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  • 201. Pfeiffer, P
    et al.
    Sörbye, H
    Ehrsson, H
    Fokstuen, T
    Mortensen, JP
    Baltesgard, L
    Tveit, KM
    Ögreid, D
    Starkhammar, Hans
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Wallin, I
    Qvortrup, C
    Glimelius, B
    Short-time infusion of oxaliplatin in combination with capecitabine (XELOX30) as second-line therapy in patients with advanced colorectal cancer after failure to irinotecan and 5-fluorouracil2006Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 17, nr 2, s. 252-258Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The efficacy of oxaliplatin combined with capecitabine (XELOX) as second-line therapy in patients with advanced colorectal cancer (ACRC) resistant to irinotecan is not well established. Oxaliplatin induces acute, cold-induced neuropathy in most patients. The incidence is claimed to be infusion rate-dependent and therefore a 2-h infusion is recommended. Patients and methods: For practical and economic reasons, but also for patient's convenience, we performed a phase II study to examine XELOX30 (capecitabine 1000 mg/m2 orally twice daily on days 1-14 and oxaliplatin 130 mg/m2 as a 30 min infusion on day 1) in patients with ACRC resistant to irinotecan. In addition the pharmacokinetics of oxaliplatin was studied. Results: From November 2002 to September 2003, 70 patients with ACRC were treated with XELOX30. Median age was 62 (range 33-74 years) years and median performance status was 1 (range 0-2). The median number of courses was four (range 1-12) and median cumulative dose of oxaliplatin was 530 (range 125-1560) mg/m2. The response rate was 17% (95% CI 10-23), median time to progression (TTP) was 5.4 months (95% CI 4.6-6.4) and median survival 9.5 months (95% CI 8.5-11.2). White blood cell count (WBC) and performance status were significantly correlated to TTP. Neurotoxicity was moderate: grade 1 56%, grade 2 17% and grade 3 6%. Other grade 3 toxicities were nausea/ vomiting 9%, diarrhoea 14% and PPE 8%. The maximum blood concentration and total body clearance of oxaliplatin was higher than previously reported in studies examining 2-h infusions, but the volume of distribution and terminal half-life was in close agreement with previous results. Conclusion: XELOX30 is a very convenient second-line regimen in ACRC with an activity and safety profile similar to other oxaliplatin schedules. © 2005 European Society for Medical Oncology.

  • 202.
    Polymeropoulos, MH
    et al.
    Novartis Pharmaceut Corp, Pharmacogenet, Gaithersburg, MD USA Linkoping Univ, Dept Biomed & Surg, Fac Hlth Sci, S-58185 Linkoping, Sweden.
    Baras, A
    Novartis Pharmaceut Corp, Pharmacogenet, Gaithersburg, MD USA Linkoping Univ, Dept Biomed & Surg, Fac Hlth Sci, S-58185 Linkoping, Sweden.
    Walz, Thomas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Kwon, I
    Novartis Pharmaceut Corp, Pharmacogenet, Gaithersburg, MD USA Linkoping Univ, Dept Biomed & Surg, Fac Hlth Sci, S-58185 Linkoping, Sweden.
    Dressman, MA
    Novartis Pharmaceut Corp, Pharmacogenet, Gaithersburg, MD USA Linkoping Univ, Dept Biomed & Surg, Fac Hlth Sci, S-58185 Linkoping, Sweden.
    Detecting gene amplification in breast cancer by combining Gene expression profiling and Gene mapping.2001Inngår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 69, nr 4, s. 440-Konferansepaper (Annet vitenskapelig)
  • 203.
    Pérez-Tenorio, Gizeh
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Alkhori, Liza
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Olsson, Birgit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Ahnstro Waltersson, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Rutqvist, Lars Erik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Skoog, Lambert
    Institutionen för Cytology, Karolinska Hospital, Stockholm, Sweden.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer2007Inngår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 13, nr 12, s. 3577-3584Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: The phosphatidylinositol 3'-kinase/Akt pathway is frequently altered in breast cancer. PTEN, a phosphatase that opposes the effect of phosphatidylinositol 3'-kinase, can be mutated or lost, whereas the PIK3CA gene is mutated. These have been proposed as alternative mechanisms, and their clinicalpathology significance is under discussion. In this study, we aimed to explore whether PIK3CA mutations and PTEN loss are mutually exclusive mechanisms, correlate with other known clinicopathologic markers, or have clinical implication in breast cancer.

    Experimental Design: Exons 9 and 20 of the PIK3CA gene were analyzed in 270 breast tumors, and mutations were detected by single-stranded conformational analysis followed by sequencing. The expression of PTEN was evaluated by immunohistochemistry in 201 tumors.

    Results: PIK3CA mutations were found in 24% of the tumors and associated with estrogen receptor(+) status, small size, negative HER2 status, high Akt1, and high cyclin D1 protein expression. PTEN was negative in 37% of the cases and PTEN loss was associated with PIK3CA mutations (P = 0.0024). Tumors presenting PTEN loss or both alterations were often estrogen receptor(+), small in size, and HER2(-). PIK3CA mutations predicted for longer local recurrence-free survival. Moreover, PTEN loss by itself or combined with mutated PIK3CA tended to confer radiosensitivity. In addition, the patients with high S-phase fraction had longer recurrence-free survival if they carried mutations in the PIK3CA gene and/or had lost PTEN, whereas the same alterations were associated with shorter recurrence-free survival among patients with low S-phase fraction.

    Conclusions: PIK3CA mutations and PTEN loss were not mutually exclusive events and associated with similar prognostic factors.

  • 204.
    Pérez-Tenorio, Gizeh
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Members of the Southeast Sweden Breast Cancer Group,
    Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients2002Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 86, nr 4, s. 540-545Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Akt/PKB is a serine/threonine protein kinase that regulates cell cycle progression, apoptosis and growth factor mediated cell survival in association with tyrosine kinase receptors. The protein is a downstream effector of erbB-2 with implications in breast cancer progression and drug resistance in vitro. We aimed to examine the role of Akt-1 in breast cancer patients, by determining whether the expression (Akt-1) and/or activation (pAkt) were related to prognostic markers and survival. The expression of erbB-2, heregulin β1 and Bcl-2 was also assessed by flow cytometry or immunohistochemistry. This study comprised 93 patients, aged < 50 who were treated with tamoxifen and/or goserelin. We found that pAkt was associated with lower S-phase fraction (P = 0.001) and the presence of heregulin β1-expressing stromal cells (P = 0.017). Neither Akt-1 nor pAkt was related with other factors Turnout cells-derived heregulin β1 was found mainly in oestrogen receptor negative (P = 0.026) and node negative (P = 0.005) cases. Survival analysis revealed that pAkt positive patients were more prone to relapse with distant metastasis, independently of S-phase fraction and nodal status (multivariate analysis; P = 0.004). The results suggest that activation of Akt may have prognostic relevance in breast cancer

  • 205.
    Qvortrup, C.
    et al.
    Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, Odense C 5000, Denmark, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
    Yilmaz, M.
    Department of Oncology, Aalborg University Hospital, Aalborg, Denmark.
    Ogreid, D.
    Department of Oncology, Rogaland Central Hospital, Stavanger, Norway.
    Berglund, A.
    Department of Oncology, Radiology and Clinical Immunology, University Hospital, Uppsala University Hospital, Uppsala, Sweden.
    Balteskard, L.
    Department of Oncology, Tromso University Hospital, Tromso, Norway.
    Ploen, J.
    Department of Oncology, Vejle Hospital, Vejle, Denmark.
    Fokstuen, T.
    Department of Oncology and Pathology, Karolinska Hospital, Stockholm, Sweden.
    Starkhammar, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Sorbye, H.
    Sørbye, H., Department of Oncology, Haukeland University Hospital, Bergen, Norway.
    Tveit, K.
    Department of Oncology, Ullevål University Hospital, Oslo, Norway.
    Pfeiffer, P.
    Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, Odense C 5000, Denmark.
    Chronomodulated capecitabine in combination with short-time oxaliplatin: A Nordic phase II study of second-line therapy in patients with metastatic colorectal cancer after failure to irinotecan and 5-flourouracil2008Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 19, nr 6, s. 1154-1159Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Oxaliplatin in combination with capecitabine prolongs survival in patients with metastatic colorectal cancer (mCRC). Chronomodulation might reduce toxicity and improve efficacy. Patients and methods: A phase II study examining chronomodulated XELOX30 (XELOX30chron): oxaliplatin: 130 mg/m2 on day 1, as a 30-min infusion between 1 and 3 p.m. Capecitabine: total daily dose of 2000 mg/m2, 20% of the dose between 7 and 9 a.m. and 80% of the dose between 6 and 8 p.m. in patients with mCRC resistant to irinotecan. Seventy-one patients were enrolled. Response rate was 18%, median progression-free survival 5.1 months and median overall survival (OS) 10.2 months. Platelet count and performance status were significantly correlated to OS in multivariate analyses. Neurotoxicity grade 2 and 3 was seen in 25% and 2% of patients, respectively, other grade 3 toxic effects were as follows: nausea 6%, vomiting 3%, diarrhoea 12% (3% experienced grade 4) and palmoplantart erytem 9%. Conclusion: XELOX30chron is a convenient second-line regimen with efficacy and safety profile similar to other oxaliplatin schedules. To further investigate chronomodulated XELOX, we have started a Nordic randomised phase II study comparing XELOX30 and XELOX30chron as first-line therapy in patients with mCRC. © The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

  • 206.
    Rosell, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Bengtsson, N-O
    Department of Oncolog, Umea University Hospital, Sweden.
    Fornander, T
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Hatschek, T
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Lindman, H
    Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
    Malmstrom, P-O
    Department of Oncology, Lund University Hospital, Lund, Sweden.
    Wallgren, A
    Department of Oncology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Hälsa och samhälle. Linköpings universitet, Hälsouniversitetet.
    Time dependent effects of adjuvant tamoxifen therapy on cerebrovascular disease: results from a randomised trial2011Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 104, nr 6, s. 899-902Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Tamoxifen has been associated with an increased risk of stroke. There is, however, little information on the effect in the post-treatment period. Using data from the Swedish Breast Cancer Group adjuvant trial of 5 vs 2 years of tamoxifen treatment, we now report both short-term and long-term effects on morbidity as well as mortality because of cerebrovascular disease. METHODS: Data from the Swedish National Hospital Discharge Registry combined with information from the Swedish Cause of Death Registry was used to define events of disease. Hazard ratios (HRs) were estimated using Cox regression. RESULTS: Comparing patients randomised to 5 years of tamoxifen with patients randomised to 2 years of tamoxifen, the incidence of cerebrovascular diseases was increased (HR 1.70, 95% CI 1.05-2.75) during the active treatment phase and reduced after the active treatment period (HR 0.78, 95% CI 0.63-0.96), and the difference in HR between the two time-periods was significant (P 0.0033). The mortality from cerebrovascular diseases was increased during the treatment period (HR 3.18, 95% CI 1.03-9.87) and decreased during the post-treatment period (HR 0.60, 95% CI 0.40-0.90) with a significant difference in HR between the two periods of follow-up (P=0.0066). Similar results were seen for subgroups of cerebrovascular diseases, such as stroke and ischaemic stroke. CONCLUSION: In an adjuvant setting, tamoxifen was associated with an increased risk of cerebrovascular disease during treatment, but a decreased risk in the post-treatment period.

  • 207.
    Rosenberg, Per
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Andersson, H
    Boman, K
    Ridderheim, M
    Sorbe, B
    Puistola, U
    Parö, G
    Randomized trial of single agent paclitaxel given weekly versus every three weeks and with peroral versus intravenous steroid premedication to patients with ovarian cancer previously treated with platinum2002Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 41, nr 5, s. 418-424Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of this study was to evaluate the efficacy and toxicity of paclitaxel given at the same dose intensity and administered weekly (arm A) or every 3 weeks (arm B), and to assess the safety of intravenous steroids versus standard peroral premedication. Two hundred and eight patients with advanced ovarian cancer previously treated with no more than one platinum-containing regimen were randomized to receive either a weekly infusion of paclitaxel or an infusion every 3 weeks. The median delivered dose intensity was 77.6 mg/m2/week in the weekly arm, and 72.7 mg/m2/week in the every 3 weeks arm. WHO grade 3-4 hematological and non-hematological toxicity occurred more frequently in arm B. No difference in number of severe events of hypersensitivity, response rate, time to progression or survival between arms was observed. Weekly paclitaxel at a dose of 67 mg/m2/week was found to have a better safety profile and seemed to be as effective as the equivalently dosed schedule every 3 weeks. Intravenous steroids are a safe alternative to oral steroids.

  • 208.
    Ryden, Lisa
    et al.
    Lund University Hospital.
    Jirstrom, Karin
    Lund University.
    Haglund, Monica
    Lund University.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Ferno, Marten
    Lund University.
    Epidermal growth factor receptor and vascular endothelial growth factor receptor 2 are specific biomarkers in triple-negative breast cancer. Results from a controlled randomized trial with long-term follow-up2010Inngår i: BREAST CANCER RESEARCH AND TREATMENT, ISSN 0167-6806, Vol. 120, nr 2, s. 491-498Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Triple-negative breast cancer (TNB) has poor prognosis and moreover patients with TNB do not benefit from established targeted drugs with endocrine therapy or trastuzumab. The aim of the study was to analyze the prevalence of candidate biomarkers in tumors from patients with TNB. Tissue microarrays were prepared from primary tumors from premenopausal breast cancer patients (500/564) randomized to adjuvant tamoxifen or no adjuvant treatment. Immunohistochemical (IHC) staining included ER, PR, HER2, epidermal receptor growth factor (EGFR), vascular endothelial growth factor A (VEGF-A), and vascular endothelial growth factor receptor 2 (VEGFR2). EGFR and HER2 gene copy number was defined by fluorescence in situ hybridization (FISH). All patients were included in the descriptive analysis, but only untreated patients in the survival analysis. TNB was diagnosed in 96 patients and correlated significantly to low age, Nottingham histological grade (NHG) III, high Ki67-index, T2 tumors, node negativity, EGFR positivity, increased EGFR gene copy number and high VEGFR2 expression. TNB was an independent prognostic factor for decreased 5-year breast cancer specific survival (BCSS) (HR 2.0 (95% CI 1.1-3.6), P = 0.01), but not for 10-year BCSS. High VEGFR2 expression was significantly correlated to decreased BCSS in TNB patients. TNB was associated with decreased BCSS and clinicopathological characteristics of an aggressive tumor type. High VEGFR2 expression, EGFR expression, and EGFR gene copy number were significantly correlated to TNB, supporting their role as putative candidate biomarkers for selection of targeted therapy in TNB.

  • 209.
    Saarinen, N M
    et al.
    University of Turku.
    Abrahamsson, Annelie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Enterolactone but not genistein decreases estradiol-induced tumor growth, angiogenesis, and secreted VEGF in vivo in human breast cancer. in CANCER RESEARCH, vol 69, issue 2, pp 325S-325S2009Inngår i: CANCER RESEARCH, 2009, Vol. 69, nr 2, s. 325S-325SKonferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 210.
    Saarinen, Niina M.
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Abrahamsson, Annelie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Estrogen-induced angiogenic factors derived from stromal and cancer cells are differently regulated by enterolactone and genistein in human breast cancer in vivo2010Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 127, nr 3, s. 737-745Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Angiogenesis is a key in cancer progression and its regulators are released both by the tumor cells and the stroma. Dietary phytoestrogens, such as the lignan enterolactone (ENL) and the isoflavone genistein (GEN), may differently affect breast cancer growth. In this study, human breast cancer cells (MCF-7) were established in mice creating a tumor with species-specific cancer and stroma cells. Ovariectomized athymic mice supplemented with estradiol (E2) were fed basal AIN-93G diet (BD) or BD supplemented with 100 mg/kg ENL, 100 mg/kg GEN or their combination (ENL+GEN). We show that ENL and ENL+GEN inhibited E2-induced cancer growth and angiogenesis, whereas GEN alone did not. Microdialysis was used to sample extracellular proteins in tumors in vivo. ENL and ENL+GEN decreased both stroma- and cancer cell-derived VEGF, whereas cancer cell-derived PlGF increased. In subcutaneous Matrigel plugs in mice, ENL and ENL+GEN decreased E2-induced endothelial cell infiltration, whereas GEN alone did not. In endothelial cells, ENL inhibited E2-induced VEGFR-2 expression, whereas GEN did not. These results suggest that ENL has potent effects on breast cancer growth, even in combination with GEN, by downregulating E2-stimulated angiogenic factors derived both from the stroma and the cancer cells, whereas dietary GEN does not possess any antiestrogenic effects.

  • 211.
    Sanchez, B. C.
    et al.
    Karolinska Institute.
    Sundqvist, M.
    Kalmar Hospital.
    Fohlin, Helena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Spyratos, F.
    Ctr Rene Huguenin, Lab Oncogenet, St Cloud, France.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Linderholm, B. K,
    Karolinska Institute.
    Prolonged tamoxifen treatment increases relapse-free survival for patients with primary breast cancer expressing high levels of VEGF2010Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 46, nr 9, s. 1580-1587Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Previous retrospective studies have shown that high intratumoural levels of vascular endothelial growth factor (VEGF) correlate with an inferior outcome for patients treated with adjuvant tamoxifen. Our objectives were to validate the impact of VEGF on survival after adjuvant tamoxifen and to investigate the interaction between VEGF and treatment duration. For this purpose tumour homogenates from 402 patients with operable oestrogen receptor positive breast cancer (BC), treated with tamoxifen for 2 (n = 149) or 5 years (n = 253) as the only systemic adjuvant therapy were included. The median follow-up time for surviving patients was 9.8 years (range 0.5-14.8 years). Expression of VEGF was assessed by an enzyme-linked immunosorbent assay and investigated in relation to the standard BC parameters and survival. In the total population, higher VEGF was significantly correlated with shorter recurrence-free survival (RFS) (HR = 1.63, 95%CI = 1.11-2.39, p = 0.010), breast cancer corrected survival (BCCS) (HR = 1.82, 95%CI = 1.13-2.93, p = 0.014) and overall survival (OS) (HR = 1.51, 95%CI = 1.11-2.05, p = 0.009). High VEGF was significantly associated with reduced RFS (HR = 2.61, 95%CI = 1.45-4.70, p = 0.001) after two years of tamoxifen, whilst no difference was seen in patients treated for five years (HR = 1.09, 95%CI = 0.64-1.84, p = 0.760). A statistically significant interaction was observed between high VEGF expression and improved RFS after 5-year tamoxifen (p = 0.034). In concordance with previous studies, high VEGF was significantly correlated with shorter survival. We present data not reported previously revealing that patients expressing high levels of VEGF display a better outcome provided that tamoxifen is given for five years. Further studies on the impact of VEGF on a 5-year regimen are motivated.

  • 212.
    Sandblom, Gabriel
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Urologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Dufmats, Monika
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Olsson, Mats
    Varenhorst, Eberhard
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Urologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Validity of a population-based cancer register in Sweden - An assessment of data reproducibility in the South-East Region prostate cancer register2003Inngår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 37, nr 2, s. 112-119Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: With a population-based setting, high coverage and accurately recorded data, the validity of a register is guaranteed. The South-East Region Prostate Cancer relies on the National Cancer Register as a basic source of data, thereby ensuring a high coverage of the corresponding geographic area. To assess the reproducibility of the data recorded a random sample of the cases were reviewed a second time and compared to the original recording. Material and methods: The South-East Region Prostate Cancer Register was started in 1987. In addition to the basic data acquired from the Swedish National Register, it also includes tumour stage, grade, treatment and, since 1992, PSA. In the first stage of quality assessment 10 cases for each of the years 1987-1996 from Link÷ping University Hospital were randomly selected for two independent recodings according to the same protocol as the original registration. In the second step 10 cases each for the same years from the remaining 8 hospitals in the region were selected for a single recoding. Results: No systematic deviations were seen between the two independent recodings from Link÷ping, a single recoding was therefore considered sufficient for assessing the reproducibility of the data from the remaining hospitals in the region. The Kappa values for agreement between the original registration and the single recoding ranged from 0.589 to 0.869. Conclusion: The population-based setting and high coverage guarantees the external validity of the register. The internal validity is ensured by the high reproducibility shown in the present study.

  • 213.
    Sandblom, Gabriel
    et al.
    Karolinska Institute.
    Varenhorst, Eberhard
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Urologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Lofman, Owe
    Norwegian University of Life Science.
    Carlsson, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Utvärdering och hälsoekonomi. Linköpings universitet, Hälsouniversitetet.
    Randomised prostate cancer screening trial: 20 year follow-up2011Inngår i: BRITISH MEDICAL JOURNAL, ISSN 0959-535X, Vol. 342, nr d1539Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To assess whether screening for prostate cancer reduces prostate cancer specific mortality. Design Population based randomised controlled trial. Setting Department of Urology, Norrkoping, and the South-East Region Prostate Cancer Register. Participants All men aged 50-69 in the city of Norrkoping, Sweden, identified in 1987 in the National Population Register (n=9026). Intervention From the study population, 1494 men were randomly allocated to be screened by including every sixth man from a list of dates of birth. These men were invited to be screened every third year from 1987 to 1996. On the first two occasions screening was done by digital rectal examination only. From 1993, this was combined with prostate specific antigen testing, with 4 mu g/L as cut off. On the fourth occasion (1996), only men aged 69 or under at the time of the investigation were invited. Main outcome measures Data on tumour stage, grade, and treatment from the South East Region Prostate Cancer Register. Prostate cancer specific mortality up to 31 December 2008. Results In the four screenings from 1987 to 1996 attendance was 1161/1492 (78%), 957/1363 (70%), 895/1210 (74%), and 446/606 (74%), respectively. There were 85 cases (5.7%) of prostate cancer diagnosed in the screened group and 292 (3.9%) in the control group. The risk ratio for death from prostate cancer in the screening group was 1.16 (95% confidence interval 0.78 to 1.73). In a Cox proportional hazard analysis comparing prostate cancer specific survival in the control group with that in the screened group, the hazard ratio for death from prostate cancer was 1.23 (0.94 to 1.62; P=0.13). After adjustment for age at start of the study, the hazard ratio was 1.58 (1.06 to 2.36; P=0.024). Conclusions After 20 years of follow-up the rate of death from prostate cancer did not differ significantly between men in the screening group and those in the control group.

  • 214.
    Sandén, Inger
    et al.
    Linköpings universitet, Institutionen för tema, Tema Kommunikation. Linköpings universitet, Filosofiska fakulteten.
    Linell, Per
    Linköpings universitet, Institutionen för tema, Tema Kommunikation. Linköpings universitet, Filosofiska fakulteten.
    Starkhammar, Hans
    Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US. Linköpings universitet, Hälsouniversitetet.
    Sätterlund Larsson, Ullabeth
    Linköpings universitet, Institutionen för tema, Tema Kommunikation. Linköpings universitet, Filosofiska fakulteten.
    Routinization and sensitivity: Interaction in oncological follow-up consultations2001Inngår i: Health, ISSN 1363-4593, E-ISSN 1461-7196, Vol. 5, nr 2, s. 139-163Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    The empirical data of this study were gathered in the form of audio-taped recordings of dialogues between 21 patients, who had had operations for testicular cancer and three physicians during follow-up consultations. The aim is to inquire into how routine practices affect the goals of checking up the medical conditions and providing patients with reassurance, and how practices affect the treatment of sensitive topics and the patients’ possibilities of bringing up their own problems are affected. The results show that the routines built up by the medical care programme are used as recurrent opportunities for the parties to confirm that the situation is under control and as resources when they talk about the sensitive topics of sexuality and fertility. How the routinization affected the patients’ possibilities of bringing up their own problems cannot be fully determined. Of the 50 initiatives by patients to present their problems, only nine did so solely on their own initiative.

  • 215.
    Schelin, Sonny
    et al.
    Kalmar County Hospital.
    Madsen, Mikael
    Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Aus, Gunnar
    Sahlgrens University Hospital.
    Long-term follow-up after triple treatment of prostate cancer stage pT32009Inngår i: SCANDINAVIAN JOURNAL OF UROLOGY AND NEPHROLOGY, ISSN 0036-5599, Vol. 43, nr 3, s. 186-191Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. Radical prostatectomy (RP) has become the most common treatment for localized prostate cancer in Sweden. Outcome is extremely good for pT2 stage with Gleason score 6 or less, but more than every fourth operated patient will have a pT3 stage on full amount specimen histology. According to several reports the risk of biochemical recurrence is quite high, especially in stage pT3, on active surveillance after surgery alone. In 1994 the authors recognized this fact at their clinic and decided to apply a new multimodality treatment concept. Material and methods. During 10 years, between 1 January 1995 and 1 January 2005, 98 pT3 patients were treated with a triple treatment: 8 months of neoadjuvant/adjuvant luteinizing hormone-releasing hormone (LH-RH) analogue treatment, RP and immediate adjuvant radiotherapy (RT) 3 months after RP. RT was delivered to 60 Gy in 30 fractions to the prostatic bed to all the patients. The cumulative risk of progression was calculated with the Kaplan-Meier method. The impact of risk factors was evaluated by the Cox proportional hazard model. Results. Ninety-eight (74 pT3a and 24 pT3b) patients were followed with a mean observation time from operation until October 2007 of 71.6 (median 65.5, range 35-146) months. The mean follow-up time to biochemical failure, death or last measurement of prostate-specific antigen (PSA) was 57.8 (median 57.0, range 3-132) months. Fifteen patients out of 98 had experienced biochemical failure. Only Gleason score had an independent impact on the risk of PSA progression. Complications were mild and temporary and no serious adverse events were registered. Conclusions. Patients with locally advanced prostate cancer have a high risk of progression after RP as single therapy. Postoperative RT has been shown to improve the outcome. Neoadjuvant/adjuvant hormonal therapy has been shown to improve the outcome after RT. Bringing this knowledge together offering a multimodality therapy with neoadjuvant/adjuvant hormonal therapy, RP followed by postoperative immediate RT seems to offer a high chance of biochemical-free survival.

  • 216.
    Schöier, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Högdahl, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk mikrobiologi.
    Söderlund, Gustaf
    Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Kihlström, Erik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Chlamydia (Chlamydophila) pneumoniae-induced cell death in human coronary artery endothelial cells is caspase-independent and accompanied by subcellular translocations of Bax and apoptosis-inducing factor.2006Inngår i: FEMS Immunology and Medical Microbiology, ISSN 0928-8244, E-ISSN 1574-695X, Vol. 47, nr 2, s. 207-216Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Atherosclerosis and coronary heart disease are causing high morbidity and mortality worldwide. Different risk factors have been demonstrated, but the exact mechanisms behind these diseases are still not fully understood. Recent studies have suggested Chlamydia pneumoniae to be involved in the pathogenesis, and increased apoptotic indexes in atherosclerotic plaques have been documented. In this study, we show that C. pneumoniae induces apoptosis and necrosis in populations of human coronary artery endothelial cells. Apoptosis was determined by TUNEL and flow cytometry after staining of cells with annexin V and propidium iodide, and defined as TUNEL-reactive or annexin V-positive, propidium iodide-negative cells. The apoptosis was induced within 2 h postinfection and increased with inoculation dose. The general caspase inhibitor z-VAD-fmk did not affect apoptotic frequencies. By immunochemistry and immunoblot, we demonstrated activation and subcellular translocation of the proapoptotic protein Bax, and translocation of apoptosis-inducing factor from the cytosol to the nucleus. These results indicate that C. pneumoniae-induced apoptosis in human coronary artery endothelial cells is caspase-independent and regulated by Bax and apoptosis-inducing factor.

  • 217. Schüle, Jana
    et al.
    Bergkvist, Leif
    Håkansson, Leif
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Gustafsson, Bertil
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och klinisk genetik.
    Håkansson, Annika
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Down-regulation of the CD3-? chain in sentinel node biopsies from breast cancer patients2002Inngår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 74, nr 1, s. 33-40Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. In several neoplastic diseases, immunosuppression has been shown to correlate with disease stage, progression, and outcome. As the prognosis for metastatic breast cancer is still pessimistic, additional strategies are being sought to improve survival. Local immunosuppression in sentinel node biopsies from 24 evaluable breast cancer patients was studied as a possible way of selecting patients for immunotherapy. Method. Sentinel node biopsy was performed in 24 out of 25 women operated on for primary breast cancer (one was not evaluable). Specimens were snap-frozen and double-stained for the ?-chain of the T-cell receptor. The degree of down-regulation of the ?-chain was evaluated in three different lymph-node areas: primary follicles, secondary follicles, and paracortex. Results. Down-regulation of varying degrees was noted in all 24 sentinel node biopsies. A high degree of down-regulation (more than 50% of T-cells not expressing ?-chain) was seen in the primary follicles in six patients (25%), in the secondary follicles in 13 patients (72%), and in the paracortex in 19 patients (79%). Conclusion. Local down-regulation of an immune function parameter was seen in sentinel node biopsies from breast cancer patients. In addition to possible prognostic implications, the sentinel node might be an appropriate location for detecting early-stage immunological down-regulation, which might open a possibility of selecting patients who could benefit from immunotherapy.

  • 218. Schüle, Jana M
    et al.
    Bergkvist, Leif
    Håkansson, Leif
    Gustafsson, Bertil
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och klinisk genetik.
    Håkansson, Annika
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    CD28 expression in sentinel node biopsies from breast cancer patients in comparison with CD3-ζ chain expression2004Inngår i: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 2Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Immunosuppression is documented in several malignant diseases, including breast cancer. Subsequently, future therapeutic concepts might include immunological approaches. However, detailed knowledge about tumor immunogenicity and host immunoreactivity, and how to assess these adequately, is still limited. We studied CD28 and CD3-ζ expression in sentinel node biopsies (SNB) from breast cancer patients to analyze tumor-related changes in T cell activity. Method: 25 women underwent surgery for primary breast cancer, including SNB. Frozen sections from 21 sentinel nodes could be analyzed with a double-staining technique. CD28 expression was studied in CD4+ and CD8+ T-lymphocyte subsets and compared with CD3-ζ expression in three specified nodal regions. Results: The degree of CD28 expression varied between the different lymph node areas. The lowest degree of CD28 expression was observed in CD4+ T-lymphocytes in the paracortex and germinal centers. Here, a good agreement with CD3-ζ expression was found. A higher CD28 expression was noted in CD4+ T-cells in the primary follicles, where concordance with CD3-ζ expression was weaker. The CD8+ T-lymphocyte subset displayed generally a higher degree of CD28 expression than the CD4+ subset. Conclusion: Sentinel lymph nodes from breast cancer patients displayed local immunosuppression of varying extent. In the areas with the lowest degree of CD28 expression an accordingly low CD3-ζ expression was found. The SNB might prove an important diagnostic tool for the evaluation of interactions between tumor and the host immune system, helping to select patients who might benefit from adjuvant immunotherapy.

  • 219.
    Shabo, Ivan
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi.
    Nordenskjöld, Kerstin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Incidensen av gallblåsecancer i Sverige har minskat. Den dåliga prognosen kan möjligen förbättras genom radikal kirurgi. [The incidence of gallbladder cancer in Sweden has decreased. The poor prognosis can possibly be improved by radical surgery.]2001Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 98, nr 42, s. 4584-4589Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [sv]

    Gallblåsecancer är en relativt sällsynt sjukdom som har dålig prognos med kort överlevnadstid. Sjukdomen drabbar framför allt kvinnor. Vi har inhämtat registerdata från cancerregistret och dödsorsaksregistret och studerat utvecklingen i Sverige mellan 1988 och 1997. Under de senaste åren har incidensen minskat, vilket möjligen kan förklaras av en hög kolecystektomifrekvens under 1950- och 1970-talen. Prognosen vid erhållen diagnos har tidigare varit dålig, med en medianöverlevnad på 3,5 månader, vilket beror på att diagnosen ofta har ställts först när sjukdomen blivit avancerad. Epidemiologiska data visar att dessa siffror kan ha förbättrats de senaste åren. I flera aktuella studier, framför allt från Japan, rapporteras bättre resultat och längre överlevnadstid efter utvidgad kirurgi. I ett material av elva patienter med gallblåsecancer, grad II–V enligt Nevin, som opererats med utvidgad kirurgi i Linköping finns hos tio inga tecken på recidiv efter en uppföljningstid på 1–8 år.

  • 220.
    Shabo, Ivan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time.2009Inngår i: International journal of cancer. Journal international du cancer, ISSN 1097-0215, Vol. 125, nr 8, s. 1826-1831Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Expression of the macrophage antigen CD163 in breast cancer cells is recently shown to be related to early distant recurrence and shortened survival. In this study, 163 patients with rectal cancer, included in the Swedish rectal cancer trial and followed up for a median of 71 months, were examined for the expression of CD163 in the primary tumors. The cancer cells expressed CD163 in the primary tumors in 23% (n = 32) of the patients. In pretreatment biopsies from 101 patients, 10 had CD163-positive cancers and these patients had earlier local recurrence (p < 0.044) and reduced survival time (p < 0.045) compared with those with CD163-negative tumors. When studying surgical specimens from 61 patients randomized to preoperative irradiation (5 x 5 Gy delivered in 1 week), it was found that 31% were CD163 positive whereas the corresponding figure was only 17% for 78 patients who were nonirradiated (p < 0.044), which tentatively may be consistent with X-rays inducing fusion. In CD163-positive tumors there was a reduced apoptotic activity as measured with the Termina deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) technique (p = 0.018). There tended also to be an increased proliferation activity measured as an expression of Ki-67 non significant (NS). It is concluded that primary rectal cancers may express CD-163, and this phenotypic macrophage trait is related to early local recurrence, shorter survival time and reduced apoptosis. Furthermore, the expression of CD163 is more common after irradiation.

  • 221.
    Shen, X-G
    et al.
    Sichuan University.
    Wang, C
    Sichuan University.
    Li, Y
    Sichuan University.
    Wang, L
    Sichuan University.
    Zhou, B
    Sichuan University.
    Xu, B
    Sichuan University.
    Jiang, X
    Sichuan University.
    Zhou, Z-G
    Sichuan University.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Downregulation of caspase-9 is a frequent event in patients with stage II colorectal cancer and correlates with poor clinical outcome2010Inngår i: COLORECTAL DISEASE, ISSN 1462-8910, Vol. 12, nr 12, s. 1213-1218Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To evaluate the clinical significance of caspase-9 mRNA expression and investigate its prognostic value in stage II colorectal cancer. Method Quantitative real-time RT-PCR was used to analyse caspase-9 mRNA expression in cancer tissue and corresponding normal mucosa from 120 patients. Results Compared with normal mucosa, the expression of caspase-9 mRNA was found to be downregulated in cancer tissue (P = 0.001). Poorly differentiated cancer showed lower mRNA expression than cancer with greater differentiation (P = 0.031). The Kaplan-Meier survival analysis demonstrated that patients with downregulated caspase-9 showed a worse overall survival (P = 0.012) and disease-free survival (P = 0.022). Coxs proportional hazards regression model confirmed that expression of caspase-9 was the strongest prognostic factor in stage II colorectal cancer. Conclusion The mRNA expression of caspase-9 can be used as an independent prognostic factor for patients with stage II colorectal cancer.

  • 222.
    Sivik, Tove
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Fornander, T
    Karolinska Institute.
    Skoog, L
    Karolinska Institute.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Jansson, Agneta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Significance of 17bHSD Type 14 as a Predictive Factor for Adjuvant Tamoxifen Treatment Response in Breast Cancer in CANCER RESEARCH, vol 69, issue 24, pp 596S-597S2009Inngår i: CANCER RESEARCH, 2009, Vol. 69, nr 24, s. 596S-597SKonferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 223. Skoglund, Johanna
    et al.
    Emterling, Anna
    Arbman, Gunnar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Anglard, Patrick
    Sun, Xiao-Feng
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Clinicopathological significance of stromelysin-3 expression in colorectal cancer2004Inngår i: Oncology, ISSN 0890-9091, Vol. 67, nr 1, s. 67-72Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Stromelysin-3 (ST3) is a member of the matrix metalloproteinases and suggested to play a role in tissue remodeling observed in growth and metastasis of tumors. ST3 overexpression in breast cancer is associated with a worse outcome. Our aims were to analyze ST3 expression in primary colorectal tumors and metastases, and further to identify relationships of the expression to clinicopathological factors. Materials and Methods: ST3 expression was immunohistochemically analyzed in 200 primary colorectal adenocarcinomas and 36 corresponding lymph node metastases. Results: Scoring was performed by counting the percentages of positive cells and the percentages of positive areas. One hundred and one (51%) cases showed ≤5% positive cells and 99 (49%) >5% positive cells. One hundred and two (51%) cases showed ≤30% positive area and 98 (49%) >30% positive area. ST3 expression determined by both scoring methods was individually related to females, distally located tumors, infiltrative growth pattern and microsatellite stability. No relationship was found with age, Dukes' stage, differentiation and survival. Conclusions: These results suggest that ST3 protein was more involved in the pathway of colorectal cancer development in females, distal locations, infiltrative growth patterns and microsatellite stability. Copyright © 2004 S. Karger AG, Basel.

  • 224.
    Sorbe, B.
    et al.
    Department of Gynecological Oncology, University Hospital, Örebro, Sweden, Department of Gynecological Oncology, University Hospital, SE-701 85 Örebro, Sweden.
    Andersson, H.
    Department of Gynecological Oncology, University Hospital, Gothenburg, Sweden.
    Boman, K.
    Department of Gynecological Oncology, University Hospital, Umeå, Sweden.
    Rosenberg, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Kalling, M.
    Department of Gynecologic Oncology, University Hospital, Lund, Sweden.
    Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel - Long-term follow-up2008Inngår i: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 18, nr 4, s. 803-808Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is no generally accepted standard chemotherapy in treatment of advanced and recurrent endometrial carcinoma. Cisplatin and doxorubicin with or without cyclophosphamide are widely used. Response rates have improved with combination chemotherapy compared with single-agent therapy. A platinum analog seems to be an important part of the chemotherapy regimen. Since few patients are cured from their disease and since the duration of response is short, further improvement of this therapy is warranted. During the past years, the taxanes (paclitaxel) are being added to prior evaluated regimens and not only improved response rates are reported but also increased toxicity is observed. In a prospective, phase II, multicenter study, carboplatin (area under the curve = 5) and paclitaxel (175 mg/m2) were evaluated in treatment of primary advanced and recurrent endometrial carcinoma. In total, 66 patients were recruited during the years 2000-2004. Eighteen primary advanced tumors and 48 recurrences were treated. All histologic types and tumor grades were allowed. The median follow-up was 57 months (range 37-69 months). The overall response rate was 67% (95% CI 55-78). The complete response rate was 29% and the partial response rate 38%. Primary advanced and recurrent tumors as well as endometrioid and nonendometrioid tumors showed similar response rates. The median response duration was 14 months. The 1- and 3-year survival rates were 82% and 33%, respectively. The main toxicities were hematologic and neurologic (sensory neuropathy). The response rates were encouraging, superior to prior platinum-containing regimens, but response duration and the long-term survival rate were still short. The neurologic toxicity was frequent and was a substantial problem in this series of patients. Further research is highly needed to improve the treatment of advanced and recurrent endometrial cancer. © 2007, Copyright the Authors.

  • 225.
    Starkhammar, Hans
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Aspects on priority settings in cancer treatment and care2005Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, nr 7, s. 667-672Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The widening gap between available resources and increasing possibilities to diagnose and treat different medical conditions has resulted in new attention to priority setting. The issue is complicated and harbours several obstacles because of different valuations concerning the needs of patient groups, the true results ( patient benefit) of medical actions, and also important ethical considerations. Earlier attempts have been unsuccessful in introducing a prioritisation milieu into the medical profession, probably due to vague requests for an open and sharp prioritisation process. With a sharpened competition of allocating resources for different medical actions, the medical profession of the cancer sector needs to have a tool for explaining consequences for the different cancer patient groups and what is achieved by the cancer treatments and the care. A model for ranking lists consisting of pairs of patient conditions and medical actions is presented, and the principle for using these lists for priority setting in medical society is discussed.

  • 226.
    Stendahl, M.
    et al.
    Department of Laboratory Medicine, Lund University, Malmö University Hospital, S-205 02 Malmö, Sweden, Department of Medicine, Ryhov Regional Hospital, Jönköping, Sweden.
    Ryden, L.
    Rydén, L., Department of Laboratory Medicine, Lund University, Malmö University Hospital, S-205 02 Malmö, Sweden.
    Nordenskjöld, Bo
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Jonsson, P.E.
    Jönsson, P.E., Department of Surgery, Helsingborg Hospital, Helsingborg, Sweden.
    Landberg, G.
    Department of Laboratory Medicine, Lund University, Malmö University Hospital, S-205 02 Malmö, Sweden.
    Jirstrom, K.
    Jirström, K., Department of Laboratory Medicine, Lund University, Malmö University Hospital, S-205 02 Malmö, Sweden.
    High progesterone receptor expression correlates to the effect of adjuvant tamoxifen in premenopausal breast cancer patients2006Inngår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 12, nr 15, s. 4614-4618Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Tamoxifen has long been the drug of choice in adjuvant endocrine therapy of steroid hormone receptor-positive breast cancer, and it still remains important due to its well-documented beneficial effect. Hormone receptor status is often reported as "positive" or "negative" using 10% positive nuclei as a cutoff. In this study, we aimed to assess whether a further subclassification of hormone receptor status could enhance the treatment predictive value. Experimental Design: The immunohistochemical expression of estrogen receptor (ER) and progesterone receptor (PR) was quantified in tissue microarrays with tumors from 500 premenopausal breast cancer patients previously included in a randomized trial of adjuvant tamoxifen compared with an untreated control group. Results: Our findings show a gradually increasing tamoxifen effect in tumors with >10% ER-positive nuclei. However, when analyzing tamoxifen response according to various PR fractions, we found that it was primarily patients with tumors showing >75% PR-positive nuclei that responded to tamoxifen treatment, with an improved recurrence-free [relative risk, 0.42 (0.25-0.70), P = 0.001] as well as overall [relative risk, 0.49 (0.28-0.84), P = 0.010] survival. Conclusions: Adjuvant tamoxifen improved recurrence-free and overall survival for premenopausal patients with tumors showing >75% PR-positive nuclei. No effect could be shown in tumors with fewer PR-positive nuclei. The PR was a stronger predictor of treatment response than the ER. Based on these findings, we suggest the implementation of a fractioned rather than dichotomized immunohistochemical evaluation of hormone receptors in clinical practice, possibly with greater emphasis on the PR than the ER. © 2006 American Association for Cancer Research.

  • 227.
    Stendahl, Maria
    et al.
    Lund University.
    Nilsson, Sofie
    University of Manchester.
    Wigerup, Caroline
    Lund University.
    Jirstrom, Karin
    Lund University.
    Jonsson, Per Ebbe
    Helsingborgs Lasarett.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Landberg, Goran
    University of Manchester.
    p27(Kip1) is a predictive factor for tamoxifen treatment response but not a prognostic marker in premenopausal breast cancer patients2010Inngår i: INTERNATIONAL JOURNAL OF CANCER, ISSN 0020-7136, Vol. 127, nr 12, s. 2851-2858Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The cell-cycle regulating protein p27(Kip1) (p27) has dual roles by acting as both a cdk inhibitor and as an assembly factor for different cdk complexes. Loss of p27 has been linked to malignant features in tumours; however, the exact role of p27 deregulation in breast cancer regarding prognostic and treatment predictive information has not been fully clarified. We have evaluated p27 expression in 328 primary, Stage II breast cancers from premenopausal patients who had been randomised to either tamoxifen treatment or no adjuvant treatment after surgery. p27 was associated with the oestrogen receptor and cyclin D1, and p27 downregulation was associated with high proliferation. There was no association between recurrence-free survival (RFS) and p27 (HR = 0.800, 95% CI 0.523-1.222, p = 0.300), indicating that p27 is not a prognostic marker. The predictive value of p27 was analysed by comparing RFS in tamoxifen-treated and untreated patients in subgroups of low and high p27 expression (HR = 0.747, 95% CI 0.335-1.664, p = 0.474 and HR = 0.401, 95% CI 0.240-0.670, p andlt; 0.001, respectively). Only patients with p27-high tumours benefited from tamoxifen (multivariate interaction analysis p = 0.034). Our study suggests that p27 downregulation is associated with tamoxifen resistance in premenopausal breast cancer but is not linked to impaired prognosis.

  • 228. Stenmark Askmalm, Marie
    et al.
    Carstensen, John
    Linköpings universitet, Institutionen för hälsa och samhälle.
    Nordenskjöld, Bo
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Olsson, Birgit
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi.
    Rutqvist, Lars Erik
    Skoog, Lambert
    Stål, Olle
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Mutation and accumulation of p53 related to results of adjuvant therapy of postmenopausal breast cancer patients2004Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 43, nr 3, s. 235-244Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    p53 protein accumulation and gene mutation have been implicated in resistance to cytotoxic treatment. This study was performed to further assess the predictive value of p53 in breast cancer. Postmenopausal patients were randomized to adjuvant chemotherapy with cyclophosphamide, metothrexate, or 5-fluorouracil (CMF) vs. Postoperative radiotherapy. The patients were also randomized to adjuvant tamoxifen vs. No endocrine treatment. Immunohistochemistry (IHC) and single-strand conformation polymorphism (SSCP), followed by direct sequencing, was performed. The p53 altered group, regarded as positive for p53 gene mutation and/or p53 protein accumulation, tended to benefit more from CMF than from radiotherapy as compared with others regarding distant recurrences. In the group lacking p53 alteration there was a significantly decreased local recurrence rate in the radiotherapy group as compared with the CMF group (RR = 0.24, 95% CI = 0.083-0.62), whereas no benefit from radiotherapy was found for patients snowing p53 alterations. Tamoxifen significantly decreased the rate of distant recurrence for estrogen receptor-positive patients with no apparent difference in relation to p53 alteration. It is suggested that p53 alteration indicates benefit from CMF compared with radiotherapy regarding distant recurrence-free survival and the best local control with radiotherapy is achieved in the absence of p53 alteration. Finally, altered p53 status is probably not a marker of resistance to tamoxifen.

  • 229.
    Stål, Olle
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Jerevall, Piiha-Lotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Institutionen för klinisk och experimentell medicin.
    Ma, Xiai-Jun
    bioTheranostics, San Diego, CA, USA.
    Li, Hongying
    bioTheranostics, San Diego, CA, USA.
    Salunga, Ranelle
    Massachusetts General Hospital, USA.
    Erlander, Mark
    Karolinska Institute, Stockholm, Sweden.
    Sgroi, Dennis
    Harvard Medical School, Boston, MA, USA.
    Holmlund, Birgitta
    Karolinska Institute, Stockholm, Sweden.
    Skoog, Lambert
    Karolinska Institute, Stockholm, Sweden.
    Fornander, Tommy
    Karolinska Institute, Stockholm, Sweden.
    Validation of Prognostic Utility of HOXB13:IL17BR and Molecular Grade Index in Early Stage Breast Cancer: in CANCER RESEARCH, vol 69, issue 24, pp 504S-504S2009Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Background. HOXB13:IL17BR (H:I) is a two gene expression index, which has been shown to be an independent prognostic factor in estrogen receptor (ER)-positive lymph node-negative (N0) breast cancer. A molecular grade index (MGI) measures the expression of five proliferation-related genes. An algorithm based on dichotomized H:I and MGI stratifying patients into three risk groups has been shown to be superior to either alone in predicting risk of distant metastasis in ER+/N0 patients. Further validation in larger cohorts is needed to establish its clinical performance. A continuous predictor combining H:I and MGI is desirable for making individualized risk assessment in the clinical setting.

    Methods. During 1976 through 1990 the Stockholm Breast Cancer Group conducted a randomized clinical trial comparing adjuvant tamoxifen with control in 1780 postmenopausal women considered to be at low risk of recurrence (N0 and tumor size < 3 cm). We measured H:I and MGI using a real time PCR assay in 769 patients from this trial based on sample availability. Correlation of gene expression indices with distant metastasis and death due to breast cancer was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. Modeling was also used to develop a continuous risk index as a function of both H:I and MGI.

    Results. Using pre-specified cutoff points and combination algorithm, H:I, MGI and their combination each was significantly associated with both distant metastasis-free survival and breast cancer-specific survival (Table 1). Furthermore, we used the ER+ tamoxifen-treated subset (n=314) to develop a continuous risk model (Breast Cancer Index or BCI) combining both H:I and MGI. The prognostic utility of BCI was then successfully validated in the untreated subset in this trial and three additional previously published cohorts. BCI consistently identified ∼50% patients with a very low 10-year recurrence risk (< 5%). Discussion. This large retrospective analysis of a randomized clinical trial cohort validated the prognostic utility of H:I, MGI, and their combination. With the continuous risk model, this RT-PCR-based assay allows prediction of risk of recurrence at the individual level, which may help tailor personalized treatment strategy.

  • 230.
    Sun, Xiao-Feng
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Clinicopathological and biological features of DNA tetraploid colorectal cancers2006Inngår i: Cancer Journal, ISSN 0765-7846, E-ISSN 1292-8658, Vol. 12, nr 6, s. 501-506Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Most studies of colorectal cancers focus on a comparison of DNA diploid to non-diploid tumors consisting of tetraploid and aneuploid tumors. Tetraploid tumors alone have not been well studied. In the present study, clinicopathological and biological features of tetraploid colorectal cancers in contrast to those of diploid and aneuploid ones were investigated. PATIENTS AND METHODS: DNA ploidy in 278 primary colorectal adenocarcinomas was determined by flow cytometry. RESULTS: Among 278 cases, 8% of the cases were tetraploidy, 44% were aneuploidy, and 48% were diploidy. Compared to diploid tumors, tetraploid tumors were more frequent in advanced stage, high index of S-phase fraction and apoptosis, higher expression of Cox-2, c-erbB-2 and heat shock protein, but had decreased inflammatory infiltration (P < 0.05). Compared to aneuploid tumors, tetraploid tumors had a high frequency of microsatellite instability, high expression of Cox-2 and heat shock protein (P < 0.05). Unlike tetraploid tumors, aneuploid tumors had increased p53 expression but did not have microsatellite instability (P < 0.05). Tetraploidy and aneploidy predicted a worse prognosis in the subgroups of stages A-C, proximal colon, p53 negative expression and higher S-phase fraction (P < 0.05). CONCLUSIONS: DNA tetraploid tumors seem, to some extent, to exhibit distinct characteristics of clinicopathology and biology compared with aneuploid or diploid colorectal cancers. Copyright © 2006 Jones and Bartlett Publishers, Inc.

  • 231.
    Sun, Xiao-Feng
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    p73 overexpression is a prognostic factor in patients with colorectal adenocarcinoma2002Inngår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 8, nr 1, s. 165-170Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To examine the expression of p73 in the different stages of colorectal cancer development and the association of p73 expression with patient survival. Experimental Design: Expression of p73 protein was evaluated by immunohistochemistry in 221 primary colorectal cancer patients, including 58 patients with matched normal mucosa and metastases in the regional lymph nodes. Results: Frequency and intensity of p73 expression were markedly increased from the normal samples (19%) to primary tumors (67%) and to metastases (95%). Overexpression of p73 predicted poor outcome in the whole group of patients (P = 0.014) and the subgroups with left-sided (P = 0.002) or ras-positive tumors (P = 0.019). The prognostic significance remained in the whole group (P = 0.008) and the subgroup with left-sided tumors (P = 0.019) after adjustment for the patient's sex, age, tumor stage, growth pattern, and differentiation. The p73 expression was positively correlated with ras expression (P = 0.006). The 5-year survival rates were 37, 53, 72, and 74% for the patients with p73+/ras+, p73+/ras-, p73-/ras+, and p73-/ras- tumors, respectively (P = 0.007). Conclusion: Our data indicate that overexpression of p73 independently predicted poor prognosis in the patients with colorectal cancer.

  • 232.
    Sun, Xiao-Feng
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Ahmadi, Ahmad
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för medicinsk cellbiologi.
    Arbman, Gunnar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Wallin, Åsa
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi.
    Asklid, Daniel
    Zhang, Hong
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för dermatologi och venereologi.
    Polymorphisms in sulfotransferase 1A1 and glutathione S-transferase P1 genes in relation to colorectal cancer risk and patients' survival2005Inngår i: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 11, nr 43, s. 6875-6879Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: To examine whether polymorphisms in SULT1A1 and GSTP1 genes contribute to colorectal cancer development and whether they are associated with clinicopathological variables are not well identified. Methods: We examined the genotypes of 125 colorectal cancer patients and 666 healthy controls in a Swedish population by using PCR restriction fragment length polymorphism (RFLP). Results: SULT1A1 *2/*2 genotype (OR = 2.49, 95%CI = 1.48-4.19, P = 0.0002) and *2 allele (OR = 1.56, 95%CI = 1.16-2.10, P = 0.002) had an effect on colorectal cancer susceptibility, while GSTP1 genotype was without effect. However, GSTP1 G-type predicted a worse prognosis in the patients independently of gender, age, Dukes' stage, growth pattern, and differentiation (P = 0.03). Conclusion: Polymorphism in SULT1A1 may predispose to colorectal cancer and GSTP1 may be a biological indicator of prognosis in the patients. © 2005 The WJG Press and Elsevier Inc. All rights reserved.

  • 233.
    Sun, Xiao-Feng
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Ekberg, Hanna
    Zhang, Hong
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för dermatologi och venereologi.
    Carstensen, John
    Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutionen för tema.
    Nordenskjöld, Bo
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Overexpression of ras is an independent prognostic factor in colorectal adenocarcinoma1998Inngår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 106, nr 6, s. 657-664Artikkel i tidsskrift (Fagfellevurdert)
  • 234.
    Sun, Xiao-Feng
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi.
    Rütten, Sabine
    Zhang, Hong
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi.
    Nordenskjöld, Bo
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Expression of the deleted in colorectal cancer gene is related to prognosis in DNA diploid and low proliferative colorectal adenocarcinoma.1999Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 17, s. 1745-1750Artikkel i tidsskrift (Fagfellevurdert)
  • 235.
    Sun, Xiao-Feng
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Zhang, Hong
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för dermatologi och venereologi.
    Clinicopathological significance of stromal variables: Angiogenesis, lymphangiogenesis, inflammatory infiltration, MMP and PINCH in colorectal carcinomas2006Inngår i: Molecular Cancer, ISSN 1476-4598, E-ISSN 1476-4598, Vol. 5Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cancer research has mainly focused on alterations of genes and proteins in cancer cells themselves that result in either gain-of-function in oncogenes or loss-of-function in tumour-suppressor genes. However, stromal variables within or around tumours, including blood and lymph vessels, stromal cells and various proteins, have also important impacts on tumour development and progression. It has been shown that disruption of stromal-epithelial interactions influences cellular proliferation, differentiation, death, motility, genomic integrity, angiogenesis, and other phenotypes in various tissues. Moreover, stromal variables are also critical to therapy in cancer patients. In this review, we mainly focus on the clinicopathological significance of stromal variables including angiogenesis, lymphangiogenesis, inflammatory infiltration, matrix metalloproteinase (MMP), and the particularly interesting new cysteine-histidine rich protein (PINCH) in colorectal cancer (CRC). © 2006 Sun and Zhang, licensee BioMed Central Ltd.

  • 236.
    Sun, Xiao-Feng
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Zhang, Hong
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för dermatologi och venereologi.
    NFKB and NFKBI polymorphisms in relation to susceptibility of tumour and other diseases2007Inngår i: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 22, nr 10-12, s. 1387-1398Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Nuclear factor-κB (NF-κB) is responsible for the expression by regulating many genes for immune response, cell adhesion, differentiation, proliferation, angiogenesis and apoptosis. The function of NF-κB is inhibited by binding to NF-κB inhibitor (IκB), and imbalance of NF-κB and IκB has been associated with development of many diseases, including tumours. In this review, we focus on polymorphisms of the NFKB and NFKBI genes in relation to development of common inflammatory diseases including ulcerative colitis (UC), Crohn's disease (CD), rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, giant cell arthritis, type 1 diabetes, multiple sclerosis, celiac disease, and Parkinson's disease, as well as susceptibility of several cancers, such as oral squamous cell carcinoma, colorectal cancer (CRC), hepatocellular carcinoma, breast cancer and myeloma.

  • 237.
    Sun, Xiao-Feng
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Zhang, Hong
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Hälsa och samhälle. Linköpings universitet, Filosofiska fakulteten.
    Jansson, Agneta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Heat shock protein 72/73 in relation to cytoplasmic p53 expression and prognosis in colorectal adenocarcinomas1997Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 74, nr 6, s. 600-604Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Heat shock proteins (hsp) are molecular chaperones that are increased by various environmental and patho-physiological stimuli. Hsp can bind to mutant/wild-type p53 in tumors and, consequently, could not only regulate p53 accumulation or localization but also modulate its biological effects on cells. However, there is little information available on the significance of hsp expression in colorectal cancer. The aim of our study was to investigate the relationship of hsp to p53 expression, clinico-pathological factors and prognosis in a series of 256 patients with colorectal adenocarcinomas, using immuno-histochemistry. Seventy-five cases exhibited hsp expression in the cytoplasm, with 11 presenting both cytoplasmic and nuclear staining. Hsp expression was related positively to cytoplasmic p53 expression but not to nuclear p53 expression. In the subgroup of rectal tumors, hsp over-expression appeared to predict unfavorable survival, though its prognostic value diminished using multivariate analysis. There were no significant relationships of hsp with patient sex or age, tumor site, Duke's stage, growth pattern or differentiation.

  • 238.
    Sundelin, Kaarina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Roberg, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Grénman, Reidar
    Department of Otorhinolaryngology – Head and Neck Surgery and Department of Medical Biochemistry, University Hospital and University of Turku, Turku, Finland.
    Håkansson, Leif
    Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Effects of cisplatin, interferon-alpha and 13-cis retinoic acid on the expression of Fas (CD95), intercellular adhesion molecule-1 (ICAM-1) and epidermal growth factor receptor (EGFR) in oral cancer cell lines2007Inngår i: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 36, nr 3, s. 177-183Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Previous studies showed that many chemotherapeutic agents can induce immuno-suppression at therapeutic drug concentrations whereas low drug doses induce immuno-augmentation.

    Methods: The effect of low-dose cisplatin, interferon-alpha, and 13-cis retinoic acid on receptors involved in immune-mediated apoptosis (Fas/CD95), cell growth (epidermal growth factor receptor) and lymphocyte adhesion (intercellular adhesion molecule-1) was investigated in two oral cancer cell lines (UT-SCC-20A and UT-SCC-24A). Different methods for cell preparation were studied: mechanical and enzymatic detachment, and culture on chamber slides. Receptor expression was investigated using immunohistochemical staining. The amount of soluble and cell-bound Fas was determined with the ELISA technique, and the functional relevance of Fas expression, apoptosis induction, was analyzed.

    Results: Cisplatin enhanced cytoplasm and membrane staining for Fas in both cell lines. After cisplatin treatment, the amount of soluble Fas was increased in UT-SCC-20A cultures, but no effect was observed in the UT-SCC-24A cell line. Apoptosis, measured as enhanced caspase-3 activity, was induced by an agonistic Fas antibody (CH11) after cisplatin treatment in UT-SCC-24A cells.

    Conclusions: Low-dose cisplatin treatment enhanced Fas expression in both cell lines and increased susceptibility to apoptosis in one of them.

  • 239.
    Söderlund Leifler, Karin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    ¨, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Skoog, Lambert
    Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden.
    Rutqvist, Lars Erik
    Department of Medicine/Huddinge, Karolinska Institute, Stockholm,Sweden.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Stenmark Askmalm, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Intact Mre11/Rad50/Nbs1 complex predicts good response to radiotherapy in early breast cancer2007Inngår i: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 68, nr 1, s. 50-58Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Post-operative radiotherapy is offered to a majority of breast cancer patients, since it significantly reduces the risk of local recurrence. However, some patients still develop recurrences. Owing to their vital roles in the repair of radiation-induced double-strand breaks, the Mre11/Rad50/Nbs1 (MRN) complex and the ATM protein might be implicated in tumour cell resistance to radiotherapy. The aim of this study was to investigate the expression and predictive role of these DNA repair proteins for the outcome of radiotherapy in breast cancer patients.

    Patients and Methods: The protein expression of ATM and the proteins in the MRN complex were investigated using immunohistochemistry in tumours from 224 women with early breast cancer, who were randomised to receive post-operative radiotherapy or adjuvant chemotherapy (CMF).

    Results: Compared to normal breast tissue, the staining intensity of Mre11, Rad50, Nbs1 and ATM was reduced in a majority of the tumours. Weak expression of the MRN complex was correlated to high histological grade and ER negativity (p=0.01 and p=0.0001). Radiotherapy significantly reduced the risk of local recurrence as compared to chemotherapy (p=0.04). The greatest benefit of radiotherapy was seen in patients with moderate/strong expression of the MRN complex (RR=0.27, 95% C.I. 0.098-0.72, p=0.009), whereas patients with negative/weak MRN had no benefit of radiotherapy compared to CMF. These results suggest that an intact MRN complex is important for the tumour cell eradicating effect of radiotherapy.

  • 240.
    Söderlund Leifler, Karin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Pérez-Tenorio, Gizeh
    Linköpings universitet, Institutionen för biomedicin och kirurgi. Linköpings universitet, Hälsouniversitetet.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Activation of the phosphatidylinositol 3-kinase/Akt pathway prevents radiation-induced apoptosis in breast cancer cells2005Inngår i: International Journal of Oncology, ISSN 1019-6439, Vol. 26, nr 1, s. 25-32Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Radiotherapy is widely used in the treatment of breast cancer and reduces the risk of loco-regional recurrence. Overexpression of the erbB2 receptor occurs in 20-30% of all breast cancers, and seems to be involved in chemotherapeutic resistance of breast cancer cells and radioresistance of lung cancer cells. The hypothesis of this study was that erbB2 confers resistance to radiation-induced apoptosis in breast cancer cells through the phosphatidylinositol 3-kinase (PI3-K)/Akt signalling pathway. Two human breast cancer cell lines were used, BT-474 and MCF-7. BT-474 cells overexpress erbB2 and have mutated p53, while MCF-7 have normal expression of erbB2 and functional p53. The cells were treated with the PI3-K inhibitor wortmannin or the erbB receptor ligand heregulin-ß1, which is expressed by both malignant and stromal cells in vivo. After pharmacological treatment, the cells were irradiated with 10 Gy gamma-radiation. Consistent with the p53 status in the cell lines, gamma-radiation caused G1 arrest in MCF-7 cells, but not in BT-474 cells. 10 Gy gamma-radiation increased apoptosis by on an average 76% (95% CI, 44-109%) in MCF-7. Treatment of MCF-7 with heregulin-ß1 decreased apoptosis by 66% (95% CI, 48-84%) compared to the untreated controls. In BT-474 cells, wortmannin in combination with radiation resulted in 119% (95% CI, 76-161%) more apoptosis compared to wortmannin alone, whereas radiation alone resulted in 45% (95% CI, 15-75%) increased apoptosis. This radiosensitising effect was not seen in MCF-7. Furthermore, transfection of MCF-7 cells with constitutively active Akt made the cells more resistant against apoptosis. Taken together, our results support the hypothesis that the erbB2/PI3-K/Akt signalling pathway is involved in resistance to radiation-induced apoptosis in breast cancer cells in which this signalling pathway is overstimulated.

  • 241. Sörensen, Peter
    et al.
    Höjer, Morten
    Jakobsen, Anders
    Malmström, Henric
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Havsteen, Hanne
    Bertelsen, Kamma
    Phase II study of vinorelbine in the treatment of platinum-resistant ovarian carcinoma2001Inngår i: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 81, nr 1, s. 58-62Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. The purpose of this phase II study was to evaluate on an intent-to-treat basis the activity and toxicity of single-agent vinorelbine (VRL) as second-line chemotherapy of patients with platinum-resistant ovarian cancer. Platinum-resistant disease was defined as disease refractory to or relapsing within 12 months after finishing platinum-containing chemotherapy. Methods. VRL (30 mg/m2) was administered intravenously as a bolus injection days 1 and 8 every 21 days. Initially, four courses of VRL were given. Patients with responding or stable disease received four more courses of VRL to a maximum of eight courses. Results. Twenty-eight of 33 eligible patients were considered evaluable for response. The overall response rate was 21% (7/33) (95% CI: 7-35). Median time to progression was 3.1 months and median survival was 10.1 months. Toxicity was generally mild. Leukopenia was the dose-limiting toxicity. CALGB grade III/IV infection was observed in 15/0% of patients. The most important nonhematologic toxicities were nausea and constipation. Grade III/IV nausea was observed in 6/0% and grade III/IV constipation in 3/3% of patients. Peripheral neurotoxicity was only a minor problem with no grade III/IV toxicity. No patients stopped treatment because of toxicity and no toxic death was reported. Conclusion. VRL was generally well tolerated, but the activity in platinum-resistant ovarian cancer was only modest, although fully comparable to other second-line treatments. Further studies are required to define the role of VRL in combination chemotherapy for ovarian cancer.

  • 242. Taube, A
    et al.
    Högberg, Thomas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Med P: n som i "programpaket" - om studier av prognostiska faktorer2002Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, s. 3302-3305Artikkel i tidsskrift (Annet vitenskapelig)
  • 243. Tejler, G
    et al.
    Norberg, B
    Dufmats, Monika
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi.
    Nordenskjöld, Bo
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Arnesson, Lars-Gunnar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Survival after treatment for breast cancer in a geographically defined population2004Inngår i: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 91, nr 10, s. 1307-1312Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: South East Sweden with 976000 inhabitants is served by nine hospitals with specialized breast surgeons. Population-based mammographic screening was introduced in 1986 for women aged 40-74 years. Patients with primary breast cancer were treated according to a joint management programme. Methods: All patients were reported to a regional cancer registry from which breast cancer incidence, treatment and survival in this defined population were reported. Results: A total of 7892 women had their first invasive breast cancer diagnosed between 1986 and 1999. The median tumour size was 17 mm and 29.9 per cent had axillary metastases. Some 49.8 per cent of these women had a modified radical mastectomy and 31.9 per cent had a segmental resection with axillary clearance. Postoperative radiotherapy was given to 40.3 per cent of the women after mastectomy and to 87.1 per cent after breast-conserving surgery. Tamoxifen and chemotherapy were used as adjuvant treatment except in low-risk patients. Breast cancer-specific survival rate for all stages was 83.5 per cent at 5 years and 74.0 per cent at 10 years. Respective values were 95.8 and 90.9 per cent for patients with stage T1 N0 M0 tumours, and 77.7 and 62.4 per cent for those with T1-2 N1 M0 tumours. Conclusion: Breast specialists treating women with breast cancer according to a joint management programme have achieved very good survival rates.

  • 244. Tian, Chao
    et al.
    Zhou, Zong-Guang
    Meng, Wen-Jian
    Sun, Xiao-Feng
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Yu, Yong-Yang
    Li, Li
    Luo, Hong-Zhi
    Yang, Lie
    Zhou, Bin
    Gu, Jun
    Overexpression of connective tissue growth factor WISP-1 in Chinese primary rectal cancer patients2007Inngår i: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 13, nr 28, s. 3878-3882Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: To clarify the expression change of Wnt-induced secreted protein-1 (WISP-1) in human rectal cancer and to determine whether it is correlated with invasion and metastasis of human rectal cancer. Methods: Eighty-six paired samples of rectal cancer and surgically resected distant normal rectal tissue were collected and allocated into cancer group and control group respectively. WISP-1 mRNA was detected by relative quantitative real-time RT-PCR and WISP-1 protein was examined by immunohistochemical staining. Results: WISP-1 gene overexpression was found in 65% (56/86) primary rectal cancers, 2-30 times that of the level in normal matched rectal tissues (P = 0.001). The mRNA expression level was correlated with Duke's staging, histological differentiation grade and lymph node status. The WISP-1 protein expression was in accordance with mRNA expression level. The positive degree of immunohistochemical staining in the cancer group (1.40 ± 0.35) was different from that in control group (1.04 ± 0.08, P < 0.001). Moreover, in cancer group the positive staining degree in high-level mRNA cancers (1.46 ± 0.37, n = 56) was higher than that in low-level mRNA (1.28 ± 0.28, n = 30, P = 0.018). Conclusion: Aberrant levels of WISP-1 expression may play a role in rectal tumorigenesis. WISP-1 may be used as a specific clinical diagnosis and prognosis marker in rectal cancer. © 2007 WJG. All rights reserved.

  • 245.
    Tishelman, C
    et al.
    Karolinska inst Stockholm.
    Bergenmar, M
    Karolinska inst Stockholm.
    Bernhardson, B M
    Karolinska inst Stockholm.
    Blomberg, K
    Karolinska inst Stockholm.
    Börjeson, Sussanne
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Omvårdnad. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Foderus, H
    Örebro.
    Leveälahti, H
    Karolinska inst Stockholm.
    Sahlberg-Blom, E
    Örebro.
    Ternestedt, B M
    Örebro.
    Using undergraduate nursing students as mediators in a knowledge transfer programme for care for patients with advanced cancer: Original article2008Inngår i: European Journal of Cancer Care, ISSN 0961-5423, E-ISSN 1365-2354, Vol. 17, nr 3, s. 253-260Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Nursing today faces numerous challenges. Societal changes lead to reorganization of health care, changing workloads with sicker patients in hospital and home care, and limited economic resources. The increasing and changing nature of knowledge needed for expert care provision challenges nurses to continually update their competencies. These are issues demanding proactive and dynamic changes in the way nurses conceive their mandates and practice. The aim of the action-research project presented here was to foster improved quality of care for patients with advanced cancer through collaborative endeavours integrating cancer nursing clinical practice, research and education in a knowledge exchange programme. The programme was based on input about caregiving needs from multi-professional staff caring for patients with advanced cancer in a variety of healthcare settings. Undergraduate baccalaureate nursing students were then engaged in literature studies to help address these needs. Results of the studies were communicated back to the involved clinicians in a variety of ways. In this paper, we discuss what we have experienced as opportunities and obstacles in conducting the project, based on our reflections and external evaluations. This is linked to a broader discussion of ways of integrating cancer nursing research, education and practice.

  • 246. Tishelman, Carol
    et al.
    Börjeson, Sussanne
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    The challenging complexities of cancer care2002Inngår i: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 16, s. 207-208Artikkel i tidsskrift (Fagfellevurdert)
  • 247.
    Trinks, Cecilia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Djerf, Emelie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Hallbeck, Anna-Lotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Jönsson, Jan-Ingvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell hematologi. Linköpings universitet, Hälsouniversitetet.
    Walz, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    The pan-ErbB receptor tyrosine kinase inhibitor canertinib induces ErbB-independent apoptosis in human leukemia (HL-60 and U-937) cells2010Inngår i: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, ISSN 0006-291X, Vol. 393, nr 1, s. 6-10Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Epidermal growth factor (EGF) receptor tyrosine kinase inhibitors have recently been shown to display anti-neoplastic effects in human malignant myeloid cells. Our study was initiated in order to determine the effect of the pan-ErbB receptor tyrosine kinase inhibitor, canertinib (CI-1033), on growth and survival of human leukemia (HL-60 and U-937) cells. We show that treatment of HL-60 and U-937 cells with canertinib significantly inhibits growth of both cell lines in a dose-dependent manner; half maximal effective dose (IC50) in HL-60 and U-937 cells was approximately 2.5 mu M and 1.0 mu M, respectively. Treatment with 2 mu M canertinib promoted a G(1) cell cycle arrest, whereas doses of 5 mu M or more induced apoptosis as determined by the Annexin V method and cleavage of poly-(ADP-ribose) polymerase (PARP). HL-60 and U-937 cells lacked EGF-receptor transcript but expressed ErbB2-4 mRNA as determined by RTPCR. However, none of the corresponding ErbB-receptor proteins could be detected by Western blot analysis. We conclude that canertinib induces apoptosis in HL-60 and U-937 cells devoid of functional ErbB1-4 receptors. Our results suggest that canertinib could be of potential clinical interest in the treatment of acute myeloid leukemia.

  • 248. Tropé, C
    et al.
    Kaern, J
    Hogberg, T
    Abeler, V
    Hagen, B
    Kristensen, G
    Onsrud, M
    Pettersen, E
    Rosenberg, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Sandvei, R
    Sundfor, K
    Vergote, I
    Randomized study on adjuvant chemotherapy in stage I high-risk ovarian cancer with evaluation of DNA-ploidy as prognostic instrument.2000Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 11, s. 281-288Artikkel i tidsskrift (Fagfellevurdert)
  • 249. Tropé, C
    et al.
    Nordal, R
    Himmelmann, A
    Kjörstad, K
    Onsrud, M
    Simonsen, E
    Högberg, Thomas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Einhorn, N
    Pettersson, F
    Frankendal, B
    Pettersson, B
    Tholander, B
    Svanberg, L
    Consolidation treatment of advanced (FIGO stage III) ovarian carcinoma in complete surgical remission after induction chemotherapy: A randomized, controlled, clinical trial comparing whole abdominal radiotherapy, chemotherapy, and no further treatment2003Inngår i: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 13, s. 278-286Artikkel i tidsskrift (Fagfellevurdert)
  • 250. Tågsjö, E-B
    et al.
    Andreescu, Gheorghe
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Rosenberg, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Jacobs index - enkelt sätt att avgöra om bäckentumör hos kvinna är malign.2003Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 100, s. 3231-3233Artikkel i tidsskrift (Annet vitenskapelig)
23456 201 - 250 of 295
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