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 therapeutic efficacy of PTT.119, p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met-ethoxy HCl, was evaluated using the transplantable L1210 leukemia and Ridgway osteogenic sarcoma tumor lines and the spontaneous C3H/StRos mammary tumor and AKR leukemia tumor models. Given in a single i.p. dose at 5-10 mg/kg on day 2 or in two injections of 5-7 mg each on days 2 and 9 to BDf1 mice with peritoneal L1210 leukemia grafts, PTT.119 increased the life spans (ILS) of the population dying of tumor by 94%-313%. In addition, 10% of the mice receiving 7 mg PTT.119 on days 2 and 9 were free of L1210 leukemic grafts when autopsied at the end of the 70-day observation period. The average life span of AKR mice with Ridgway osteogenic sarcoma grafts was significantly increased from 36-40 days to greater than 79 days following one or two s.c. injections of 5, 7, or 12.5 mg/kg PTT.119. Administration of PTT.119 at 14 or 14 and 21 days after tumor graft not only induced regression of palpable tumors but resulted in the absence of grafts in 60%-70% of the mice in several of the treated groups on autopsy at 180 days. In contrast, spontaneous mammary tumors were less susceptible to PTT.119; an ILS of only 15%-38% was observed in C3H/StRos mice, which eventually succumbed to tumor. Nevertheless, the total regression of initial tumors and the absence of further tumor incidence (greater than 180 days) was confirmed by autopsy in 5%-10% of the C3H/StRos mice receiving multiple i.p. injections of 5 or 7.5 mg/kg PTT.119. The drug was highly effective against spontaneous AKR leukemia; multiple s.c. or i.p. injections for a total of 15-40 mg/kg PTT.119 increased the average 25-day life span up to 723% and sustained remission in 9%-40% of the animals for greater than 6 months.
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PMID:Evaluation of p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met-ethoxy HCl against transplantable and spontaneous murine neoplasia. 235 70

Anti-peptide and anti-protein antisera were produced which both recognize bone acidic glycoprotein-75 (Mr = 75,000) and an apparent fragment or biosynthetic intermediate (Mr = 50,000) in calcified tissues and/or serum. A fragment-precursor relationship is suggested from the fact that closely spaced doublet polypeptides of Mr = 50,000 could be produced by proteolysis of the purified protein upon long term storage. No reactivity was detected with osteopontin, bone sialoprotein, or small bone proteoglycans. Bone acidic glycoprotein-75 represents 0.5-1% of the total radiolabeled proteins synthesized by explant cultures of neonatal calvaria or growth plate, by calvarial outgrowth cultures, and by rat osteosarcoma cells. Amounts produced by explant cultures and calvarial outgrowth cultures were similar to that for osteopontin, a major product of osteoblasts. In osteosarcoma cultures, 80% of labeled antigens were associated with the cell layer fraction wherein specific immunoprecipitation pelleted Mr = 50,000 and 75,000 sized antigens. Bone acidic glycoprotein-75 (Mr = 75,000) is enriched in 4 M guanidine HCl/0.5 EDTA extracts of neonatal rat bone and growth plate tissues, whereas largely absent from heart, lung, spleen, liver, brain, and kidney. Explant cultures of these noncalcifying tissues also synthesized bone acidic glycoprotein-75 antigen, but the quantities produced were only 5% or less that obtained with calvaria. By immunohistochemistry, antigenicity is associated with the bony shaft and calcified cartilage of long bones, but is absent from associated soft tissues. These finding demonstrate that bone acidic glycoprotein-75 is antigenically distinct, predominantly localized to calcified tissues, represents a major product of normal osteoblastic cells and may undergo a characteristic fragmentation in vivo and in vitro.
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PMID:Bone acidic glycoprotein-75 is a major synthetic product of osteoblastic cells and localized as 75- and/or 50-kDa forms in mineralized phases of bone and growth plate and in serum. 239 8

The SK-Luci-6 cell line, established from a large-cell anaplastic lung tumor of a patient with humoral hypercalcemia of malignancy (HHM), was investigated to identify osteolytic factors produced that might mediate HHM. Most HHM-associated tumors are thought to produce parathyroid hormone-related proteins or transforming growth factor (TGF) alpha. SK-Luci-6 cells formed s.c. tumors and induced hypercalcemia in athymic nude mice. Serum-free conditioned medium from SK-Luci-6 cultures induced bone resorption in neonatal mouse calvariae in vitro, and also contained TGF-beta activity and mitogenic activity. SK-Luci-6 cell conditioned medium did not displace [125I]epidermal growth factor binding to cell receptors or stimulate cyclic AMP formation in rat osteosarcoma cells, suggesting that the conditioned medium did not contain TGF-alpha or parathyroid hormone-related proteins. The osteolytic, TGF-beta, and mitogenic activities copurified in several chromatographic separations: gel filtration in acid and then in guanidine HCl; ion exchange; and reverse phase. The results suggest that in the HHM-associated SK-Luci-6 tumor, the causative osteolytic factor produced by the tumor cells is not a parathyroid hormone-related protein or TGF-alpha but, rather, may be a TGF-beta.
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PMID:Copurification of osteolytic and transforming growth factor beta activities produced by human lung tumor cells associated with humoral hypercalcemia of malignancy. 253 57

Heterotopic osteogenesis induced by lyophilized powder of a murine osteosarcoma was greatly enhanced by treating the powder with the following acids: 0.01 N HCl (pH 2.0), 0.1 N HCl (pH 1.7), 1 N HCl (pH 1.2), 0.5 M acetic acid (pH 2.8), 0.5 M lactic acid (pH 2.0), and 0.5 M citric acid (pH 1.8). The acid-treated preparations were neutralized before implantation into back muscles of ddY mice. Acid treatment resulted in almost a fivefold increase in the amount of new bone formation, as measured by uptake of strontium-85 into the implants. In addition bone-inducing activity was increased by longer exposure to 0.01 N HCl up to 24 h. These findings suggest that the bone-inducing activity of the osteosarcoma is enhanced by various acids below pH 2.8. A possible role for hydrogen ion concentration in the regulation of osteogenesis is discussed.
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PMID:Acid solutions enhance bone-inducing activity of a murine osteosarcoma. 345 79

Human interferon was prepared by superinduction of cultures of either diploid embryonic skin and muscle cells or of the osteosarcoma cell line MG-63. The interferon so obtained was concentrated and partially purified by adsorption to controlled pore glass (CPG) beads at neutral pH and desorption by glycine-HCl buffer at pH 2. After neutralization, this interferon was applied to a column of zinc chelate which was eluted with buffers of decreasing pH. Most of the proteins eluted ahead of the interferon activity, which itself eluted in two distinct peaks. The first peak occurred in the effluent fractions around pH 5.9, and the second one in fractions around pH 5.2. The interferon found in fractions of pH 5.9 contained 5% of the original contaminating proteins. In contrast, the amount of total protein in the pH 5.2 peak was so small that it could not accurately be assayed by the fluorescamine method. Consequently, the interferon in the peak fraction was estimated to have a specific activity of about 2 x 10(9) units/mg. This material was radiolabelled and analysed by electrophoresis. A major peak of about 22000 mol. wt. with only minor contaminating proteins appeared on the autoradiographs. The total recovery of the zinc chelate chromatographical procedure was nearly 100%, and the interferon recovered from each peak behaved consistently on rechromatography. Fibroblast interferon produced by most diploid cells contained less than 10% of the variant eluting at pH 5.9. MG-63 cells and high-passage cultures of some diploid cell strains produced up to 50% of this variant.
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PMID:Purification of human fibroblast interferon by zinc chelate chromatography. 616 89

The simultaneous analysis of methotrexate (MTX) and its putatively nephrotoxic metabolite, 7-hydroxymethotrexate (7OH-MTX), by high-performance liquid chromatography (HPLC) and ultraviolet spectrophotometric detection is described. Serum extraction employs SEP-PAK C-18 cartridges. Recovery ranges from 78.3 to 84.9% for MTX and 67.6 to 76.1% for 7OH-MTX. Between-day precision studies of serum (controls), containing 2.76 microM MTX and 4.40 microM 7OH-MTX, yielded coefficients of variation of 8.6 and 8.9%, respectively. Reconstitution of the dried residue in 5 mM HCl increases the retention times of 7OH-MTX and MTX, thereby enhancing their separation from extraneous serum peaks. A comparison of MTX levels determined by HPLC and a competitive protein binding assay yielded consistently lower results by HPLC. However, in comparing HPLC to EMIT, two relationships were observed: below 100 microM MTX the methods were in agreement, whereas above 100 microM MTX HPLC again provided lower values. Preliminary pharmacokinetic studies on two patients with osteogenic sarcoma are reported. After receiving 218.2 mg/kg and 148.5 mg/kg MTX in a 6-h infusion, their beta half-lives for MTX were 2.6 and 2.0 h, while their gamma half-lives were 26.2 and 42.9 h, respectively. The 7OH-MTX beta half-lives were 5.8 and 4.0 h, and the gamma half-lives were 10.2 and 15.8 h. Plasma concentration ratios of 7OH-MTX to MTX were 28.5 and 18.1 at 24 h after MTX infusion. 7OH-MTX was detected in the 15-min sample after the beginning of the MTX infusion.
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PMID:Analysis of methotrexate and 7-hydroxymethotrexate by high-performance liquid chromatography and preliminary clinical studies. 676 Apr 71

The osteogenic factor from murine osteosarcoma was soluble in 4M guanidine-HCl. The precipitate that appeared after dialysis of the guanidine solution against deionized water showed a higher osteogenetic activity than did the initial dry powder of tumor tissue. Electron-microscopically, this bone-inducing fraction seems to be homogenous. Neither a fibrous nor collagenous cross-banded structure was observed in the fraction. Since the chemical analysis of the fraction also showed a relatively low content of hydroxyproline, the osteogenic factor is probably not collagen.
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PMID:Solubilization and concentration of a bone-inducing substance from a murine osteosarcoma. 676 29

Devitalized cultured cells of a murine osteosarcoma preserved strong osteogenic activity even after incubation in neutral and acidic buffer at 37 degrees for six days. This observation suggested that an osteosarcoma-derived osteogenic factor was considerably stable to endogenous proteases, or that osteosarcomas do not synthesize enzymes for degradation of the osteogenic factor. EDTA decalcification or extraction of the osteosarcoma at 37 degrees for six days had no apparent effect on the osteogenic factor. Disulfide-bond reducing agents (2-mercaptoethanol and dithiothreitol) completely inactivated the osteogenic activity and in the presence of guanidine HCl, the loss of activity was irreversible by reoxidation. There findings support the view that disulfide-bonds in the molecular structure of the osteogenic factor are essential for the biological activity.
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PMID:Biochemical stability of a bone-inducing substance from murine osteosarcoma. 695 Aug 22

Bone-inducing substance from a murine osteosarcoma (BFO osteosarcoma) was partially purified by biochemical procedures, i.e., extraction by 4M Gu-HCl, fractionation by ethanol, precipitation in neutral buffer solution with low ionic strength and two steps of gel filtration. The yield of the final preparation was 2 mg from 10 g (wet weight) of BFO osteosarcoma. The preparation constantly induced ectopic bone in situ when implanted into allogenic mice. SDS polyacrylamide electrophoresis revealed that the biologically active fraction contained two distinct substances, the molecular weights of which were 19,500 and 22,500, respectively. Further purification of the bone-inducing substance is now in progress.
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PMID:Partial purification of bone-inducing substances from a murine osteosarcoma. 695 Aug 23

At the onset of the mineralization of bone, small membranous matrix vesicles are often observed. The information available on the production and release of these vesicles is limited. When treated with 10-20 nM of the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA), the human osteosarcoma cell line U-2 OS developed long cytoplasmic processes connecting adjacent cells. SEM and TEM show that TPA triggers a production and release of matrix vesicle-like membrane vesicles, mainly from the cellular processes. Tetracycline HCl was used to label intracellular bound calcium. The tetracycline HCl label was primarily localized to the end-feet of the cytoplasmic processes, indicating that these contain high concentrations of Ca2+, and to endoplasmic reticulum-like structures in the cell bodies. Together with our previous demonstration of the release of alkaline phosphatase-containing vesicles into the culture medium (Ringbom-Anderson T, Akerman KEO 1992 Calcif Tissue Int 50:533-540), the results presented here indicate that TPA induces a rapid induction of the primary steps of mineralization in U-2 OS osteosarcoma.
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PMID:Production and release of matrix vesicles in the cell processes of TPA-treated human osteoblast-like cells. 805 95


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