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Sarcoma Cells (sarcoma + cell)
Selected AbstractsInhibitory effects of a new bisphosphonate, minodronate, on proliferation and invasion of a variety of malignant bone tumor cellsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2006Tadahiko Kubo Abstract Little is known about the biological effects of bisphosphonates on primary malignant bone tumors. The purpose of this study was to investigate the antitumor effects of newly developed minodronate (MIN) on a variety of human malignant bone tumors. We examined the effects of MIN and clinically relevant incadronate (INC) on the proliferation, apoptosis, and cell cycle of two osteosarcoma (Saos-2, MG-63), two chondrosarcoma (SW1353, OUMS27), and two Ewing's sarcoma (RD-ES, SK-ES-1) cell lines. Furthermore, we investigated the anti-invasion effects of MIN on sarcoma cells and the effects of MIN on tumor growth in nude mice. MIN inhibited the viability of all six cell lines in a dose-dependent manner with IC50 values of 2.7 to 5.0 µM, which were significantly lower than those of INC. Importantly, both bisphosphonates affected the viability of normal bone marrow stromal cells much less than sarcoma cells. Both bisphosphonates induced cell cycle perturbation in all sarcoma cells tested and apoptosis in Saos-2 and SW1353 cells, although they failed to induce apoptosis in RD-ES and SK-ES-1 cells. MIN significantly suppressed invasion, even at a low concentration of 1 µM (p,<,0.01). Daily injection of 5 µg of MIN inhibited the growth of SK-ES-1 xenograft sarcoma in nude mice without loss of body weight. These findings suggest that MIN may have a beneficial adjuvant role in the treatment of patients with malignant bone tumors. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1138,1144, 2006 [source] Paclitaxel induces apoptosis via caspase-3 activation in human osteogenic sarcoma cells (U-2 OS)JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2005K.-H. Lu Abstract Paclitaxel has been found to exhibit cytotoxic and antitumor activity. There is little information regarding the mechanisms of apoptotic-inducing effect of paclitaxel on human osteogenic sarcoma U-2 OS cells. Several key regulatory proteins are involved in the initiation of apoptosis. Caspase-3 plays a direct role in proteolytic cleavage of cellular proteins responsible for progression to apoptosis. We examined the effect of paclitaxel on the cell cycle arrest and apoptosis in U-2 OS cells using flow cytometric analysis and Western blotting. We also measured the inhibition of paclitaxel-induced apoptosis and the caspase-3 activity by the broad-spectrum caspase inhibitor z-VAD-fmk on U-2 OS cells. The increased levels of casapse-3 were also confirmed by cDNA microarray. Our observations were: (1) paclitaxel treatment resulted in G2/M-cycle arrest in U-2 OS cells; (2) time and dose dependent apoptosis of U-2 OS cells was induced by paclitaxel; (3) in U-2 OS cells, z-VAD-fmk blocked the paclitaxel-induced apoptosis and caspase-3 activation. These results suggest that paclitaxel-induced G2/M-cycle arrest of the G2/M phase and apoptosis via a caspase-3 pathway in U-2 OS cells. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] 1141160720 Does the anti-proliferative action of ovine uterine serpin involve apoptosis?AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2006MB Padua Ovine uterine serpin (OvUS) is the major progesterone-induced protein in the uterus of the pregnant sheep. This protein is a member of the serine proteinase inhibitor superfamily and it has been proposed to down-regulate uterine immune function during pregnancy to protect the fetus. In vitro experiments have shown that both the native and the recombinant (r) form of the protein can inhibit mitogen-induced lymphocyte proliferation and growth of canine primary osteogenic sarcoma cells, mouse lymphoma cells, human prostatic adenocarcinoma cells (PC-3 cell line) and bovine preimplantation embryos. The mechanism by which OvUS inhibits cell proliferation is still unknown. Accordingly, experiments were conducted to test whether rOvUS exerts its anti-proliferative action through apoptosis. In the first experiment, the anti-proliferative effect of rOvUS on PC-3 cells was tested to determine the minimal concentration effective at inhibiting proliferation. Proliferation was inhibited by concentrations of OvUS at 8 ,g/mL and higher. The incorporation of [3H]thymidine was 4043, 3998, 3464, 2785, 2827, 2310, and 2332 dpm for 0, 0.5, 2, 8, 32, 125, and 250 ,g/mL, respectively. In the second experiment, PC-3 cells were cultured for 48 hr with 50, 100 and 200 ,g/mL of rOvUS or ovalbumin. Cells were then fixed and apoptotic cells identified using the TUNEL assay to detect DNA fragmentation. There was no effect of OvUS at any concentration tested on the percent of cells that were apoptotic. Percent apoptosis was 1.3% for control cells, 3.8%, 4.8% and 2% for cells cultured with 50, 100 and 200 ,g/mL rOvUS, and 2% for cells cultured with 200 ,g/mL ovalbumin. Results confirm that OvUS inhibits proliferation of PC-3 cells and indicate that inhibition does not involve induction of apoptosis. Further experiments are warranted to elucidate the anti-proliferative mechanism of action of OvUS. [source] Autoantibody production from a thymoma and a follicular dendritic cell sarcoma associated with paraneoplastic pemphigusBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2005J. Wang Summary Background, Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease. We previously reported that B cells in a Castleman tumour associated with PNP produced autoantibodies. However, it is uncertain whether the production of autoantibodies from the associated tumour is a common mechanism in PNP. Objectives, To investigate autoantibody production in a thymoma and a follicular dendritic cell sarcoma that were excised from two patients with PNP. Methods, Tumour cells were cultured, and their surface markers were identified. Indirect immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay (ELISA) using culture media from the tumours were used to detect PNP autoantibodies. Results, B cells with markers (CD22+, surface membrane IgG+ and surface membrane IgM+) of mature B lymphocytes constituted a proportion of cultured tumour cells in both tumours. Western blot showed that the medium from both the thymoma and the follicular dendritic cell sarcoma cells recognized 190-kDa periplakin and 210-kDa envoplakin bands of human epithelial proteins as well as recombinant linker regions of periplakin, envoplakin, desmoplakin and bullous pemphigoid antigen 1. ELISA was positive for antidesmoglein 3 antibody. Conclusions, The presence and localization in tumours of B-lymphocyte clones against proteins of the plakin family and desmoglein 3 in skin may not be confined to PNP with Castleman disease, but is possibly a common mechanism in PNP associated with various tumours. [source] Sex steroid receptors expression and hormone-induced cell proliferation in human osteosarcomaCANCER SCIENCE, Issue 3 2008Osamu Dohi Sex steroid receptors including estrogen receptors (ER), progesterone receptors (PR), and androgen receptors (AR) have been sporadically reported in human osteosarcoma or its cell lines. Therefore, sex steroids have been considered to play some roles in human osteosarcoma, but no systematic and detailed studies regarding the correlation between the status of these receptors in sarcoma cells and clinicopathological parameters have been reported. We examined the existence of ER, PR and AR in 28 cases of osteosarcoma using immunohistochemistry. We then characterized the potential influence of sex steroids on cell proliferation of osteosarcoma cells using MG-63 human osteosarcoma cell line, which expressed all of these receptors. ER-, and PR were detected in the great majority of the cases (23 and 24 cases, respectively) but ER-, and aromatase were not detected in all the cases, and AR was detected only in eight cases. There was a significant positive correlation between ER-, and Ki-67 (MIB1) labeling indexes. The absence of aromatase in tumors also suggests the relative importance of concentrations of circulating sex steroids. Proliferation of MG-63 cells was significantly stimulated by estradiol, progesterone, and 5,-dihydrotestosterone (DHT), and was significantly suppressed by the addition of fulvestrant (ICI), mifepristone (RU), and hydroxiflutamide, blockers for ER, PR and AR, respectively. Sex steroids, particularly estrogen and progesterone, are considered to play important roles in the regulation of cell proliferation in human osteosarcoma. In addition, these data suggest the potential for a novel endocrine therapy in osteosarcoma using clinically available inhibitors of progesterone and estrogen actions. (Cancer Sci 2008; 99: 518,523) [source] | ||||||||||