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  • 1.
    Green, Henrik
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Division of Gene Technology, Royal Institute of Technology, Solna, Sweden/ Royal Institute Technology, Sweden; National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Hasmats, Johanna
    Royal Institute Technology, Sweden.
    Kupershmidt, Ilya
    Royal Institute Technology, Sweden; NextBio, CA USA.
    Edsgard, Daniel
    Royal Institute Technology, Sweden.
    de Petris, Luigi
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Lewensohn, Rolf
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Blackhall, Fiona
    Christie Hospital, England; University of Manchester, England.
    Vikingsson, Svante
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Besse, Benjamin
    University of Paris 11, France.
    Lindgren, Andrea
    Linköpings universitet, Institutionen för medicin och hälsa. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Lungmedicinska kliniken US. Linköpings universitet, Medicinska fakulteten.
    Branden, Eva
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Koyi, Hirsh
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Peterson, Curt
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Lundeberg, Joakim
    Royal Institute Technology, Sweden.
    Using Whole-Exome Sequencing to Identify Genetic Markers for Carboplatin and Gemcitabine-Induced Toxicities2016Inngår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, nr 2, s. 366-373Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Chemotherapies are associated with significant interindividual variability in therapeutic effect and adverse drug reactions. In lung cancer, the use of gemcitabine and carboplatin induces grade 3 or 4 myelosuppression in about a quarter of the patients, while an equal fraction of patients is basically unaffected in terms of myelosuppressive side effects. We therefore set out to identify genetic markers for gemcitabine/carboplatin-induced myelosuppression. Experimental Design: We exome sequenced 32 patients that suffered extremely high neutropenia and thrombocytopenia (grade 3 or 4 after first chemotherapy cycle) or were virtually unaffected (grade 0 or 1). The genetic differences/polymorphism between the groups were compared using six different bioinformatics strategies: (i) whole-exome nonsynonymous single-nucleotide variants association analysis, (ii) deviation from Hardy-Weinberg equilibrium, (iii) analysis of genes selected by a priori biologic knowledge, (iv) analysis of genes selected from gene expression meta-analysis of toxicity datasets, (v) Ingenuity Pathway Analysis, and (vi) FunCoup network enrichment analysis. Results: A total of 53 genetic variants that differed among these groups were validated in an additional 291 patients and were correlated to the patients myelosuppression. In the validation, we identified rs1453542 in OR4D6 (P = 0.0008; OR, 5.2; 95% CI, 1.8-18) as a marker for gemcitabine/carboplatin-induced neutropenia and rs5925720 in DDX53 (P = 0.0015; OR, 0.36; 95% CI, 0.17-0.71) as a marker for thrombocytopenia. Patients homozygous for the minor allele of rs1453542 had a higher risk of neutropenia, and for rs5925720 the minor allele was associated with a lower risk for thrombocytopenia. Conclusions: We have identified two new genetic markers with the potential to predict myelosuppression induced by gemcitabine/ carboplatin chemotherapy. (C)2015 AACR.

  • 2.
    Gulyas, Miklos
    et al.
    Genetics and Pathology , Uppsala University , Uppsala , Sweden.
    Mattsson, Johanna Sofia Margareta
    Genetics and Pathology , Uppsala University , Uppsala , Sweden.
    Lindgren, Andrea
    Region Östergötland, Hjärt- och Medicincentrum, Allergicentrum US. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Ek, Lars
    Skane University Hospital , Lund , Sweden.
    Lamberg Lundström, Kristina
    Akademiska Hospital , Uppsala , Sweden.
    Behndig, Annelie
    Norrland University Hospital , Umeå , Sweden.
    Holmberg, Erik
    Sahlgrenska Academy at University of Gothenburg , Sweden.
    Micke, Patrick
    Genetics and Pathology , Uppsala University , Uppsala , Sweden.
    Bergman, Bengt
    Sahlgrenska Academy at University of Gothenburg , Sweden..
    COX-2 expression and effects of celecoxib in addition to standard chemotherapy in advanced non-small cell lung cancer2018Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, nr 2, s. 244-250Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: Inhibition of cyclooxygenase-2 (COX-2) is proposed as a treatment option in several cancer types. However, in non-small cell lung cancer (NSCLC), phase III trials have failed to demonstrate a benefit of adding COX-2 inhibitors to standard chemotherapy. The aim of this study was to analyze COX-2 expression in tumor and stromal cells as predictive biomarker for COX-2 inhibition.

    METHODS: In a multicenter phase III trial, 316 patients with advanced NSCLC were randomized to receive celecoxib (400 mg b.i.d.) or placebo up to one year in addition to a two-drug platinum-based chemotherapy combination. In a subset of 122 patients, archived tumor tissue was available for immunohistochemical analysis of COX-2 expression in tumor and stromal cells. For each compartment, COX-2 expression was graded as high or low, based on a product score of extension and intensity of positively stained cells.

    RESULTS: An updated analysis of all 316 patients included in the original trial, and of the 122 patients with available tumor tissue, showed no survival differences between the celecoxib and placebo arms (HR 1.01; 95% CI 0.81-1.27 and HR 1.12; 95% CI 0.78-1.61, respectively). High COX-2 scores in tumor (n = 71) or stromal cells (n = 55) was not associated with a superior survival outcome with celecoxib vs. placebo (HR =0.96, 95% CI 0.60-1.54; and HR =1.51; 95% CI 0.86-2.66), and no significant interaction effect between COX-2 score in tumor or stromal cells and celecoxib effect on survival was detected (p = .48 and .25, respectively).

    CONCLUSIONS: In this subgroup analysis of patients with advanced NSCLC treated within the context of a randomized trial, we could not detect any interaction effect of COX-2 expression in tumor or stromal cells and the outcome of celecoxib treatment in addition to standard chemotherapy.

  • 3.
    Koch, Andrea
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Allergicentrum US.
    Clinical Aspects of Inflammation in Non-small Cell Lung Cancer2011Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Lung cancer is the most common cause of cancer death worldwide, with about 1.2 million deaths every year. In Sweden, about 3500 new cases are diagnosed every year. The majority of patients presents with advanced non-small cell lung cancer (NSCLC) and is treated with palliative intent. Standard treatment in these patients in performance status 0-2 is combination chemotherapy. Radiotherapy may be added for palliative purposes. Median survival time with such treatment is 6-10 months. New treatment strategies are urgently needed. There is growing evidence for a link between cancer and inflammation and consequently, inflammation may be a possible target for the treatment of lung cancer.

    The aim of this thesis was to study clinical aspects of inflammation in non-small cell lung cancer. A central issue was to adapt the projects as close to clinical routine as possible.

    In a retrospective study of 289 patients (paper I), we investigated the prognostic value of Creactive protein (CRP), a nonspecific marker of systemic inflammation, and smoking in patients with advanced NSCLC treated with palliative first-line chemotherapy. We found that patients with elevated CRP values (≥10 mg/ml) and current smokers at onset of treatment had inferior survival compared to patients with normal CRP values and patients who were not smoking. CRP and smoking status were independent prognostic factors and provided additional information to established prognostic factors such as stage of disease and performance status.

    The expression of COX-2, an important enzyme involved in inflammation, was prospectively analysed in 53 patients with cytologically diagnosed lung cancer (paper II). The study showed that the analysis of COX-2 expression in cytological material is technically easy to perform with routine diagnostic methods and results in good quality slides. There was great variation in the proportion of COX-2 positive cells between the patients as well as in the intensity of staining between individual cells in many single cases.

    The major project (paper III) of this thesis was the CYCLUS study, an academic, randomised, double-blind, phase III trial. The scientific question was if addition of the COX-2 inhibitor celecoxib to first-line palliative chemotherapy would prolong survival in patients with advanced NSCLC. 316 patients were included at 13 centres in Sweden. There was no survival difference between the treatment arms. Celecoxib appeared to have more favourable effect on survival in women than in men, but the differences were not significant. Small but not statistically significant differences in global quality of life and pain were seen favouring the celecoxib group. No increased incidence of cardiovascular events was observed in the celecoxib group.

    Delarbeid
    1. Prognostic significance of C-reactive protein and smoking in patients with advanced non-small cell lung cancer treated with first-line palliative chemotherapy.
    Åpne denne publikasjonen i ny fane eller vindu >>Prognostic significance of C-reactive protein and smoking in patients with advanced non-small cell lung cancer treated with first-line palliative chemotherapy.
    2009 (engelsk)Inngår i: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, ISSN 1556-1380, Vol. 4, nr 3, s. 326-32Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    HYPOTHESIS: The objective of the study was to analyze if C-reactive protein (CRP) and smoking status provide prognostic information in patients with advanced non-small cell lung cancer (NSCLC) receiving palliative first-line chemotherapy. METHODS: Retrospective, single-institutional study, comprising all patients with NSCLC stage IIIB/IV and World Health Organization performance status (PS) 0-2 who started palliative first-line chemotherapy between January 1, 2002, and January 31, 2007. Patient records were reviewed. Cox's proportional hazards model was used to identify prognostic factors. RESULTS: Two hundred eight-nine consecutive patients were evaluable. Sixty-eight percent had stage IV disease and 67% had PS 0 or 1. Median survival was 7.4 months. At onset of chemotherapy, 206 patients (71%) had elevated CRP values (> or = 10 mg/liter). One-hundred-forty-four patients (50%) were current smokers. On univariate analysis, patients with elevated CRP levels had inferior survival (hazard ratio [HR] = 1.67, 95% confidence interval [CI], 1.28-2.19, p < 0.001). Smoking at onset of treatment was associated with shorter survival (HR 1.56, 95% CI, 1.22-1.98, p < 0.001). Ever smokers had shorter survival than never smokers (HR 1.80, 95% CI, 1.25-2.59, p = 0.001). On multivariate analysis, with stage, PS, albumin, and gender as covariates, both smoking at start of chemotherapy and CRP elevation were independent negative prognostic factors for survival. CONCLUSIONS: CRP and smoking status are independent prognostic factors for survival in patients with advanced NSCLC receiving palliative first-line chemotherapy and provide additional information to established prognostic factors such as stage of disease and performance status.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-18964 (URN)10.1097/JTO.0b013e31819578c8 (DOI)19155996 (PubMedID)
    Tilgjengelig fra: 2009-06-06 Laget: 2009-06-06 Sist oppdatert: 2014-04-08
    2. Cyclooxygenase-2 expression in lung cancer cells evaluated by immunocytochemistry
    Åpne denne publikasjonen i ny fane eller vindu >>Cyclooxygenase-2 expression in lung cancer cells evaluated by immunocytochemistry
    2011 (engelsk)Inngår i: Diagnostic Cytopathology, ISSN 8755-1039, E-ISSN 1097-0339, Vol. 39, nr 3, s. 188-193Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Cyclooxygenase-2 (COX-2) expression may be a prognostic factor in lung cancer. In previous studies, COX-2 expression has almost exclusively been evaluated with immunohistochemical methods performed on histology sections of tissue biopsies. However, in clinical practice, lung cancer is often diagnosed with cytological techniques only. We present methodology and results from analysis of COX-2 expression with immunochemistry on cytological material in 53 patients with lung cancer. Preparation and staining with the method established at our laboratory were easy to perform and resulted in good quality slides. The percentage COX-2-stained cells and the intensity of staining varied widely between and within the different cases. The proportion of positively stained tumor cells was as follows: <1% in 20 patients, 1-10% in 7 patients, 11-50% in 17 patients, and more than 50% in 9 patients. In 17 cases, groups of cells with different intensity of COX-2 staining were found in the same slide. In conclusion, immunocytochemical analysis of COX-2 expression is technically easy to perform with routine diagnostic procedures. There is a great variation in the proportion of COX-2-positive cells among patients and in the intensity of staining among individual cells in many single cases. Diagn. Cytopathol.2011;39:188-193. © 2010 Wiley-Liss, Inc.

    sted, utgiver, år, opplag, sider
    John Wiley and Sons, 2011
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-66083 (URN)10.1002/dc.21366 (DOI)000288035400006 ()21319320 (PubMedID)
    Tilgjengelig fra: 2011-03-04 Laget: 2011-03-02 Sist oppdatert: 2017-12-11bibliografisk kontrollert
    3. Effect of celecoxib on survival in patients with advanced non-small cell lung cancer: A double blind randomised clinical phase III trial (CYCLUS study) by the Swedish Lung Cancer Study Group
    Åpne denne publikasjonen i ny fane eller vindu >>Effect of celecoxib on survival in patients with advanced non-small cell lung cancer: A double blind randomised clinical phase III trial (CYCLUS study) by the Swedish Lung Cancer Study Group
    Vise andre…
    2011 (engelsk)Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 47, nr 10, s. 1546-1555Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND: Increased expression of cyclooxygenase-2 (COX-2) is common in non-small cell lung cancer (NSCLC) and has been associated with poor prognosis. Experimental and clinical phase II trials have indicated that the addition of the COX-2 inhibitor celecoxib to palliative chemotherapy might increase survival time in patients with advanced NSCLC.

    METHODS: We performed a double-blind, placebo-controlled multicentre phase III trial at 13 centres in Sweden. Three hundred and nineteen patients with advanced NSCLC stage IIIB-IV and performance status 0-2 were randomised to receive celecoxib 400mg b.i.d. or placebo in addition to palliative chemotherapy. The primary objective was to compare overall survival. Other end-points were quality of life, progression-free survival, toxicity, cardiovascular events and biological markers. The trial is registered with ClinicalTrials.gov, No. NCT00300729.

    FINDINGS: Three hundred and sixteen patients were included in the analysis, 158 in each treatment group. Median survival time was 8.5months. There was no survival difference between the treatment arms. Small but not statistically significant differences in global quality of life and pain were seen favouring the celecoxib group. No increased incidence of cardiovascular events was observed in the celecoxib group.

    INTERPRETATION: This study failed to demonstrate a survival benefit of the addition of celecoxib to palliative chemotherapy.

    sted, utgiver, år, opplag, sider
    Elsevier, 2011
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-68748 (URN)10.1016/j.ejca.2011.03.035 (DOI)000292946200015 ()21565487 (PubMedID)
    Tilgjengelig fra: 2011-06-01 Laget: 2011-06-01 Sist oppdatert: 2017-12-11bibliografisk kontrollert
  • 4.
    Koch, Andrea
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Allergicentrum US.
    Bergman, Bengt
    Department of Respiratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Holmberg, Erik
    Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sweden.
    Sederholm, Christer
    Linköpings universitet, Institutionen för medicin och hälsa, Lungmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Lungmedicinska kliniken US.
    Ek, Lars
    Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund, Sweden.
    Kosieradzki, Jaroslaw
    Department of Respiratory Medicine and Allergology, Skåne University Hospital, Malmö, Sweden.
    Lamberg, Kristina
    Department of Pulmonary Medicine, Uppsala University Hospital, Uppsala, Sweden.
    Thaning, Lars
    Department of Pulmonary Medicine, University Hospital, Örebro, Sweden.
    Ydreborg, Sven-Olof
    Department of Medicine, County Hospital Ryhov, 551 85 Jönköping, Sweden.
    Sörenson, Sverre
    Linköpings universitet, Institutionen för medicin och hälsa, Lungmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Lungmedicinska kliniken US.
    Effect of celecoxib on survival in patients with advanced non-small cell lung cancer: A double blind randomised clinical phase III trial (CYCLUS study) by the Swedish Lung Cancer Study Group2011Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 47, nr 10, s. 1546-1555Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Increased expression of cyclooxygenase-2 (COX-2) is common in non-small cell lung cancer (NSCLC) and has been associated with poor prognosis. Experimental and clinical phase II trials have indicated that the addition of the COX-2 inhibitor celecoxib to palliative chemotherapy might increase survival time in patients with advanced NSCLC.

    METHODS: We performed a double-blind, placebo-controlled multicentre phase III trial at 13 centres in Sweden. Three hundred and nineteen patients with advanced NSCLC stage IIIB-IV and performance status 0-2 were randomised to receive celecoxib 400mg b.i.d. or placebo in addition to palliative chemotherapy. The primary objective was to compare overall survival. Other end-points were quality of life, progression-free survival, toxicity, cardiovascular events and biological markers. The trial is registered with ClinicalTrials.gov, No. NCT00300729.

    FINDINGS: Three hundred and sixteen patients were included in the analysis, 158 in each treatment group. Median survival time was 8.5months. There was no survival difference between the treatment arms. Small but not statistically significant differences in global quality of life and pain were seen favouring the celecoxib group. No increased incidence of cardiovascular events was observed in the celecoxib group.

    INTERPRETATION: This study failed to demonstrate a survival benefit of the addition of celecoxib to palliative chemotherapy.

  • 5.
    Koch, Andrea
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Allergicentrum US.
    Fohlin, Helena
    Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Sörenson, Sverre
    Linköpings universitet, Institutionen för medicin och hälsa, Allmänmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Lungmedicinska kliniken US.
    Prognostic significance of C-reactive protein and smoking in patients with advanced non-small cell lung cancer treated with first-line palliative chemotherapy.2009Inngår i: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, ISSN 1556-1380, Vol. 4, nr 3, s. 326-32Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    HYPOTHESIS: The objective of the study was to analyze if C-reactive protein (CRP) and smoking status provide prognostic information in patients with advanced non-small cell lung cancer (NSCLC) receiving palliative first-line chemotherapy. METHODS: Retrospective, single-institutional study, comprising all patients with NSCLC stage IIIB/IV and World Health Organization performance status (PS) 0-2 who started palliative first-line chemotherapy between January 1, 2002, and January 31, 2007. Patient records were reviewed. Cox's proportional hazards model was used to identify prognostic factors. RESULTS: Two hundred eight-nine consecutive patients were evaluable. Sixty-eight percent had stage IV disease and 67% had PS 0 or 1. Median survival was 7.4 months. At onset of chemotherapy, 206 patients (71%) had elevated CRP values (> or = 10 mg/liter). One-hundred-forty-four patients (50%) were current smokers. On univariate analysis, patients with elevated CRP levels had inferior survival (hazard ratio [HR] = 1.67, 95% confidence interval [CI], 1.28-2.19, p < 0.001). Smoking at onset of treatment was associated with shorter survival (HR 1.56, 95% CI, 1.22-1.98, p < 0.001). Ever smokers had shorter survival than never smokers (HR 1.80, 95% CI, 1.25-2.59, p = 0.001). On multivariate analysis, with stage, PS, albumin, and gender as covariates, both smoking at start of chemotherapy and CRP elevation were independent negative prognostic factors for survival. CONCLUSIONS: CRP and smoking status are independent prognostic factors for survival in patients with advanced NSCLC receiving palliative first-line chemotherapy and provide additional information to established prognostic factors such as stage of disease and performance status.

  • 6.
    Koch, Andrea
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Allergicentrum US.
    Gustafsson, Bertil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Fohlin, Helena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Sörenson, Sverre
    Linköpings universitet, Institutionen för medicin och hälsa, Lungmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Lungmedicinska kliniken US.
    Cyclooxygenase-2 expression in lung cancer cells evaluated by immunocytochemistry2011Inngår i: Diagnostic Cytopathology, ISSN 8755-1039, E-ISSN 1097-0339, Vol. 39, nr 3, s. 188-193Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cyclooxygenase-2 (COX-2) expression may be a prognostic factor in lung cancer. In previous studies, COX-2 expression has almost exclusively been evaluated with immunohistochemical methods performed on histology sections of tissue biopsies. However, in clinical practice, lung cancer is often diagnosed with cytological techniques only. We present methodology and results from analysis of COX-2 expression with immunochemistry on cytological material in 53 patients with lung cancer. Preparation and staining with the method established at our laboratory were easy to perform and resulted in good quality slides. The percentage COX-2-stained cells and the intensity of staining varied widely between and within the different cases. The proportion of positively stained tumor cells was as follows: <1% in 20 patients, 1-10% in 7 patients, 11-50% in 17 patients, and more than 50% in 9 patients. In 17 cases, groups of cells with different intensity of COX-2 staining were found in the same slide. In conclusion, immunocytochemical analysis of COX-2 expression is technically easy to perform with routine diagnostic procedures. There is a great variation in the proportion of COX-2-positive cells among patients and in the intensity of staining among individual cells in many single cases. Diagn. Cytopathol.2011;39:188-193. © 2010 Wiley-Liss, Inc.

  • 7.
    Koch, Andrea
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Lungmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Lungmedicinska kliniken US. Lungeavdelingen, Haukeland Universitetssykehus, Bergen, Norge.
    Sörenson, Sverre
    Linköpings universitet, Institutionen för medicin och vård, Lungmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Lungmedicinska kliniken US. Lungeavdelingen, Haukeland Universitetssykehus, Bergen, Norge.
    Askeland, Asgeir
    Yrkesmedisinsk avdeling, Haukeland Universitetssykehus, Bergen, Norge.
    Aasen, Tor
    Yrkesmedisinsk avdeling, Haukeland Universitetssykehus, Bergen, Norge.
    Rapportering av yrkesrelatert lungekreft.2003Inngår i: Lungeforum, ISSN 0803-4079, E-ISSN 1891-1587, Vol. 13, s. 12-16Artikkel i tidsskrift (Annet vitenskapelig)
  • 8.
    Koch, Andrea
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Sörenson, Sverre
    Linköpings universitet, Institutionen för medicin och hälsa, Lungmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Lungmedicinska kliniken US.
    Fohlin, H
    Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Gustafsson, B
    Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och klinisk genetik.
    Expression of cyclooxygenase-2 in cytological material from patients with lung cancer in EJC SUPPLEMENTS, vol 7, issue 2, pp 513-5132009Inngår i: EJC SUPPLEMENTS, 2009, Vol. 7, nr 2, s. 513-513Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 9.
    Sörenson, Sverre
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Lungmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Lungmedicinska kliniken US. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Allergicentrum US.
    Fohlin, Helena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Lindgren, Andrea
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Allergicentrum US.
    Lindskog, Magnus
    Uppsala University, Sweden .
    Bergman, Bengt
    Sahlgrens University Hospital, Sweden .
    Sederholm, Christer
    Linköpings universitet, Institutionen för medicin och hälsa, Lungmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Lungmedicinska kliniken US.
    Ek, Lars
    Skåne University Hospital, Sweden .
    Lamberg, Kristina
    University of Uppsala Hospital, Sweden .
    Clinchy, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Predictive role of plasma vascular endothelial growth factor for the effect of celecoxib in advanced non-small cell lung cancer treated with chemotherapy2013Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, nr 1, s. 115-120Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim of the study: The primary purpose of this study is to investigate if pretreatment plasma levels of vascular endothelial growth factor (VEGF) are predictive of the effect of celecoxib on survival in advanced non-small cell lung cancer (NSCLC) treated with palliative chemotherapy. A secondary objective is to describe the course of plasma VEGF levels during and after treatment with cytotoxic chemotherapy combined with celecoxib or placebo. less thanbrgreater than less thanbrgreater thanMethods: In a previously published double-blind multicenter phase III trial, 316 patients with NSCLC stage IIIB or IV and World Health Organisation (WHO) performance status 0-2 were randomised to receive celecoxib 400 mg b.i.d. or placebo in combination with two-drug platinum-based chemotherapy. Chemotherapy cycle length was three weeks and planned duration of chemotherapy was four cycles. Celecoxib was given for a maximum of one year but was stopped earlier in case of disease progression or prohibitive toxicity. In a subset of patients, plasma VEGF levels were examined at onset of treatment and at 6, 12 and 20 weeks. less thanbrgreater than less thanbrgreater thanResults: VEGF levels at start of treatment were obtained in 107 patients at four study sites. The median value was 70 pg/ml. Mean values declined during the first 12 weeks and then increased at 20 weeks. A subpopulation treatment effect pattern plot (STEPP) analysis showed an inverse relationship between initial plasma VEGF and the impact of celecoxib on survival with zero effect at 200 pg/ml. The effect on survival by celecoxib in the whole subset of patients was positive (hazard ratio (HR)=0.64 [confidence interval (CI) 0.43-0.95], p=0.028). less thanbrgreater than less thanbrgreater thanConclusion: Low pretreatment plasma levels of VEGF appear to be predictive of a positive effect of celecoxib on survival.

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