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)

Cultured SK-OS-10 cells (human osteogenic sarcoma metastatic to lung) shed microvesicles (dia. 300-1000 nm) that contained procoagulant and proaggregatory activities inhibitable by hirudin, by anti-tissue factor antibody and by phospholipase A2. These results show that SK-OS-10 cells belong to a group including U87MG human glioblastoma and HL-60 promyelocytic leukemia in which these activities are due to a thrombin-dependent mechanism arising from the presence of tissue factor on the surface of the tumor cells and their shed microvesicles.
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PMID:Tissue factor-dependent activation of platelets by cells and microvesicles of SK-OS-10 human osteogenic sarcoma cell line. 303 40

A new cytokine has been recognized in the conditioned media (CM) of freshly isolated acute myelocytic leukemia cells, cultured with 12-0-tetradecanayl phorbol acetate (TPA) 10(-8)M. The fraction with 70,000 MW was separated from CM by ammonium sulfate precipitation, ion-exchange cation and anion chromatography, and Sephadex G-200 gel filtration. It was a fibroblast growth inhibitor (FGI). This substance stopped fetal and skin (MALME 3 line) fibroblast propagation. The cytostatic effect was reversible on removal of FGI. At the same time, FGI did not inhibit macrophage proliferation. The fraction stimulated formation of monocytic and granulocytic colonies altered the phenotype of human U-2 osteosarcoma cells grown from epithelial-like to fibroblast-like cells, and stimulated differentiation of leukemic cells along the macrophage path. Some cells of promyelocytic leukemia line HL-60, grown in the presence of FGI, were stimulated to differentiate and some underwent lysis. The response to FGI of cells from different patients varied.
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PMID:Fibroblast growth inhibitor. 322 59

Studies were completed to establish the comparative cytotoxicity of 5'-deoxy-5-fluorouridine (5'-dFUrd) and other fluoropyrimidines in human bone marrow stem cells and several cultured human tumor cell lines (i.e., 47-DN and MCF-7 breast carcinomas, MG-63 osteosarcoma, HCT-8 colon tumor, Colo-357 pancreatic tumor, and HL-60 promyelocytic leukemia). In vitro clonogenic assays were used to measure cytotoxicity following a 3-hr drug exposure. 5'-dFUrd was less potent than was 5-fluorouracil or 5-fluoro-2'-deoxyuridine in all cells examined, exhibiting its best activity against the 47-DN [concentration that prevented 50% clonal growth compared to untreated control (LD50) = 32 microM] and MCF-7 (LD50 = 35 microM) breast carcinomas and MG-63 osteosarcoma (LD50 = 41 microM). Intermediate activity was observed against HCT-8 (LD50 = 200 microM) and Colo-357 (LD50 = 150 microM) gastrointestinal tumors. 5'-dFUrd had very poor activity against the HL-60 leukemia (LD50 = 470 microM). The suppression of the clonal growth of human bone marrow stem cells required the greatest amount of 5'-dFUrd (LD50 = 580 microM). With use of these studies, a therapeutic ratio (concentration that prevented 25% clonal growth compared to untreated control of bone marrow divided by LD50 of tumor) was calculated for each drug in each tumor. 5'-dFUrd had values ranging from 1.2 to 7.5 for the solid tumors and 0.5 in HL-60 cells. This was in marked contrast to 5-fluorouracil, or 5-fluoro-2'-deoxyuridine, which failed in all cases to have ratios greater than or equal to one. The results indicate that 5'-dFUrd can exhibit a cytotoxic selectivity for human tumor cells compared to human bone marrow stem cells that does not exist for 5-fluorouracil or 5-fluoro-2'-deoxyuridine. This suggests that 5'-dFUrd may be of greater therapeutic benefit in the treatment of certain human cancers than the fluoropyrimidines used currently.
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PMID:5'-Deoxy-5-fluorouridine selective toxicity for human tumor cells compared to human bone marrow. 622 92

The cytotoxic activity of 5'-deoxy-5-fluorouridine (5'-ddFUrd) was established in six cultured human tumor lines: 47-DN and MCF-7 breast carcinomas, MG-63 osteosarcoma, HCT-8 colon carcinoma, Colo-357 pancreatic carcinoma, and HL-60 promyelocytic leukemia. Cells were exposed to a wide range of 5'-dFUrd concentrations (from 0.1 microM to 1.0 mM) for 3, 6, or 24 hrs, and then cloned using standard in vitro clonogenic assays. 5'-dFUrd exhibited its best activity in the 47-DN and MCF-7 breast cell lines and in the MG-63 osteosarcoma line (3-hr LD50 values of 32, 34, and 38 microM, respectively). Less activity was observed in the HCT-8 colon (LD50 = 195 microM) and Colo-357 pancreatic (LD50 = 155 microM) tumor lines, and ver poor activity was noted in the HL-60 leukemia cell line (LD50 = 465 microM). The metabolism of 5'-dFUrd to 5-FU (FUra) and FUra-nucleotides was determined and found to directly correlate with the potency of 5'-FUrd in these cell lines. These results suggest that: (a) there is a marked variation in sensitivity of human cancer cells of different tissue origin to 5'-dFUrd, (b) there is a direct relationship between the sensitivity of human cells to 5'-dFUrd and the ability of the cell to metabolize 5'-dFUrd to FUra, and (c) increasing exposure period of cells to 5'-dFUrd did not markedly alter 5'-dFUrd potency in all human cancer cells examined, with the exception of the 47-DN breast cancer cells.
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PMID:Cytotoxic activity of 5'-deoxy-5-fluorouridine in cultured human tumors. 622 89

The inositol 1,4,5-trisphosphate (InsP3) receptor is essential for signal Ca2+ release from intracellular stores and for capacitative Ca2+ entry. We have isolated the promoter and proximal DNA segments of the human type I InsP3 receptor gene. Transcription initiation in human G-292 osteosarcoma and HL-60 promyelocytic leukemia cells was shown to occur predominantly from an adenine residue located 39 base pairs downstream of a consensus TATA box element. Upstream DNA including the TATA box promoted directional transcription of a chloramphenicol acetyltransferase reporter gene when transfected into G-292 cells. A negative regulatory element in the distal promoter and a positive element in the proximal region were identified by deletion mapping and transcription assays. The proximal region enhanced transcription in response to 12-O-tetradecanoylphorbol-13-acetate or serum, but conferred transcriptional repression in response to 1,25-dihydroxyvitamin D3 or 17beta-estradiol. The repressive effect of 17beta-estradiol was mediated by the nuclear estrogen receptor, as estrogen-dependent transcriptional repression was inhibited by the antiestrogen tamoxifen and the estrogen receptor antagonist ICI 182,780. This is the first study of the type I InsP3 receptor gene promoter, and the results suggest a mechanism by which chronic estrogen treatment of osteoblasts affects type I InsP3 receptor gene expression, signal transduction, and secretion.
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PMID:Cloning and characterization of the type I inositol 1,4,5-trisphosphate receptor gene promoter. Regulation by 17beta-estradiol in osteoblasts. 927 93

Human cartilage glycoprotein 39 (HC gp-39) has been described as a major secreted product of cultured articular chondrocytes, synovial fibroblasts, and the osteosarcoma line MG63. However, its expression in these cells types has not been directly linked to corresponding cell types in vivo. In this report, expression of HC gp-39 is demonstrated from peripheral blood-derived macrophages in association with their differentiation from monocytes to macrophages. Consistent with macrophage specificity, HC gp-39 expression is also induced upon selective stimulation of the pluripotent promyelocytic leukemia cell line HL-60 toward the monocyte/macrophage lineage with vitamin D3 or phorbol 12-myristate 13-acetate (PMA), while treatments stimulating granulocyte and eosinophilic pathways do not induce expression. Furthermore, HC gp-39 expression levels correlate with the degree of morphological differentiation induced by PMA and vitamin D3 treatments. PMA-induced mRNA expression occurs by 36 h and is a secondary transcriptional response since its synthesis is inhibited by cycloheximide. Apparently, HC gp-39 expression is tied to later events in the differentiation of monocytes into macrophages. The in vivo significance of these results is validated by the in situ detection of HC gp-39 mRNA in inflammatory macrophages associated with rheumatoid synovium. Thus, macrophages appear to be an important source of HC gp-39, which has been shown to be present at elevated levels in the blood and synovium of rheumatoid arthritis patients. The implications of this extend well beyond the previously restricted observations in cell types associated with the joint and suggest a potential involvement of macrophage-derived HC gp-39 in other aspects of inflammation, tissue remodeling, and host defense.
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PMID:Induction and expression of human cartilage glycoprotein 39 in rheumatoid inflammatory and peripheral blood monocyte-derived macrophages. 941 65

A number of thiosemicarbazones have been tested previously and herein are included three bis(thiosemicarbazones) for comparison to the previous derivatives. In general the uncomplexed thiosemicarbazones were more potent in the cytotoxic screens than the bis(thiosemicarbazone) except in the murine L1210 and the human colon SW480 screens. Mode of action studies have only demonstrated slight differences in the effects of the two types of compounds on nucleic acid metabolism. The symmetrical and unsymmetrical bis(thiosemicarbazones) complexes of copper, nickel, zinc, and cadmium have been examined to compare them to the heterocyclic N(4)-substituted thiosemicarbazones metal complexes. These new derivatives demonstrated excellent activity against the growth of suspended lymphomas and leukemias although it should be pointed out that generally they were not as active as the copper complexes of N(4)-substituted thiosemicarbazones. Nevertheless, selected bis(thiosemicarbazones) complexes were active against the growth of human lung MB9812, KB nasopharynx, epidermoid A431, glioma UM-86, colon SW480, ovary 1-A9, breast MCK-7, and osteosarcoma Saos-2. In human HL-60 promyelocytic leukemia cells the complexes preferentially inhibited DNA and purine syntheses over 60 min. The regulatory enzyme of the de novo purine pathway, IMP dehydrogenase, appeared to be a major target of the complexes. However, minor inhibition of the activities of DNA polymerase alpha, PRPP-amido transferase, ribonucleotide reductase, and nucleoside kinases occurred over the same time period. No doubt these effects of the complexes on nucleic acid metabolism were additive since the d[NTP] pool levels were reduced after 60 min as was DNA synthesis. The symmetrical and unsymmetrical bis(thiosemicarbazones) and their metal complexes did not cause as severe DNA fragmentation as the heterocyclic N(4)-substituted thiosemicarbazone metal complexes; furthermore, their metabolic effects in the tumor cell were more focused on a single synthetic pathway.
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PMID:The cytotoxicity of symmetrical and unsymmetrical bis(thiosemicarbazones) and their metal complexes in murine and human tumor cells. 1096 96

We recently identified 1alpha,25-dihydroxy-3-epi-vitamin D3 [1alpha,25(OH)2-3-epi-D3] as a metabolite of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] produced in rat osteosarcoma cells (UMR 106). We now report the isolation of 24R,25-dihydroxy-3-epi-vitamin D3 [24R,25(OH)2-3-epi-D3] as a metabolite of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] by high-performance liquid chromatography (HPLC) with chiral column and its structure assignment by proton nuclear magnetic resonance (1H-NMR) and liquid chromatography-mass spectrometry (LC-MS) analysis. We also demonstrated the production of 24R,25(OH)2-3-epi-D, in two other cell lines [human colon carcinoma cells (Caco-2) and porcine kidney cells (LLC-PK1)] which were previously shown to convert 1alpha,25(OH)2D3 into 1alpha,25(OH)2-3-epi-D3. It can be seen that the production of 24R,25(OH)2- 3-epi-D3 from 24R,25(OH)2D3 is lower than that of 1alpha,25(OH)2-3-epi-D3 from 1alpha,25(OH)2D3 in all the cells studied. 24R,25(OH)2-3-epi-D3 was found to be inactive in terms of its ability to bind to the vitamin D receptor (VDR), in inhibiting proliferation and in inducing differentiation of human promyelocytic leukemia cells (HL-60). Thus, our study indicates that the C-3 epimerization pathway is common to both 1alpha,25(OH)2D3 and 24R,25(OH)2D3 and may play an important role in modulating the concentration and the biological activity of these two major vitamin D3 metabolites in target tissues.
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PMID:Isolation, identification and biological activity of 24R,25-dihydroxy-3-epi-vitamin D3: a novel metabolite of 24R,25-dihydroxyvitamin D3 produced in rat osteosarcoma cells (UMR 106). 1150

The two known mechanisms for telomere maintenance in eukaryocytes are telomerase in telomerase-positive cells and alternative lengthening of telomeres (ALT) in telomerase-negative cells. We report here that telomere maintenance in the telomerase-positive human ovarian SKOV-3 cells was not affected by inhibition of telomerase. For comparison, the effect of telomerase inhibitors on telomere maintenance in another telomerase-positive cell line (i.e. human pharynx FaDu cells) and the telomerase-negative human osteosarcoma Saos-2 cells was examined. Telomerase activity was measured using a modified telomeric repeat amplification protocol and telomere length was measured using a solution hybridization-based method and fluorescence in situ hybridization. A reverse transcriptase inhibitor (3'-azido-deoxythymidine or AZT) and an antisense against a component of human telomerase RNA (antisense hTR) were used to inhibit telomerase. FaDu and SKOV-3 cells showed comparable baseline telomerase activity. Telomerase activity in both cells was inhibited about equally by AZT (maximal inhibition of approximately 80%) and by expression of antisense hTR (complete inhibition in SKOV-3 cells and maximal inhibition of approximately 80% in FaDu cells). However, treatment with telomerase inhibitors resulted in approximately 50% telomere shortening in FaDu cells but had no effect on SKOV-3 nor Saos-2 cells. SKOV-3 cells did not show the characteristic features of ALT (i.e. heterogeneous telomere length and promyelocytic leukemia bodies), whereas these ALT features were observed in Saos-2 cells. Collectively, these results suggest the existence of a telomerase-independent mechanism of telomere maintenance in the telomerase-positive SKOV-3 cells.
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PMID:Telomere maintenance in telomerase-positive human ovarian SKOV-3 cells cannot be retarded by complete inhibition of telomerase. 1222 Jun 25

The substituted ethyl-2-phenacyl-3-phenylpyrrole-4-carboxylates were synthesized by a condensation of a beta-chloroenal and an alpha-aminoketone under neutral conditions. They proved to be potent cytotoxic agents against the growth of murine L1210 and P388 leukemias and human HL-60 promyelocytic leukemia, HuT-78 lymphoma, and HeLa-S(3) uterine carcinoma. Selective compounds were active against the growth of Tmolt(3) and Tmolt(4) leukemias and THP-1 acute monocytic leukemia, liver Hepe-2, ovary 1-A9, ileum HCT-8 adenocarcinoma, and osteosarcoma HSO. A mode of action study in HL-60 cells demonstrated that DNA and protein syntheses were inhibited after 60 min at 100 microM. DNA and RNA polymerases, PRPP-amido transferase, dihydrofolate reductase, thymidylate synthase, and TMP kinase activities were interfered with by the agent with reduction of d[NTP] pools. Nonspecific interaction with the bases of DNA and cross-linking of the DNA may play a role in the mode of action of these carboxylates.
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PMID:Synthesis and cytotoxicity of substituted ethyl 2-phenacyl-3-phenylpyrrole-4-carboxylates. 1282 84


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