uu.seUppsala University Publications
Change search
Refine search result
1 - 48 of 48
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 1.
    Bergqvist, Michael
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Brattström, Daniel
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Larsson, Anders
    Department of Medical Sciences. klinisk kemi.
    Hesselius, Patrik
    Brodin, Ola
    Wagenius, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enh för onkologi.
    The role of circulating anti-p53 antibodies in patients with advanced non-small cell lung cancer and their correlation to clinical parameters and survival.2004In: BMC Cancer, ISSN 1471-2407, Vol. 4, no 1, 66- p.Article in journal (Refereed)
  • 2.
    Bergqvist, Michael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Umea Univ, Dept Radiat Sci, Umea, Sweden.
    Holgersson, Georg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Bondarenko, Igor
    Grechanaya, Elena
    Maximovich, Alexey
    Andor, György
    Klockare, Maria
    Thureson, Marcus
    Jerling, Markus
    Harmenberg, Johan
    Phase II randomized study of the IGF-1R pathway modulator AXL1717 compared to docetaxel in patients with previously treated, locally advanced or metastatic non-small cell lung cancer2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 3, 441-447 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The primary objective of this study was to compare the progression-free survival (PFS) at 12 weeks between patients treated with IGF-1R pathway modulator AXL1717 (AXL) and patients treated with docetaxel (DCT).

    MATERIAL AND METHODS: The study was conducted at 19 study centers in five countries. A total of 99 patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) of the squamous cell carcinoma (SCC) or adenocarcinoma (AC) subtypes in need of additional treatment were randomized and treated with either 300 or 400 mg of AXL as daily BID treatment (58 patients) or DCT given as 75 mg/m(2) in three-week cycles (41 patients) as monotherapy in a 3:2 ratio for each NSCLC subtype. Patients were treated in the primary study treatment period for a maximum of four treatment cycles.

    RESULTS: The 12-week PFS rate, median PFS and overall survival (OS), as well Kaplan-Meier hazard ratio for PFS and OS, did not show any statistically significant differences between the treatment groups. For the primary endpoint, the AXL group had a lower percentage of patients (25.9%) who were progression-free at Week 12 as compared to the DCT group (39.0%), although the difference was not statistically significant. The most notable difference in the incidence of treatment emergent adverse effects (TEAEs) was the lower incidence of treatment-related grade 3/4 neutropenia in patients treated with AXL.

    CONCLUSION: These results suggest neither of the treatments to be superior of the other when treating locally advanced or metastatic NSCLC. Considering the lower incidence of grade 3/4 neutropenia in the AXL group this treatment warrants further research.

  • 3.
    Bergqvist, Michael
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    O, Brodin
    Linder, Arne
    Department of Surgical Sciences.
    A, Hesselius
    Blomquist, Erik
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Radiation treatment of T1-T4 squamous cell carcinoma of the larynx: a retrospective analysis and long-term follow-up of 135 patients2002In: Anticancer, ISSN Mar-Apr;22(2B):1239-42, Vol. 22, 1239-42 p.Article in journal (Refereed)
  • 4.
    Bergström, Stefan
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Dreilich, Martin
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Wagenius, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enh för onkologi.
    Brattström, Daniel
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Larsson, Anders
    Department of Medical Sciences. klinisk kemi.
    Hesselius, Patrik
    Bergqvist, Michael
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enh för onkologi.
    The presence of anti-p53 antibodies in sera from patients with oesophageal carcinoma: correlation to treatment, tumour volume and survival.2004In: In Vivo, ISSN 0258-851X, Vol. 18, no 5, 615-20 p.Article in journal (Refereed)
  • 5.
    Blomberg, Carl
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Nilsson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Holgersson, Georg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Edlund, Per
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Adwall, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Brattström, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Randomized Trials of Systemic Medically-treated Malignant Mesothelioma: A Systematic Review2015In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 5, 2493-2501 p.Article, review/survey (Refereed)
    Abstract [en]

    Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy mainly localized to the pleura. Malignant mesothelioma grows highly invasive into surrounding tissue and has a low tendency to metastasize. The median overall survival (OS) of locally advanced or metastatic disease without treatment is 4-13 months but, during recent years, improvement in survival has been achieved since treatment for patients with mesothelioma has improved with better palliative care, systemic medical treatment, surgery and improved diagnostics methods. The present review aims at describing available data from randomized trials considering systemic medical treatment for this patient category.

  • 6.
    Bolander, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Agnarsdóttir, Margrét
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Strömberg, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Hesselius, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Uhlen, Mathias
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    The protein expression of TRP-1 and galectin-1 in cutaneous malignant melanomas2008In: Cancer Genomics & Proteomics, ISSN 1109-6535, E-ISSN 1790-6245, Vol. 5, no 6, 293-300 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients with metastazing malignant melanoma have a poor outcome and determination of thickness of the primary tumor remains as the most important prognostic predictor. The aim of this study was to use an antibody-based proteomics strategy to search for new molecular markers associated with melanoma progression. Two proteins, TRP-1 and galectin-1, were identified as proteins with enhanced expression in cells from the melanocytic lineage. PATIENTS AND METHODS: Protein profiling of TRP-1 and galectin-1 together with proliferation marker Ki-67 and melanocyte marker Melan-A was performed in normal tissues from 144 individuals and in 216 different tumors using tissue microarrays and immunohistochemistry. The protein expression pattern was further analyzed in a defined cohort of 157 patients diagnosed with invasive cutaneous malignant melanoma. RESULTS: Both TRP-1 and galectin-1 were highly expressed in normal melanocytes and melanoma. The expression of TRP-1 was inversely correlated with tumor stage (p=0.002, (R=-0.28)). Neither TRP-1 or galectin-1 was associated with overall or disease free survival (p>0.14, p>0.46 respectively). Ki-67 was associated with tumor stage and survival (p<0.001). CONCLUSION: TRP-1 and galectin-1 protein expression patterns were determined in normal and cancer tissues and both proteins were expressed in the majority of the malignant melanomas. There was no correlation between TRP-1 or galectin-1 expression and survival.

  • 7.
    Bolander, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Wagenius, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Brattström, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ullenhag, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Hesselius, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The Role of Circulating Angiogenic Factors in Patients Operated on for Localized Malignant Melanoma2007In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 27, no 5A, 3211-3217 p.Article in journal (Refereed)
    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.

  • 8.
    Botling, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Edlund, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Lohr, Miriam
    Hellwig, Birte
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lambe, Mats
    Berglund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    König, André
    Fernandes, Oswaldo
    Karlsson, Mats
    Helenius, Gisela
    Karlsson, Christina
    Rahnenführer, Jörg
    Hengstler, Jan G
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Biomarker discovery in non-small cell lung cancer: integrating gene expression profiling, meta-analysis and tissue microarray validation2013In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 19, no 1, 194-204 p.Article in journal (Refereed)
    Abstract [en]

    Background:

    Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multi-gene signatures in clinical practice is unclear and the biological importance of individual genes is difficult to assess as the published signatures virtually do not overlap

    Methods:

    Here we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data was used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level p<0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n=860).

    RESULTS:

    The meta-analysis revealed 14 genes that were significantly associated with survival (p<0.001) with a false discovery rate <1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from two independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup.

    CONCLUSIONS:

    Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics.

  • 9.
    Brattström, Daniel
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enh för onkologi.
    Bergqvist, Michael
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enh för onkologi.
    Wester, Kenneth
    Department of Genetics and Pathology.
    Hesselius, Patrik
    Ren, Zhi-Ping
    Department of Genetics and Pathology.
    Scheibenpflug, Lena
    Department of Genetics and Pathology.
    Wagenius, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enh för onkologi.
    Brodin, Ola
    Endothelial markers and circulating angiogenic factors and p53 may be potential markers for recurrence in surgically resected non-small cell lung cancer patients.2004In: Med Sci Monit, ISSN 1234-1010, Vol. 10, no 9, BR331-8 p.Article in journal (Other scientific)
  • 10.
    Brattström, Daniel
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enh för onkologi.
    Wester, Kenneth
    Department of Genetics and Pathology.
    Bergqvist, Michael
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enh för onkologi.
    Hesselius, Patrik
    Malmström, Per-Uno
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Department of Surgical Sciences. BMS.
    Nordgren, Hans
    Wagenius, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enh för onkologi.
    Brodin, Ola
    HER-2, EGFR, COX-2 expression status correlated to microvessel density and survival in resected non-small cell lung cancer.2004In: Acta Oncol, ISSN 0284-186X, Vol. 43, no 1, 80-6 p.Article in journal (Refereed)
  • 11.
    Byström, Sanna
    et al.
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Fredolini, Claudia
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Edqvist, Per-Henrik D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nyaiesh, Etienne-Nicholas
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Drobin, Kimi
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Uhlen, Mathias
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gavle Sjukhus, S-80188 Gavle, Sweden.;Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden..
    Ponten, Fredrik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Schwenk, Jochen M.
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Affinity Proteomics Exploration of Melanoma Identifies Proteins in Serum with Associations to T-Stage and Recurrence2017In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 10, no 3, 385-395 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Blood-based proteomic profiling may aid and expand our understanding of diseases and their different phenotypes. The aim of the presented study was to profile serum samples from patients with malignant melanoma using affinity proteomic assays to describe proteins in the blood stream that are associated to stage or recurrence of melanoma. MATERIAL AND METHODS: Multiplexed protein analysis was conducted using antibody suspension bead arrays. A total of 232 antibodies against 132 proteins were selected from (i) a screening with 4595 antibodies and 32 serum samples from melanoma patients and controls, (ii) antibodies used for immunohistochemistry, (iii) protein targets previously related with melanoma. The analysis was performed with 149 serum samples from patients with malignant melanoma. Antibody selectivity was then assessed by Western blot, immunocapture mass spectrometry, and epitope mapping. Lastly, indicative antibodies were applied for IHC analysis of melanoma tissues. RESULTS: Serum levels of regucalcin (RGN) and syntaxin 7 (STX7) were found to be lower in patients with both recurring tumors and a high Breslow's thickness (T-stage 3/4) compared to low thickness (T-stage 1/2) without disease recurrence. Serum levels of methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) were instead elevated in sera of T3/4 patients with recurrence. The analysis of tissue sections with S100A6 and MTHFD1L showed positive staining in a majority of patients with melanoma, and S100A6 was significantly associated to T-stage. CONCLUSIONS: Our findings provide a starting point to further study RGN, STX7, MTHFD1L and S100A6 in serum to elucidate their involvement in melanoma progression and to assess a possible contribution to support clinical indications.

  • 12.
    Dreilich, Martin
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enh för onkologi.
    Bergström, Stefan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enh för onkologi.
    Wagenius, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enh för onkologi.
    Brattström, Daniel
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enh för onkologi.
    Bergqvist, Michael
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enh för onkologi.
    A retrospective study focusing on clinical predictive factors in 126 patients with oesophageal carcinoma.2004In: Anticancer Res, ISSN 0250-7005, Vol. 24, no 3b, 1915-20 p.Article in journal (Other scientific)
  • 13. Dreilich, Martin
    et al.
    Wagenius, Gunnar
    Bergström, Stefan
    Brattström, Daniel
    Larsson, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Hesselius, Patrik
    Bergqvist, Michael
    Department of Oncology, Radiology and Clinical Immunology.
    The role of cystatin C and the angiogenic cytokines VEGF and bFGF in patients with esophageal carcinoma.2005In: Med Oncol, ISSN 1357-0560, Vol. 22, no 1, 29-38 p.Article in journal (Refereed)
  • 14.
    Dreilich, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Brattström, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Hesselius, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Wagenius, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    HER-2 overexpression (3+) in patients with squamous cell carcinoma correlates with poorer survival2006In: Diseases of the esophagus, ISSN 1120-8694, E-ISSN 1442-2050, Vol. 19, no 4, 224-231 p.Article in journal (Refereed)
    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.

  • 15.
    Edlund, Karolina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Lindskog, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Saito, Akira
    Berglund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Göransson-Kultima, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Isaksson, Anders
    Jirström, Karin
    Planck-Sturegård, Maria
    Johansson, Leif
    Lambe, Mats
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Nyberg, Fredrik
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Landelius, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Lamberg, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Östman, Arne
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    CD99 is a novel prognostic stromal marker in non-small cell lung cancer2012In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 131, no 10, 2264-2273 p.Article in journal (Refereed)
    Abstract [en]

    The complex interaction between cancer cells and the microenvironment plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumour-stroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer (NSCLC). A list encompassing 203 stromal candidate genes was compiled based on gene expression array data and available literature. The protein expression of these genes in human NSCLC was screened using the Human Protein Atlas. Twelve proteins were selected that showed a differential stromal staining pattern (BGN, CD99, DCN, EMILIN1, FBN1, PDGFRB, PDLIM5, POSTN, SPARC, TAGLN, TNC, VCAN). The corresponding antibodies were applied on tissue microarrays, including 190 NSCLC samples, and stromal staining was correlated with clinical parameters. Higher stromal expression of CD99 was associated with better prognosis in the univariate (p=0.037) and multivariate (p=0.039) analysis. The association was independent from the proportion of tumour stroma, the fraction of inflammatory cells, and clinical and pathological parameters like stage, performance status and tumour histology. The prognostic impact of stromal CD99 protein expression was confirmed in an independent cohort of 240 NSCLC patients (p=0.008). Furthermore, double-staining confocal fluorescence microscopy showed that CD99 was expressed in stromal lymphocytes as well as in cancer associated fibroblasts. Based on a comprehensive screening strategy the membrane protein CD99 was identified as a novel stromal factor with clinical relevance. The results support the concept that stromal properties have an important impact on tumour progression.

  • 16.
    Ekman, Simon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Heldin, Carl-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Lennartsson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Activation of growth factor receptors in esophageal cancer: implications for therapy2007In: The Oncologist, ISSN 1083-7159, E-ISSN 1549-490X, Vol. 12, no 10, 1165-1177 p.Article, review/survey (Refereed)
    Abstract [en]

    Esophageal cancer is a highly aggressive disease and is the seventh most common cause of cancer-related death in the western world. Worldwide, it ranks as the sixth most frequent cause of cancer death. Despite advances in surgical techniques and treatment, the prognosis of esophageal cancer remains poor, with very few long-term survivors. The need for novel strategies to detect esophageal cancer earlier and to improve current therapy is urgent. It is well established that growth factors and growth factor receptor-mediated signaling pathways are important components of the transformation process in many forms of cancer, including esophageal cancer. With the recent advances in drug development, there are emerging possibilities to use growth factor signal transduction pathways in targeted therapy. This review provides a summary of the role of growth factors and their receptors in esophageal cancer and discusses their potential roles as biomarkers and as targets in therapy.

  • 17.
    Ekman, Simon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Eriksson, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Johansson, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Goike, Helena
    Gullbo, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Henriksson, Roger
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Clinical value of using serological cytokeratins as therapeutic markers in thoracic malignancies2007In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 27, no 5B, 3545-3553 p.Article, review/survey (Refereed)
    Abstract [en]

    In recent years, there has been an increasing awareness among physicians of the value of therapeutic interventions in patients suffering from lung cancer and mesothelioma. A search for an optimal approach using surgery, irradiation and chemotherapy in different settings of the tumour disease, including curatively aimed adjuvant chemotherapy after locoregional surgery or radiotherapy, has resulted in gradually improved survival rates. Still, early detection is crucial if there is to be a possibility of curing patients or prolonging life in cases of relapsed disease. Several studies have been initiated in which surrogate markers are evaluated in comparison to chest X-rays and computer tomography. The present review focuses on the predictive and prognostic value of using serological cytokeratins as tumour markers for patients suffering from thoracic malignancies.

  • 18.
    Elsir, Tamador
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Edqvist, Per-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Carlson, Joseph
    Ribom, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Popova, Svetlana N
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nistér, Monica
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    A study of embryonic stem cell-related proteins in human astrocytomas: Identification of Nanog as a predictor of survival2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, no 5, 1123-1131 p.Article in journal (Refereed)
    Abstract [en]

    Recent studies suggest that the regulatory networks controlling the functions of stem cells during development may be abnormally active in human cancers. An embryonic stem cell (ESC) gene signature was found to correlate with a more undifferentiated phenotype of several human cancer types including gliomas, and associated with poor prognosis in breast cancer. In the present study, we used tissue microarrays of 80 low-grade (WHO grade II) and 98 high-grade human gliomas (WHO grade III and IV) to investigate the presence of the ESC-related proteins Nanog, Klf4, Oct4, Sox2 and c-Myc by immunohistochemistry. While similar patterns of co-expressed proteins between low- and high-grade gliomas were present, we found up-regulated protein levels of Nanog, Klf4, Oct4 and Sox2 in high-grade gliomas. Survival analysis by Kaplan-Meier analysis revealed a significant shorter survival in the subgroups of low-grade astrocytomas (n=42) with high levels of Nanog protein (p=0.0067) and of Klf4 protein (p=0.0368), in high-grade astrocytomas (n=85) with high levels of Nanog (p=0.0042), Klf4 (p=0.0447), and c-Myc (p=0.0078) and in glioblastomas only (n=71) with high levels of Nanog (p=0.0422) and of c-Myc (p= 0.0256). In the multivariate model, Nanog was identified as an independent prognostic factor in the subgroups of low-grade astrocytomas (p=0.0039), high-grade astrocytomas (p=0.0124) and glioblastomas only (p=0.0544), together with established clinical variables in these tumors. These findings provide further evidence for the joint regulatory pathways of ESC-related proteins in gliomas and identify Nanog as one of the key players in determining clinical outcome of human astrocytomas.

  • 19. Eriksson, P
    et al.
    Brattström, Daniel
    Hesselius, P
    Larsson, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Bergström, S
    Ekman, Simon
    Goike, Helena
    Wagenius, Gunnar
    Brodin, Ola
    Bergqvist, Michael
    Role of circulating cytokeratin fragments and angiogenic factors in NSCLC patients stage IIIa-IIIb receiving curatively intended treatment.2006In: Neoplasma, ISSN 0028-2685, Vol. 53, no 4, 285-90 p.Article in journal (Refereed)
  • 20. Garpenstrand, Håkkan
    et al.
    Bergqvist, Michael
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Brattström, Daniel
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Larsson, Anders
    Department of Medical Sciences. klinisk kemi.
    Oreland, Lars
    Hesselius, Patrik
    Wagenius, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Serum semicarbazide-sensitive amine oxidase (SSAO) activity correlates with VEGF in non-small-cell lung cancer patients.2004In: Med Oncol, ISSN 1357-0560, Vol. 21, no 3, 241-50 p.Article in journal (Refereed)
  • 21. Hellman, Björn
    et al.
    Brodin, David
    Andersson, Maria
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Dahlman-Wright, Karin
    Isacsson, Ulf
    Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Onkologi.
    Brattstrom, Daniel
    Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Onkologi.
    Bergqvist, Michael
    Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Onkologi.
    Radiation-induced DNA-damage and gene expression profiles in human lung cancer cells with different radiosensitivity.2005In: Exp Oncol, ISSN 1812-9269, Vol. 27, no 2, 102-7 p.Article in journal (Refereed)
  • 22.
    Holgersson, Georg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nyman, Jan
    Hoye, Even
    Helsing, Martin
    Friesland, Signe
    Holgersson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ekberg, Lars
    Morth, Charlotte
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Blystad, Thomas
    Ewers, Sven-Borje
    Loden, Britta
    Henriksson, Roger
    Bergstrom, Stefan
    The impact of hyperfractionated radiotherapy regimen in patients with non-small cell lung cancer2013In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 30, no 1, 320- p.Article in journal (Refereed)
    Abstract [en]

    The prognosis for patients with lung cancer is poor with an average of 5-year overall survival rate of only 10-15 % taking all clinical stages together. The aim of this study was to elucidate the impact of the radiotherapy regimen on survival. Clinical data were collected from all the Swedish Oncology Departments for 1,287 patients with a diagnosed non-small cell lung cancer (NSCLC) subjected to curatively intended irradiation (>= 50 Gy) during the years 1990 to 2000. The included patients were identified based on a manual search of all medical and radiation charts at the oncology departments from which the individual patient data were collected. Patients who did not have a histopathological diagnosis date and/or death date/last follow-up date as well as patients being surgically treated were excluded from the study (n = 592). Thus, 695 patients were included in the present study. Patients who received hyperfractionated radiotherapy (HR) had a higher local control rate compared with patients receiving conventional fractionation (CF) (38 vs. 49 % local relapse). The difference in survival between the two radiotherapy regimens was statistically significant in a univariate Cox analysis (p = 0.023) in favor of HR. This significance was, however, not retained in a multivariate Cox analysis (p = 0.56). Thus, the possible beneficial effects of hyperfractionation are still unclear and need to be further investigated in well-controlled prospective clinical trials, preferably including systemic treatment with novel drugs.

  • 23.
    Holgersson, Georg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nyman, Jan
    Hoye, Even
    Helsing, Martin
    Friesland, Signe
    Holgersson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Birath, Elisabet
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Blystad, Thomas
    Ewers, Sven-Borje
    Morth, Charlotte
    Loden, Britta
    Henriksson, Roger
    Swedish Lung Cancer Radiation Study Group: Predictive value of histology for radiotherapy response in patients with non-small cell lung cancer2011In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 47, no 16, 2415-2421 p.Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to evaluate the potential predictive value of histology in non-small cell lung cancer (NSCLC) treated with curatively intended radiotherapy. In a collaborative effort among all the Swedish Oncology Departments, clinical data were collected for 1146 patients with a diagnosed non-small cell lung cancer subjected to curatively intended irradiation (>= 50 Gy) during the years 1990 to 2000. The included patients were identified based on a manual search of all medical and radiation charts at the oncology departments from which the individual patient data were collected. Only patients who did not have a histological diagnosis date and death date/last follow-up date were excluded (n = 141). Among the 1146 patients with non-small cell carcinoma eligible for analysis, 919 were diagnosed with either adenocarcinoma (n = 323) or squamous cell carcinoma (n = 596) and included in this study. The median survival for the 919 patients was 14.8 months, while the 5-year survival rate was 9.5%. Patients with adenocarcinoma had a significantly better overall survival compared with patients with squamous cell carcinoma (p = 0.0062, log-rank test). When comparing different stages, this survival benefit was most pronounced for stages IIA-IIB (p<0.0001, log-rank test). The difference in survival between the two histological groups was statistically significant in a univariate Cox analysis (p = 0.0063) as well as in two multivariate Cox analyses including demographic and treatment variables (p = 0.037 and p = 0.048, respectively). In this large population based retrospective study we describe for the first time that patients with adenocarcinoma have a better survival after curatively intended radiation therapy in comparison with squamous cell carcinoma patients, particularly those with clinical stages IIA-IIB.

  • 24.
    Holgersson, Georg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala Univ Hosp, Dept Immunol Genet & Pathol.
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala Univ Hosp, Dept Immunol Genet & Pathol.
    Hallqvist, A.
    Sahlgrens Univ Hosp, Dept Oncol.
    Liv, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Nilsson, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Umeå Univ Hosp, Dept Radiat Sci & Oncol.
    Willen, L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Umeå Univ Hosp, Dept Radiat Sci & Oncol.
    Nyman, J.
    Sahlgrens Univ Hosp, Dept Oncol.
    Ekman, S.
    Karolinska Univ Hosp, Dept Oncol.
    Henriksson, R.
    Umeå Univ Hosp, Dept Radiat Sci & Oncol.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Umeå Univ Hosp, Dept Radiat Sci & Oncol.
    The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy2017In: Neoplasma (Bratislava), ISSN 0028-2685, E-ISSN 1338-4317, Vol. 64, no 6, 909-915 p.Article in journal (Refereed)
    Abstract [en]

    Chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC). This treatment, however, offers only a small chance of cure and is associated with many side effects. Little research has been made concerning which patients benefit most/least from the treatment. The present study evaluates the prognostic value of anemia, leukocytosis and thrombocytosis at diagnosis in this treatment setting. In the present study, data were collected retrospectively for 222 patients from two different phase II studies conducted between 2002-2007 in Sweden with patients treated with chemoradiotherapy for stage IIIA-IIIB NSCLC. Clinical data and the serum values of hemoglobin (Hgb), White blood cells (WBC) and Platelets (Plt) at enrollment were collected for all patients and studied in relation to overall survival using Kaplan-Meier product-limit estimates and a multivariate Cox proportional hazards regression model.

    The results showed that patients with thrombocytosis (Plt > 350 x 109/L) had a shorter median overall survival (14.5 months) than patients with normal Plt at baseline (23.7 months). Patients with leukocytosis (WBC > 9 x 109/L) had a shorter median survival (14.9 months) than patients with a normal WBC at baseline (22.5 months). However, in a multivariate model including all lab parameters and clinical factors, only thrombocytosis and performance status displayed a prognostic significance.

    In Conclusion, thrombocytosis showed to be an independent prognostic marker associated with shorter overall survival in stage III NSCLC treated with curatively intended chemoradiotherapy. This knowledge can potentially be used together with established prognostic factors, such as performance status when choosing the optimal therapy for the individual patient in this clinical setting.

  • 25.
    Holgersson, Georg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gavle Cent Hosp, Dept Oncol, SE-80187 Gavle, Sweden..
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gavle Cent Hosp, Dept Oncol, SE-80187 Gavle, Sweden..
    Liv, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Nilsson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gavle Cent Hosp, Dept Oncol, SE-80187 Gavle, Sweden..
    Edlund, Per
    Gavle Cent Hosp, Dept Oncol, SE-80187 Gavle, Sweden..
    Blomberg, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gavle Cent Hosp, Dept Oncol, SE-80187 Gavle, Sweden..
    Nyman, Jan
    Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden..
    Friesland, Signe
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden..
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Asklund, Thomas
    Umea Univ Hosp, Dept Radiat Sci & Oncol, S-90185 Umea, Sweden..
    Henriksson, Roger
    Umea Univ Hosp, Dept Radiat Sci & Oncol, S-90185 Umea, Sweden..
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Umea Univ Hosp, Dept Radiat Sci & Oncol, S-90185 Umea, Sweden..
    Effect of Increased Radiotoxicity on Survival of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Radiotherapy2015In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 10, 5491-5497 p.Article in journal (Refereed)
    Abstract [en]

    Aim: To elucidate the impact of different forms of radiation toxicities (esophagitis, radiation pneumonitis, mucositis and hoarseness), on the survival of patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). Patients and Methods: Data were individually collected retrospectively for all patients diagnosed with NSCLC subjected to curatively intended radiotherapy (>= 50 Gy) in Sweden during the time period 1990 to 2000. Results: Esophagitis was the only radiation-induced toxicity with an impact on survival (hazard ratio=0.83, p=0.016). However, in a multivariate model, with clinical-and treatment-related factors taken into consideration, the impact of esophagitis on survival was no longer statistically significant (hazard ratio=0.88, p=0.17). Conclusion: The effect on survival seen in univariate analysis may be related to higher radiation dose and to the higher prevalence of chemotherapy in this group. The results do not suggest that the toxicities examined have any detrimental effect on overall survival.

  • 26.
    Holgersson, Georg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Hoye, Even
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nyman, Jan
    Helsing, Martin
    Friesland, Signe
    Holgersson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ekberg, Lars
    Blystad, Thomas
    Ewers, Sven-Borje
    Morth, Charlotte
    Loden, Britta
    Henriksson, Roger
    Bergstrom, Stefan
    Swedish Lung Cancer Radiation Study Group: Predictive value of age at diagnosis for radiotherapy response in patients with non-small cell lung cancer2012In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 6, 759-767 p.Article in journal (Refereed)
    Abstract [en]

    Introduction. The aim of the present study was to investigate the impact of age at diagnosis on prognosis in patients treated with curatively intended radiotherapy for NSCLC.

    Material and methods. This is a joint effort among all the Swedish Oncology Departments that includes all identified patients with a diagnosed non-small cell lung cancer that have been subjected to curatively intended irradiation (>= 50 Gy) treated during 1990 to 2000. Included patients had a histopathological/cytological diagnosis date as well as a death date or a last follow-up date. The following variables were studied in relation to overall and disease-specific survival: age, gender, histopathology, time period, smoking status, stage and treatment.

    Results. The median overall survival of all 1146 included patients was 14.7 months, while the five-year overall survival rate was 9.5%. Younger patients (<55 years), presented with a more advanced clinical stage but had yet a significantly better overall survival compared with patients in the age groups 55-64 years (p = 0.035) and 65-74 years (p = 0.0097) in a multivariate Cox regression analysis. The overall survival of patients aged >= 75 years was comparable to those aged <55 years.

    Conclusion. In this large retrospective study we describe that patients younger than 55 years treated with curatively intended radiotherapy for NSCLC have a better overall survival than patients aged 55-64 and 65-74 years and that younger patients seem to benefit more from the addition of surgery and/or chemotherapy to radiotherapy. Due to the exploratory nature of the study, these results should be confirmed in future prospective trials.

  • 27.
    Holgersson, Georg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Hoye, Even
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Henriksson, Roger
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nyman, Jan
    Helsing, Martin
    Friesland, Signe
    Brodin, Ola
    Holgersson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lamberg Lundström, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Ekberg, Lars
    Morth, Charlotte
    Blystad, Thomas
    Ewers, Sven-Borje
    Loden, Britta
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    The Value of Induction Chemotherapy for Survival in Patients with Non-small Cell Lung Cancer Treated with Radiotherapy2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 4, 1339-1346 p.Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of the present study was to retrospectively investigate the impact of induction chemotherapy on treatment outcome in patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). Patients and Methods: Patients with a diagnosed NSCLC that have been subjected to curatively intended irradiation (>= 50 Gy) and treated in an oncology department in Sweden during the years 1990-2000 were included in the study. Operated patients and patients having received concomitant chemotherapy were excluded. The included patients were localised by a manual search of all the oncology departments' medical records and radiation charts. Results: Patients treated with induction chemotherapy (n=79) had a significantly better overall survival compared with patients treated with radiotherapy alone (p=0.0097) in a univariate Cox regression analysis. A platinum/taxane combination produced the greatest survival benefit; hazard ratio=0.49 (95% confidence interval=0.31 to 0.75). Conclusion: We found that patients treated with induction chemotherapy in addition to radiotherapy for NSCLC have a better overall survival than patients treated with radiotherapy alone and that the best results are achieved using a platinum/taxane combination.

  • 28.
    Holgersson, Georg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Hoye, Even
    Bergström, Stefan
    Henriksson, Roger
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nyman, Jan
    Helsing, Martin
    Friesland, Signe
    Holgersson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lamberg, Kristina Lundström
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Birath, Elisabet
    Mörth, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Blystad, Thomas
    Ewers, Sven-Börje
    Löden, Britta
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Swedish lung cancer radiation study group: the prognostic value of anaemia, thrombocytosis and leukocytosis at time of diagnosis in patients with non-small cell lung cancer2012In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 29, no 5, 3176-3182 p.Article in journal (Refereed)
    Abstract [en]

    There is a need to improve the prognostic and predictive indicators in non-small cell lung cancer (NSCLC). At present, the main focus is on genetic predictive markers while the prognostic value of the standard blood variables related to haematopoiesis has been subjected to relatively limited attention. To study the prognostic potential of haemoglobin (Hgb), platelet (Plt) and white blood cell (WBC) levels at time of diagnosis in NSCLC patients, 835 NSCLC patients, stage I-IV, who received radiotherapy with curative intention (> 50 Gy), were included in the study. WBC, Plt, Hgb, gender, age at diagnosis, stage, surgery and first-line chemotherapy were studied in relation to overall survival. For patients with Hgb < 110 g/L and Hgb a parts per thousand yen 110 g/L), the median survival was 11.2 and 14.5 months, respectively (p = 0.0032). For WBC > 9.0 x 10(9)/L and < 9.0 x 10(9)/L, the median survival was 11.6 and 15.4 months, respectively (p < 0.0001). For Plt > 350 x 10(9)/L and < 350 x 10(9)/L, the median survival was 11.2 and 14.9 months, respectively (p < 0.0001). The median survival in patients with pathological results in all three markers was half of that in patients with normal levels of all three markers (8.0 and 16.0 months, respectively (p < 0.0001). The level of the three studied haematological biomarkers corresponds significantly to outcome in NSCLC. These results indicate that standard haematological variables may be used as guidance for the clinician in the decision-making regarding treatment intensity and patient information.

  • 29.
    Johansson, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Henriksson, Roger
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    A Review of Dose-dense Temozolomide Alone and in Combination with Bevacizumab in Patients with First Relapse of Glioblastoma2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 9, 4001-4006 p.Article, review/survey (Refereed)
    Abstract [en]

    Treatment of patients with glioblastoma improved dramatically when concomitant and adjuvant temozolomide was added to external radiation therapy. The addition of this new treatment schedule as well as the improvements in individually-tailored radiation treatment, has resulted in a larger proportion of patients being fit for further treatment after first relapse. One of the most interesting combinations that have started to become part of the therapeutic arsenal in the daily clinic is dose-dense temozolomide in combination with bevacizumab. We reviewed and compiled the literature concerning the present topic based on a search of the PubMed database (http://www.ncbi.nlm.nih.gov/pubmed/) for the years between 1995 and 2011. The clinical studies that have been performed are small and divergent, making it difficult to grade the scientific evidence for the combinatorial treatment of dose-dense temozolomide and bevacizumab. However, the available studies and the experience we have at our departments suggest that this combination is of interest for glioblastoma patients experiencing first relapse. More randomized clinical trials are needed in order to establish the standard of treatment at first relapse in patients with glioblastoma.

  • 30.
    Lohr, Miriam
    et al.
    Department of Statistics, Technical University Dortmund, Germany.
    Edlund, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Hammad, Seddik
    Leibniz Research Centre for Working Environment and Human Factors (IfADo) at Dortmund TU, Dortmund, Germany.
    Hellwig, Birte
    Department of Statistics, Technical University Dortmund, Germany.
    Othman, Amnah
    Leibniz Research Centre for Working Environment and Human Factors (IfADo) at Dortmund TU, Dortmund, Germany.
    Berglund, Anders
    Lambe, Mats
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Cadenas, Cristina
    Leibniz Research Centre for Working Environment and Human Factors (IfADo) at Dortmund TU, Dortmund, Germany.
    Marchan, Rosemarie
    Leibniz Research Centre for Working Environment and Human Factors (IfADo) at Dortmund TU, Dortmund, Germany.
    Hengstler, Jan G.
    Leibniz Research Centre for Working Environment and Human Factors (IfADo) at Dortmund TU, Dortmund, Germany.
    Rahnenfuhrer, Jörg
    Department of Statistics, Technical University Dortmund, Germany.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    The prognostic relevance of tumour-infiltrating plasma cells and immunoglobulin kappa C indicates an important role of the humoral immune response in non-small cell lung cancer2013In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 333, no 2, 222-228 p.Article in journal (Refereed)
    Abstract [en]

    A prognostic impact of immunoglobulin kappa C (IGKC) expression has been described in cancer. We analysed the influence of B-cell and plasma cell markers, as well as IGKC expression, in non-small lung cancer (NSCLC) using immunohistochemistry on a tissue microarray. IGKC protein expression was independently associated with longer survival, with particular impact in the adenocarcinoma subgroup. Moreover, a correlation was seen with CD138+ cells, but not with CD20. CD138 expression revealed a comparable association with survival. In conclusion, IGKC expression in stroma–infiltrating plasma cells is a prognostic marker in NSCLC, supporting emerging treatment concepts that exploit the humoral immune response.

  • 31.
    Micke, Patrick
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Edlund, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Göransson Kultima, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Scheibenflug, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Lamberg, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Myrdal, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Berglund, Anders
    Andersson, Annsofie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lambe, Mats
    Nyberg, Fredrik
    Thomas, Andrew
    Isaksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Gene Copy Number Aberrations Are Associated with Survival in Histologic Subgroups of Non-small Cell Lung Cancer2011In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 6, no 11, 1833-1840 p.Article in journal (Refereed)
    Abstract [en]

    Introduction:

    Non-small cell lung cancer (NSCLC) is characterized by a multitude of genetic aberrations with unknown clinical impact. In this study, we aimed to identify gene copy number changes that correlate with clinical outcome in NSCLC. To maximize the chance to identify clinically relevant events, we applied a strategy involving two prognostically extreme patient groups.

    Methods:

    Short-term (<20 month; n = 53) and long-term survivors (>58 month; n = 47) were selected from a clinically well-characterized NSCLC patient cohort with available fresh frozen tumor specimens. The samples were analyzed using high-resolution single-nucleotide polymorphism array technology to assess gene copy number variations and array-based gene expression profiling. The molecular data were combined with information on clinical parameters.

    Results:

    Genetic aberrations were strongly associated with tumor histology. In adenocarcinoma (n = 50), gene copy number gains on chromosome 8q21-q24.3 (177 genes) were more frequent in long-term than in short-term survivors. In squamous cell carcinoma (n = 28), gains on chromosome 14q23.1-24.3 (133 genes) were associated with shorter survival, whereas losses in a neighboring region, 14q31.1-32.33 (110 genes), correlated with favorable outcome. In accordance with copy number gains and losses, messenger RNA expression levels of corresponding genes were increased or decreased, respectively.

    Conclusion:

    Comprehensive tumor profiling permits the integration of genomic, histologic, and clinical data. We identified gene copy number gains and losses, with corresponding changes in messenger RNA levels that were associated with prognosis in adenocarcinoma and squamous cell carcinoma of the lung.

  • 32.
    Nilsson, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gävle Cent Hosp, Cty Council Gavleborg, Gävle, Sweden.;Umeå Univ Hosp, Dept Radiat Sci & Oncol, Umea, Sweden.;Gävle Cent Hosp, Dept Radiol, Gävle, Sweden..
    Berglund, Anders
    EpiStat, Uppsala, Sweden..
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gavle Cent Hosp, Cty Council Gavleborg, Gavle, Sweden.;Gavle Cent Hosp, Dept Oncol, Gavle, Sweden..
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Umeå Univ Hosp, Dept Radiat Sci & Oncol, Umeå, Sweden.;Gävle Cent Hosp, Dept Oncol, Gävle, Sweden..
    Lambe, Mats
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Reg Canc Ctr Uppsala Örebro, Uppsala, Sweden..
    The role of comorbidity in the management and prognosis in nonsmall cell lung cancer: a population-based study2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 7, 949-956 p.Article in journal (Refereed)
    Abstract [en]

    Background: Coexisting disease constitutes a challenge for the provision of optimal cancer care. The influence of comorbidity on lung cancer management and prognosis remains incompletely understood. We assessed the influence of comorbidity on treatment intensity and prognosis in a population-based setting in patients with nonsmall cell lung cancer.Material and methods: Our study was based on information available in Lung Cancer Data Base Sweden (LcBaSe), a database generated by record linkage between the National Lung Cancer Register (NLCR) and several other population-based registers in Sweden. The NLCR includes data on clinical characteristics on 95% of all patients with lung cancer in Sweden since 2002. Comorbidity was assessed using the Charlson Comorbidity Index. Logistic regression and time to event analysis was used to address the association between comorbidity and treatment and prognosis.Results: In adjusted analyses encompassing 19,587 patients with a NSCLC diagnosis and WHO Performance Status 0-2 between 2002 and 2011, those with stage-IA-IIB disease and severe comorbidity were less likely to be offered surgery (OR: 0.45; 95% CI: 0.36-0.57). In late-stage disease (IIIB-IV), severe comorbidity was also associated with lower chemotherapy treatment intensity (OR: 0.76; 95% CI: 0.65-0.89). In patients with early, but not late-stage disease, severe comorbidity in adjusted analyses was associated with an increased all-cause mortality, while lung cancer-specific mortality was largely unaffected by comorbidity burden.Conclusions: Comorbidity contributes to the poor prognosis in NSCLC patients. Routinely published lung cancer survival statistics not considering coexisting disease conveys a too pessimistic picture of prognosis. Optimized management of comorbid conditions pre- and post-NSCLC-specific treatment is likely to improve outcomes.

  • 33.
    Nilsson, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Umea Univ Hosp, Dept Radiat Sci & Oncol, SE-90187 Umea, Sweden.;Gavle Cent Hosp, Dept Radiol, SE-80188 Gavle, Sweden..
    Holgersson, Georg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gavle Cent Hosp, Dept Oncol, 1 Lasarettvagen, SE-80188 Gavle, Sweden..
    Carlsson, Tobias
    Gavle Cent Hosp, Dept Oncol, 1 Lasarettvagen, SE-80188 Gavle, Sweden..
    Henriksson, Roger
    Umea Univ Hosp, Dept Radiat Sci & Oncol, SE-90187 Umea, Sweden.;Reg Canc Ctr Stockholm Gotland, Vastgotagatan 2, SE-10239 Stockholm, Sweden..
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gavle Cent Hosp, Dept Oncol, 1 Lasarettvagen, SE-80188 Gavle, Sweden..
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Umea Univ Hosp, Dept Radiat Sci & Oncol, SE-90187 Umea, Sweden.;Gavle Cent Hosp, Dept Oncol, 1 Lasarettvagen, SE-80188 Gavle, Sweden..
    Incidence trends in high-grade primary brain tumors in males and females2017In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 13, no 4, 2831-2837 p.Article in journal (Refereed)
    Abstract [en]

    The focus of the present review is to investigate whether there is a variation in the incidence rates between male and female patients with high-grade primary brain tumors and if there are altered incidence rates associated with the time at which they were diagnosed. Previous studies identified in internationally peer-reviewed journals were identified using a systematic search of the PubMed database. Due to the difficulties in data interpretation, studies that exclusively included patient data classified prior to the 2nd edition of the World Health Organization histological classification system of brain tumors were excluded. The overall incidence rates and incidence trends of male and female patients were analyzed separately. The mean age-adjusted overall incidence rate in the male population was 1.27 per 100,000 compared with 0.89 per 100,000 in the female population. The variance between the two genders differed and a Wilcoxon rank-sum test indicated that there was no significant difference in the incidence rate of high-grade primary brain tumors between males and females (P=0.3658). Furthermore, there was no significant difference in incidence rate trend between 1996-2004 and 2005-2010 for male or female populations (P=0.101 and P=0.472, respectively). The results from the present systematic review did not demonstrate a significant difference in incidence rate between the two genders. Therefore, the results from the current study are considered to be preliminary and further studies are required to elucidate this issue.

  • 34.
    Nilsson, Jonas
    et al.
    Gavle Univ Hosp, Ctr Res & Dev, Gavle, Sweden.;Gavle Univ Hosp, Dept Radiol, Gavle, Sweden.;Umea Univ Hosp, Dept Radiat Sci & Oncol, Umea, Sweden..
    Kallman, Mikael
    Gavle Univ Hosp, Dept Oncol, Gavle, Sweden..
    Ostlund, Ulrika
    Gavle Univ Hosp, Ctr Res & Dev, Gavle, Sweden..
    Holgersson, Georg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Gavle Univ Hosp, Ctr Res & Dev, Gavle, Sweden.;Gavle Univ Hosp, Dept Oncol, Gavle, Sweden..
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gavle Univ Hosp, Ctr Res & Dev, Gavle, Sweden.;Gavle Univ Hosp, Dept Oncol, Gavle, Sweden.;Umea Univ Hosp, Dept Radiat Sci & Oncol, Umea, Sweden..
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gavle Univ Hosp, Ctr Res & Dev, Gavle, Sweden.;Gavle Univ Hosp, Dept Oncol, Gavle, Sweden..
    The Use of Complementary and Alternative Medicine in Scandinavia2016In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 36, no 7, 3243-3251 p.Article, review/survey (Refereed)
    Abstract [en]

    Background: Complementary alternative medicine (CAM) is widely used among patients with cancer. This usage may have potentially harmful effects, especially when combined with anticancer drugs. However, some complementary methods may benefit patients. This review investigated the prevalence of CAM use among patients with cancer in Scandinavia and secondly studied the educational levels of CAM users compared to non-users. Materials and Methods: A systematic search of the PubMed library was carried out to locate articles published between January 2000 and October 2015 that investigated prevalence of CAM use among Scandinavian patients with cancer. Results: Twenty-two articles were found, of which nine were included in the review. The prevalence of CAM use was 7.9% to 53%, with an average of 36.0% across all studies. Conclusion: Use of CAM is widespread among patients with cancer. Knowledge about CAM should be disseminated to both patients and staff in order to optimise discussions about CAM in clinical practice.

  • 35.
    Popova, Svetlana N
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Dimberg, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Edqvist, Per-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sooman, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Subtyping of gliomas of various WHO grades by the application of immunohistochemistry2014In: Histopathology, ISSN 0309-0167, E-ISSN 1365-2559, Vol. 64, no 3, 365-379 p.Article in journal (Refereed)
    Abstract [en]

    Aims

    In 2010, four subtypes (classical, proneural, mesenchymal, and neural) of glioblastoma multiforme (GBM) were defined by molecular genetic analyses. The objective of this study was to assess whether gliomas, independently of the type and grade, could be subdivided into protein-based subtypes.

    Methods and results

    A tissue microarray (TMA) approach was applied to incorporate tissue samples of low-grade and high-grade gliomas into five TMAs. High expression levels of epidermal growth factor receptor (EGFR), CD44, c-MER proto-oncogene tyrosine kinase (MERTK), platelet-derived growth factor receptor α, p53, oligodendrocyte transcription factor 2 (OLIG2) and isocitrate dehydrogenase 1 with the R132H mutation were assessed using immunohistochemistry (IHC). Glioma could be subdivided into four subtypes by IHC. The majority of the low-grade gliomas were of the proneural subtype, i.e. high p53 expression (63% of grade II). The classical subtype, with high EGFR and low p53 expression, was most common in GBMs (39%), followed by the proneural (29%) and mesenchymal (with high CD44 and MERTK expression) (29%) subtypes, a frequency that is in line with previously published data based on molecular genetics.

    Conclusions

    Assessment of the expression of the five proteins EGFR, CD44, MERTK, p53 and OLIG2 is sufficient for subtyping gliomas, and can be recommended for implementation in clinical practice for both low-grade and high-grade gliomas.

  • 36. Reizenstein, Johan A
    et al.
    Holmberg, Lars
    Regional Cancer Centre, Uppsala, Sweden.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Linder, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lödén, Britta
    Holmqvist, Marit
    Regional Cancer Centre, Uppsala, Sweden.
    Hellström, Karin
    von Beckerath, Mattias
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergström, Stefan N
    Time trends in T3 to T4 laryngeal cancer: a population-based long-term analysis2014In: Head and Neck, ISSN 1043-3074, E-ISSN 1097-0347, Vol. 36, no 12, 1727-1731 p.Article in journal (Refereed)
    Abstract [en]

    Background:

    A decline in laryngectomies and survival in laryngeal cancer has been reported, especially among advanced tumors.

    Methods:

    Out of 1058 patients with laryngeal cancer diagnosed 1978-2007 in the Uppsala-Örebro-region in Sweden 263 T3-4 tumors treated with curative intent were studied retrospectively. Two time periods were defined, 1978-1992 and 1993-2007.

    Results:

    Glottic tumors decreased constituting 68.6% of cases 1978-1992 and 47.9% 1993-2007. Laryngectomy was performed in 38.8% and in 34.5% in the corresponding time periods. The use of laryngectomy was not strongly prognostic. A decline in overall survival over time could only be identified for the first year of follow-up. Chemotherapy was only used in a minority of cases.

    Conclusion:

    The marked decrease of glottic site may mark a shift in etiology. Laryngectomy was not strongly associated with improved survival. The absence of improved survival calls for intensified research.

  • 37.
    Rexhepaj, Elton
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Agnarsdóttir, Margrét
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergman, Julia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Edqvist, Per-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Uhlen, Mathias
    Gallagher, William M.
    Lundberg, Emma
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    A Texture Based Pattern Recognition Approach to Distinguish Melanoma from Non-Melanoma Cells in Histopathological Tissue Microarray Sections2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 5, e62070- p.Article in journal (Refereed)
    Abstract [en]

    Aims: Immunohistochemistry is a routine practice in clinical cancer diagnostics and also an established technology for tissue-based research regarding biomarker discovery efforts. Tedious manual assessment of immunohistochemically stained tissue needs to be fully automated to take full advantage of the potential for high throughput analyses enabled by tissue microarrays and digital pathology. Such automated tools also need to be reproducible for different experimental conditions and biomarker targets. In this study we present a novel supervised melanoma specific pattern recognition approach that is fully automated and quantitative. Methods and Results: Melanoma samples were immunostained for the melanocyte specific target, Melan-A. Images representing immunostained melanoma tissue were then digitally processed to segment regions of interest, highlighting Melan-A positive and negative areas. Color deconvolution was applied to each region of interest to separate the channel containing the immunohistochemistry signal from the hematoxylin counterstaining channel. A support vector machine melanoma classification model was learned from a discovery melanoma patient cohort (n = 264) and subsequently validated on an independent cohort of melanoma patient tissue sample images (n = 157). Conclusion: Here we propose a novel method that takes advantage of utilizing an immuhistochemical marker highlighting melanocytes to fully automate the learning of a general melanoma cell classification model. The presented method can be applied on any protein of interest and thus provides a tool for quantification of immunohistochemistry-based protein expression in melanoma.

  • 38. Ronquist-Nii, Yuko
    et al.
    Eksborg, Staffan
    Axelson, Magnus
    Harmenberg, Johan
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Beck, Olof
    Determination of picropodophyllin and its isomer podophyllotoxin in human serum samples with electrospray ionization of hexylamine adducts by liquid chromatography-tandem mass spectrometry2011In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 879, no 5-6, 326-334 p.Article in journal (Refereed)
    Abstract [en]

    A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of the new anticancer agent picropodophyllin (AXL1717) and its isomer podophyllotoxin levels in human serum has been developed. Monitoring of hexylamine adducts rather than proton adducts was used to optimize sensitivity. The chromatography system was an Acquity BEN C18, 2.1 mm x 50 mm 1.7 mu m column with gradient elution (mobile phase A: 2.5 mM hexylamine and 5 mM formic acid in Milli-Qwater and mobile phase B: methanol). The retention times were 1.4 min for picropodophyllin, 1.5 min for podophyllotoxin and 1.9 min for internal standard deoxypodophyllotoxin. The isomers were base-line separated. The analytes were detected after electrospray ionization in positive mode with selected reaction monitoring (SRM) with ion transitions m/z 516 --> 102 for picropodophyllin and podophyllotoxin and m/z 500 --> 102 for internal standard. The sample preparation was protein precipitation with acetonitrile (1:3) containing internal standard followed by dilution of the supernatant with mobile phase A (1:1). The limit of quantification (LOQ) was 0.01 mu mol/L for picropodophyllin and podophyllotoxin. The limit of detection (LOD) at 3 times the signal to noise (S/N) was estimated below 0.001 mu mol/L for picropodophyllin and podophyllotoxin. The quantification range of the method was between 0.01 mu mol/L and 5 mu mol/L for both isomers. The accuracy was within +/-15% of the theoretical value for both picropodophyllin and podophyllotoxin and inter-assay precision did not exceed +/-15%, except for the 0.016 mu mol/L level of podophyllotoxin, which was 18%. The selectivity of the method was verified by analysis of two different product ions for each analyte and by analysis for interference of seven different batches of blank human serum. The combined recovery and matrix effects were about 83% for picropodophyllin and podophyllotoxin. The new LC-MS/MS method showed sufficient sensitivity and selectivity for determination of picropodophyllin and its isomer podophyllotoxin levels in human serum from subjects receiving therapeutic doses of AXL1717.

  • 39. Sherwood, Victoria
    et al.
    Chaurasiya, Shivendra Kumar
    Ekström, Elin J
    Guilmain, William
    Liu, Qing
    Koeck, Tomas
    Brown, Kate
    Hansson, Karin
    Agnarsdóttir, Margrét
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Jirström, Karin
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    James, Peter
    Andersson, Tommy
    WNT5A-mediated β-catenin-independent signalling is a novel regulator of cancer cell metabolism2014In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 35, no 4, 784-794 p.Article in journal (Refereed)
    Abstract [en]

    WNT5A has been identified as an important ligand in the malignant progression of a number of tumours. Although WNT5A signalling is often altered in cancer, the ligands role as either a tumour suppressor or oncogene varies between tumour types and is a contemporary issue for investigators of -catenin-independent WNT signalling in oncology. Here, we report that one of the initial effects of active WNT5A signalling in malignant melanoma cells is an alteration in cellular energy metabolism and specifically an increase in aerobic glycolysis. This was found to be at least in part due to an increase in active Akt signalling and lactate dehydrogenase (LDH) activity. The clinical relevance of these findings was strengthened by a strong correlation (P < 0.001) between the expression of WNT5A and LDH isoform V in a cohort of melanocytic neoplasms. We also found effects of WNT5A on energy metabolism in breast cancer cells, but rather than promoting aerobic glycolysis as it does in melanoma, WNT5A signalling increased oxidative phosphorylation rates in breast cancer cells. These findings support a new role for WNT5A in the metabolic reprogramming of cancer cells that is a context- dependent event.

  • 40.
    Sooman, Linda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ekman, S.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Gullbo, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Bergstrom, S.
    Johansson, M.
    Wu, Xuping
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lennartsson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    SHP1 expression is epigenetically regulated and influences the sensitivity to chemotherapeutic agents in glioblastoma cells2012In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 14, no suppl 3, iii18-iii18 p.Article in journal (Other academic)
    Abstract [en]

    INTRODUCTION: Glioblastoma is characterized by chemoresistance. One factor than can contribute to chemoresistance is aberrant DNA methylation of specific genes relevant for drug response, e.g. tumor suppressor genes. AIM: The aim of this study was to investigate whether the tumor suppressor gene SHP1 is epigenetically regulated and if its overexpression affects the sensitivity to chemotherapeutic drugs with different mechanisms of action in glioblastoma cell lines.

    METHODS: Differences in methylation levels in the SHP1 promoter and SHP1 protein expressions between untreated cells and cells treated with the demethylating agent decitabine were analyzed with bisulfite Pyrosequencing and Western blotting. Differences in drug sensitivity to a panel of chemotherapeutic drugs with different mechanisms of action between SHP1 overexpressing clones and control clones were analyzed with the fluorometric microculture cytotoxicity assay.

    RESULTS: We demonstrated that SHP1 promoter methylation was correlated to SHP1 expression and that the expression was increased upon demethylation. Overexpression of SHP1 resulted in lower (p < 0.05) sensitivity to the proteasome inhibitor bortezomib and the alkylating agents cisplatin and melphalan.

    CONCLUSION: SHP1 expression may be epigenetically regulated and its overexpression influences the sensitivity to chemotherapeutic drugs in glioblastoma derived cells.

  • 41.
    Sooman, Linda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Andersson, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Johansson, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Göransson-Kultima, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Isaksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lennartsson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Gullbo, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Synergistic Effects of PI3K or P38 MAPK Inhibition in Combination With Vandetanib Treatment in Glioblastoma Cells2012In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 48, no S5, S244-S244 p.Article in journal (Refereed)
  • 42.
    Sooman, Linda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Andersson, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Kultima, Hanna Göransson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Isaksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Johansson, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lennartsson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Gullbo, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Synergistic interactions between camptothecin and EGFR or RAC1 inhibitors and between imatinib and Notch signaling or RAC1 inhibitors in glioblastoma cell lines2013In: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 72, no 2, 329-340 p.Article in journal (Refereed)
    Abstract [en]

    The current treatment strategies for glioblastoma have limited health and survival benefits for the patients. A common obstacle in the treatment is chemoresistance. A possible strategy to evade this problem may be to combine chemotherapeutic drugs with agents inhibiting resistance mechanisms. The aim with this study was to identify molecular pathways influencing drug resistance in glioblastoma-derived cells and to evaluate the potential of pharmacological interference with these pathways to identify synergistic drug combinations. Global gene expressions and drug sensitivities to three chemotherapeutic drugs (imatinib, camptothecin and temozolomide) were measured in six human glioblastoma-derived cell lines. Gene expressions that correlated to drug sensitivity or resistance were identified and mapped to specific pathways. Selective inhibitors of these pathways were identified. The effects of six combinations of inhibitors and chemotherapeutic drugs were evaluated in glioblastoma-derived cell lines. Drug combinations with synergistic effects were also evaluated in non-cancerous epithelial cells. Four drug combinations had synergistic effects in at least one of the tested glioblastoma-derived cell lines; camptothecin combined with gefitinib (epidermal growth factor receptor inhibitor) or NSC 23766 (ras-related C3 botulinum toxin substrate 1 inhibitor) and imatinib combined with DAPT (Notch signaling inhibitor) or NSC 23766. Of these, imatinib combined with DAPT or NSC 23766 did not have synergistic effects in non-cancerous epithelial cells. Two drug combinations had at least additive effects in one of the tested glioblastoma-derived cell lines; temozolomide combined with gefitinib or PF-573228 (focal adhesion kinase inhibitor). Four synergistic and two at least additive drug combinations were identified in glioblastoma-derived cells. Pathways targeted by these drug combinations may serve as targets for future drug development with the potential to increase efficacy of currently used/evaluated chemotherapy.

  • 43.
    Sooman, Linda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Tsakonas, Georgios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Jaiswal, Archita
    Navani, Sanjay
    Edqvist, Per-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Johansson, Mikael
    Wu, Xuping
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Gullbo, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Lennartsson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    PTPN6 expression is epigenetically regulated and influences survival and response to chemotherapy in high-grade gliomas2014In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 35, no 5, 4479-4488 p.Article in journal (Refereed)
    Abstract [en]

    Background: The prognosis of high-grade glioma patients is poor and the tumors are characterized by resistance to therapy. The aims of this study were to analyze the prognostic value of the expression of the protein tyrosine phosphatase, non-receptor type 6 (PTPN6, also referred to as SHP1) in high-grade glioma patients and the epigenetic regulation of the expression of PTPN6 and the role of its expression in chemotherapy resistance in glioma-derived cells.

    Material and methods: PTPN6 expression was analyzed with immunohistochemistry in 89 high-grade glioma patients. Correlation between PTPN6 expression and overall survival was analyzed with Kaplan-Meier univariate analysis and Cox regression multivariate analysis. Differences in drug sensitivity to a panel of 16 chemotherapeutic drugs between PTPN6 overexpressing clones and control clones were analyzed in vitro with the fluorometric microculture cytotoxicity assay. Cell cycle analysis was done with Krishan staining and flow cytometry. Apoptosis was analyzed with a cell death detection ELISA kit as well as cleaved caspase-3 and caspase-9 Western blotting. Autophagy was analyzed with LC3B Western blotting. Methylation of the PTPN6 promoter was analyzed with bisulfite-Pyrosequencing and demethylation of PTPN6 was done with decitabine treatment.

    Results: PTPN6 expression correlated in univariate analysis to poor survival for anaplastic glioma patients (p=0.026). In glioma-derived cell lines, overexpression of PTPN6 caused increased resistance (p<0.05) to the chemotherapeutic drugs bortezomib, cisplatin and melphalan. PTPN6 expression did not affect bortezomib-induced cell cycle arrest, apoptosis or autophagy. Low PTPN6 promoter methylation correlated to protein expression and the protein expression was increased upon demethylation in glioma-derived cells.

    Conclusion: PTPN6 expression may be a factor contributing to poor survival for anaplastic glioma patients and in glioma-derived cells its expression is epigenetically regulated and influences the response to chemotherapy.

  • 44.
    Sooman, Linda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Freyhult, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jaiswal, Archita
    Navani, Sanjay
    Edqvist, Per-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tchougounova, Elena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Elsir, Tamador
    Cancer Center Karolinska, Karolinska University Hospital Solna, Stockholm, Sweden.
    Gullbo, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Lennartsson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    FGF2 as a potential prognostic biomarker for proneural glioma patients2015In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 3, 385-394 p.Article in journal (Refereed)
    Abstract [en]

    Background. The survival of high-grade glioma patients is poor and the treatment of these patients can cause severe side effects. This fosters the necessity to identify prognostic biomarkers, in order to optimize treatment and diminish unnecessary suffering of patients. The aim of this study was to identify prognostic biomarkers for high-grade glioma patients.

    Methods. Eleven proteins were selected for analysis due to their suggested importance for survival of patients with other types of cancers and due to a high variation in protein levels between glioma patients (according to the Human Protein Atlas, www.proteinatlas.org). Protein expression patterns of these 11 proteins were analyzed by immunohistochemistry in tumor samples from 97 high-grade glioma patients. The prognostic values of the proteins were analyzed with univariate and multivariate Cox regression analyses for the high-grade glioma patients, including subgroup analyses of histological subtypes and immunohistochemically defined molecular subtypes.

    Results. The proteins with the most significant (univariate and multivariate p < 0.05) correlations were analyzed further with cross-validated Kaplan-Meier analyses for the possibility of predicting survival based on the protein expression pattern of the corresponding candidate. Random Forest classification with variable subset selection was used to analyze if a protein signature consisting of any combination of the 11 proteins could predict survival for the high-grade glioma patients and the subgroup with glioblastoma patients. The proteins which correlated most significantly (univariate and multivariate p < 0.05) to survival in the Cox regression analyses were Myc for all high-grade gliomas and FGF2, CA9 and CD44 for the subgroup of proneural gliomas, with FGF2 having a strong negative predictive value for survival. No prognostic signature of the proteins could be found.

    Conclusion. FGF2 is a potential prognostic biomarker for proneural glioma patients, and warrants further investigation.

  • 45.
    Sooman, Linda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lennartsson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Gullbo, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Tsakonas, Georgios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Johansson, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Edqvist, Per-Henrik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Pontén, Fredrik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Jaiswal, Archita
    The Human Protein Atlas Project, Mumbai Site, Lab Surgpath, 204 Bombay Market, 731/1 Tardeo Main Road, Mumbai 400034, India.
    Navani, Sanjay
    The Human Protein Atlas Project, Mumbai Site, Lab Surgpath, 204 Bombay Market, 731/1 Tardeo Main Road, Mumbai 400034, India.
    Alafuzoff, Irina
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Popova, Svetlana
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Vandetanib combined with a p38 MAPK inhibitor synergistically reduces glioblastoma cell survival2013In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 30, no 3, 638- p.Article in journal (Refereed)
    Abstract [en]

    The survival for patients with high-grade glioma is poor, and only a limited number of patients respond to the therapy. The aim of this study was to analyze the significance of using p38 MAPK phosphorylation as a prognostic marker in high-grade glioma patients and as a therapeutic target in combination chemotherapy with vandetanib. p38 MAPK phosphorylation was analyzed with immunohistochemistry in 90 high-grade glioma patients. Correlation between p38 MAPK phosphorylation and overall survival was analyzed with Mann-Whitney U test analysis. The effects on survival of glioblastoma cells of combining vandetanib with the p38 MAPK inhibitor SB 203580 were analyzed in vitro with the median-effect method with the fluorometric microculture cytotoxicity assay. Two patients had phosphorylated p38 MAPK in both the cytoplasm and nucleus, and these two presented with worse survival than patients with no detectable p38 MAPK phosphorylation or phosphorylated p38 MAPK only in the nucleus. This was true for both high-grade glioma patients (WHO grade III and IV, n = 90, difference in median survival: 6.1 months, 95 % CI [0.20, 23], p = 0.039) and for the subgroup with glioblastoma patients (WHO grade IV, n = 70, difference in median survival: 6.1 months, 95 % CI [0.066, 23], p = 0.043). The combination of vandetanib and the p38 MAPK inhibitor SB 203580 had synergistic effects on cell survival for glioblastoma-derived cells in vitro. In conclusion, p38 MAPK phosphorylation may be a prognostic marker for high-grade glioma patients, and vandetanib combined with a p38 MAPK inhibitor may be useful combination chemotherapy for glioma patients.

  • 46.
    Wu, Xuping
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Hedman, Håkan
    Department of Radiation Sciences and Oncology, Umeå University.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Henriksson, Roger
    Department of Radiation Sciences and Oncology, Umeå University.
    Gullbo, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Lennartsson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Hesselius, Patrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Economics.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Expression of EGFR and LRIG proteins in oesophageal carcinoma with emphasis on patient survival and cellular chemosensitivity2012In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 1, 69-76 p.Article in journal (Refereed)
    Abstract [en]

    Background. Leucine-rich and immunoglobulin-like domains 1-3 (LRIG1-3) proteins have been implicated in the regulation of EGFR signalling. In the present study, we investigated the clinical implications of the expression of EGFR and LRIG1-3 in oesophageal carcinoma, as well as the correlation between their expression levels and the chemosensitivity of oesophageal carcinoma cell lines.

    Patients and methods. Tumours from 80 patients with oesophageal carcinoma were investigated for the expression of EGFR and LRIG proteins by immunohistochemistry. Oesophageal carcinoma cell lines were investigated for their expression of EGFR and LRIG1, 2, and 3 by quantitative real time RT-PCR and for their sensitivity to commonly used chemotherapeutics by a cytotoxicity assay.

    Results and discussion: Based on a total score of intensity and expression rates, a trend towards survival difference was found for EGFR (p = 0.09) and LRIG2 (p = 0.18) whereas for LRIG1 and -3 there was no trend towards any association with survival. Correlation analysis revealed a correlation with the clinical expression of EGFR and LRIG3 (p = 0.0007). Significant correlations were found between LRIG1 expression levels and sensitivity to cisplatin (r = -0.74), docetaxel (r = -0.69), and vinorelbine (r = -0.82) in oesophageal carcinoma cell lines. EGFR and the LRIG proteins may be functionally involved in oesophageal carcinoma, but larger materials are needed to fully elucidate the clinical implication.

  • 47.
    Wu, Xuping
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Smavadati, Shirin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nordfjäll, Katarina
    Karlsson, Krister
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Qvarnström, Fredrik
    Simonsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Gryaznov, Sergei
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Paulsson-Karlsson, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Telomerase antagonist imetelstat inhibits esophageal cancer cell growth and increases radiation-induced DNA breaks2012In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, Vol. 1823, no 12, 2130-2135 p.Article in journal (Refereed)
    Abstract [en]

    Telomerase is mainly active in human tumor cells, which provides an opportunity for a therapeutic window on telomerase targeting. We sought to evaluate the potential of the thio-phosphoramidate oligonucleotide inhibitor of telomerase, imetelstat, as a drug candidate for treatment of esophageal cancer. Our results showed that imetelstat inhibited telomerase activity in a dose-dependent manner in esophageal cancer cells. After only 1. week of imetelstat treatment, a reduction of colony formation ability of esophageal cancer cells was observed. Furthermore, long-term treatment with imetelstat decreased cell growth of esophageal cancer cells with different kinetics regarding telomere lengths. Short-term imetelstat treatment also increased γ-H2AX and 53BP1 foci staining in the esophageal cancer cell lines indicating a possible induction of DNA double strand breaks (DSBs). We also found that pre-treatment with imetelstat led to increased number and size of 53BP1 foci after ionizing radiation. The increase of 53BP1 foci number was especially pronounced during the first 1 h of repair whereas the increase of foci size was prominent later on. This study supports the potential of imetelstat as a therapeutic agent for the treatment of esophageal cancer.

  • 48.
    Wu, Xuping
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sooman, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lennartsson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Gullbo, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Microtubule inhibition causes epidermal growth factor receptor inactivation in oesophageal cancer cells2013In: International Journal of Oncology, ISSN 1019-6439, Vol. 42, no 1, 297-304 p.Article in journal (Refereed)
    Abstract [en]

    Drugs that interfere with microtubule function can prevent cells from mitosis and may cause cell cycle arrest or apoptosis. Various microtubule targeting agents, both stabilizers and inhibitors, are used in a clinical setting to treat cancer. In the current study, we investigated the sensitivity of oesophageal cancer cells to different microtubule targeting agents. The current study demonstrated that different microtubule targeting agents disrupted the microtubule network and inhibited survival of oesophageal cancer cells in a dose-dependent manner. Interestingly, an additional cellular effect with inhibition of tyrosine phosphorylation of the EGFR and subsequent downregulation of EGFR-induced signalling was also observed, suggesting an additional mechanism of action for microtubule destabilising agents. A tyrosine phosphatase inhibitor, sodium orthovanadate, could reverse the EGFR dephosphorylation effects induced by microtubule targeting agents. The EGFR dephosphorylation could be reversed by a tyrosine phosphatase inhibitor, indicating that disruption of the microtubule network may lead to activation of a protein tyrosine phosphatasc (PTP) that can regulate EGFR phosphorylation and activation, an effect of potential clinical relevance for combination therapies in patients.

1 - 48 of 48
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf