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  • 1.
    Bohr Mordhorst, Louise
    et al.
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Ahlin, Cecilia
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Sorbe, Bengt
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Prognostic impact of the expression of Wnt-signaling proteins in cervical carcinoma FIGO stage I-IV treated with radiotherapy or chemoradiotherapy2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 39, p. 63042-63053Article in journal (Refereed)
    Abstract [en]

    Wnt signaling proteins were assessed in patients with primary cervical carcinomas who received chemoradiation. The associations between three Wnt signaling proteins and prognosis were assessed. Specimens from 122 patients with cervical carcinomas (FIGO stage I-IV) were immunohistochemically (IHC) analyzed for β-catenin, APC and axin protein expression. Associations between these Wnt-protein expressions, clinicopathological factors, and clinical outcome data were examined.Positive IHC staining for the β-catenin protein (cell-membranes, cytoplasm and nuclei) was recorded in 88%, 58% and 5%, respectively. There was a strong association between β-catenin staining of the cell-membranes and prediction of recurrences and prognosis (p = 0. 002). Tumors with > 5% of nuclear β-catenin staining were associated with inferior cancer-specific survival (p = 0.048) compared with no staining. The overall recurrence rate was significantly higher in the group with increased nuclear staining (67%) compared with the group with no staining (33%). Nuclear APC staining of high intensity was associated with a significantly worse cancer-specific survival and increased overall recurrence rate compared to tumors with weak staining. Distant recurrences were recorded in 29% of cases with intense staining and in 14% of cases with low staining.The Wnt signaling pathway seems to be of importance in the process of cervical oncogenesis. A predictive and prognostic value was found for β-catenin, where strong cell-membrane staining was favorable, and > 5% positive nuclear staining was associated with poorer cancer-specific survival and overall recurrence rate. Nuclear APC staining intensity was also associated with a less favorable prognosis.

  • 2.
    Isaksson, Helena S.
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Torbjörn K.
    Department of Medical Biosciences/Clinical Chemistry, Umeå University, Umeå, Sweden.
    Whole genome expression profiling of blood cells in ovarian cancer patients: prognostic impact of the CYP1B1, MTSS1, NCALD, and NOP14 genes2014In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 5, no 12, p. 4040-4049Article in journal (Refereed)
    Abstract [en]

    Ovarian cancer patients with different tumor stages and cell differentiation might be distinguished from each other by gene expression profiles in whole blood cell mRNA by the Affymetrix Human Gene 1.0 ST Array. We also examined if there is any association with other clinical variables, response to therapy, and residual tumor burden after surgery. Patients were divided into two groups, one with poor prognosis, advanced stage and poorly differentiated tumors (n = 22), and one group with good prognosis, early stage and well-to medium differentiated tumors (n = 11). Six genes were found to be differentially expressed: the PDIA3, LYAR, NOP14, NCALD and MTSS1 genes were down-regulated and the CYP1B1 gene expression was up-regulated in the poor prognosis group, all with p value <0.05, adjusted for mass comparison. In survival analyses, CYP1B1, MTSS1, NCALD and NOP14 remained significantly different (p<0.05). Patient groups did not differ in any transcript related to acute phase or immune responses. This minimal gene expression signature of prognostic ovarian cancer-related genes opens up an avenue for more practicable monitoring of ovarian cancer patients by simple peripheral blood tests, which may evolve into a tool to guide selection of curative and postoperative supportive therapies.

  • 3.
    Kaliff, Malin
    et al.
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Sorbe, Bengt
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Mordhorst, Louise Bohr
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Helenius, Gisela
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Karlsson, Mats G.
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Lillsunde-Larsson, Gabriella
    Örebro University, School of Health Sciences. Department of Laboratory Medicine.
    Findings of multiple HPV genotypes in cervical carcinoma are associated with poor cancer-specific survival in a Swedish cohort of cervical cancer primarily treated with radiotherapy2018In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 9, no 27, p. 18786-18796Article in journal (Refereed)
    Abstract [en]

    Cervical cancer (CC) is one of the most common cancers in women and virtually all cases of CC are a result of a persistent infection of human papillomavirus (HPV). For disease detected in early stages there is curing treatment but when diagnosed late with recurring disease and metastasis there are limited possibilities. Here we evaluate HPV impact on treatment resistance and metastatic disease progression. Prevalence and distribution of HPV genotypes and HPV16 variants in a Swedish CC patient cohort (n=209) was evaluated, as well as HPV influence on patient prognosis. Tumor samples suitable for analysis (n=204) were genotyped using two different real-time PCR methods. HPV16 variant analysis was made using pyrosequencing. Results showed that HPV prevalence in the total series was 93%. Of the HPV-positive samples, 13% contained multiple infections, typically with two high-risk HPV together. Primary cure rate for the complete series was 95%. Recurrence rate of the complete series was 28% and distant recurrences were most frequent (20%). Patients with tumors containing multiple HPV-strains and particularly HPV genotypes belonging to the alpha 7 and 9 species together had a significantly higher rate of distant tumor recurrences and worse cancer-specific survival rate.

  • 4.
    Peng, Qiliang
    et al.
    Department of Radiotherapy & Oncology, Second Affiliated Hospital of Soochow University, Suzhou, China; Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China; Suzhou Key Laboratory for Radiation Oncology, Suzhou, China.
    Zhang, Xueli
    Örebro University, School of Medical Sciences. Department of Radiotherapy & Oncology, Second Affiliated Hospital of Soochow University, Suzhou, China; Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China; Suzhou Key Laboratory for Radiation Center for Systems Biology, Soochow University, Suzhou, China.
    Min, Ming
    Center for Systems Biology, Soochow University, Suzhou, China.
    Zou, Li
    Department of Radiotherapy & Oncology, Second Affiliated Hospital of Soochow University, Suzhou, China; Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China; Suzhou Key Laboratory for Radiation Oncology, Suzhou, China.
    Shen, Peipei
    Department of Radiotherapy & Oncology, Second Affiliated Hospital of Soochow University, Suzhou, China; Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China; Suzhou Key Laboratory for Radiation Oncology, Suzhou, China.
    Zhu, Yaqun
    Department of Radiotherapy & Oncology, Second Affiliated Hospital of Soochow University, Suzhou, China; Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China; Suzhou Key Laboratory for Radiation Oncology, Suzhou, China.
    The clinical role of microRNA-21 as a promising biomarker in the diagnosis and prognosis of colorectal cancer: a systematic review and meta-analysis2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 27, p. 44893-44909Article in journal (Refereed)
    Abstract [en]

    This systematic analysis aimed to investigate the value of microRNA-21 (miR-21) in colorectal cancer for multiple purposes, including diagnosis and prognosis, as well as its predictive power in combination biomarkers. Fifty-seven eligible studies were included in our meta-analysis, including 25 studies for diagnostic meta-analysis and 32 for prognostic meta-analysis. For the diagnostic meta-analysis of miR-21 alone, the overall pooled results for sensitivity, specificity, and area under the curve (AUC) were 0.64 (95% CI: 0.53-0.74), 0.85 (0.79-0.90), and 0.85 (0.81-0.87), respectively. Circulating samples presented corresponding values of 0.72 (0.63-0.79), 0.84 (0.78-0.89), and 0.86 (0.83-0.89), respectively. For the diagnostic meta-analysis of miR-21-related combination biomarkers, the above three parameters were 0.79 (0.69-0.86), 0.79 (0.68-0.87), and 0.86 (0.83-0.89), respectively. Notably, subgroup analysis suggested that miRNA combination markers in circulation exhibited high predictive power, with sensitivity of 0.85 (0.70-0.93), specificity of 0.86 (0.77-0.92), and AUC of 0.92 (0.89-0.94). For the prognostic meta-analysis, patients with higher expression of miR-21 had significant shorter disease-free survival [DFS; pooled hazard ratio (HR): 1.60; 95% CI: 1.20-2.15] and overall survival (OS; 1.54; 1.27-1.86). The combined HR in tissues for DFS and OS were 1.76 (1.31-2.36) and 1.58 (1.30-1.93), respectively. Our comprehensive systematic review revealed that circulating miR-21 may be suitable as a diagnostic biomarker, while tissue miR-21 could be a prognostic marker for colorectal cancer. In addition, miRNA combination biomarkers may provide a new approach for clinical application.

  • 5.
    Vainio, Paula
    et al.
    Medical Biotechnology, VTT Technical Research Centre of Finland, Turku Centre for Biotechnology, University of Turku, Turku, Finland.
    Lehtinen, Laura
    Medical Biotechnology, VTT Technical Research Centre of Finland, Turku Centre for Biotechnology, University of Turku, Turku, Finland.
    Mirtti, Tuomas
    Haartman Institute, Department of Pathology, University of University of Helsinki, Helsinki, Finland; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland; HUSLAB, Department of Pathology, Helsinki University Central Hospital, Helsingfors, Finland.
    Hilvo, Mika
    Bio and Process Technology, VTT Technical Research Centre of Finland, Espoo, Finland.
    Seppänen-Laakso, Tuulikki
    Bio and Process Technology, VTT Technical Research Centre of Finland, Espoo, Finland.
    Virtanen, Johannes
    Medical Biotechnology, VTT Technical Research Centre of Finland, Turku Centre for Biotechnology, University of Turku, Turku, Finland.
    Sankila, Anna
    HUSLAB, Department of Pathology, Helsinki University Central Hospital, Helsingfors, Finland.
    Nordling, Stig
    HUSLAB, Department of Pathology, Helsinki University Central Hospital, Helsingfors, Finland.
    Lundin, Johan
    Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
    Rannikko, Antti
    Department of Urology, Helsinki University Central Hospital, Helsinki, Finland.
    Oresic, Matej
    Bio and Process Technology, VTT Technical Research Centre of Finland, Espoo, Finland.
    Kallioniemi, Olli
    Medical Biotechnology, VTT Technical Research Centre of Finland, Turku Centre for Biotechnology, University of Turku, Turku, Finland: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
    Iljin, Kristiina
    Medical Biotechnology, VTT Technical Research Centre of Finland, Turku Centre for Biotechnology, University of Turku, Turku, Finland.
    Phospholipase PLA2G7, associated with aggressive prostate cancer, promotes prostate cancer cell migration and invasion and is inhibited by statins2011In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 2, no 12, p. 1176-1190Article in journal (Refereed)
    Abstract [en]

    Prostate cancer is the second leading cause of cancer mortality in men in developed countries. Due to the heterogeneous nature of the disease, design of novel personalized treatments is required to achieve efficient therapeutic responses. We have recently identified phospholipase 2 group VII (PLA2G7) as a potential drug target especially in ERG oncogene positive prostate cancers. Here, the expression profile of PLA2G7 was studied in 1137 prostate cancer and 409 adjacent non-malignant prostate tissues using immunohistochemistry to validate its biomarker potential and putative association with disease progression. In order to reveal the molecular alterations induced by PLA2G7 impairment, lipidomic and gene expression profiling was performed in response to PLA2G7 silencing in cultured prostate cancer cells. Moreover, the antineoplastic effect of statins combined with PLA2G7 impairment was studied in prostate cancer cells to evaluate the potential of repositioning of in vivo compatible drugs developed for other indications towards anti-cancer purposes. The results indicated that PLA2G7 is a cancer-selective biomarker in 50 % of prostate cancers and associates with aggressive disease. The alterations induced by PLA2G7 silencing highlighted the potential of PLA2G7 inhibition as an anti-proliferative, pro-apoptotic and anti-migratorial therapeutic approach in prostate cancer. Moreover, the anti-proliferative effect of PLA2G7 silencing was potentiated by lipid-lowering statins in prostate cancer cells. Taken together, our results support the potential of PLA2G7 as a biomarker and a drug target in prostate cancer and present a rationale for combining PLA2G7 inhibition with the use of statins in prostate cancer management.

1 - 5 of 5
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