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)

Treatment of human fibroblast FS-4 cultures with human type II interferon preparations induced the synthesis of at least four proteins that were similar in size to four of the five proteins induced by type I interferons (Mr 120,000, 88,000, 67,000, and 56,000). However, the Mr 67,000 and 56,000 proteins were induced more strongly by type II than by type I interferon, and a counterpart of a Mr 80,000 protein induced by type I interferons was not noticeably induced by type II interferon preparations. We therefore compared type I and type II interferons for relative antiviral activities against different viruses (vesicular stomatitis, encephalomyocarditis, and vaccinia viruses and reovirus) and for cell growth-inhibitory activities on various cell types. The replication of vesicular stomatitis and encephalomyocarditis viruses was inhibited more strongly by type I interferon, whereas reovirus and vaccinia virus showed greater sensitivity to type II interferon preparations. This indicates that viruses may differ in their sensitivity to human type I and type II interferons and that the antiviral mechanisms induced by type I and type II interferons may have significant differences. The type I and type II interferons may have significant differences. The type I and type II interferons may also differ in their efficacies as antiproliferative agents. Type II interferon preparations at 2.5 units/ml inhibited the incorporatin of [3H]thymidine to a greater extent than did type I interferon at 400 units/ml. (For both type I and type II interferons, the unit of interferon activity was defined as the concentration that decreased the yield of vesicular stomatitis virus by 50% in FS-4 cultures.) Furthermore, whereas type II interferon preparations had a reversible cytostatic effect on normal human fibroblasts at 10 units/ml, the transformed cells tested (HeLa, osteosarcoma, U-amnion) showed extensive cell death, thus indicating that it may have a cytocidal effect on certain tumor cells. It appears that human type II interferon (or a factor present in these preparations) may be a potent antitumor agent.
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PMID:Differential efficacies of human type I and type II interferons as antiviral and antiproliferative agents. 616 May 87

A consecutive series of patients with osteocarcoma have been receiving adjuvant interferon therapy at the Karolinska Hospital in Stockholm. We report here a case of tibial chondroblastic Grade III osteosarcoma, a boy aged 17 years, who received interferon therapy for 15 months and survived more than 5 years. The first sign of tumour spread was multiple cerebral metaseases--an observation suggesting an antitumour effect of human leucocyte interferon on osteosarcoma.
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PMID:Adjuvant interferon treatment and the late development of cerebral metastases in a patient with osteosarcoma. 616 Jul 20

A variety of solid and hematological human tumors and normal human bone marrow specimens were assayed for colony formation in a short-term soft-agar culture system. The effect of human fibroblast, lymphoid, and myeloid interferons on inhibition of colony formation was assessed. The effect of interferon on colony formation formed a continuum from complete inhibition to stimulation of growth. Of 40 evaluable tumor specimens, 18 showed at least a 70% inhibition of colony formation in the presence of interferon, at concentrations of 1000 units/ml or less. Four specimens (acute myelogenous leukemia, osteogenic sarcoma, neuroblastoma, ovarian carcinoma) showed at least 3-fold stimulation of colony formation with interferon. Two of 12 normal bone marrow specimens grown with colony-stimulating, factor-conditioned media showed greater than 70% colony inhibition with interferon. A dose-response relationship was seen in all tumor specimens tested. While fibroblast interferon was the most active in this system, all interferons showed the same magnitude and direction of activity. Continuous exposure and 1-hr incubation of tumor cells with interferon were identical in terms of colony inhibition. These data support the ability of this assay system to select tumors responsive in vitro to interferon, suggest the optimal species and concentration for inhibition or stimulation of growth, and support a direct role of interferon in the regulation of cell growth independent of other immunoregulatory actions of interferon. Such information may prove useful for predicting response in vivo to interferon in Phase II trials.
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PMID:Effect of fibroblast, lymphoid, and myeloid interferons on human tumor colony formation in vitro. 616 Sep 5

Twenty patients with osteosarcoma were treated with exogenous human leukocyte interferon for periods ranging from 6 to 18 months. Eleven of them remained free from detectable tumour growth during this treatment. Blood samples from all patients were tested for antibodies against interferon and against impurities in the interferon preparations. No patient developed detectable levels of neutralizing antibodies against interferon. All patients formed antibodies against contaminants in the concentrated crude interferon and the partially purified interferon preparation which had been used for treatment.
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PMID:Immune reactions and long-term therapy with human leukocyte interferon. 616 28

Purified rat interferon preparations proved effective in inhibiting cell multiplication in a rat osteosarcoma cell line. A pronounced increase in the inhibitory activity was found with increasing temperature. At 39 degrees C 20 Interferon units/ml appeared to be cytotoxic whereas incubation of cells with 2,000 Interferon units/ml at 35 degrees C resulted in a cytostatic effect.
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PMID:Influence of increased temperature on the inhibition of rat osteosarcoma cell multiplication "in vitro" by interferon. 616 8

RT-4 tumor cells, derived from human carcinoma of urinary bladder, were destroyed following exposure to partially purified human fibroblast interferon (IFN). The cytocidal effect of IFN was detected after addition of more than 200 IU IFN/ml and incubation of cell cultures for 2 days or longer. This effect was observed as morphologic changes and decrease in either dye uptake as morphologic changes and decrease in either dye uptake or colony formation by the IFN-treated cells. The cytocidal response of RT-4 tumor cells to IFN was the most pronounced, whereas the responses of three other tumor cell lines [HT-29 (colon adenocarcinoma) and SAOS-2 and 5959 (osteosarcoma)] were markedly weaker. Diploid fibroblasts were completely resistant to the cell-killing effect of IFN. Susceptibilities of the four tumor cell lines and two normal fibroblasts strains tested to the three effects of IFN (cytocidal, antiproliferative, and antiviral) appeared to be distinct.
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PMID:Cytocidal effect of purified human fibroblast interferon on tumor cells in vitro. 616 12

Clinical trials of the antiviral action of interferon have shown an effect on the replication of several viruses including varicella zoster, herpes simplex, cytomegalovirus and hepatitis B. These studies indicate that administration early in the course of infection, or in some clinical circumstances, prophylactic administration, is likely to result in viral inhibition. The studies of interferon efficacy in topical application, as in prevention of recurrent herpes simplex keratitis, have shown limited efficacy except with very high doses. These studies are being pursued with more concentrated preparations of interferon. The evaluation of interferon in human malignancy is just beginning, but some encouraging results have been obtained in open trials of the drug in patients with non-Hodgkin's lymphoma, melanoma, osteogenic sarcoma, and other diseases. With newer methods for the production of interferon, it may be possible to evaluate its antiviral and anti-tumor effects in carefully controlled studies with larger numbers of subjects.
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PMID:Interferon as an antiviral and anti-tumor therapeutic agent. 616 51

Human leukocyte interferon was given as adjuvant treatment for osteosarcoma in 26 patients. Blood from these patients was studied at regular intervals for antibodies to various micro-organisms. A continuous record of clinically manifest infections during the course of interferon therapy was made in 23 of the 26 patients. Distant metastases arose in 14 patients - the metastasis group. The report presents comparisons between these patients and the non-metastasis group. Seroconversion in tests with any of the studied micro-organisms was not common. Most of the seroconversions were not associated with clinical symptoms. Seroconversion during interferon therapy was confined to patients in the metastasis group. In some cases there was a chronologic link with early evidence of metastasis. The results of the serologic investigations are discussed and are correlated to the course of interferon therapy and of the neoplastic disease.
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PMID:Virus infections and recurrence of osteosarcoma in patients receiving human leukocyte interferon. 616 73

The iv inoculation of a suspension of osteogenic sarcoma cells induced metastatic tumor nodules in the lungs of C57BL/6 mice. The administration of 50,000-100,000 U of interferon daily for 7 days strikingly reduced the tumor mass in the lung and the number of tumor nodules present in histopathologic sections when the interferon treatment was initiated immediately after tumor cell inoculation. In some animals the development of any detectable metastatic lesion was completely prevented. Extending the therapy form 7 days to 21 days failed to improve the protective effect. Interferon therapy delayed until 7 days after tumor cell inoculation had no effect. These findings indicate the effectiveness of exogenous interferon in this murine osteogenic sarcoma model when interferon treatment is initiated within 1 hour of tumor cell inoculation, but not when it is delayed until tumor nodules are established in the lungs.
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PMID:Effect of interferon administration on pulmonary osteogenic sarcomas in an experimental murine model. 616 80

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


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