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Céline Chipoy Martine Berreur Séverine Couillaud Gilbert Pradal Fran?ois Vallette Caroline Colombeix Fran?oise Rédini Dominique Heymann Frédéric Blanchard 《Journal of bone and mineral research》2004,19(11):1850-1861
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. 相似文献
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Drew T. Marshall John D. Gilbert Roger W. Byard 《Forensic science, medicine, and pathology》2007,3(1):53-55
A 26-year-old man who presented with a 2-year history of intermittent gynecomastia with recent onset of fever, night sweats,
and abdominal distension was found to have a left-sided adrenocortical carcinoma with metastases to the liver and spine. Sudden
death occurred 1 month after his presentation. At autopsy a saddle pulmonary thromboembolus was found occluding the pulmonary
outflow tract, with smaller more peripheral pulmonary thromboemboli. No tumor deposits were identified in the thromboemboli.
The thromboemboli had arisen from a tongue of tumor that had grown through the left adrenal vein into the inferior vena cava.
Despite a high rate of angio-invasion there are very few reports of sudden death resulting from this phenomenon in patients
with adrenocortical carcinoma. 相似文献
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A V Pinto V F Ferreira R S Capella B Gilbert M C Pinto J S da Silva 《Transactions of the Royal Society of Tropical Medicine and Hygiene》1987,81(4):609-610
Accidental transmission of Chagas disease to man by blood transfusion is a serious problem in Latin America. This paper describes the testing of several naphthoquinones, some of which were active against blood trypomastigotes in vitro at 4 degrees C and might therefore warrant further study for preventing transmission of Chagas disease by blood transfusion. 相似文献