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 general principles of chemotherapy in oncology and the various types of antineoplastic drugs are discussed. Particular attention was paid to the results of chemotherapy in dogs and cats as reported in the literature. Chemotherapy is indicated in neoplastic disease characterised by early metastasis and/or local invasive growth. The results of chemotherapy in dogs and cats are so far moderate. Chemotherapy studies in the Netherlands are discussed: predictive in vitro, PEG-asparaginase studies in canine lymphosarcoma and regional perfusion in canine osteosarcoma.
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PMID:[Chemotherapy of tumors in dogs]. 328 98

An oncogene product, p53, interacts with a simian virus 40-encoded T-antigen, which is an initiation protein for the viral DNA replication and also works as DNA helicase during elongation. Here we examine the interaction of p53 with cellular DNA helicase. A recombinant human wild type p53 fused with glutathione S-transferase was immobilized on glutathione-agarose as a ligand for affinity column. Hela cell extract was applied to the p53 column and the adsorbed proteins were eluted with buffers containing salt, 50% ethylene glycol, and glutathione. The ethylene glycol fraction contained a number of p53 binding proteins, and this fraction showed a DNA helicase activity measured by the displacement of DNA fragment from partially duplexed M13 DNA. The DNA helicase translocated in a 5'-to-3' direction on the single-stranded DNA using ATP as an energy source. The glutathione fraction that contained the p53 glutathione S-transferase fused protein also showed the same activity. The corresponding fractions from a control column carrying glutathione S-transferase showed only a trace amount of activity of DNA helicase. Therefore, the binding may be specific. Furthermore, an anti-p53 antibody column retained a p53-DNA helicase complex when the crude extracts of human placenta and of osteosarcoma cells were applied. These results indicate that p53 physically interacts with DNA helicase in vitro as well as in vivo.
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PMID:Anti-oncogene product p53 binds DNA helicase. 795 81

Pegylated-liposomal doxorubicin (Doxil) is a unique form of liposomal doxorubicin in which the liposomes are coated with methoxypoly (ethylene glycol), resulting in a diminished uptake by the reticuloendothelial system, leading to a longer half-life in blood and a different toxicity profile than nonpegylated liposomes. We performed a phase II study of Doxil in sarcoma. The patient population was primarily previously treated or had diagnoses considered unresponsive to chemotherapy. The initial dose per course was 55 mg/m2 every four weeks with dose modification based on mucositis and hand-foot syndrome (the main limiting toxicities). Treatment was generally well tolerated. Of 214 evaluable treatment courses in 47 patients, toxicities were mild and similar to previous reports, but dose reduction was common. No definite cardiac toxicity was observed. There were: 6 osteosarcomas, 3 Ewings, 1 extraosseous osteosarcoma, 1 chondrosarcoma, 2 alveolar soft part sarcomas, 15 gastrointestinal stromal cell tumors (GIST), and 19 other soft tissue sarcomas. Three of the 47 patients received a CR or PR, although 15 of the 47 patients were felt to have derived clinical benefit from the treatment. Some responses were delayed. These data suggest that pegylated-liposomal doxorubicin has activity in this population of poor prognosis sarcoma and that this treatment is associated with modest toxicity.
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PMID:Phase II trial of pegylated-liposomal doxorubicin (Doxil) in sarcoma. 1274 96

An ideal gene carrier requires both safety and transfection efficiency. Polyethylenimine (PEI) is a well-known cationic polymer, which has high transfection efficiency owing to its buffering capacity. But it has been reported that PEI is cytotoxic in many cell lines and non-degradable. In this study, we synthesized degradable PEI-alt-poly(ethylene glycol) (PEG) copolymers using Michael-type addition reactions as a new gene carrier and characterized them. These copolymers were complexed with plasmid DNA and the resulting complexes were characterized by dynamic light scattering, gel retardation and atomic force microscopy to determine particle sizes, complex formation and complex shape, respectively. Cytotoxicity and transfection efficiency of the copolymers were also checked in cultured HeLa human cervix epithelial carcinoma cells, HepG2 human hepatoblastoma cell line and MG63 human osteosarcoma cells. PEG to PEI ratio in the copolymers was near 1 and the molecular weight of the copolymer ranged from around 8000 to 12,900. These copolymers degraded rapidly at 37 degrees C in 0.1 M phosphate buffered saline (PBS, pH 7.4). The complete copolymer/DNA complex was formed at an N/P ratio of 12, producing a complex resistant to DNase I. Particle sizes decreased with increasing N/P ratio and PEG molecular weight, exhibiting a minimum value of 75 nm at an N/P ratio of 45 with PEI-alt-PEG (700). Cytotoxicity study showed that copolymers exhibited no cytotoxic effects on cells even at high copolymer concentration. Also, transfection efficiency was influenced by PEG molecular weight and, in case of PEI-alt-PEG (258), the transfection efficiency was higher than that for PEI 25 K in HepG2 and MG63, whereas it was lower than that for PEI 25K in HeLa cells.
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PMID:Degradable polyethylenimine-alt-poly(ethylene glycol) copolymers as novel gene carriers. 1593 8

We report the development and in vitro study of a nanoconjugate serving as a targeted magnetic resonance imaging (MRI) contrast enhancement agent for detection of cancer cells overexpressing the folate receptor. The nanoconjugate was synthesized by coating superparamagnetic iron oxide nanoparticles with covalently bound bifunctional poly(ethylene glycol) (PEG), followed by conjugation with folic acid (FA). The specificity of the nanoconjugate targeting cancerous cells was demonstrated by comparative intracellular uptake of the nanoconjugate and PEG-/dextran-coated nanoparticles by human adenocarcinoma HeLa cells. Preferential targeting to cancerous cells was studied by comparing the uptake of the nanoconjugate by HeLa cells and by non-FR expressing osteosarcoma MG-63 cells. Uptake of the nanoconjugate by HeLa cells after 4 h incubation was found to be a 12-fold higher than that of PEG- or dextran-coated nanoparticles as quantified by inductively coupled plasma spectroscopy. A significant negative contrast enhancement was observed with magnetic resonance (MR) phantom imaging for HeLa cells over MG-63 cells, when both were cultured with the nanoconjugate. Specificity of the nanoconjugate for folate receptors was also verified with a competitive inhibition assay, in which HeLa cells were incubated with both NP-PEG-FA and free FA. The bifunctional PEG used has amide linkages within the PEG chains that can form interchain hydrogen bonding, leading to improved stability of the PEG coating. Self-assembled PEG can be controlled at the molecular level and are suitable for nanoscale coatings.
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PMID:Folic acid-PEG conjugated superparamagnetic nanoparticles for targeted cellular uptake and detection by MRI. 1673 84

Self-assembled monolayers (SAMs) on gold containing a thermo-responsive poly( N-isopropylacrylamide)-poly(ethylene glycol)-thiol copolymer were formed. These layers show considerable potential for inducing enzyme-free and gentle detachment of cultivated cells. In an effort to optimize detachment of cells, including strongly adhering ones, two approaches are presented. First, two thermo-responsive copolymers with different poly(ethylene glycol) (PEG) contents of 15 wt % ("P15") and 19 wt % ("P19") were grafted to Au surfaces. Second, mixed monolayers were formed containing P19 and various concentrations of thiol bearing PEG. X-ray photoelectron spectroscopy (XPS) on pure and mixed P19 containing layers confirmed the expected layer compositions. Contact angle measurements showed good functionality of all surfaces prepared. Upon a temperature decrease below the lower critical solution temperature (LCST), the duration until cultivated fibroblasts detached from pure P19 surfaces was half of the one determined on P15. Strongly adherent human osteosarcoma cells could not be detached from pure P19 layers. Through co-adsorption of P19 and thiol-bearing PEG of a molar composition of 1:6, layers were formed that allowed good spreading of osteosarcoma cells above LCST and their efficient detachment below LCST.
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PMID:Tuning of thermo-responsive self-assembly monolayers on gold for cell-type-specific control of adhesion. 1871 27

Researchers in the field of tumor suppressor genes are actively attempting to discover new tumor suppressor genes and/or characterize known tumor suppressor genes with the intention of treating and diagnosing cancers. A number of recent patents and patent applications have been published that discuss some of these discoveries. Some of the patents and patent applications discuss newly discovered tumor suppressor genes, including WW Domain-Containing Oxidoreductase (WWOX), Cancer Associated Ring-1 (CAR-1), Human Cervical Cancer Suppressor 1 (HCCS-1), Src-suppressed C kinase substrate (SSeCKS), ADP-Ribosylation factor-like putative Tumor Suppressor gene 1 (ARTS1), and Deleted in Osteosarcoma (DOS). One recent patent describes the discovery that known caspase family member caspase-8 (CASP8) is a tumor suppressor. Another recent patent describes the use of Wilms Tumor suppressor gene (WT1) peptides as a cancer vaccine. In addition, Sakai et al. received a patent describing a fragment of the p51 tumor suppressor gene containing a promoter region, which is useful for identifying compounds that modulate p51 activity. Another patent application recently published describes a chimeric tumor suppressor gene generated by combining a portion of the rat PEG-3 protein with the human GADD34 protein, thus creating a protein with apoptotic activity. These patents and patent applications provide valuable information that may be useful in fighting cancer by focusing on tumor suppressor gene activities.
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PMID:Recent patents relating to tumor suppressor genes. 1907 17

Silk fibroin protein, isolated from cocoons of the domesticated mulberry silkworm, Bombyx mori, finds extensive application in biomaterial design. In this study, poly(ethylene glycol) (PEG) 4000 has been used for blending fibroin from both B. mori and Antheraea mylitta, the wild tropical non-mulberry silkworm. PEG-blended films have shown marked changes from the pure fibroin films with respect to thermal properties and mechanical properties. FT-IR spectroscopy confirmed incorporation of new functional groups like quinone oximes. Pure fibroin and PEG-blended fibroin films showed biocompatibility with the HOS osteosarcoma cell line. Von Kossa staining confirmed nodule formation due to mineralization and differentiation of osteoblasts on pure and blended matrices. On account of increased surface roughness, higher elongation percentage, higher thermostability and better activity of osteoblasts in terms of intracellular alkaline phosphatase production, PEG-blended A. mylitta fibroin film shows better potential than PEG-blended B. mori fibroin film for use as potential biomaterial.
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PMID:Characterization of fibroin and PEG-blended fibroin matrices for in vitro adhesion and proliferation of osteoblasts. 1932 75

The goal of this study was to develop a polymeric carrier for delivery of anti-tumor drugs and sustained release of these agents in order to optimize anti-tumor activity while minimizing systemic effects. We used oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels modified with small negatively charged molecules, sodium methacrylate (SMA), for delivery of doxorubicin (DOX). SMA at different concentrations was incorporated into the OPF hydrogel with a photo-crosslinking method. The resulting hydrogels exhibited sensitivity to the pH and ionic strength of the surrounding environment. Our results revealed that DOX was bound to the negatively charged hydrogel through electrostatic interaction and was released in a timely fashion with an ion-exchange mechanism. Release kinetics of DOX was directly correlated to the concentration of SMA in the hydrogel formulations. Anti-tumor activity of the released DOX was assessed using a human osteosarcoma cell line. Our data revealed that DOX released from the modified, charged hydrogels remained biologically active and had the capability to kill cancer cells. In contrast, control groups of unmodified OPF hydrogels with or without DOX did not exhibit any cytotoxicity. This study demonstrates the feasibility of using SMA-modified OPF hydrogels as a potential carrier for chemotherapeutic drugs for cancer treatments.
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PMID:A stimuli-responsive hydrogel for doxorubicin delivery. 2069 70

Osteosarcoma is the most common primary malignant bone tumor, occurring mainly in children and adolescents, and survival largely depends on their response to chemotherapy. However, the risk of relapse and adverse outcomes is still high. We investigated the synergistic anti-cancer effects of ionizing radiation combined with arsenic trioxide (ATO) and the mechanisms underlying apoptosis or autophagy induced by combined radiation and ATO treatment in human osteosarcoma cells. We found that exposure to radiation increased the population of HOS cells in the G(2)/M phase within 12 h in a time-dependent manner. Radiation combined with ATO induced a significantly prolonged G(2)/M arrest, consequently enhancing cell death. Furthermore, combined treatment resulted in enhanced ROS generation compared to treatment with ATO or radiation alone. The enhanced cytotoxic effect of combined treatment occurred from the increased induction of autophagy and apoptosis through inhibition of the PI3K/Akt signaling pathway in HOS cells. The combined treatment of HOS cells pretreated with Z-VAD, 3-MA or PEG-catalase resulted in a significant reduction of cytotoxicity. In addition, G(2)/M arrest and ROS generation could be involved in the underlying mechanisms. The data suggest that a combination of radiation and ATO could be a new potential therapeutic strategy for the treatment of osteosarcoma.
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PMID:Synergistic effects of arsenic trioxide and radiation in osteosarcoma cells through the induction of both autophagy and apoptosis. 2138 95


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