with extensive regressive changes in 75-100% of the analysed biopsies were also found to have a longer overall survival (P = 0.019). In patients with regional disease there was a close correlation between a larger number of CD4+ lymphocytes pre-treatment and a higher degree of regressive changes post-treatment (P < 0.05). Thus, immunohistochemical analysis of tumour biopsies shortly after treatment seems to be a good surrogate endpoint This technique also allows detailed analysis of antitumour reactivity and escape mechanisms. ⌐ 2003 Lippincott Williams & Wilkins.
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| 12. |
- Schüle, Jana, et al.
(författare)
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Down-regulation of the CD3-ζ chain in sentinel node biopsies from breast cancer patients
- 2002
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Ingår i: Breast Cancer Research and Treatment. - 0167-6806 .- 1573-7217. ; 74:1, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- Background. In several neoplastic diseases, immunosuppression has been shown to correlate with disease stage, progression, and outcome. As the prognosis for metastatic breast cancer is still pessimistic, additional strategies are being sought to improve survival. Local immunosuppression in sentinel node biopsies from 24 evaluable breast cancer patients was studied as a possible way of selecting patients for immunotherapy.Method. Sentinel node biopsy was performed in 24 out of 25 women operated on for primary breast cancer (one was not evaluable). Specimens were snap-frozen and double-stained for the zeta-chain of the T-cell receptor. The degree of down-regulation of the zeta-chain was evaluated in three different lymph-node areas: primary follicles, secondary follicles, and paracortex.Results. Down-regulation of varying degrees was noted in all 24 sentinel node biopsies. A high degree of down-regulation (more than 50% of T-cells not expressing zeta-chain) was seen in the primary follicles in six patients (25%), in the secondary follicles in 13 patients (72%), and in the paracortex in 19 patients (79%).Conclusion. Local down-regulation of an immune function parameter was seen in sentinel node biopsies from breast cancer patients. In addition to possible prognostic implications, the sentinel node might be an appropriate location for detecting early-stage immunological down-regulation, which might open a possibility of selecting patients who could benefit from immunotherapy.
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| 13. |
- Schüle, Jana M, et al.
(författare)
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CD28 expression in sentinel node biopsies from breast cancer patients in comparison with CD3-ζ chain expression
- 2004
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Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Immunosuppression is documented in several malignant diseases, including breast cancer. Subsequently, future therapeutic concepts might include immunological approaches. However, detailed knowledge about tumor immunogenicity and host immunoreactivity, and how to assess these adequately, is still limited. We studied CD28 and CD3-ζ expression in sentinel node biopsies (SNB) from breast cancer patients to analyze tumor-related changes in T cell activity. Method: 25 women underwent surgery for primary breast cancer, including SNB. Frozen sections from 21 sentinel nodes could be analyzed with a double-staining technique. CD28 expression was studied in CD4+ and CD8+ T-lymphocyte subsets and compared with CD3-ζ expression in three specified nodal regions. Results: The degree of CD28 expression varied between the different lymph node areas. The lowest degree of CD28 expression was observed in CD4+ T-lymphocytes in the paracortex and germinal centers. Here, a good agreement with CD3-ζ expression was found. A higher CD28 expression was noted in CD4+ T-cells in the primary follicles, where concordance with CD3-ζ expression was weaker. The CD8+ T-lymphocyte subset displayed generally a higher degree of CD28 expression than the CD4+ subset. Conclusion: Sentinel lymph nodes from breast cancer patients displayed local immunosuppression of varying extent. In the areas with the lowest degree of CD28 expression an accordingly low CD3-ζ expression was found. The SNB might prove an important diagnostic tool for the evaluation of interactions between tumor and the host immune system, helping to select patients who might benefit from adjuvant immunotherapy.
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| 14. |
- Håkansson, Annika, 1962-
(författare)
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Interferon-alpha based treatment of metastatic malignant melanoma : Effect of immune parameters of importance for monitoring immunotherapy
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cutaneous malignant melanoma is a rapidly increasing disease. Most patients are cured by surgical excision of their primary tumour, but for patients with metastatic disease the prognosis is still very poor despite various attempts with chemotherapeutic agents, and during the last decade with immunotherapy, using several different biological agents alone or in combination. Thus, there is a great need for a better understanding of various functions of the immune system, tools for monitoring immunotherapy and predictive tests for choosing patients who are suitable for this therapy.The aims of the present investigation was therefore to study factors of possible importance for the immune control of tumours such as the occurrence and distribution of tumour-infiltrating mononuclear cells, expression ofTNFa, ICAM-1 and down-regulation of the function of tumour-infiltrating mononuclear cells. Using fine-needle aspiration of melanoma metastases we show a correlation between the occurrence of CD4+ lymphocytes in the metastases and the therapeutic benefit ofiFN-a. Thus, the degree of infiltration of these cells seems to be a useful predictive test for choosing patients suited to this therapy. We report that the expression of ICAM-1 on tumour cells is up-regulated after IFN-a treatment and describe a correlation between the expression of ICAM-1 by tumour cells and infiltration of CD4+ lymphocytes in the metastases. Thus, deternllning of ICAM:- 1 expression by tumour cells obtained by fine needle aspiration could perhaps be a valuable supplement to detennining the occurrence of tumour-infiltrating CD4+ lymphocytes tocorrelate with the response to IFN-a treatment.We demonstrate a low immune reactivity in melanoma metastases with a high expression of TNF-a by the tumour cells in untreated metastases and that IFN-a treatment could increase the immune reactivity. We also demonstrate that during the second week ofiFN-a treatment tumour-infiltrating CD4+ lymphocytes migrate from the stromal areas into the tumour nodules, close to the tumour cells, and that the extent of the tumour areas with regressive changes was significantly enhanced compared to untreated patients. Markers of the function of tumour infiltrating lymphocytes, the ~-chain and CD28, were found to be down-regulated, especially in areas of extensive tumour regression. Taken together our results are compatible with the view that the immunostimulating effect of IFNa, resulting in immune-mediated tumour cell destruction, occurs early during the treatment period and is followed within a few weeks by down-regulation of the anti-tumour immune response. Thus, in immunotherapy the possibility of inducing immunosuppression due to the lysis of tumour cells and the release of immunosuppressor factors should be considered and monitored.
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| 15. |
- Håkansson, Olof
(författare)
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Addressing the need of transition by socializing and making new friends : A socio-technical perspective on large-scale change in construction
- 2022
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This research took its point of departure in the aspiration of large-scale change of the construction industry, where existing industry structures has been frequently criticized. To facilitate innovation and change in the Swedish construction industry, a strategic innovation program has been established based on the idea that research, innovation, and development should manifest itself through the mobilization of collaborative and actor-driven networks. Using a strategic innovation program to support inter-organizational collaboration and actor-driven change is a fairly new phenomenon in the context of construction and thus the subject of inquiry for this research. From a theoretical point of view, this can be understood in terms of a transition of a socio-technical system. Therefore, the purpose was to gain a deeper understanding of how a socio-technical transition of the construction industry could be facilitated.The research presented in this licentiate thesis has been conducted between September 2019 – March 2022 and has been a part of a research project called Program Generic Measurement Methods. This research has a qualitative inquiry and has been designed as a longitudinal case study to understand, and follow, this process of change. The data that has been collected consist of document collection, structured interviews, semi-structured interviews and an autoethnographic approach including observations and self-reflection. Actor-network theory, and specifically the concepts related to the translation process and black boxing, has been used as an analytical framework and facilitated the analysis of the collected data.This thesis increases the understanding of how a socio-technical transition in construction could be facilitated by analyzing the events that lead to the development of the strategic innovation program as well as events from the operational part of the program. Key actors in these processes are identified as well as their roles in a transition of the construction industry. The results indicates that this is far from a linear process that contains a lot of negotiation between participating actors. During this process, the role of digitalization changes when the intention of the program moves from its initiators to the actors engaged in different technological niches. A better integration of academia is asked for due to the complexity that digitally driven transition processes brings. Moreover, actors in the construction industry are encouragedto engage in technological niches to interact and collaborate in new, or modified, ways outside traditional construction activities since it stimulates learning and facilitate a deeper understanding of the challenges that actors in the construction process face together.
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| 16. |
- Håkansson, Olof, et al.
(författare)
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Challenges in measuring performance of collaborative R&D projects
- 2021
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Ingår i: Managing collaborative R&D projects. - Cham : Springer Nature. - 9783030616045 - 9783030616052 ; , s. 317-329, s. 317-329
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Bokkapitel (refereegranskat)abstract
- While measuring the performance of collaborative research and development (R&D) projects is critical for both practitioners and academics, it is rarely straightforward in practice. Based on firsthand experience of the performance measurement practice within an extensive, long-term, Swedish innovation programme named Smart Built Environment, this chapter provides a reflective account of the setup and challenges experienced. The programme was launched in 2016 and is a long-term initiative of up to 12 years. Backed by three state research agencies, it is, to date, the single largest investment in innovation, R&D in digitalisation made in the Swedish built environment sector. This chapter is written as a collaborative autoethnography, with three out of the five authors having had firsthand experience of the specific measurement initiative analysed. The chapter describes how the visionary objectives of the programme, related to sustainability, time, cost and business logics, were developed and operationalised in practice. Furthermore, it is explained how several emergent challenges related to ambiguity in goal formulation, adaptation to contingencies of moving targets and temporal scope, and development of a multiplicity of assessment methods, were managed.
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| 17. |
- Johansson, Malin, 1972-, et al.
(författare)
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Quantitative analysis of tyrosinase and tyrosinase-related protein-2 mRNA from melanoma cells in blood by real-time polymerase chain reaction
- 2000
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Ingår i: Melanoma research. - 0960-8931 .- 1473-5636. ; 10:3, s. 213-222
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have evaluated the use of polymerase chain reaction (PCR) amplification of tyrosinase mRNA to detect melanoma cells in blood. However, contradictory results have been obtained from different groups. We therefore have developed and validated a quantitative PCR method for tyrosinase and tyrosinase-related protein-2 (TRP-2) mRNA. An important methodological finding was that high concentrations of reverse transcriptase or RNA sample inhibited the following PCR. This could be abolished by dilution of the cDNA sample before the PCR. Standard curves with a linear range over at least five logs were obtained with dilutions of melanoma cell cDNA. Controls (RNA and cDNA) consisting of melanoma cells (1000/ml) added to blood were analysed repeatedly over 3 months, resulting in means between 880 and 1074 AU/ml. The RNA controls were stable, whereas the cDNA controls, as well as the calibrators, showed a tendency to change over time. The variation in the RNA controls was 25% for tyrosinase and 22% for TRP-2. Seven stage III-IV melanoma patients were tested for tyrosinase and TRP-2 transcripts in blood drawn from a peripheral vein and from a Port-a-cath. Tyrosinase mRNA was found in three patients (0.8-12.4 AU/ml). For TRP-2, the same amount was found in the patients as in healthy donors. No differences were seen between blood from a peripheral vein and from the Port-a-cath. We here present fast and sensitive methods for the quantification of tyrosinase and TRP-2 mRNA in blood.
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| 18. |
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