Downregulation of osteoblast markers and induction of the glial fibrillary acidic protein by oncostatin M in osteosarcoma cells require PKCdelta and STAT3.

The effects of OSM on proliferation and differentiation of osteosarcoma and nontransformed osteoblasts were analyzed. OSM downregulates osteoblast markers but induces the glial fibrillary acidic protein by the combined activation of PKCdelta and STAT3, offering new lines of therapeutic investigations. INTRODUCTION: Oncostatin M (OSM) is a multifunctional cytokine of the interleukin-6 family implicated in embryonic development, differentiation, inflammation, and regeneration of various tissues, mainly the liver, bone, and the central nervous and hematopoietic systems. One particularity of OSM relies on its growth inhibitory and pro-differentiating effects on a variety of tumor cell lines such as melanoma, providing arguments for a therapeutic application of OSM. The objective of this study was to analyze the effects of OSM on osteosarcoma cell lines proliferation and differentiation. MATERIALS AND METHODS: Proliferation was analyzed by 3H thymidine incorporation. Differentiation was analyzed by semiquantitative RT-PCR and immunocytochemistry for various markers. Alizarin red S staining was used to evaluate bone nodule formation. Morphological changes were studied by confocal and electron microscopy. Western blotting, kinases inhibitors, and dominant negative STAT3 were used to identified the signaling pathways implicated. RESULTS: OSM inhibits the growth of rat osteosarcoma cell lines as well as normal osteoblasts, in correlation with induction of the cyclin-dependent kinases inhibitor p21WAF1. However, OSM reduces osteoblast markers such as alkaline phosphatase, osteocalcin, and bone sialoprotein, leading to strong inhibition of mineralized nodule formation. This inhibitory effect is restricted to mature osteoblasts and differentiated osteosarcoma because OSM effectively stimulates osteoblast markers and bone nodule formation in early, but not late, bone marrow mesenchymal stem cell (BMSC) cultures. In osteosarcoma cells or BMSC, OSM induces expression of the glial fibrillary acidic protein (GFAP) as well as morphological and ultrastructural changes, for example, elongated shape and bundles of microfilaments in cell processes. Rottlerin (PKCdelta inhibitor), and to a lesser degree UO126 (MEK/ERK inhibitor), prevents the loss of osteoblastic markers by OSM, whereas dominant negative STAT3 prevents GFAP induction. CONCLUSIONS: These results highlight the particular gene expression profile of OSM-treated osteosarcoma cells and BMSCs, suggesting either a osteocytic or a glial-like phenotype. Together with the implication of PKCdelta, ERK1/2, and STAT3, these results offer new lines of investigations for neural cell transplantation and osteosarcoma therapy.     

Okulokutane Hypopigmentierung und thrombozytäre Gerinnungsstörung

Ohne Zusammenfassung     

123I-amphetamine-SPECT in classical migraine and migraine accompagnée

Migraine is considered to be a functional neurological disorder. In classical migraine (headache associated with prodromal visual field disturbances) and migraine accompagnée (headache associated with transient neurological symptoms), disturbances of cerebral blood flow and amine metabolism are thought to be pathogenetic factors. However, conventional methods of neuroimaging (CAT, NMR) usually do not yield any pathological findings in patients. Since 123I-iodoamphetamine (123I-IMP) crosses the intact blood brain barrier, 123I-IMP-SPECT is used for the assessment of cerebral perfusion in various neurological diseases, including functional disorders. 123I-IMP-SPECT was performed on 5 patients with classical migraine and 18 patients with migraine accompagnée. At the time of investigation, all patients were symptom-free. Cerebral blood flow was decreased in all patients with migraine accompagnée, and often corresponded to the site of headache as well as to the topography of transient neurological symptoms. This reduction was most obvious in a patient with persisting neurological symptoms. Most patients with classical migraine, however, did not show any alteration of cerebral perfusion. It appears that migraine--and in particular migraine accompagnée--is characterized by a permanent alteration not only of cerebral blood flow but also of neuronal activity. Migraine attacks may occur in connection with exacerbations of preexisting metabolic alterations.     

<Emphasis Type="Italic">Bcl11b</Emphasis>mutations identified in murine lymphomas increase the proliferation rate of hematopoietic progenitor cells

Background  

The telomeric region of mouse chromosome 12 has previously shown frequent allelic loss in murine lymphoma. The Bcl11b gene has been identified and suggested as a candidate tumor suppressor gene within this region. In this study, we aimed to elucidate whether Bcl11b is mutated in lymphomas with allelic loss, and whether the mutations we detected conferred any effect on cell proliferation and apoptosis.     

Totale mesometriale Resektion

Abdominal radical hysterectomy (Wertheim operation), currently the standard surgical treatment for cervical carcinoma, is based on historical ideas of the female pelvic anatomy and of locoregional tumor spread. Total mesometrial resection (TMMR) uses new insights derived from developmental biology for a new oncological concept of radicality, i.e. resection of a malignant tumor within the borders of the morphogenetic unit of its origin. The morphogenetic uterovaginal unit that relates to the local spread of cervical carcinoma can be deduced from the embryological and fetal development. Anatomical structures that do not belong to this tissue unit can be left in situ despite close proximity to the tumor. When combined with nerve-sparing therapeutic lymph node dissection, TMMR yields a high locoregional control rate without adjuvant radiotherapy and with relatively little treatment-related morbidity.     

Karzinomassoziierte Retinopathie (CAR) bei Mammakarzinom und Karzinoid

Fragestellung: Die Karzinomassoziierte Retinopathie (CAR) stellt ein seltenes paraneoplastisches Syndrom dar, das bislang am h?ufigsten bei kleinzelligen Bronchialkarzinomen beschrieben wurde. Wir berichten über 3 Patientinnen mit CAR in Gegenwart eines Mammakarzinoms bzw. eines Karzinoids der Cervix uteri. Patienten und Methode: Es wurden biomikroskopische, perimetrische, angiographische und elektrophysiologische Befunde erhoben. Au?erdem erfolgte eine Testung der Immunreaktivit?t der Seren an humaner Retina. Ergebnisse: Die Befunde umfa?ten ringf?rmige Gesichtsfelddefekte mit statokinetischer Dissoziation und eine pathologische St?bchen- und Zapfenantwort im ERG. Bei 1 Patientin wurde immunhistochemisch eine Reaktion im Bereich der Photorezeptorinnensegmente, der ?u?eren K?rnerschicht sowie der ?u?eren plexiformen Schicht bei fehlendem Nachweis von Antik?rpern gegen Recoverin gefunden. Diskussion: Neben dem kleinzelligen Bronchialkarzinom k?nnen auch andere Prim?rtumoren mit einer CAR vergesellschaftet sein. Der Nachweis von retinalen Autoantik?rpern unterstützt die Annahme einer tumorinduzierten Immunantwort aufgrund der Expression identischer Epitope durch die Tumorzellen. Dabei kommen offensichtlich verschiedene retinale Proteine als Autoantigene in Betracht.      

The effect of physeal traction applied to the triradiate cartilage on acetabular growth

Summary Physeal distraction was applied with an external fixator to the triradiate cartilage of dogs with the aim of increasing the capacity of the acetabulum. The force was continued for from 2 to 6 weeks and the consequent changes were evaluated with regard to function and structure by radiography and microscopy. The distraction, without producing epiphysiolysis and destruction of the cartilage, resulted in expansion of the pelvic bones. The depth and volume of the acetabulum were increased, but the acetabular angle was decreased. Distraction also caused proliferation of the lacunar cells and the number of mammillary processes in the cartilage columns increased. Distraction can therefore be applied to the triradiate cartilage to enlarge the capacity of the acetabulum without producing epiphysiolysis.

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Résumé Dans cette étude une distraction a été appliquée sur le cartilage en Y. Douze chiens bâtards, âgés de 2.5 à 4 mois, ont été utilisés pour cette expérimentation. Une force de distraction de 80 Newton a été appliquée d'emblée sur le cartilage en Y. L'application de cette force a été poursuivie sur les animaux pendant 2, 4 ou 6 semaines. A la fin de cette période, les changements de la cavité cotyloïde et du cartilage en Y ont été évalués sur le plan fonctionnel, morphologique, radiologique et histopathologique Aucune altération fonctionnelle n'a été mise en évidence dans les groupes opérés par rapport au groupe de contrôle. On a observé que la distraction a déterminé une expansion massive de l'ilion, du pubis et de l'ischion. Sur les hanches de contrôle la profondeur de la cavité cotyloïde a été évaluée à 13.5 mm, le volume à 1.96 cc et l'angle de la cavité cotyloïde à 29.9°. Après distraction ces valeurs ont été respectivement de 14.4 mm, de 2.10 cc et de 25.7°. La distraction entraîne donc un accroissement de profondeur et de volume de la cavité cotyloïde, mais inversement une diminution de l'angle de cette cavité. Ces résultats montrent que la distraction détermine une prolifération des cellules lacunaires et un accroissement des processus mammaires dans les colonnes du cartilage en Y. Ils montrent également qu'elle peut augmenter la taille de l'acetabulum.