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)

Tyrosine phosphorylation plays a central role in intracellular signaling by many hormones and growth factors. Termination of the signal is thought to involve dephosphorylation of target proteins by phosphotyrosine phosphatases (PTPase). Soluble protein PTPases from neonatal rat osteoblasts (ROBs) and rat osteosarcoma (ROS 17/2.8) cells were chromatographically distinguished and characterized using 32P-labelled glutamate/tyrosine co-polymer as substrate. Two activities from both cell types were chromatographically separable. The dominant PTPase activity in the presence of 60-125 mM salt (E1), was eluted from phosphocellulose by 180-280 mM NaCl, bound weakly to a strong anion exchange column (QAE-trisacryl), had an apparent Km for [32P]glutamate/tyrosine copolymer of 52 micrograms/ml, was enhanced (5-10-fold, ROS; 1.5-3-fold, ROB) by assay in 125 mM NaCl, had no significant alkaline, acid, or serine phosphatase activity and had an M(r) of 53,000. A second activity (E2) was not retained by phosphocellulose but eluted from QAE-trisacryl in a single peak at 90-130 mM NaCl. It had an apparent Km for [32P]glutamate/tyrosine copolymer of 30 micrograms/ml (ROS) and its activity was not enhanced by NaCl in the assay. Activity E1 from both cells was 50% inhibited by 0.05 microM Na3VO4, 20 microM ZnCl2, or 5-10 microM CoCl2, but not by 1 mM NaF; activity E2 had a similar inhibition profile, but was more sensitive to ZnCl2 (IC50, 5 microM). Co2+ is a relatively non-toxic metal which may be a useful tool for investigating the role of phosphotyrosine in osteoblast proliferation and function. The similarity between the E1 activity from ROS cells and ROBs suggests that ROS cells may be useful in studying PTPase regulation by hormones, but molecular approaches will be required to establish the identity of PTPases in ROBs and ROS cells.
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PMID:Rat osteoblasts and ROS 17/2.8 cells contain a similar protein tyrosine phosphatase. 790 81

Heterocyclic thiosemicarbazones, thioureas and 2-substituted pyridine N-oxides as well as representative nickel, cobalt and copper complexes were shown to be potent antineoplastic/cytotoxic agents. The cytotoxicity was demonstrated against single cell leukemia as well as cell lines derived from solid tissue (colon adenocarcinoma, HeLa, KB, skin, bronchogenic lung, bone osteosarcoma and glioma). In L1210 cells, DNA synthesis and subsequently RNA synthesis were particularly inhibited by the agents. IMP dehydrogenase activity and thus purine de novo synthesis was reduced significantly by the agents. Dihydrofolate reductase, ribonucleoside reductase, nucleoside kinase and DNA polymerase alpha activities were inhibited by the agents. d(NTP) pool levels were reduced by most of the agents. DNA strand scission was present with all of the derivatives; however, there was no evidence of intercalation, cross linking or alkylation/binding to bases of DNA. This new group of compounds may offer novel exploratory derivatives for future investigations in the treatment of cancer.
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PMID:The cytotoxicity of heterocyclic thiosemicarbazones and their metal complexes on human and murine tissue culture cells. 849 Feb 2

The treatment modalities and prognosis of 636 retinoblastoma (RB) cases diagnosed and treated in our specialist center between 1963 and 1994 were evaluated. Patient age ranged from 20 days to 16 years, the mean age being 2.2 years (26.4 months). Of the 636 cases, 441 were unilateral and 195 were bilateral. Enucleation was the most frequent treatment employed in unilateral RB patients (412 cases). Follow-up treatment included exenteration (48 cases), radiotherapy (154 cases) and chemotherapy (108 cases) for cases with optic nerve invasion and/or orbital recurrence following enucleation. Seventeen cases displayed massive proptosis, ocular damage and blindness at initial presentation and underwent exenteration as the initial treatment. Two cases were subjected to external beam radiotherapy without invasive surgical procedures. Ten cases regressed spontaneously without treatment. For bilateral cases, the most frequent treatment used was enucleation for one eye and radiotherapy for the other (132 cases). Adjuvant treatment included exenteration (9 cases) and chemotherapy (50 cases) depending on orbital recurrence and/or systemic metastasis. Spontaneous bilateral regression was noted in one case. Six cases underwent bilateral external beam radiotherapy without surgery. One eye of the remaining 56 bilateral cases underwent enucleation. The treatment for the contralateral eyes included cryotherapy in 14 cases, enucleation in 11 cases, Cobalt plaque (Co plaque) therapy in 10 cases, photocoagulation in 6 cases and exenteration in one case. No treatment was undertaken in the contralateral eyes of 14 cases. Secondary treatment modalities employed in these 56 bilateral cases were radiotherapy (11 cases), chemotherapy (8 cases), Co plaque (8 cases) and exenteration (5 cases). Treatment complications were detected in 25 cases followed for at least 18 months. Eighteen cases had radiation cataracts and 6 of these 18 patients underwent intraocular lens implantation. Post-radiation orbital malignancy (osteosarcoma) was noted in two cases aged 14 and 15 years. Phthisis bulbi was observed in three cases and radiation keratitis in two cases. The overall survival rate was 82.2% after a mean follow-up of 5 years. The survival rate of unilateral cases was 82.8% and that of bilateral cases was 81.1% at 5 years.
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PMID:Retinoblastoma in Turkey--treatment and prognosis. 873 6

The release of metals from total joint prostheses may contribute to periprosthetic bone loss manifested as osteolysis. The effects of titanium, cobalt, and chromium on human osteogenic sarcoma cells (osteoblastlike cells) were investigated in vitro. Titanium, cobalt, and chromium at concentrations of 1, 10, and 100 ng/ml did not cause any changes in the cell growth, viability, and injury after 72-hour incubation with the cells. Titanium, cobalt, and chromium at concentrations ranging from 0.01 to 100 ng/ml significantly enhanced the release of interleukin-1 beta and tumor necrosis factor-alpha by lipopolysaccharide stimulated human osteogenic sarcoma cells, whereas they did not alter the release of transforming growth factor-beta 1. Cobalt at concentrations ranging from 0.1 to 100 ng/ml significantly enhanced the release of interleukin-6, but titanium and chromium did not. Cobalt and chromium at concentrations of 10 and 100 ng/ml significantly inhibited the release of osteocalcin by human osteogenic sarcoma cells, whereas titanium had no effect. Titanium, cobalt, and chromium at concentrations of 10 and 100 ng/ml significantly inhibited the synthesis of Type I collagen by human osteogenic sarcoma cells. Cobalt and chromium inhibited the cell proliferation in response to lipopolysaccharide stimulation, whereas titanium did not. The data presented in this article suggest that the metal induced disregulation of cytokine release and osteoblast dysfunction may play an important role in the induction of osteolysis in patients with total joint arthroplasties.
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PMID:Prosthetic metals interfere with the functions of human osteoblast cells in vitro. 918 23

A 59-year-old woman who had received cobalt-60 (60Co) interstitial radiation therapy (total 44 Gy) in the right bucco-gingival region for inflammatory pseudotumour was found to have metachronous double malignant neoplasms. Initial osteosarcoma of the right mandibular angle and subsequent squamous cell carcinoma of the right buccal mucosa were identified 28 and 33 years after the radiation, respectively. Since both tumours were located very close to the focus of previous radiation, the therapy was considered to be responsible for their genesis. The patient had systemic metastases of the osteosarcoma.
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PMID:Double malignant neoplasms occurring long after local radiation to the oral mucosa. 980 43

Severe disruption of mitochondrial function is generally considered to provide a powerful trigger for apoptosis in mammalian cells. We report here that intact cells may undergo the mitochondrial permeability transition and mitochondria swell in a fully reversible manner, without inducing cell death. Cultured human osteosarcoma cells (143B TK-) stained with JC-1, MitoTracker dyes, or calcein plus Co2+ were imaged by confocal microscopy to visualize changes of mitochondrial membrane potential (DeltaPsim), morphology, and permeability transition, respectively, during treatment with a protonophore, carbonyl cyanide m-chlorophenylhydrazone (CCCP). Cells rapidly exhibited mitochondrial permeability transition and swelling after addition of CCCP, but the swelling subsided within hours, leaving mitochondria that appeared in punctate form, not filamentous as before CCCP treatment. Cyclosporin A impeded the permeability transition and swelling, although complete inhibition was not observed. Cells survived the dissipation of DeltaPsim by CCCP for up to 6 h without developing any obvious cell damage or signs of apoptosis. With the restoration of DeltaPsim after removal of CCCP (following 6 h of CCCP treatment), permeability transition pores were closed. These results suggest that none of the following events represent a point of no return in the process of apoptotic cell death: loss of DeltaPsim, mitochondrial permeability transition, or mitochondrial swelling.
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PMID:Mitochondrial permeability transition and swelling can occur reversibly without inducing cell death in intact human cells. 988 12

A 2-year-old neutered female Rottweiler diagnosed with an intradural extramedullary spinal cord tumor at T12-T13 was successfully treated with cytoreductive surgery followed by Cobalt 60 teletherapy. The dog was euthanised 5-and-a-half years later following diagnosis of an osteosarcoma involving the L1 and L2 vertebrae. Evidence of the initial tumor was not present at necropsy. The vertebral neoplasm fulfilled all of the accepted criteria for a radiation induced tumor. It was concluded that adjunctive irradiation should be considered for treatment of intradural extramedullary tumors of young dogs when total surgical resection is not possible. Although tumor induction is a rare late effect of radiation therapy, the risk of this occurrence should be considered when irradiating young animals. Radiation induced tumors in dogs have been associated with coarse fractionation schemes, or when large intraoperative doses have been administered. A lower dose per fraction, e.g., 3 Gy/fraction or less, is advisable when irradiating young dogs or any dog in which the life expectancy is 3-5 or more years after irradiation.
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PMID:Radiation induced vertebral osteosarcoma following treatment of an intradural extramedullary spinal cord tumor in a dog. 1167 71

Advances with implantation of synthetic biomaterials in the setting of orthopedic surgery have clearly resulted in improvements in patient outcomes. However, all implants have been shown to have associated risks. For example, ionic and particulate debris from implants have been shown to engage in biological interactions with the native tissue, and have been associated with a wide range of metabolic, bacteriologic, immunologic, and oncogenic effects. The propensity of synthetic biomaterials to undergo degradation, producing an inflammatory reaction or other sequelae, has been well recognized. The use of porous implants, which allow for a greater interface area between native tissue and the prosthesis, may magnify the interaction between biologically active tissue and synthetic devices in some situations, giving rise to new and intriguing issues concerning biocorrosion and biocompatibility. In this article, we report the case of a high-grade conventional osteosarcoma occurring at the site of a modular porous-surfaced titanium and cobalt alloy total hip prosthesis 3 years after device implantation. Detailed spectroscopic trace metal analysis was performed and elevated levels of both vanadium and chromium, but not aluminum, nickel, or titanium were identified in the tumor.
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PMID:Prosthetic implant associated sarcomas: a case report emphasizing surface evaluation and spectroscopic trace metal analysis. 1261 73

Cobalt(II) complexes with 6-(2-hydroxybenzylamino)purine (HL1), 6-(2-methoxybenzylamino)purine (HL2), 6-(3-methoxybenzylamino)purine (HL3) and 6-(4-methoxybenzylamino)purine (HL4) of the composition [Co(L1)Cl(H2O)2].H2O (1), [Co(L2)Cl(H2O)2] (2), [Co(L3)2(H2O)2].2H2O (3), [Co(L4)2(H2O)2].2H2O (4) have been synthesized. The compounds have been characterized by elemental analysis, FT-IR, ES+ MS (electrospray mass spectra in the positive ion mode) and electronic spectroscopies, magnetic and conductivity data as tetrahedral high-spin cobalt(II) complexes. The thermal stability of the complexes has also been studied. The cytotoxicity of the complexes (1-4) was determined by a Calcein acetoxymethyl (AM) assay. Human malignant melanoma (G361), human chronic myelogenous erythroleukemia (K562), human osteogenic sarcoma (HOS) and human breast adenocarcinoma (MCF7) cell lines were used for the testing. The molecular structure of 6-(3-methoxybenzylamino)purinium chloride monohydrate, H2L3+.Cl.H2O, i.e. a protonated form of the free HL(3) ligand, has been determined by a single crystal X-ray analysis. The geometry optimisation and infrared frequencies calculations of HL1, HL2, and H2L3+ and H2L4+ were performed using density-functional theory (DFT) calculations at the B3LYP/6-31G* level of the theory. The geometry of complex (1) was optimised at the same level of the theory.
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PMID:Synthetic, spectral, magnetic and in vitro cytotoxic activity studies of cobalt(II) complexes with cytokinin derivatives: X-ray structure of 6-(3-methoxybenzylamino)purinium chloride monohydrate. 1570 99

The radiosensitizing effect of inducible nitric oxide synthase (iNOS) was evaluated, in vitro, in a feline vaccine-associated sarcoma (VAS) cell line and a canine osteosarcoma cell line (D17). The gene encoding the human iNOS was cloned into an expression plasmid under the control of a cytomegalovirus immediate early promoter. Transient transfections were performed in feline VAS cells and D17 cells. Nitric oxide was measured in the supernatant media 48 h later as an indirect measurement of iNOS expression. Cells were irradiated using cobalt-60 under hypoxic or oxic conditions, and clonogenic assays were used to evaluate the effects of gene transfer on the sensitivity of cells to radiation. The results demonstrated that iNOS had no significant effect on improving the radiosensitivity of cells under oxic conditions. However, under hypoxic conditions, iNOS gene transfer significantly improved radiosensitization in osteosarcoma cells. These results demonstrate the feasibility of improving the outcome of radiotherapy in dogs with large bulky tumours using iNOS gene therapy.
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PMID:Evaluation of the gene for inducible nitric oxide synthase as a radiosensitizer under hypoxic and oxic conditions. 1975 83


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