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)

Anthracyclines, such as daunorubicin (DNR), rubidazone (RBD) and adriamycin (ADR) are intercalating drugs used in cancer chemotherapy. They inhibit synthesis of DNA and RNA, break DNA and inhibit mitochondrial oxidative chain. Their antitumoral experimental activities depend upon type of drug, tumor and route of administration. After i.v. administration, the drug is present in all tissues except central nervous system. Its disappearance from the plasma is biphasic with a long terminal half life, justifying intermittent chemotherapy. Anthracyclines metabolism occurs mainly in liver micrososomes, and 90% metabolites are excreted in the bile. The main toxicity is cardiac, as a congestive heart failure which appears when a cumulated drug dose is overcome. In man only, a few derivatives have been studied, compounds with activity and no cardiotoxicity are still in research. Action of malignancies depends on type of derivative. We use DNR since 1967, it is a remarkable active drug in induction treatment of AML, it is the only active drug on acute promyelocytic leukemia, and it increases number of remissions in all of adult patients and severe forms of children ALL. Adriamycin (ADR) is active on solid tumors (osteosarcoma, breast and thyroid cancers) and lymphomas. With rubidazone (RBD) we obtain 2/3 of remissions in acute monoblastic leukemia, and it is easier to use than DNR and equally active on AML. RBD is also active on severe cases of lymphomas (lymphosarcomas and Hodgkin's disease). A new compound DEA 14 DNR seems interesting: experimental antitumor activity is high (compared to DNR, RBD and ADR) and it appears to possess activity on solid tumors in man.
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PMID:[Survey of anthracyclines derivatives in haematology (author's transl)]. 67 74

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

We report a rare case of complete remission for 32 months with continuous treatment with all-trans retinoic acid (ATRA) alone in a patient with acute promyelocytic leukemia which developed as a second malignancy after the treatment of osteosarcoma after failure of conventional chemotherapy. The adverse effects of ATRA were apparently tolerable.
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PMID:Successful continuous treatment with all-trans retinoic acid for acute promyelocytic leukemia; secondary malignancy after the treatment of osteosarcoma. 782 86

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

The tumor necrosis factor receptor, p60 (TNF-R1), transduces death signals via the association of its cytoplasmic domain with several intracellular proteins. By screening a mammalian cDNA library using the yeast two-hybrid cloning technique, we isolated a ubiquitin-homology protein, DAP-1, which specifically interacts with the cytoplasmic death domain of TNF-R1. Sequence analysis reveals that DAP-1 shares striking sequence homology with the yeast SMT3 protein that is essential for the maintenance of chromosome integrity during mitosis (Meluh, P. B., and Koshland, D. (1995) Mol. Biol. Cell 6, 793-807). DAP-1 is nearly identical to PIC1, a protein that interacts with the PML tumor suppressor implicated in acute promyelocytic leukemia (Boddy, M. N., Howe, K., Etkin, L. D., Solomon, E., and Freemont, P. S. (1996) Oncogene 13, 971-982), and the sentrin protein, which associates with the Fas death receptor (Okura, T., Gong, L., Kamitani, T., Wada, T., Okura, I., Wei, C. F., Chang, H. M., and Yeh, E. T. (1996) J. Immunol. 157, 4277-4281). The in vivo interaction between DAP-1 and TNF-R1 was further confirmed in mammalian cells. In transient transfection assays, overexpression of DAP-1 suppresses NF-kappaB/Rel activity in 293T cells, a human kidney embryonic carcinoma cell line. Overexpression of either DAP-1 or sentrin causes apoptosis of TNF-sensitive L929 fibroblast cell line, as well as TNF-resistant osteosarcoma cell line, U2OS. Furthermore, the dominant negative Fas-associated death domain protein (FADD) protein blocks the cell death induced by either DAP-1 or FADD. Collectively, these observations highly suggest a role for DAP-1 in mediating TNF-induced cell death signaling pathways, presumably through the recruitment of FADD death effector.
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PMID:The ubiquitin-homology protein, DAP-1, associates with tumor necrosis factor receptor (p60) death domain and induces apoptosis. 1018 98

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


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