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  • 1.
    Bohr Mordhorst, Louise
    et al.
    Örebro University Hospital.
    Sorbe, Bengt
    Örebro University Hospital.
    Ahlin, Cecilia
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    A study of serum biomarkers associated with relapse of cervical cancer2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 11, p. 4913-22Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIM: To discover candidate protein biomarkers in the serum of patients with cervical cancer that differentiate between patients with relapse from those who are tumor-free after primary treatment with (platinum-based chemo-) radiation.

    PATIENTS AND METHODS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) with cation exchange (CM10) and hydrophobic/reverse-phase (H50) was used to examine 44 serum samples from patients with advanced cervical cancer, primarily treated with (platinum-based chemo-) radiation.

    RESULTS: Ten candidate biomarkers were identified in the serum of 34 patients. Six candidate markers were elevated in patients with no relapse and four were elevated in patients with relapse [p=0.007-0.11; area under the curve (AUC)=0.70-0.75]. Masses of candidate biomarkers ranged from 2,022 to 116,165 Da.

    CONCLUSION: Patients with relapse from primary advanced cervical cancer exhibit different serum protein expression profiles from those with no relapse.

  • 2. Djureinovic, Tatjana
    et al.
    Lindblom, Annika
    Dalén, Johan
    Dedorson, Stefan
    Edler, David
    Hjern, Fredrik
    Holm, Jörn
    Lenander, Claes
    Lindforss, Ulrik
    Lundqvist, Nils
    Olivecrona, Hans
    Olsson, Louise
    Påhlman, Lars
    Rutegård, Jörgen
    Örebro University, School of Health and Medical Sciences.
    Smedh, Kennet
    Törnqvist, Anders
    Eiberg, Hans
    Bisgaard, Marie Luise
    The CHEK2 1100delC variant in Swedish colorectal cancer2006In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 26, no 6C, p. 4885-4888Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The cell cycle checkpoint kinase 2 (CHEK2) 1100delC variant has recently been identified at high frequency in families with both breast and colorectal cancer, suggesting the possible role of this variant in colorectal cancer predisposition. PATIENTS AND METHODS: To evaluate the role of CHEK2 ll00delC among Swedish colorectal cancer patients, the variant frequency was determined in 174 selected familial cases, 644 unselected cases and 760 controls, as well as in l8 families used in the genome-wide linkage analysis, where weak linkage was seen for the region harboring the CHEK2 gene. RESULTS: CHEK2 l100delC was found in 1.15% of familial and in 0.93% of unselected cases, compared to 0.66% of controls, showing no significant difference between groups. One out of 45 familial cases with a family history of breast cancer was shown to be a carrier. The variant was not identified in the 18 families included in the linkage analysis. CONCLUSION: The CHEK2 1100delC was not significantly increased in Swedish colorectal cancer patients, however, in order to determine the role of the variant in colorectal cancer families with the history of breast cancer a larger sample size is needed.

  • 3.
    Hakelius, Malin
    et al.
    Dept Surg Sci, Uppsala University, Uppsala, Sweden.
    Koskela, Anita
    Örebro University Hospital. Clin Res Ctr.
    Ivarsson, Mikael
    Clin Res Ctr, Örebro University Hosp, Örebro, Sweden.
    Grenman, Reidar
    Dept Otorhinolaryngol Head & Neck Surg & Med Bio, Turku University Hosp, Turku, Finland; University Turku, Turku, Finland.
    Rubin, Kristofer
    Dept Med Biochem & Microbiol, Uppsala University, Uppsala, Sweden.
    Gerdin, Bengt
    Dept Surg Sci, Uppsala University, Uppsala, Sweden.
    Nowinski, Daniel
    Dept Surg Sci, Uppsala University, Uppsala, Sweden.
    Keratinocytes and Head and Neck Squamous Cell Carcinoma Cells Regulate Urokinase-type Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Fibroblasts2013In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 33, no 8, p. 3113-3118Article in journal (Refereed)
    Abstract [en]

    Background: To investigate possible differences in the effects of soluble factors from oral squamous cell carcinoma (SCC) cells (UT-SCC-87) and normal oral keratinocytes (NOK) on fibroblast expression of genes involved in tumor stroma turnover. Materials and Methods: Transwell co-cultures with fibroblasts in collagen gels, and SCC cells or NOK in inserts were carried out. Fibroblast gene expression was measured with real-time polymerase chain reaction (PCR). Results: The expression of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) was up-regulated in co-cultures with SCC cells but not with NOK. In contrast, both SCC cells and NOK regulated matrix metalloproteinase-1 (MMP1) and -3, and tissue inhibitor of metalloproteinases-2 (TIMP2) and -3 to a similar extent, while MMP2 and TIMP1 were largely unaffected. Interleukin 1 alpha (IL1 alpha) up-regulated both MMP1 and MMP3 and down-regulated PAI-1, TIMP2 and -3. Conclusion: SCC and NOK regulate fibroblast expression of genes involved in tumor stroma turnover differentially in vitro. These observations may contribute to a better understanding of the mechanisms behind extracellular matrix turnover in tumors.

  • 4.
    Hoefig, Kai P
    et al.
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Thorns, Christoph
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Roehle, Anja
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Kaehler, Christian
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Wesche, Kai O
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Repsilber, Dirk
    Biomathematics / Bioinformatics Group, Research Institute for the Biology of Farm Animals FBN, Dummerstorf, Germany.
    Branke, Biggi
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Thiere, Marlen
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Feller, Alfred C
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Merz, Hartmut
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Unlocking pathology archives for microRNA-profiling2008In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 28, no 1A, p. 119-23Article in journal (Refereed)
    Abstract [en]

    Background: MicroRNAs (miRNAs) are approximately 22 nucleotide long, non-coding RNAs that regulate gene expression by binding to the 3'-untranslated region of target mRNAs and also a variety of cellular processes. It has recently been established that dysregulation of miRNA expression can be detected in the majority of human cancers. A variety of high-throughput screening methods has been developed to identify dysregulated miRNA species in tumours. For retrospective clinical studies formalin-fixed, paraffin-embedded (FFPE) tissue is the most widely used material.

    Materials and methods: The miRNA expression profiles of freshly frozen (CRYO) and FFPE tissues of seven tonsil and four liver samples were compared, using a qPCR-based assay, profiling 157 miRNA species.

    Results: The significance of miRNA-profiles was barely influenced by FFPE treatment in both tissues and the variance induced by FFPE treatment was much smaller than the variance caused by biologically based differential expression.

    Conclusion: FFPE material is well suited for miRNA profiling.

  • 5.
    Johansson, Andreas K
    et al.
    Section of Medical Physics, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden.
    Lennernäs, Bo
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Isacsson, Ulf
    Section of Medical Physics, Department of Immunology, Genetics and Pathology, Uppsala University, Rudbecklaboratoriet, Uppsala, Sweden.
    Neurovascular Bundle Infiltration Can Explain Local Relapses Using Conformal Radiotherapy of Prostate Cancer2017In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 37, no 4, p. 1825-1830Article in journal (Refereed)
    Abstract [en]

    AIM: To quantify the impact of decreased margins for two treatment techniques, three-dimensional conformal radiotherapy (3D-CRT) and volumetric-modulated arc therapy (VMAT), on local control in curative treatment of prostate cancer.

    MATERIALS AND METHODS: The planning target volume (PTV) margins were decreased in steps of 1 mm from 10 to 1 mm. Treatment plans using 3D-CRT and VMAT technique were produced for all margin sizes and the dose to the neuro vascular bundles (NVB), that was not included in the PTV, was investigated.

    RESULTS: Due to the more conformal dose delivery using VMAT, the dose to the NVB decreased more rapidly by VMAT compared to the 3D-CRT plans. The dose difference was significant for margins from 1-7 mm.

    CONCLUSION: One should be very cautious before clinical routines are changed, bearing in mind whether the change means more conformal treatment technique, smaller margins or target segmentation in different imaging modalities.

  • 6.
    Landström, Fredrik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Otolaryngology, Örebro University Hospital, Örebro, Sweden.
    Ivarsson, Mikael
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    von Sydow, Anita Koskela
    Örebro University Hospital. Clinical Research Center, Örebro University Hospital, Örebro, Sweden.
    Magnuson, Anders
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Clinical Research Center, Örebro University Hospital, Örebro, Sweden.
    von Beckerath, Mathias
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Otolaryngology, Örebro University Hospital, Örebro, Sweden.
    Möller, Claes
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Electrochemotherapy: Evidence for Cell-type Selectivity In Vitro2015In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 11, p. 5813-5820Article in journal (Refereed)
    Abstract [en]

    Aim: Electrochemotherapy (ECT) is a new cancer treatment modality that uses electroporation to potentiate chemotherapeutic agents, especially bleomycin. ECT causes both a direct toxic effect and an anti-vascular effect. The aim of the present study was to investigate a possible selective effect of ECT on the survival of fibroblasts, endothelial cells (HUVEC) and two squamous cell carcinoma cell lines (CAL-27 and SCC-4).

    Materials and Methods: Cells were electroporated using two bleomycin concentrations. The survival rate was assessed 1, 2, 3 and 4 days after treatment, by two different assays.

    Results: The survival rate of the fibroblasts was statistically significantly higher than the other cell lines at day 4. The HUVEC survival rate was statistically significantly lower than the other cell types at day 1 after electroporation-alone.

    Conclusion: A selective survival effect after ECT was observed in vitro, supporting the anti-vascular effect seen in vivo.

  • 7.
    Lundin, Erik
    et al.
    Örebro University, School of Medical Sciences. Department of Oncology.
    Bergqvist, Michael
    Department of Oncology, Gävle Hospital, Gävle, Sweden.
    Ahlgren, Johan
    ppsala Örebro Regional Cancer Center, Uppsala University Hospital, Uppsala, Sweden.
    Reizenstein, Johan
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Lennernäs, Bo
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Validation of a Clinical Cancer Register at the Head and Neck Oncology Center in Orebro2019In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 39, no 1, p. 285-289Article in journal (Refereed)
    Abstract [en]

    Background: This was a validation study of a regional register of oral cancer in Örebro, Sweden. The purpose was to assess the rate of errors in baseline, and treatment, and the completeness and accuracy of data on recurrences.

    Materials and Methods: A total of 653 cases with squamous cell cancer in the oral cavity were identified from the register. A randomized sample of 73 (11%) was selected, and a set of relevant data was compared to medical records.

    Results: Data on patient and tumour characteristics showed high accuracy, with 98% correct data and more than 99% of treatment data were correct. Follow-up data had a higher rate of errors, with 23% of recurrences not recorded, 13.6% misclassified, and 9.1% of cases showing errors in timing of the recurrence.

    Conclusion: data concerning patients, tumour status, and treatment in the Regional Head and Neck Register in Örebro are highly accurate. However, the follow-up data contain a higher rate of errors, that must be taken into consideration when evaluating outcome after treatment.

  • 8.
    Paulsson, Gunnar
    et al.
    Dept Gynecol & Obstet, Cent Hosp Skövde, Skövde, Sweden.
    Andersson, Solveig
    Dept Gynecol & Obstet, Malarsjukhuset, Eskilstuna, Sweden.
    Sorbe, Bengt
    Örebro University Hospital. Dept Oncol.
    A Population-based Series of Ovarian Carcinosarcomas with Long-term Follow-up2013In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 33, no 3, p. 1003-1008Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of the present study was to evaluate a consecutive series of ovarian carcinosarcomas with regard to prognosis, treatment and prognostic factors. Patients and Methods: A consecutive series of 81 ovarian carcinosarcomas from two well-defined geographic regions were studied with regard to survival, type of primary and adjuvant therapy and prognostic factors. All patients but one underwent primary surgery and some patients also received adjuvant chemotherapy (platinum-based) alone or in combination with radiotherapy. Univariate and multivariate Cox proportional regression analysis was used. Survival was analyzed by the Kaplan-Meier technique and differences were assessed by the log-rank test. Results: The mean age of the patients was 73 years. Fifty-one patients received adjuvant chemotherapy and nine patients pelvic irradiation. The 5-year overall survival rate was 10%. Adjuvant therapy (any type) and six completed cycles of chemotherapy were highly significant factors with regard to improved overall survival rate. The only significant tumor-associated prognostic factor was the International Federation of Gynecology and Obstetrics (FIGO) grade of the tumor. FIGO stage, site of metastatic spread, tumor size, histology, DNA ploidy, and tumor necrosis were nonsignificant factors. Therapy was rather well-tolerated and 29 patients (57%) completed at least six cycles of adjuvant chemotherapy. Conclusion: Adjuvant and completed chemotherapy according to the treatment plan were the most important prognostic factors. FIGO grade (grade 3 vs. 1-2) of the epithelial component of the tumor was also a significant prognostic factor in multivariate Cox analysis.

  • 9.
    Prenkert, Malin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Research Center, Örebro University Hospital, Örebro; Sweden.
    Uggla, Bertil
    Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Strid, Hilja
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    CRIM1 is expressed at higher levels in drug-resistant than in drug-sensitive myeloid leukemia HL60 cells2010In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 30, no 10, p. 4157-61Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to explore possible differences in the mRNA expression levels of CRIM1, SMAD5, BMP4 and BMP7 in sensitive (S) and multidrug-resistant (R0.5) myeloid leukemia HL60 cells.

    Materials and Methods: HL60S and HL60R0.5 cells were exposed to daunorubicin (DNR) or cytarabine (Ara-C).

    Results: Baseline levels of CRIM1 were found to be 15-fold higher in HL60R0.5 than in HL60S. Sixteen hours of exposure to DNR resulted in a 5.6-fold increase in CRIM1 levels in HL60S. Exposure to either DNR or Ara-C resulted in modest increases in CRIM1 levels in HL60R0.5. Similarly, baseline levels of SMAD5 and BMP4 were higher in HL60R0.5 than in HL60S cells. Analysis of the drug SMAD5-resistance marker permeability-glycoprotein (Pgp) revealed that CRIM1 and Pgp exhibit a covariance pattern of expression.

    Conclusion: This study demonstrated that CRIM1 is expressed at high levels in resistant leukemia cells, indicating that CRIM1 may play a role in drug-resistance.

  • 10.
    Prenkert, Malin
    et al.
    Örebro University, School of Health and Medical Sciences.
    Uggla, Bertil
    Karolinska Institutet.
    Tina, Elisabet
    Örebro University, School of Health and Medical Sciences.
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences.
    Strid, Hilja
    Örebro University, School of Health and Medical Sciences.
    Rapid Induction of P-Glycoprotein mRNA and Protein Expression by Cytarabine in HL-60 Cells2009In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 29, no 10, p. 4071-4076Article in journal (Refereed)
    Abstract [en]

    Background: Overexpression of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and glutathione-S-transferase π (GSTπ) is associated with drug resistance in acute myeloid leukemia (AML). The short-term effects of drug exposure on their expression levels were investigated.

    Materials and Methods: HL-60 cells and drug-resistant sublines were cultured with or without daunorubicin (DNR) and cytarabine (Ara-C). At several time-points the expression levels of P-gp, BCRP and GSTπ were determined.

    Results: After exposure to Ara-C, P-gp mRNA rapidly increased in all the cell lines. P-gp protein was detected in the sensitive cells after 8 h exposure to Ara-C. GSTπ mRNA increased in the resistant cells, but no change in BCRP mRNA was observed. Exposure to DNR revealed rapidly increased P-gp and GSTπ mRNA in the resistant cells.

    Conclusion: Ara-C rapidly increases P-gp mRNA and protein expression in sensitive and resistant cells, and GSTπ mRNA in resistant cells, in vitro. This may be of clinical importance during AML induction chemotherapy.

  • 11.
    Sorbe, Bengt
    et al.
    Örebro University Hospital. Dept Oncol.
    Soderstrom, Karin
    Dept Oncol, Umeå Univ Hosp, Umeå, Sweden..
    Treatment of Vaginal Recurrences in Endometrial Carcinoma by High-dose-rate Brachytherapy2013In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 33, no 1, p. 241-247Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of the present study was to evaluate the efficacy and safety of high-dose-rate brachytherapy alone or in combination with external pelvic irradiation in treatment of vaginal recurrences in endometrial carcinomas. Predictive and prognostic factors were also evaluated. Patients and Methods: Between 1990 and 2005, forty patients were consecutively treated for vaginal recurrences with or without extravaginal tumoral spread from endometrial carcinoma of International Federation of Gynecology and Obstetrics (FIGO) stages IA-IIIA. Thirty-five patients were treated primarily with surgery and five patients with primary radiotherapy. Six patients were treated with adjuvant external beam irradiation and seven patients with vaginal brachytherapy upfront. The medium time from diagnosis to recurrence was 17 months. The recurrences were treated with a combination of high-dose-rate brachytherapy (mean 25.8 Gy) and external beam pelvic irradiation (mean 46.7 Gy) in 24 cases (60%) and with external therapy-alone or brachytherapy-alone in 12 cases. Results: The local control of vaginal recurrences treated with a combination of external beam therapy and brachytherapy was 92%. The local control rate was lower for external beam therapy-alone. In eleven patients (28%), a second recurrence occurred (five vaginal and six distant metastases). The overall 5-year survival rate was 50%. Age, FIGO grade and time from diagnosis to recurrence were the only independent and significant prognostic factors. Upfront external beam therapy was associated with a worse overall survival rate. Site of recurrence was significant only in univariate analysis. Late gastrointestinal toxicity (grade 3-4) was recorded in 11% of irradiated patients. Conclusion: Combined high-dose-rate brachytherapy and external beam therapy was an effective treatment for vaginal recurrences. Age, FIGO grade, and time-to-recurrence were significant and independent prognostic factors. Upfront radiotherapy was an unfavorable prognostic factor in univariate analysis.

  • 12.
    Wikström, Johan
    et al.
    Department of Surgical Sciences, Section of Radiology, Uppsala University, Uppsala, Sweden.
    Isacsson, Ulf
    Department of Immunology, Genetics and Pathology, Section of Medical Radiation Sci-ence, Uppsala University, Uppsala, Sweden.
    Johansson, Bengt
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Lennernäs, Bo
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Magnetic Resonance Compatibility of a Transponder Aimed for Radiotherapy Positioning - A Phantom Study2017In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 37, no 9, p. 4993-4996Article in journal (Refereed)
    Abstract [en]

    Background/Aim: Electromagnetic Positioning Systems (EMP) is a new position-ing technique in four-dimensional radiotherapy. Patients with implanted transponders may be referred for magnetic resonance imaging (MRI) making it important to establish the MR safety.

    Materials and Methods: Oranges were prepared with transponders and imaged on a 3T MR scanner with different sequences. Computed tomography (CT) was performed as comparison. MR artifacts were assessed. An estimation of the maximum transponder de-flection force and heating was made.

    Results: The mean measured displacement of transponders was 0.1 mm (range=0.03-0.3 mm). Artifacts were observed adjacent to transponders using all sequences. The deflection force on the transponder in the gantry was less than 38 mN. No heating was observed.

    Conclusion: The absence of any substantial movement, the weak measured deflection force and absence of observed heating speaks for the safe use of MR imaging with transponder 3T. Local artefacts makes evaluation impossible adjacent to transponders.

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