Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor effects of 2'-C-cyano-2'-deoxy-1-beta-D- arabinofuranosylcytosine (CN-DAC), a synthetic 1-beta-D-arabinofuranosyl-cytosine (ara-C) derivative, were examined and compared with that of ara-C in murine tumors and in various human tumors using three different chemosensitivity tests. CNDAC extended the life span of mice bearing P388 leukemia. CNDAC had a unique in vitro antitumor spectrum for human cancers different from that of ara-C. Compared with ara-C, CNDAC was more effective in 10 human tumors (2 lung, 4 stomach and 4 osteosarcoma), equal in 2 tumors (lung and fibrosarcoma) and less potent in 11 tumors (4 lung, 4 osteosarcoma, bladder, renal and epidermoid). Characteristically CNDAC showed excellent activities against tumors, refractory to ara-C, such as HT-1080 human fibrosarcoma implanted in chick embryos or athymic mice, although its cytotoxicity against HT-1080 was almost equal to that of ara-C. Thus, CNDAC is an interesting and promising agent that should be considered for further detailed preclinical evaluation.
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PMID:Antitumor activity of a novel nucleoside, 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosylcytosine (CNDAC) against murine and human tumors. 159 80

Newcastle disease virus (NDV), strain 73-T, has previously been shown to be cytolytic to mouse tumor cells. In this study, we have evaluated the ability of NDV to replicate in and kill human tumor cells in culture and in athymic mice. Plaque assays were used to determine the cytolytic activity of NDV on six human tumor cell lines, fibrosarcoma (HT1080), osteosarcoma (KHOS), cervical carcinoma (KB8-5-11), bladder carcinoma (HCV29T), neuroblastoma (IMR32), and Wilm's tumor (G104), and on nine different normal human fibroblast lines. NDV formed plaques on all tumor cells tested as well as on chick embryo cells (CEC), the native host for NDV. Plaques did not form on any of the normal fibroblast lines. To detect NDV replication, virus yield assays were performed which measured virus particles in infected cell culture supernatants. Virus yield increased 10,000-fold within 24 hr in tumor and CEC supernatants. Titers remained near zero in normal fibroblast supernatants. In vivo tumoricidal activity was evaluated in athymic nude Balb-c mice by subcutaneous injection of 9 x 10(6) tumor cells followed by intralesional injection of either live or heat-killed NDV (1.0 x 10(6) plaque forming units [PFU]), or medium. After live NDV treatment, tumor regression occurred in 10 out of 11 mice bearing KB8-5-11 tumors, 8 out of 8 with HT-1080 tumors, and 6 out of 7 with IMR-32 tumors. After treatment with heat-killed NDV no regression occurred (P less than 0.01, Fisher's exact test). Nontumor-bearing mice injected with 1.0 x 10(8) PFU of NDV remained healthy. These results indicate that NDV efficiently and selectively replicates in and kills tumor cells, but not normal cells, and that intralesional NDV causes complete tumor regression in athymic mice with a high therapeutic index.
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PMID:Newcastle disease virus selectively kills human tumor cells. 161 12

The aim of this study was to determine biocompatibility of glass ceramics and adhesion of cultured cells to glass ceramics. Four established cultured cell lines, human fibrosarcoma cells (HT-1080), human gingival carcinoma cells (Ca9-22), human osteosarcoma cells (NY) and mouse osteoblasts (MC3T3-E1), were used. For phase-contrast and electron microscopic observation they were cultured on substrates of glass ceramics or polystyrene coverslips as a control. The results obtained were as follows. Glass ceramics caused neither cellular degeneration nor death, as revealed by phase-contrast microscopy. By transmission electron microscopy an amorphous structure similar to the basal lamina was observed at the interface between the substrates and Ca9-22, and between glass ceramics and NY. A similar structure sometimes existed between the substrates and MC3T3-E1. On the other hand HT-1080 showed no such structure. The findings suggest that the biocompatibility of glass ceramics was satisfactory. Furthermore, from the clinical point of view it seems to be possible to close the material-tissue interface with epithelial, fibrocytic and osteocytic cells.
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PMID:[Basic studies on CaO-P2O5-MgO-SiO2-CaF system glass ceramics. 2. Ultrastructural study on interface between culture cells and glass ceramics]. 263 4

Growth inhibition assays indicated that the IC50 values for methotrexate (MTX) and 5-fluorodeoxyuridine (FdUrd) in HS-18, a liposarcoma cell line lacking retinoblastoma protein (pRB), and SaOS-2, an osteosarcoma cell line with a truncated and nonfunctional pRB, were 10- to 12-fold and 4- to 11-fold higher, respectively, than for the HT-1080 (fibrosarcoma) cell line, which has wild-type pRB. These Rb-/- cell lines exhibited a 2- to 4-fold increase in both dihydrofolate reductase (DHFR) and thymidylate synthase (TS) enzyme activities as well as a 3- to 4-fold increase in mRNA levels for these enzymes compared to the HT-1080 (Rb+/+) cells. This increase in expression was not due to amplification of the DHFR and TS genes. Growth inhibition by MTX and FdUrd was increased and DHFR and TS activities and expression were correspondingly decreased in Rb transfectants of SaOS-2 cells. In contrast, there was no significant difference in growth inhibition among these cell lines for the nonantimetabolites VP-16, cisplatin, and doxorubicin. A gel mobility-shift assay showed that parental SaOS-2 cells had increased levels of free E2F compared to the Rb-reconstituted SaOS-2 cells. These results indicate that pRB defective cells may have decreased sensitivity to growth inhibition by target enzymes encoded by genes whose transcription is enhanced by E2F proteins and suggest mechanisms of interaction between cytotoxic agents and genes involved in cell cycle progression.
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PMID:Lack of functional retinoblastoma protein mediates increased resistance to antimetabolites in human sarcoma cell lines. 747

Osteonectin (OTN) has been implicated in controlling cell adhesivity onto substratum and extracellular matrix (ECM) remodeling. Significant amounts of OTN were synthesized not only by normal fibroblasts and endothelial cells, but also by HT-1080 fibrosarcoma and MG-63 osteosarcoma cells. Levels of secreted OTN were likely to be slightly elevated by the addition of exogenous placental laminin (LN), but not by supplementation of plasma fibronectin (FN). Exogenously supplemented purified bone OTN was not apparently incorporated into the ECM of the adhering cells and had no effect on cell spreading and growth, whereas secretion of type I collagen or FN in the tumor cells was moderately diminished in the presence of soluble OTN. Concentration-dependent down-regulation of cellular LN secretion appeared to be most significant, suggesting that OTN participates in regulating extracellular secretion of ECM components in the cells either with or without the ability to synthesize cellular OTN.
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PMID:Osteonectin/SPARC regulates cellular secretion rates of fibronectin and laminin extracellular matrix proteins. 816 15

The effects of heat treatment on the viability and fibrinolytic potential of four cultured human carcinoma cell lines, fibrosarcoma cells (HT-1080), lung adenocarcinoma cells with highly metastatic potential (HAL-8), melanoma cells (Bowes) and osteosarcoma cells (NY), determined by measuring their levels of urokinase-type plasminogen activator (u-PA) and its specific receptor (u-PAR), were investigated by comparing them with those of human umbilical vein endothelial cells (HUVECs). HUVECs incubated at 43 degrees C for 120 min exhibited no decrease in viability but exhibited an increase in both u-PA and u-PAR. HT-1080 and HAL-8 showed a moderately high heat-resistance (viability, 60-90%) that correlated with the reduction of u-PAR but not u-PA. On the other hand, Bowes and NY cells, with poor heat-resistance (viability, 20-50%), exhibited stronger cell-associated u-PA activity when they survived at 43 degrees C for 120 min. Since the u-PA/u-PAR system is directly involved in the invasiveness and metastatic potential of carcinoma cells, hyperthermia would alter the biological activity of these carcinoma cells.
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PMID:Effect of hyperthermia on the viability and the fibrinolytic potential of human cancer cell lines. 1080 68

Cell culture in collagen lattice is known to be a more physiological model than monolayer for studying the regulation of extracellular matrix protein deposition. The synthesis of sulfated glycosaminoglycans (GAG) and dermatan sulfate (DS) proteoglycans by 3 cell strains were studied in confluent monolayers grown on plastic surface, in comparison to fully retracted collagen lattices. Cells were labelled with 35S-sulfate, followed by GAG and proteoglycan analysis by cellulose acetate and SDS-polyacrylamide gel electrophoresis, respectively. The 3 cell strains contracted the lattice in a similar way. In monolayer cultures, the major part of GAG was secreted into culture medium whereas in lattice cultures of dermal fibroblasts and osteosarcoma MG-63 cells but not fibrosarcoma HT-1080 cells, a higher proportion of GAGs, including dermatan sulfate, was retained within the lattices. Small DS proteoglycans, decorin and biglycan, were detected in fibroblasts and MG-63 cultures. They were preferentially trapped within the collagen gel. In retracted lattices, decorin had a higher Mr than in monolayer. Biglycan was detected in monolayer and lattice cultures of MG-63 cells but in lattice cultures only in the case of fibroblasts. In this last case, an up regulation of biglycan mRNA steady state level and down regulation of decorin mRNA was observed, in comparison to monolayers, indicating that collagen can modulate the phenotypical expression of small proteoglycan genes.
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PMID:Modulation of sulfated glycosaminoglycan and small proteoglycan synthesis by the extracellular matrix. 1082 30

In orthopedic surgery, reconstruction of bone segments afflicted with cancer is done in various ways, including devitalization of the bone or replacement of the bone by artificial bone constructs. To devitalize bone cells, extracorporal irradiation or autoclaving is used although both methods have substantial disadvantages. We now introduce the technique of extracorporal high hydrostatic pressure (HHP) treatment to disintegrate tumor cells in suspension or in their adherent state. The effect of HHP on cell viability, adherence and morphology of four different tumor cell lines (fibrosarcoma HT-1080, osteosarcoma SAOS-2, ovarian cancer OV-MZ-6, breast cancer MCF-7) was investigated. For this, adherently growing (with fibronectin serving as the growth-promoting substrate) or suspended tumor cells were placed into a test vial which was transferred into the pressure chamber of a high hydrostatic pressure device. After pressure treatment, the pressure was relaxed to atmospheric pressure and subsequently cell viability, adherence and morphology assessed. High hydrostatic pressure as high as 350 MPa (10 min, 37 degrees C) did not detach the tumor cells from the fibronectin-coated surface although at these conditions all of the four cell lines tested were irreversibly damaged. Adherently growing tumor cells were considerably more sensitive to HHP than tumor cells detached from the surface and treated by HHP in suspension. HHP-treated tumor cells showed drastic morphological changes, evident by cell membrane ruffling and bleb formation. At 150 MPa adherently growing or suspended tumor cells are irreversibly damaged by short-term treatment with HHP. In another investigation, we experienced that treatment of freshly excised bones or tendons by HHP has no adverse effect on their stability or biomechanical properties. Therefore, we anticipate that in orthopedic surgery HHP could be used as a new gentle way of treating resected cancer-afflicted bones or tendons to inactivate tumor cells before autologous reimplantation.
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PMID:Effect of extracorporal high hydrostatic pressure on tumor cell adherence and viability. 1525 4

For the control of tumor metastasis it is important to identify chemical compounds with antimigratory potency. Agents acting against single cell and cluster type migration are necessary for successful antimetastatic therapy. In the present study, the migration of HT-1080 fibrosarcoma cells and OSCORT osteosarcoma cells was compared in a Boyden chamber and in an extracellular matrix (ECM)-based three-dimensional cell culture (3-DCC) model system. The Boyden chamber offers a model of single tumor cell migration, whereas the 3-DCC model system demonstrates invasive growth in the form of a cluster. Since PD98059 (MEK inhibitor) exclusively reduced migration in the 3-DCC model, it may be plausible that the ERK/MAPK signaling pathway is essential for cluster type migration. Interestingly, single cell migration was stimulated upon blocking phosphatidylinositol 3-kinase (PI3K) and also p38-MAPK by treatment with LY294002 and SB203580 respectively. A remarkable reduction of single cell migration was observed following treatment with okadaic acid, a phosphatase 1 (PP1) and 2A (PP2A) inhibitor, which was rather intriguing. This study provided evidence that certain cytotoxic/cytostatic agents at appropriate concentrations were able to preferentially inhibit certain types of migration relative to cell proliferation. Single cell migration was selectively inhibited by taxol at very low subtoxic concentration, whereas 5-hexyl-2'-deoxyuridine (HUdR) exclusively inhibited the cluster type of migration. The borrelidin compound was able to inhibit both types of tumor cell migration, but single tumor cell migration was much less affected. It is interesting that migration was more reduced than proliferation by borrelidin, especially at the advanced growth stage. Taxol is recommended as an agent acting against single cell migration, as well as HUdR and borrelidin as leading compounds for developing antimetastatic drugs against cluster type migration.
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PMID:Differential inhibition of single and cluster type tumor cell migration. 1966 4

We investigated the cell-killing efficacy of UV light on cancer cells expressing GFP in the nucleus and RFP in the cytoplasm (dual-color cells). After exposure to various doses of UVA, UVB, or UVC, apoptotic and viable cells were quantitated under fluorescence microscopy using dual-color 143B human osteosarcoma cells, HT-1080 human fibrosarcoma cells, Lewis lung carcinoma (LLC), and XPA-1 human pancreatic cancer cells in vitro. UV-induced cancer cell death was wave-length and dose dependent, as well as cell-line dependent. After UVA exposure, most cells were viable even when the UV dose was increased up to 200 J/m(2). With UVB irradiation, cell death was observed with irradiation at 50 J/m(2). For UVC, as little as 25 J/m(2) UVC irradiation killed approximately 70% of the 143B dual-color cells. This dose of UVB or UVA had almost no effect on the cancer cells. UV-induced cancer cell death varied among the cell lines. Cell death began about 4 h after irradiation and continued until 10 h after irradiation. UVC exposure also suppressed cancer cell growth in nude mice in a model of minimal residual cancer (MRC). No apparent side effects of UVC exposure were observed. This study opens up the possibility of UVC treatment for MRC after surgical resection.
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PMID:UV light killing efficacy of fluorescent protein-expressing cancer cells in vitro and in vivo. 2050 55


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