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

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

  • 2. Holgersson, Georg
    et al.
    Ekman, Simon
    Reizenstein, Johan
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Uhlén, Mattias
    Magnusson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Jonnalagadda, Pallavi
    Asplund, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Strömberg, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Linder, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Blomquist, Erik
    Liljeholm, Martin
    Lödén, Britta
    Hellström, Karin
    Bergström, Stefan
    Molecular profiling using tissue microarrays as a tool to identify predictive biomarkers in laryngeal cancer treated with radiotherapy2010In: Cancer Genomics & Proteomics, ISSN 1109-6535, E-ISSN 1790-6245, Vol. 7, no 1, p. 1-7Article in journal (Refereed)
    Abstract [en]

    AIM: To explore the usefulness of the expression of five potential cancer biomarkers in predicting outcome in patients with laryngeal cancer. MATERIALS AND METHODS: In the present study, the Swedish National Cancer Registry databases were used to identify patients with laryngeal cancer diagnosed during the years 1978-2004 in the Uppsala-Orebro region and treated with radiotherapy. The expression of Ki-67, MutS homolog 2, (MSH2), p53, B-cell CLL/lymphoma 2 (Bcl-2) and cyclin D1 in the cancer cells was assessed immunohistochemically using tissue microarrays (TMAs) and its predicitve value on survival and relapse was analyzed using Cox regression models. RESULTS: A total of 39 patients were included in the present study. Nuclear MSH2 staining was statistically significantly correlated to Ki-67 expression (p=0.022). However, univariate and multivariate Cox analyses showed no statistically significant association between the expression of the investigated biomarkers and overall survival or relapse. CONCLUSION: The present exploratory study does not show any significant predictive value of the biomarkers examined with respect to survival or relapse. However, with larger patient cohorts, we believe that protein profiling using TMAs and immunohistochemistry is a feasible strategy for prognostic and predictive biomarker screening in laryngeal cancer.

  • 3.
    Skirnisdottir, Ingiridur
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Seidal, Tomas
    Department of Pathology, Halmstad Medical Central Hospital, Halmstad, Sweden.
    Association of p21, p21 p27 and p21 p53 Status to Histological Subtypes and Prognosis in Low-stage Epithelial Ovarian Cancer2013In: Cancer Genomics & Proteomics, ISSN 1109-6535, E-ISSN 1790-6245, Vol. 10, no 1, p. 27-34Article in journal (Refereed)
    Abstract [en]

    Aim: The objective of this study was to evaluate the prognostic value of p21 alone and in combination with p53 or p27 for different histological subtypes of epithelial ovarian cancer and disease-free survival. Patients and Methods: The specimens were obtained at primary surgery from a series of 29 ovarian carcinomas in FIGO stages I-II. The technique of tissue microarray and immunohistochemistry was used for detection of positivity of the markers. Results: Positive staining for p21, p27 and p53 was detected in 36%, 58% and 25% of cases, respectively. The p21 status, p27 status and concomitant p21 p27 and p21 p53 status in four subgroups were related to histological subtypes (p=0.016, p=0.036, p=0.004 and p=0.001). Mucinous tumors mostly stained negatively for p27 and concomitantly negatively for p21 and p53. Clear cell tumors generally stained positively for p21 and p27 but negatively for p53. Serous tumors usually stained concomitantly negatively for p21 and positively for p53. In a multivariate Cox regression analysis, FIGO stage, p21 p53 and p53 status were independent prognostic factors for disease-free survival.  Conclusion: A subgroup, constituting 25/129 (19%) of the patients with predominantly serous tumors with concomitant p21 negativity and p53 positivity had a poor survival. Another subgroup of 11/129 (9%) patients with non-serous tumors with concomitant p21 and p27 positivity had excellent survival.

  • 4.
    Skírnisdottir, Ingiridur
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Seidal, Tomas
    Department of Pathology, Halmstad Medical Center Hospital, Halmstad, Sweden.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Cell Cycle Regulator p27 Mediates Body Mass IndexEffects in Ovarian Cancer in FIGO-stages I-II2019In: Cancer Genomics & Proteomics, ISSN 1109-6535, E-ISSN 1790-6245, Vol. 16, no 6, p. 443-450Article in journal (Refereed)
    Abstract [en]

    Background/Aim: The aim of the present study was to evaluate the association between body mass index (BMI), the biomarker p27, and the clinical factors in FIGO-stages I-II ovarian cancer. Patients and Methods: A total of 128 patients with ovarian cancer were included in the study. For testing differences in univariate analyzes we used the Pearson's Chi-square test and the log-rank test. For multivariate analyses the logistic regression and Cox regression models were used with recurrent disease and disease free survival as endpoints, respectively. Results: Patients with BMI <= 25 kg/m(2) had a significantly better 5-year disease free survival compared with patients with BMI >25 kg/m(2) in the total series of patients (p=0.008), and in the series of patients (n=77) with non-serous tumors (p=0.047). Patients with p27-positive non-serous tumors had higher survival compared to patients with p27-negative non-serous tumors (p=0.020). Conclusion: The cell cycle regulator p27 mediates BMI effects in ovarian cancer in FIGO-stages I-II.

  • 5. Tinge, Beatrice
    et al.
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ekman, Simon
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Mast cells in squamous cell esophageal carcinoma and clinical parameters2010In: Cancer Genomics & Proteomics, ISSN 1109-6535, E-ISSN 1790-6245, Vol. 7, no 1, p. 25-29Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Esophageal carcinoma is a malignancy with a poor prognosis and new treatment modalities must be sought. One possibility that has been tested in patients with malignant melanoma is treatment which aims towards boosting the immune system. In the present study, we investigated the role of mast cells in patients with esophageal carcinoma. The intention was to determine whether a higher number of mast cells is associated with better survival and may thus be a marker for future immunotherapeutic studies.

    MATERIALS AND METHODS:

    A total of 61 archived tumor samples were retrieved of patients having received treatment due to esophageal carcinoma at the Department of Oncology, Uppsala University Hospital, Sweden. The tissue specimens were fixed in formalin, embedded in paraffin and sectioned in 3 microm-thick sections. The monoclonal antibody G3, recognizing the mast cell-specific protein tryptase was used, and the avidin-biotin-horseradish peroxidase complex (ABC/HRP) and diaminobenzidine (DAB) techniques were used to visualize tryptase-positive cells. The positive cells were counted in 10 randomly selected high power fields.

    RESULTS:

    When the number of mast cells was investigated in conjunction with relapse, no correlation was found (p=0.38). The number of mast cells was also not associated with survival (p=0.96). Using a pre-defined cut-off value of 31, no significant changes in survival was found (p=0.79) between patients with mast cell numbers above this value compared to those with numbers below.

    CONCLUSION:

    We conclude that mast cells do not seem to be related to prognosis in patients with esophageal carcinoma.

  • 6.
    Zakharchenko, Olena
    et al.
    Department of Oncology-Pathology, Karolinska Biomics Center, Karolinska Institute, Stockholm.
    Greenwood, Christina
    Helen Rollason Research Laboratory, Anglia Ruskin University, Chelmsford, United Kingdom.
    Lewandowska, Anna
    Faculty of Biology, University of Warmia and Mazury, Olsztyn, Poland.
    Hellman, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Alldridge, Louise
    Griffith University, School of Medicine, Gold Coast, Australia.
    Souchelnytskyi, Serhiy
    Department of Oncology-Pathology, Karolinska Biomics Center, Karolinska Institute, Stockholm.
    Meta-data analysis as a strategy to evaluate individual and common features of proteomic changes in breast cancer2011In: Cancer Genomics & Proteomics, ISSN 1109-6535, E-ISSN 1790-6245, Vol. 8, no 1, p. 1-14Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Individual differences among breast tumours in patients is a significant challenge for the treatment of breast cancer. This study reports a strategy to assess these individual differences and the common regulatory mechanisms that may underlie breast tumourigenesis. MATERIALS AND METHODS: The two-step strategy was based firstly on a full-scale proteomics analysis of individual cases, and secondly on the analysis of common features of the individual proteome-centred networks (meta-data). RESULTS: Proteomic profiling of human invasive ductal carcinoma tumours was performed and each case was analysed individually. Analysis of primary datasets for common cancer-related proteins identified keratins. Analysis of individual networks built with identified proteins predicted features and regulatory mechanisms involved in each individual case. Validation of these findings by immunohistochemistry confirmed the predicted deregulation of expression of CK2α, PDGFRα, PYK and p53 proteins. CONCLUSION: Meta-data analysis allowed efficient evaluation of both individual and common features of the breast cancer proteome.

1 - 6 of 6
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