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  • 1.
    Daskalakis, Kosmas
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 1st Department of Propaupedic Internal Medicine, Endocrine Oncology Unit, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece.
    Alexandraki, Krystallenia I.
    1st Department of Propaupedic Internal Medicine, Endocrine Oncology Unit, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece.
    Kloukina, Ismini
    Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
    Kassi, Evanthia
    1st Department of Propaupedic Internal Medicine, Endocrine Oncology Unit, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece; Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
    Felekouras, Evangelos
    First Department of Surgery, Laikon General Hospital, University of Athens Medical School, Athens, Greece.
    Xingi, Evangelia
    Microscopy Unit, Hellenic Pasteur Institute, Athens, Greece.
    Pagakis, Stamatis N.
    Biological Imaging Unit, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
    Tsolakis, Apostolos V.
    Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.
    Andreakos, Evangelos
    Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
    Kaltsas, Gregory
    1st Department of Propaupedic Internal Medicine, Endocrine Oncology Unit, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece.
    Kambas, Konstantinos
    Laboratory of Molecular Genetics, Department of Immunology, Hellenic Pasteur Institute, Athens, Greece.
    Increased autophagy/mitophagy levels in primary tumours of patients with pancreatic neuroendocrine neoplasms2020Ingår i: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/aims: We assessed the levels of autophagy and mitophagy, that are linked to cancer development and drug resistance, in well differentiated pancreatic neuroendocrine neoplasms (PanNENs) and correlated them with clinico-pathological parameters.

    Methods: Fluorescent immunostaining for the autophagy markers LC3 Beta and p62/or LAMP1 was performed on 22 PanNENs and 11 controls of normal pancreatic tissues and validated through Western blotting. Autophagy quantitative scoring was generated for LC3B-positive puncta and analysed in relation to clinico-pathological parameters. TOMM20/LC3B qualitative assessment of mitophagy levels was undertaken by fluorescent immunostaining. The presence of autophagy/mitophagy was validated by transmission electron microscopy.

    Results: Autophagy levels (LC3B-positive puncta/cell) were discriminative for normal vs. NEN pancreatic tissue (p = 0.007). A significant association was observed between autophagy levels and tumour grade (Ki67 < 3% vs. Ki67 >= 3%; p = 0.021), but not functionality (p = 0.266) size (cut-off of 20 mm; p = 0.808), local invasion (p = 0.481), lymph node- (p = 0.849) and distant metastases (p = 0.699). Qualitative assessment of TOMM20/LC3B demonstrated strong mitophagy levels in PanNENs by fluorescent immunostaining as compared with normal tissue. Transmission electron microscopy revealed enhanced autophagy and mitophagy in PanNEN tissue. Response to molecular targeted therapies in metastatic cases (n = 4) did not reveal any patterns of association to autophagy levels.

    Conclusions: Increased autophagy levels are present in primary tumours of patients with PanNENs and are partially attributed to upregulated mitophagy. Grade was the only clinico-pathological parameter associated with autophagy scores.

  • 2.
    Falhammar, Henrik
    et al.
    Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Juhlin, Carl Christofer
    Department of Clinical Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Barner, Caroline
    Department of Medicine, Capio S:t Görans Hospital, Stockholm, Sweden.
    Catrina, Sergiu-Bogdan
    Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Karefylakis, Christos
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Diabetes, Endocrinology and Metabolism.
    Calissendorff, Jan
    Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Riedel's thyroiditis: clinical presentation, treatment and outcomes2018Ingår i: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 60, nr 1, s. 185-192Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Riedel´s thyroiditis (RT) is a rare inflammatory disease of the thyroid gland, causing compression and fibrosis of adjacent tissues. Typically the goiter is hard and firm. Hoarseness, dyspnea, and dysphagia may be present.

    METHODS: We retrospectively reviewed all patients known by us with RT in addition to all patients with appropriate ICD-10 codes evaluated at the Karolinska University Hospital 2003-2015. Clinical, biochemical, and histological data of patients with RT were recorded in detail. Histological preparations were re-examined when available.

    RESULTS: RT was diagnosed in six patients. Five were females and the median age at first presentation was 50 years (25-81 years). Median follow-up time was 3.75 years (1-22 years). At diagnosis five had hypothyroidism. Four had extrathyroidal manifestations, and one of these had also distant fibrosis. One patient had a clear IgG4/IgG ratio over 40%. One patient was treated with tracheostomy, one with isthmectomy and one with total thyroidectomy. Four had been treated with glucocorticoids, four with tamoxifen, and two with both drugs. One had also been treated with mycophenolate mofetil combined with Rituximab. At the end of follow-up four was doing fine, one had recurrent episodes of inflammation and one had died of possible complications to RT.

    CONCLUSION: It is important to recognize RT and give adequate treatment. Steroids are still the mainstay of therapy but other medications against fibrosclerosis can be considered. Wakefulness of other fibrosing manifestations is essential. Immunohistochemistry can show whether IgG-4 plasma cells are increased which could lead to fibrosis in other organs.

  • 3.
    Karefylakis, Christos
    et al.
    Department of Endocrinology, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Särnblad, Stefan
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Pediatrics.
    Ariander, Annaclara
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Ehlersson, Gustaf
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Rask, Eva
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Endocrinology.
    Rask, Peter
    Region Örebro län. Örebro universitet, Institutionen för medicinska vetenskaper. Department of Clinical Physiology.
    Effect of Vitamin D supplementation on body composition and cardiorespiratory fitness in overweight men: a randomized controlled trial2018Ingår i: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 61, nr 3, s. 388-397Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Several observational studies have shown an association between vitamin D deficiency and non-skeletal major health issues including impaired cardiorespiratory fitness and adiposity. Only a few studies have examined the impact of vitamin D supplementation on these conditions and the results are ambiguous. The aim of this study was to examine the effect of vitamin D supplementation on body composition and cardiorespiratory fitness in overweight/obese men with vitamin D deficiency.

    Methods: This study was a prospective, placebo controlled, double blinded, randomized trial with a study period of 6 months. Forty overweight/obese men (BMI > 25 kg/m2) with vitamin D deficiency (25(OH)D ≤ 55 nmol/L) were randomized to receive either 2000 IU Cholecalciferol drops or the equivalent amount of drops of placebo. At baseline and follow up body composition and cardiorespiratory fitness were measured and blood samples were obtained. Body composition was measured using bioelectrical impedance analysis (BIA) and cardiorespiratory fitness using cardiopulmonary exercise test (CPET). The primary outcomes were changes in percentage body fat and in maximum oxygen uptake (VO2max).

    Results: No statistically significant difference between the placebo and the intervention group regarding changes in percentage body fat (p = 0.54) and VO2max (p = 0.90) was observed. Moreover, there was no statistically significant difference between the groups concerning changes in BMI (p = 0.26), maximum load (p = 0.89) and oxygen uptake at anaerobic threshold (AT) (p = 0.14).

    Conclusions: We conclude that treatment with 2000 IU/d vitamin D for 6 months does not impact body composition or maximum oxygen uptake in overweight/obese men with vitamin D deficiency.

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