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)

A monoclonal antibody 791T/36 prepared against human osteogenic sarcoma has been used to detect primary and metastatic colorectal carcinomas by external imaging of patients following injection of 131I-labelled antibody. In 10 of 11 patients radiolabelled 791T/36 antibody localized in tumours, the tumour: non tumour ratio of radioactivity ranging from 1.5:1 to 8.1. 791T/36 antibody was also evaluated for its potential for targeting anti-tumour agents including cytotoxic drugs (Vindesine) and immunomodulating agents (interferon0. Vindesine-791T/36 conjugates were preferentially cytotoxic in vitro for target cells expressing the 791T/36 antibody defined antigen. Also interferon conjugated to 791T/36 antibody, like free interferon activated peripheral blood natural killer cell activity. These in vitro tests together with related studies on antibody localization in vivo indicate the potential of monoclonal antibody targeting of anti-tumour agents.
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PMID:Monoclonal antibodies for radioimmunodetection of tumours and for targeting. 657 42

We studied the effect of human leukocyte interferon (HuIFN-alpha) on a human osteosarcoma (OS-OH) transplanted and passed serially in athymic mice. The growth of OS-OH was strikingly inhibited by HuIFN-alpha (50,000 IU/mouse), regardless of whether the interferon treatment was initiated 24 hr after tumor inoculation or 2 weeks later, when tumors had grown to an appreciable size (4-6 mm). The antitumor effect of HuIFN-alpha was found to be dose-dependent and a daily administration of HuIFN-alpha (50,000 IU/mouse) all but completely arrested the tumor growth.
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PMID:Antitumor effect of human leukocyte interferon on human osteosarcoma transplanted into nude mice. 658 Jan 70

To evaluate the outcome for osteosarcoma patients treated with different forms of adjuvant therapy in nonrandomized series, it is important to realize the possible influence of different prognostic factors. In two series of patients with primary classic osteosarcoma, survival was analyzed in relation to tumor size and site. In the first series comprising 57 patients, no adjuvant therapy was given and the five-year survival rate for all patients was 19%. A significantly (p less than 0.01) higher survival rate (43%) was noted for patients with tumors distally located and less than 0 cm in size (as measured by their largest diameter on radiograms), as compared to 12% for patients with larger and proximally located tumors. These figures were the same at three-and five-year follow-up. In the second series, comprising 22 patients, all received adjuvant interferon treatment. The three-year survival rate was 68%, and the five-year survival rate for the 12 patients followed was 58%. The survival rate for patients with tumors distally located and less than 10 cm in size was 88%, as compared to 57% for patients with larger and proximally located tumors. In the interferon series, tumor size appeared more important than location.
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PMID:Survival in osteosarcoma in relation to tumor size and location. 695 21

During the period from 1971 to 1990 all osteosarcoma patients referred to the Karolinska Hospital without signs of metastases received human leukocyte interferon (IFN) as adjuvant treatment. Patients referred between 1985 and 1990 were given more intensive human leukocyte IFN treatment, i.e. a standard dose of 3 MU s.c. daily for 3-5 years. These 19 patients, all followed for 5 years, were included in a pilot study which entailed patients with central localization where radical surgery was not feasible. Metastases developed in 9 patients, of whom 3 had local recurrences. Sixty-three percent are free of disease at 5 years. Side-effects were negligible and long-term toxicity practically non-existent. It is suggested that a randomized multicenter IFN trial should be instituted on patients with poor prognosis receiving chemotherapy and/or that IFN treatment should be combined with other therapeutic modalities--irradiation, chemotherapy or anti-angiogenic substances--in osteosarcoma.
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PMID:Long-term adjuvant interferon treatment of human osteosarcoma. A pilot study. 757 58

Fifteen patients with primary classical osteosarcoma tumours are presented, all of whom have been operated on with local en bloc resection of the tumour mass in combination with adjuvant treatment with human leucocyte interferon. All patients have at present been followed up for more than fifteen years and half of them have shown no tumour recurrence. One patient committed suicide and eight died of generalized tumour disease. Two patients developed lung metastases five and eight years after primary surgery. This form of treatment, allowing limb preservation, is presented as an alternative to conventional ablative surgery providing that it is reserved for centres with specialized surgical teams.
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PMID:Local tumour resection in interferon treated osteosarcoma patients. 764 12

An update of the adjuvant trial on osteosarcoma in Sweden comparing patients receiving natural interferon (IFN) alpha with a high-dose chemotherapy group and a nonadjuvant group is presented. The overall survival for the IFN group is 49%, for the chemotherapy group 54%, and for the nonadjuvant group 35%. Trial evaluation was complicated by group differences with respect to various clinicopathologic features of prognostic significance. The role of IFN in the treatment of osteosarcoma can still not be established.
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PMID:Adjuvant interferon treatment in human osteosarcoma. 809 44

The purine nucleoside analogs fludarabine, 2-chlorodeoxyadenosine, and 2'-deoxycoformycin exhibit impressive activity in lymphoproliferative malignancies of adults and children. Their mechanism of action is not clear. Studies have suggested that their use is associated with significant myelosuppression, immunosuppression, and in some circumstances, increased infection with viral and opportunistic pathogens. Because interferons (IFNs) are known to have immunomodulatory activity as well as potent antiproliferative and antiviral activity, we examined whether the chemotherapeutic purine nucleoside analogs alter interferon-beta (IFN-B) gene expression in MG63 in human osteosarcoma cells. Northern blot analysis showed a dose-dependent inhibition of IFN-B mRNA accumulation in response to a known inducer (Poly I-Poly C) all three purine analogs. Hybridization analysis also revealed that inhibition of IFN-beta mRNA accumulation by the purine analogs is not a result of decreased mRNA stability. Further analysis of gene expression by PCR differential display indicated that the effect of the purine analogs was restricted to only a limited number of inducible genes. The data suggest that these molecules alter the signaling process involved in regulating the expression of specific genes, including IFN-beta. These findings predict that the use of purine nucleoside analogs may reduce IFN production in vivo and thereby abrogate host defenses against infectious pathogens.
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PMID:Chemotherapeutic purine analogs alter the level of interferon-beta mRNA induced by poly I-poly C in cultured osteosarcoma cells. 918 62

The CD95/APO-1 Fas receptor/ligand system plays a crucial role in growth control by mediating apoptosis in lymphoid and non-lymphoid cells. To investigate the role of CD95-mediated apoptosis in osteosarcoma, we studied 3 human osteosarcoma cell lines (HOS/TE 85, MG 63 and Saos-2) and osteoblasts derived from bone biopsies. In contrast to osteoblast-like cells, all cell lines were resistant to anti-APO-1-induced apoptosis despite constitutive CD95 expression at intermediate levels. Blocking of macromolecular synthesis by cycloheximide or actinomycin D or modulation of CD95 expression by cytokines (TNF-alpha and/or gamma-interferon) restored sensitivity to anti-APO-1-induced cell death. PCR analysis of the CD95 transcripts revealed the production of a truncated splice variant that codes for a soluble form of the CD95 receptor. Synthesis and secretion of soluble CD95 protein into the culture supernatant was demonstrated by Western blot analysis. Treatment with sensitizing cytokines led to up-regulation of full-length CD95 transcripts and the encoded membrane-bound CD95 protein but not the truncated mRNA splice variant and the corresponding soluble receptor, as shown by PCR and Western blot analysis. The biological activity of soluble CD95 secreted by osteosarcoma cells was demonstrated by the ability of osteosarcoma supernatants to protect the sensitive T-cell line Jurkat from anti-APO-1-mediated apoptosis. Our results suggest that the production of soluble CD95 by osteosarcoma cell lines that may block physiological death signals and the production of membrane-bound CD95 are differently regulated by cytokines via modulation of RNA splicing.
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PMID:Modulation of resistance to anti-APO-1-induced apoptosis in osteosarcoma cells by cytokines. 924 1

The hepatitis C virus (HCV) nonstructural 5A (NS5A) protein has been implicated in the inherent resistance of HCV to interferon (IFN) antiviral therapy in clinical studies. Biochemical studies have demonstrated that NS5A interacts in vitro with and inhibits the IFN-induced, RNA-dependent protein kinase, PKR, and that NS5A interacts with at least one other cellular kinase. The present study describes the establishment and characterization of various stable NS5A-expressing human cell lines, and the development of a cell culture-based assay for determining the inherent IFN resistance of clinical NS5A isolates. Human epithelioid (Hela) and osteosarcoma (U2-OS) cell lines were generated that express NS5A under tight regulation by the tetracycline-dependent promoter. Maximal expression of NS5A occurred at 48 hours following the removal of tetracycline from the culture medium. The half-life of NS5A in these cell lines was between 4 to 6 hours. NS5A protein expression was localized cytoplasmically, with a staining pattern consistent with the location of the Golgi apparatus and endoplasmic reticulum. In the majority of cell lines, no obvious phenotypic changes were observed. However, three genotype 1b NS5A-expressing osteosarcoma cell lines exhibited cytopathic effect and severely reduced proliferation as a result of high-level NS5A expression. Full-length NS5A protein isolated from a genotype 1b IFN-nonresponsive patient (NS5A-1b) was capable of rescuing encephalomyocardititis virus replication during IFN challenge up to 40-fold, whereas a full-length NS5A-1a and an interferon sensitivity determining region (ISDR) deletion mutant (NS5A-1a-triangle upISDR) isolated from a genotype 1a IFN-nonresponsive patient showed no rescue activity. The NS5A-1b and NS5A-1a proteins also rescued vesicular stomatitis virus replication during IFN treatment by two- to threefold. These data cummulatively suggest that NS5A expression alone can render cells partially resistant to the effects of IFN against IFN-sensitive viruses, and that in some systems, these effects may be independent of the putative ISDR. A scenario is discussed in which the NS5A protein may employ multiple strategies contributing to IFN resistance during HCV infection.
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PMID:Characterization of the effects of hepatitis C virus nonstructural 5A protein expression in human cell lines and on interferon-sensitive virus replication. 1009 74

Using the experimental modeling of late effects induced by intake of radionuclides (131I, 238,239Pu, 90Sr) the attempt to investigate the possibility of protection using immune modulators was made. Co-polymer of 2-methil-5-vinilprilidin and N-vinilpirrholidon (sovidon), G immunoglobulin and interferon, Fc fragment of immunoglobulin and S. parathyphi B. Breslau vaccine were used as immune modulators. The positive prophyletie influence of immune modulators was found for average life span, radiation action, immune status, of rates of occurrence and developments of breast tumors induced by 131I, 239Pu and 90Sr. At the same time the increase in osteosarcoma cumulative rate induced by immune modulators in case of body intake of 238Pu and 90Sr was registered.
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PMID:[On the problem of prophylaxis of late effects induced by internal irradiation using immunomodulators]. 1125 90


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