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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Immunological reviews 208 (2005), S. 0 
    ISSN: 1600-065X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary:  The osteoclast (OCL) is the primary cell involved in the pathogenesis of Paget's disease (PD) and the destructive bone process in multiple myeloma (MM). Both of these diseases are characterized by increased numbers of OCLs actively resorbing bone, but they differ in that bone formation is greatly increased in PD and is suppressed in MM. The marrow microenvironment plays a critical role in both disease processes, through the increased expression of inflammatory cytokines that enhance osteoclastogenesis and, in the case of MM, also suppress osteoblast (OBL) activity. In addition, the OCLs in PD are intrinsically abnormal, are markedly increased in number and size, and are hyper-responsive to inflammatory cytokines and 1,25-(OH)2D3. This article discusses the role of immune cells and inflammatory cytokines and chemokines in the increased OCL activity in PD and MM bone disease, as well as the potential role of interleukin-3 in the suppression of OBL activity in MM.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature medicine 13 (2007), S. 25-26 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Patients with a variety of tumors, including those with breast cancer, are often treated with granulocyte–monocyte colony stimulating factor (GM-CSF), a cytokine that increases white cell counts. GM-CSF stimulates the proliferation and differentiation of hematopoietic precursors, thereby ...
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 53 (1993), S. S94 
    ISSN: 1432-0827
    Keywords: Osteoclast ; Cytokines ; Bone resorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The process of bone remodeling involves complex interactions between the osteoclast, the primary bone-resorbing cell, and other cells in its microenvironment. These interactions can regulate bone resorption through two processes: (1) effects on the number of osteoclasts present at a given site and (2) effects on the bone-resorbing capacity of individual osteoclasts. Cells present in the osteoclast microenvironment include marrow stromal cells, osteoblasts, macrophages, T-lymphocytes, and marrow cells. These cells, as well as the osteoclast itself, produce cytokines that can affect osteoclast formation and osteoclast activity.In vitro model systems using rodent organ cultures or long-term marrow culture systems, andin vivo models have demonstrated that cytokines such as interleukin-1, M-CSF, tumor necrosis factor, and interleukin-6 can stimulate the formation and bone-resorbing capacity of osteoclasts. In contrast, cytokines such as interleukin-4, γ-interferon, and transforming factor-β inhibit both osteoclast formation and osteoclast activity. The relative proportions of these cytokines in the marrow microenvironment may play a critical role in regulating osteoclast activity. Knowledge of cytokines that affect osteoclast formation and activity and their capacity to modulate the bone-resorbing process should provide critical insights into normal calcium homeostasis and disorders of bone turnover such as osteoporosis and Paget's disease of bone.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 19 (1991), S. 289-296 
    ISSN: 1573-7217
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1435-5604
    Keywords: Key words: 1 ; 25(OH)2D3 ; 1 ; 25(OH)2D3-lactone ; osteoclast-like cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: We have used a human bone marrow culture system that forms multinucleated cells (MNCs), 50% of which express the osteoclast phenotype, to examine the 23(S)25(R)-1,25-dihydroxyvitamin D3-26,23-lactone (1,25-D3-lactone) on osteoclast-like cell formation. The 1,25-D3-lactone is a vitamin D3 metabolite that has recently been detected in human serum under physiological conditions at concentrations of approximately 131 pg/ml (3 × 10−10 M) and can inhibit bone resorption induced by 1,25-dihydroxyvitamin D3 (1,25-D3) in vivo and in vitro. We examined the effects of the 1,25-D3-lactone on the formation of MNC that cross-reacted with 23C6 monoclonal antibody (23C6-positive MNC), which preferentially binds to osteoclasts. All metabolites of 1,25-D3 except the 1,25-D3-lactone increased both total and 23C6-positive MNC formation in a dose-dependent manner. In contrast, the 1,25-D3-lactone inhibited both total and 23C6-positive MNC formation, whether the cultures were treated with 1,25-D3, parathyroid hormone, or interleukin-1β, all potent stimulators of MNC formation. This inhibitory action of 1,25-D3-lactone on MNC formation was very similar to the inhibitory effects of calcitonin. These data suggest that (1) 1,25-D3-lactone is a potent natural inhibitor of formation of cells with the osteoclast phenotype at physiological concentrations and (2) the inhibition of these cells by 1,25-D3-lactone may not result solely from its competitive binding to the 1,25-D3 receptor.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-0646
    Keywords: dacarbazine ; autologous bone marrow transplantation ; solid tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Dacarbazine (DTIC) is a chemotherapy drug which has antitumor activity at standard doses, exhibits a steep dose-response effect in vitro, and is associated with relatively few non-hematologic toxicities. These characteristics suggest a potential role for this drug in bone marrow transplant preparative regimens. To pursue this hypothesis, 16 patients with refractory solid tumors were enrolled in a phase I study of single agent DTIC to determine the dose of DTIC requiring bone marrow reinfusion and to define the dose-limiting toxicity and maximum tolerated dose when given with autologous bone marrow rescue. Pharmacokinetics were evaluated at the 4394 mg/m2 dose level. The marrow requiring dose was 2000 mg/m2 when given as a single intravenous (IV) infusion. The extramyeloid dose-limiting toxicity of DTIC was hypotension, with the maximum tolerated dose of DTIC being 3380 mg/m2 when given with bone marrow transplantation (BMT). Other toxicities were transient and tolerable. At 4394 mg/m2 of DTIC, plasma concentrations declined biexponentially with a terminal half-life of 3 hours. The mean clearance was 10.6 L/hr/m2 with a volume of distribution at steady state of 37.5 L/m2 and a mean maximum plasma concentration of 150 mcg/ml. One patient with melanoma developed a partial response of short duration after receiving 2600 mg/m2 of DTIC. Dacarbazine can be significantly dose escalated with an acceptable toxicity profile, when given with BMT. Future trials should focus on the addition of this drug to current BMT preparative regimens used for the treatment of patients with lymphoma.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Using an expression cloning approach, we identified and cloned a novel intracellular protein produced by osteoclasts that indirectly induces osteoclast formation and bone resorption, termed OSF. Conditioned media from 293 cells transiently transfected with the 0.9 kb OSF cDNA clone stimulated osteoclast-like cell formation in both human and murine marrow cultures in the presence or absence 10-9 M 1,25-dihydroxyvitamin D3. In addition, conditioned media from 293 cells transfected with the OSF cDNA clone enhanced the stimulatory effects of 1,25-(OH)2D3 on bone resorption in the fetal rat long bone assay. In situ hybridization studies using antisense oligomers showed expression of OSF mRNA in highly purified osteoclast-like cells from human giant cell tumors of the bone. Northern blot analysis demonstrated ubiquitous expression of a 1.3 kb mRNA that encodes OSF in multiple human tissues. Sequence analysis showed the OSF cDNA encoded a 28 kD peptide that contains a c-Src homology 3 domain (SH3) and ankyrin repeats, suggesting that it was not a secreted protein, but that it was potentially involved in cell signaling. Consistent with these data, immunoblot analysis using rabbit antisera against recombinant OSF demonstrated OSF expression in cell lysates but not in the culture media. Furthermore, recombinant OSF had a high affinity for c-Src, an important regulator of osteoclast activity. Taken together, these data suggest that OSF is a novel intracellular protein that indirectly enhances osteoclast formation and osteoclastic bone resorption through the cellular signal transduction cascade, possibly through its interactions with c-Src or other Src-related proteins. J Cell Physiol 177:636-645, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
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