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Wagenius, Gunnar
Publications (10 of 15) Show all publications
Eriksson, H., Lyth, J., Mansson-Brahme, E., Frohm-Nilsson, M., Ingvar, C., Lindholm, C., . . . Hansson, J. (2013). Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma: A nationwide population-based study in Sweden. European Journal of Cancer, 49(12), 2705-2716
Open this publication in new window or tab >>Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma: A nationwide population-based study in Sweden
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2013 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, no 12, p. 2705-2716Article in journal (Refereed) Published
Abstract [en]

Background: A worse outcome has been reported for cutaneous malignant melanoma (CMM) patients with low socioeconomic status. We have investigated the association between level of education, clinical stage at diagnosis (stage at diagnosis) and CMM-specific survival in Sweden. Methods: We identified 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based, health and census registers with a follow-up to 2010. Results: The odds ratio (OR) of higher disease stage at diagnosis was significantly increased in lower education groups (OR stage II versus I = 1.6; 95% confidence interval (CI) = 1.5-1.7. OR stage III-IV versus I = 2.3; 95% CI = 1.8-2.9). The risk of dying of CMM, was significantly increased in patients with low (hazard ratio (HR) low versus high = 2.02; 95% CI = 1.80-2.26; p < 0.0001) and intermediate (HR intermediate versus high = 1.35; 95% CI = 1.20-1.51; p < 0.0001) level of education. After adjustment for age, gender, stage at diagnosis and other known prognostic factors, the HRs remained significant for low versus high (HR = 1.13; 95% CI = 1.01-1.27; p = 0.04) but not for intermediate versus high (HR = 1.11; 95% CI = 0.99-1.24; p = 0.08) education. The HR associated with low level of education was significantly higher among female patients, patients <55 years, patients with truncal tumours and during the first 5 years after diagnosis. Conclusion: Lower level of education is associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. These results emphasise the need for improved early detection strategies. 

Keywords
Melanoma, Survival, Socioeconomic status, Level of education, Stage at diagnosis, Population-based
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-204837 (URN)10.1016/j.ejca.2013.03.013 (DOI)000321336800010 ()
Available from: 2013-08-13 Created: 2013-08-12 Last updated: 2017-12-06Bibliographically approved
Lyth, J., Hansson, J., Ingvar, C., Mansson-Brahme, E., Naredi, P., Stierner, U., . . . Lindholm, C. (2013). Prognostic subclassifications of T1 cutaneous melanomas based on ulceration, tumour thickness and Clark's level of invasion: results of a population-based study from the Swedish Melanoma Register. British Journal of Dermatology, 168(4), 779-786
Open this publication in new window or tab >>Prognostic subclassifications of T1 cutaneous melanomas based on ulceration, tumour thickness and Clark's level of invasion: results of a population-based study from the Swedish Melanoma Register
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2013 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 168, no 4, p. 779-786Article in journal (Refereed) Published
Abstract [en]

Background Survival and prognostic factors for thin melanomas have been studied relatively little in population-based settings. This patient group accounts for the majority of melanomas diagnosed in western countries today, and better prognostic information is needed. Objectives The aim of this study was to use established prognostic factors such as ulceration, tumour thickness and Clark's level of invasion for risk stratification of T1 cutaneous melanoma. Methods From 1990 to 2008, the Swedish Melanoma Register included 97% of all melanomas diagnosed in Sweden. Altogether, 13 026 patients with T1 melanomas in clinical stage I were used for estimating melanoma-specific 10- and 15-year mortality rates. The Cox regression model was used for further survival analysis on 11 165 patients with complete data. Results Ulceration, tumour thickness and Clark's level of invasion all showed significant, independent, long-term prognostic information. By combining these factors the patients could be subdivided into three risk groups: a low-risk group (67.9% of T1 cases) with a 10-year melanoma-specific mortality rate of 1.5% (1.2-1.9%); an intermediate-risk group (28.6% of T1 cases) with a 10-year mortality rate of 6.1% (5.0-7.3%); and a high-risk group (3.5% of T1 cases) with a 10-year mortality rate of 15.6% (11.2-21.4%). The high-and intermediate-risk groups accounted for 66% of melanoma deaths within T1. Conclusions Using a population-based melanoma register, and combining ulceration, tumour thickness and Clark's level of invasion, three distinct prognostic subgroups were identified.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-199712 (URN)10.1111/bjd.12095 (DOI)000317016100030 ()
Available from: 2013-05-13 Created: 2013-05-13 Last updated: 2017-12-06Bibliographically approved
Sadeghi, A., Ullenhag, G., Wagenius, G., Tötterman, T. H. & Eriksson, F. (2013). Rapid expansion of T cells: Effects of culture and cryopreservation and importance of short-term cell recovery. Acta Oncologica, 52(5), 978-986
Open this publication in new window or tab >>Rapid expansion of T cells: Effects of culture and cryopreservation and importance of short-term cell recovery
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2013 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 5, p. 978-986Article in journal (Refereed) Published
Abstract [en]

Background

Successful cell therapy relies on the identification and mass expansion of functional cells for infusion. Cryopreservation of cells is an inevitable step in most cell therapies which also entails consequences for the frozen cells.

Material and methods

This study assessed the impact of cryopreservation and the widely used protocol for rapid expansion of T lymphocytes. The effects on cell viability, immunocompetence and the impact on apoptotic and immunosuppressive marker expression were analyzed using validated assays.

Results and conclusion

Cryopreservation of lymphocytes during the rapid expansion protocol did not affect cell viability. Lymphocytes that underwent mass expansion or culture in high dose IL-2 were unable to respond to PHA stimulation by intracellular ATP production immediately after thawing (ATP = 16 ± 11 ng/ml). However, their reactivity to PHA was regained within 48 hours of recovery (ATP = 356 ± 61 ng/ml). Analysis of mRNA levels revealed downregulation of TGF-β and IL-10 at all time points. Culture in high dose IL-2 led to upregulation of p73 and BCL-2 mRNA levels while FoxP3 expression was elevated after culture in IL-2 and artificial TCR stimuli. FoxP3 levels decreased after short-term recovery without IL-2 or stimulation. Antigen specificity, as determined by IFNγ secretion, was unaffected by cryopreservation but was completely lost after addition of high dose IL-2 and artificial TCR stimuli. In conclusion, allowing short-time recovery of mass expanded and cryopreserved cells before reinfusion could enhance the outcome of adoptive cell therapy as the cells regain immune competence and specificity.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-188656 (URN)10.3109/0284186X.2012.737020 (DOI)000318655300013 ()23126547 (PubMedID)
Available from: 2012-12-18 Created: 2012-12-18 Last updated: 2017-12-06Bibliographically approved
Ullenhag, G. J., Sadeghi, A. M., Carlsson, B., Ahlström, H., Mosavi, F., Wagenius, G. & Tötterman, T. H. (2012). Adoptive T-cell therapy for malignant melanoma patients with TILs obtained by ultrasound-guided needle biopsy. Cancer Immunology and Immunotherapy, 61(5), 725-732
Open this publication in new window or tab >>Adoptive T-cell therapy for malignant melanoma patients with TILs obtained by ultrasound-guided needle biopsy
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2012 (English)In: Cancer Immunology and Immunotherapy, ISSN 0340-7004, E-ISSN 1432-0851, Vol. 61, no 5, p. 725-732Article in journal (Refereed) Published
Abstract [en]

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) can mediate objective responses in up to 50% of malignant melanoma patients with a good performance status refractory to standard treatments. Current protocols for generation of TILs rely on open surgery for access to tumor tissue. We obtained tumor material by ultrasound-guided core needle biopsy or surgery from melanoma patients with progressive disease and were able to isolate >5 × 10(6) TILs from 23 of 24 patients who were subsequently treated with these cells. One-third of the individual TIL-positive cultures displayed interferon gamma activity after stimulation with relevant melanoma cell lines. When expanded TILs were used for treatment in combination with daily low dose s.c. IL-2 after prior lymphodepleting chemotherapy, we observed objective clinical responses in one patient treated with TILs obtained from surgery and 4 patients treated with TILs from core biopsies. The results of this study demonstrate for the first time the potential of core biopsies for generation of relevant numbers of TILs that can mediate objective responses in patients with metastatic malignant melanoma. Ultrasound-guided core needle biopsy is a robust, safe and inexpensive approach to obtain tumor tissue for TIL generation, and is especially valuable in instances where surgery is contraindicated.

Keywords
Melanoma, Tumor-infiltrating lymphocyte, Adoptive cell therapy, Core needle biopsy
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-167979 (URN)10.1007/s00262-011-1182-4 (DOI)000303509600011 ()22202906 (PubMedID)
Available from: 2012-02-03 Created: 2012-02-03 Last updated: 2017-12-08Bibliographically approved
Bolander, Å., Wagenius, G., Larsson, A., Brattström, D., Ullenhag, G., Hesselius, P., . . . Bergqvist, M. (2007). The Role of Circulating Angiogenic Factors in Patients Operated on for Localized Malignant Melanoma. Anticancer Research, 27(5A), 3211-3217
Open this publication in new window or tab >>The Role of Circulating Angiogenic Factors in Patients Operated on for Localized Malignant Melanoma
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2007 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 27, no 5A, p. 3211-3217Article in journal (Refereed) Published
Abstract [en]

Malignant melanoma is a disease capable of rapid progression and rapidly developing metastases. Angiogenesis is a key event signalling tumour progression and elevated levels of angiogenic markers may indicate metastatic disease. No previously published work has, so far, examined plasma vascular endothelial growth factor (VEGF) and its receptor, VEGFR-1, in melanoma. This study investigated circulating levels of the angiogenic factors, VEGF-A and -D, their receptors 1-3 and hepatocyte growth factor (HGF)/scatter factor, in patients shortly after primary surgery for localized malignant melanoma. Elevated circulating levels of VEGF and its receptors, and of HGF, were found postoperatively, possibly derived from the reactive stroma adjacent to the tumours. Using univariate analysis, a correlation between levels of VEGFR-1 and relapse was found, but a correlation between the investigated angiogenic factors and survival could not be established. The results of the present study indicate that production of these angiogenic factors may be due to sources other than malignant melanoma cells.

Keywords
Malignant melanoma, angiogenesis, survival, relapse, vascular endothelial growth factor, hepatocyte growth factor, hepatocyte scatter factor
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-97931 (URN)000250266600022 ()17970063 (PubMedID)
Available from: 2008-12-22 Created: 2008-12-22 Last updated: 2017-12-14Bibliographically approved
Dreilich, M., Wanders, A., Brattström, D., Bergström, S., Hesselius, P., Wagenius, G. & Bergqvist, M. (2006). HER-2 overexpression (3+) in patients with squamous cell carcinoma correlates with poorer survival. Diseases of the esophagus, 19(4), 224-231
Open this publication in new window or tab >>HER-2 overexpression (3+) in patients with squamous cell carcinoma correlates with poorer survival
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2006 (English)In: Diseases of the esophagus, ISSN 1120-8694, E-ISSN 1442-2050, Vol. 19, no 4, p. 224-231Article in journal (Refereed) Published
Abstract [en]

The incidence of esophageal carcinoma is increasing worldwide. In Sweden, approximately 400 patients are diagnosed each year. The present study retrospectively investigates survival in 97 patients with esophageal carcinoma in regard to their HER-2 status as examined by immunohistochemistry (IHC) and chromogen in situ hybridization (CISH). Sixty-eight patients had localised disease and 29 patients had advanced disease. Seventy patients had squamous cell carcinoma, and nine of these patients (13%) had HER-2 overexpression (3+). Eight (30%) of 27 adenocarcinoma patients overexpressed (3+) HER-2. In patients overexpressing (3+) HER-2 a statistical trend towards poorer survival was observed (P = 0.057). In squamous cell carcinoma patients, HER-2 overexpression (3+) correlated with poorer survival (P = 0.035), whereas in adenocarcinoma patients, HER-2 status (3+) did not. HER-2 amplification according to CISH was present in five (two squamous cell carcinomas and three adenocarcinomas) out of 17 HER-2 overexpressing (3+) tumours. In conclusion, HER-2 overexpression (3+) seems to be associated with poorer survival in esophageal carcinomas, especially in patients with squamous cell esophageal carcinoma.

Keywords
Adenocarcinoma/genetics/metabolism/mortality/therapy, Aged, Esophageal Neoplasms/genetics/*metabolism/*mortality/therapy, Female, Gene Expression, Genes; erbB-2, Humans, Immunohistochemistry, In Situ Hybridization, Male, Neoplasm Metastasis, Neoplasms; Squamous Cell/genetics/*metabolism/*mortality/therapy, Radiation Tolerance, Receptor; erbB-2/*metabolism, Retrospective Studies, Survival Analysis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-94406 (URN)10.1111/j.1442-2050.2006.00570.x (DOI)16866851 (PubMedID)
Available from: 2006-04-28 Created: 2006-04-28 Last updated: 2017-12-14Bibliographically approved
Eriksson, P., Brattström, D., Hesselius, P., Larsson, A., Bergström, S., Ekman, S., . . . Bergqvist, M. (2006). Role of circulating cytokeratin fragments and angiogenic factors in NSCLC patients stage IIIa-IIIb receiving curatively intended treatment.. Neoplasma, 53(4), 285-90
Open this publication in new window or tab >>Role of circulating cytokeratin fragments and angiogenic factors in NSCLC patients stage IIIa-IIIb receiving curatively intended treatment.
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2006 (English)In: Neoplasma, ISSN 0028-2685, Vol. 53, no 4, p. 285-90Article in journal (Refereed) Published
Keywords
Carcinoma; Non-Small-Cell Lung/*diagnosis/therapy, Female, Fibroblast Growth Factor 2/*blood, Humans, Immunohistochemistry/methods, Keratins/*blood, Lung Neoplasms/*diagnosis/therapy, Male, Risk, Survival Analysis, Tumor Markers; Biological/*blood, Vascular Endothelial Growth Factor A/*blood
Identifiers
urn:nbn:se:uu:diva-21811 (URN)16830054 (PubMedID)
Available from: 2007-01-04 Created: 2007-01-04 Last updated: 2011-01-11
Dreilich, M., Wagenius, G., Bergström, S., Brattström, D., Larsson, A., Hesselius, P. & Bergqvist, M. (2005). The role of cystatin C and the angiogenic cytokines VEGF and bFGF in patients with esophageal carcinoma.. Med Oncol, 22(1), 29-38
Open this publication in new window or tab >>The role of cystatin C and the angiogenic cytokines VEGF and bFGF in patients with esophageal carcinoma.
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2005 (English)In: Med Oncol, ISSN 1357-0560, Vol. 22, no 1, p. 29-38Article in journal (Refereed) Published
Keywords
Cystatins/*blood, Esophageal Neoplasms/*blood/mortality, Female, Fibroblast Growth Factor 2/*blood, Humans, Male, Prognosis, Vascular Endothelial Growth Factor A/*blood
Identifiers
urn:nbn:se:uu:diva-21831 (URN)15750194 (PubMedID)
Available from: 2007-01-04 Created: 2007-01-04 Last updated: 2011-01-12
Dreilich, M., Bergström, S., Wagenius, G., Brattström, D. & Bergqvist, M. (2004). A retrospective study focusing on clinical predictive factors in 126 patients with oesophageal carcinoma.. Anticancer Res, 24(3b), 1915-20
Open this publication in new window or tab >>A retrospective study focusing on clinical predictive factors in 126 patients with oesophageal carcinoma.
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2004 (English)In: Anticancer Res, ISSN 0250-7005, Vol. 24, no 3b, p. 1915-20Article in journal (Other scientific) Published
Keywords
Aged, Esophageal Neoplasms/*drug therapy/pathology/*radiotherapy, Female, Humans, Male, Neoplasm Staging, Prognosis, Retrospective Studies, Risk Factors, Survival Rate, Treatment Outcome
Identifiers
urn:nbn:se:uu:diva-69920 (URN)15274376 (PubMedID)
Available from: 2005-04-12 Created: 2005-04-12 Last updated: 2011-01-12
Brattström, D., Bergqvist, M., Wester, K., Hesselius, P., Ren, Z.-P., Scheibenpflug, L., . . . Brodin, O. (2004). Endothelial markers and circulating angiogenic factors and p53 may be potential markers for recurrence in surgically resected non-small cell lung cancer patients.. Med Sci Monit, 10(9), BR331-8
Open this publication in new window or tab >>Endothelial markers and circulating angiogenic factors and p53 may be potential markers for recurrence in surgically resected non-small cell lung cancer patients.
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2004 (English)In: Med Sci Monit, ISSN 1234-1010, Vol. 10, no 9, p. BR331-8Article in journal (Other scientific) Published
Keywords
Adult, Aged, Aged; 80 and over, Angiogenic Proteins/*metabolism, Antigens; CD34/genetics/metabolism, Biological Markers, Carcinoma; Non-Small-Cell Lung/*metabolism/pathology/surgery, Endothelial Cells/*metabolism, Endothelium; Vascular/cytology/metabolism, Female, Humans, Lung Neoplasms/*metabolism/pathology/surgery, Male, Middle Aged, Prognosis, Protein p53/genetics/*metabolism, Recurrence, Research Support; Non-U.S. Gov't, Risk Factors, Statistics, Survival Rate, Vascular Cell Adhesion Molecule-1/genetics/metabolism
Identifiers
urn:nbn:se:uu:diva-69919 (URN)15328478 (PubMedID)
Available from: 2007-04-19 Created: 2007-04-19 Last updated: 2011-01-12
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