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Håkansson, Annika
Publications (10 of 18) Show all publications
Kågedal, B., Farnebäck, M., Håkansson, A., Gustafsson, B. & Håkansson, L. (2007). How useful are housekeeping genes?: variable expression in melanoma metastases. Clinical Chemistry and Laboratory Medicine, 45(11), 1481-1487
Open this publication in new window or tab >>How useful are housekeeping genes?: variable expression in melanoma metastases
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2007 (English)In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 45, no 11, p. 1481-1487Article in journal (Refereed) Published
Abstract [en]

Background: There is a certain difference in opinion regarding the optimal choice of housekeeping genes used as normalization factors in gene expression analysis. We have therefore examined the suitability of three housekeeping genes, hypoxanthine phosphoribosyl transferase, β-glucuronidase and β2-micro-globulin, for normalization of expression data from melanoma metastases.

Methods: The expression of the three housekeeping genes was quantified by quantitative reverse transcription PCR in snap-frozen sections from 44 melanoma metastases, of which 19 were from patients treated with cisplatinum, dacarbazine and interferon-α2b.

Results: The expression of each housekeeping gene varied considerably between the different metastases. Histopathological examination of the tissue sections revealed variation in the amount of tumor cells in the tissue, necrosis, varying degrees of lymphocyte infiltration, and lymph node remnants. Based on this examination, 16 biopsies were omitted from further analysis because they had cracked, contained empty or necrotic areas, or were dominated by lymph node tissue. Even in sections with more than 90% tumor cells, a wide variation in the expression of the three housekeeping genes was found. The amount of lymphatic infiltrate in the tumors can have an effect on the expression of housekeeping genes in the meta-stases, whereas treatment did not seem to influence the expression.

Conclusions: We conclude that the choice of housekeeping genes can have great impact on the normalization of specific genes in melanoma metastases. Furthermore, in the analysis of mRNA expression in tumor tissue, microscopic examination is of great importance to evaluate the integrity and cellular composition of the biopsy.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-39472 (URN)10.1515/CCLM.2007.303 (DOI)48767 (Local ID)48767 (Archive number)48767 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Clinchy, B., Fransson, A., Druvefors, P., Hellsten, A., Håkansson, A., Gustafsson, B., . . . Håkansson, L. (2007). Preoperative interleukin-6 production by mononuclear blood cells predicts survival after radical surgery for colorectal carcinoma. Cancer, 109(9), 1742-1749
Open this publication in new window or tab >>Preoperative interleukin-6 production by mononuclear blood cells predicts survival after radical surgery for colorectal carcinoma
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2007 (English)In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 109, no 9, p. 1742-1749Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-39824 (URN)10.1002/cncr.22623 (DOI)51413 (Local ID)51413 (Archive number)51413 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Clinchy, B., Gunnerås, M., Håkansson, A. & Håkansson, L. (2006). Production of IL-1Ra by human mononuclear blood cells in vitro: Influence of serum factors. Cytokine, 34( 5-6), 320-330
Open this publication in new window or tab >>Production of IL-1Ra by human mononuclear blood cells in vitro: Influence of serum factors
2006 (English)In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 34, no 5-6, p. 320-330Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-37607 (URN)10.1016/j.cyto.2006.06.010 (DOI)36685 (Local ID)36685 (Archive number)36685 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Håkansson, A., Håkansson, L., Gustafsson, B. & Kågedal, B. (2004). Bcl-2 monitoring in malignant melanoma. Hospital Pharmacy, 46-47
Open this publication in new window or tab >>Bcl-2 monitoring in malignant melanoma
2004 (English)In: Hospital Pharmacy, ISSN 0018-5787, E-ISSN 1945-1253, p. 46-47Article in journal (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-23814 (URN)3337 (Local ID)3337 (Archive number)3337 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Schüle, J. M., Bergkvist, L., Håkansson, L., Gustafsson, B. & Håkansson, A. (2004). CD28 expression in sentinel node biopsies from breast cancer patients in comparison with CD3-ζ chain expression. Journal of Translational Medicine, 2
Open this publication in new window or tab >>CD28 expression in sentinel node biopsies from breast cancer patients in comparison with CD3-ζ chain expression
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2004 (English)In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 2Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24394 (URN)10.1186/1479-5876-2-45 (DOI)6488 (Local ID)6488 (Archive number)6488 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Håkansson, A., Gustafsson, B., Abdiu, A., Krysander, L. & Håkansson, L. (2003). Bcl-2 expression in metastatic malignant melanoma. Importance for the therapeutic efficacy of biochemotherapy. Cancer Immunology and Immunotherapy, 52(4), 249-254
Open this publication in new window or tab >>Bcl-2 expression in metastatic malignant melanoma. Importance for the therapeutic efficacy of biochemotherapy
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2003 (English)In: Cancer Immunology and Immunotherapy, ISSN 0340-7004, E-ISSN 1432-0851, Vol. 52, no 4, p. 249-254Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24822 (URN)10.1007/s00262-003-0373-z (DOI)9219 (Local ID)9219 (Archive number)9219 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Bernsen, M. R., Smetsers, T., van der Westerlo, E., Ruiter, D., Håkansson, L., Gustafsson, B., . . . Håkansson, A. (2003). Heparan sulphate epitope-expression is associated with the inflammatory response in metastatic malignant melanoma. Cancer Immunology and Immunotherapy, 52(12), 780-783
Open this publication in new window or tab >>Heparan sulphate epitope-expression is associated with the inflammatory response in metastatic malignant melanoma
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2003 (English)In: Cancer Immunology and Immunotherapy, ISSN 0340-7004, E-ISSN 1432-0851, Vol. 52, no 12, p. 780-783Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25094 (URN)10.1007/s00262-003-0421-8 (DOI)9526 (Local ID)9526 (Archive number)9526 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Bernsen, M., Håkansson, L., Gustafsson, B., Krysander, L., Rettrup, B., Ruiter, D. & Håkansson, A. (2003). On the biological relevance of MHC class II and B7 expression by tumour cells in melanoma metastases. British Journal of Cancer, 88(3), 424-431
Open this publication in new window or tab >>On the biological relevance of MHC class II and B7 expression by tumour cells in melanoma metastases
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2003 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 88, no 3, p. 424-431Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25093 (URN)10.1038/sj.bjc.6600703 (DOI)9525 (Local ID)9525 (Archive number)9525 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Håkansson, A., Håkansson, L., Gustafsson, B., Krysander, L., Rettrup, B., Ruiter, D. & Bernsen, M. R. (2003). On the effect of biochemotherapy in metastatic malignant melanoma: An immunopathological evaluation. Melanoma research, 13(4), 401-407
Open this publication in new window or tab >>On the effect of biochemotherapy in metastatic malignant melanoma: An immunopathological evaluation
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2003 (English)In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 13, no 4, p. 401-407Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25095 (URN)10.1097/00008390-200308000-00010 (DOI)9527 (Local ID)9527 (Archive number)9527 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Håkansson, A., Håkansson, L., Gustafsson, B., Krysander, L., Rettrup, B., Ruiter, D. & Bernsen, M. (2002). Biochemotherapy of metastatic malignant melanoma. On down-regulation of CD28. Cancer Immunology and Immunotherapy, 51(9), 499-504
Open this publication in new window or tab >>Biochemotherapy of metastatic malignant melanoma. On down-regulation of CD28
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2002 (English)In: Cancer Immunology and Immunotherapy, ISSN 0340-7004, E-ISSN 1432-0851, Vol. 51, no 9, p. 499-504Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25090 (URN)10.1007/s00262-002-0304-4 (DOI)9522 (Local ID)9522 (Archive number)9522 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
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