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)

With the object of examining the anti-tumour effect of exogenous interferon therapy in man a research programme has been initiated at the Karolinska Hospital. Established cell lines obtained from patients with Burkitt's and other types of lymphoma, leukaemia, osteosarcoma, mammary carcinoma and fibrosarcoma and from fibroblast cultures displayed a variable sensitivity to the cell multiplication inhibitory activity of interferon. All the monolayer cultures tested were found to be sensitive to interferon at concentrations between 10 and 300 units/ml. Some lymphoma cell lines were not sensitive to interferon even at concentrations as high as 10.000 units/ml, while others were sensitive at concentrations between 2 and 300 units/ml. The interferons tested appeared to show a degree of tissue specificity. Controlled studies in vivo are being performed on osteosarcoma, juvenile papilloma of the larynx, multiple myeloma and small-cell carcinoma of the lung. The clinical results of this research obtained to date, together with the results obtained in model experiments, would appear to warrant accelerated production of human interferon.
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PMID:Interferon therapy for neoplastic diseases in man in vitro and in vivo studies. 72 40

MG-63 cells, a line derived from an osteosarcoma, produced high yields of interferon after superinduction with polyinosinic acid.polycytidylic acid, cycloheximide, and actinomycin D. Advantages of MG-63 cells over diploid fibroblasts as a substrate are: no requirement for aging between confluency and induction, no requirement for priming, and 3.7-fold higher yields per square centimeter of culture surface. Physicochemically and biologically, MG-63 cell interferon resembles fibroblast rather than leukocyte interferon.
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PMID:Human interferon: mass production in a newly established cell line, MG-63. 88 13

The incidence of acute infections in eight patients with osteosarcoma who are receiving interferon regularly is currently being compared with the incidence among their family members. Observations thus far indicate that the patients treated with interferon are less frequently and less severely ill than their untreated family contacts. The study is continuing, and the patients will also be observed after discontinuation of interferon treatment. Sera are regularly frozen for future viral serologic tests. The preliminary clinical data indicate that therapy with exogenous interferon may afford protection against common acute infections.
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PMID:Acute infections in interferon-treated patients with osteosarcoma: preliminary report of a comparative study. 106 74

More than 200 nitro compounds, most of them nitroaniline derivatives substituted with one or more radicals having a basic reaction, were prepared and investigated as to their therapeutic activity against bacteria, fungi, protozoa, helminths, viruses and tumors. Several mono-nitrobenzenes with a radical having a basic reaction showed weak in-vitro activity against gram-positive bacteria and against Crocker's sarcoma 180; they also showed systemic activity against nematodes (Aspiculuris tetraptera) and viruses. The majority of therapeutically active compounds with pronounced in-vivo activity against Trichomonas fetus, Entamoeba histolytica, Schistosoma mansoni, cestodes, nematodes (Ancylostoma caninum), viruses (influenza, MHV, SAV and EMC) and various types of carcinoma (Ehrlich's carcinoma, leukemia 1210, Crocker's sarcoma 180) were dinitrobenzene derivatives with one radical having a basic reaction and electropositive groups or unreactive or reactive chlorine atom, and di-nitrobenzene with two equal or two different radicals having a basic reaction. Compound No. 70 revealed a marked in-vitro activity against fungi (Trichophyton; Microsporum, Candida albicans). Other nitro compounds such as bis-mono- and bis-dinitrobenzene derivatives likewise showed a systemic action against E. histolytica, viruses and, in particular, carcinoma (Crocker's sarcoma 180, Ridgway's osteosarcoma). Oxygen and sulfur analogue compounds as well as compounds produced by reduction also possessed a distinct activity against E. histolytica and viruses. On the basis of the present results particularly the dinitrobenzenes substituted with two radicals having a basic reaction include a number which have in common that a structure/activity relationship is recognizable in respect of E. histolytica, Schistosoma mansoni and different types of viruses. The activity against viruses in this class of compounds is probably due to an increased interferon production in the host animal. Whether the mechanism of action is the same against E. histolytica or Schistosoma mansoni has not been determined so far. A tumorigenic effect was observed mainly in those di-nitrobenzenes which are classed as alkylating compounds. Because of the small chemotherapeutic index the trials were not continued with the most effective compounds mentioned.
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PMID:[Chemotherapeutic effects of nitro compounds. 1. Nitroanilines]. 124 9

In this study we have evaluated the ability of interferons (IFNs) alpha, beta, gamma and Tumor Necrosis Factor (TNF) alpha to modulate the expression of the Major Histocompatibility Complex (MHC) antigens in human osteosarcoma cells. The osteosarcoma cell lines Saos-2 and U-2 OS, treated in vitro with IFNs and TNF alpha, showed an increased expression of class I HLA antigens. However, only IFN gamma and, to a lower extent, IFN beta induced the expression of class II HLA antigens. These effects were dose and time-dependent. Simultaneous treatment with IFN gamma and IFN beta or TNF alpha, which by itself was unable to induce the expression of class II HLA antigens, produced different effects on the two osteosarcoma cell lines: in Saos-2 IFN beta and TNF alpha amplified the effects obtained with IFN gamma alone; in U-2 OS, TNF alpha increased the expression induced by IFN gamma on class II HLA antigens, whereas IFN beta antagonized the effects of IFN gamma. IFN alpha did not influence the induction of class II HLA antigens by IFN gamma in the two osteosarcoma cell lines. IFNs have been introduced in some clinical protocols for the treatment of osteosarcoma, based on their antiproliferative activity. Our findings may contribute to a better knowledge of the effects of IFNs and TNF alpha in osteosarcoma by showing the existence of more complex interactions.
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PMID:Induction of HLA class II antigens in osteosarcoma cells by interferons and tumor necrosis factor alpha. 162 36

Recombinant human interferon-alpha 2C and recombinant human interferon-gamma (5-1000 U/ml) inhibit the proliferation of normal human bone-derived cells and a human osteosarcoma cell line. In the bone-derived cells the inhibitory effect of interferon-gamma was significantly greater than that of interferon-alpha, whereas in the osteosarcoma cell line the inhibitory effects of both interferons were quantitatively similar. Interferon-alpha did not affect the alkaline phosphatase activity of either type of cells. In contrast, interferon-gamma affected the activity of the enzyme in both cell types: in the bone-derived cells the effect of interferon-gamma was stimulatory whereas in the osteosarcoma cells the effect was inhibitory. In both cell types interferon-gamma selectively inhibited the incorporation of radiolabelled proline into type I collagen. In the osteosarcoma cells, the effects of both interferons on collagen synthesis were quantitatively similar. In the bone-derived cells, however, interferon-alpha decreased proline incorporation into collagen and non-collagen proteins to a similar extent and thus did not affect collagen synthesis when expressed as a percentage of total protein synthesis. Two-dimensional polyacrylamide gel electrophoresis of the radiolabelled proteins of the cell layer synthesised by both cell types in the presence of either interferon demonstrated that this treatment enhanced or induced the synthesis of a total of 21 individual proteins (19 in bone cells, 14 in osteosarcoma), ranging in apparent molecular mass over 14-87 kDa. The set of proteins induced was different in all four combinations of cells and interferon. A tentative identification of several of the proteins was possible based upon estimation of molecular mass, preferential induction by interferon-alpha or interferon-gamma and differential induction in normal and transformed bone-derived cells. The results of this study demonstrate that interferons have complex effects upon the proliferative and biosynthetic activities of human bone-derived cells and demonstrate significant differences between the responses of normal cells and transformed bone-derived cell line. Further investigations will be required in order to determine whether or not these differences are unique to the osteosarcoma cell line or are a characteristic of the effects of interferons on bone-derived cells in general.
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PMID:Interferons and bone. A comparison of the effects of interferon-alpha and interferon-gamma in cultures of human bone-derived cells and an osteosarcoma cell line. 212 83

A case of extraskeletal osteosarcoma was observed in the thigh of a 33-year-old male patient. Ultrastructurally the tumor was characterized by the presence of a particular dense type of cell, the nucleus of which showed a characteristic combination of features: large amounts of condensed marginated chromatin, prominent perichromatin granules, vermicellar bodies, and undulating microtubules. The tumor also contained intermediate-type cells with a more typical osteoblastic appearance, and more blastic cells. All three cell types contained varying amounts of dilated rough endoplasmic reticulum with prominent inclusions of crystalline material showing a hexagonal or banded pattern, indicating that the cells represent different stages of maturation rather than genuinely different types of cells. Dense cells showing the same characteristic combination of nuclear features have been described once before in a case of parosteal osteosarcoma. Our results indicate that these cells are a particular form of osteogenic cell. The presence of undulating microtubules and vermicellar bodies suggest a possible association with the presence of virus and/or increased levels of interferon.
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PMID:Extraskeletal osteosarcoma with unusual ultrastructural features. 216 72

Interferon-alpha is currently under evaluation as an antineoplastic agent in several types of tumour. Despite its clear in vitro effects, the effectiveness of interferon in vivo is limited. To assess whether this discrepancy reflects pharmacokinetic limitations, the authors analysed interferon distribution in 2 osteosarcoma patients by scintigraphy using 123I-interferon-alpha-2a. Numerical analysis of the scintigraphic records demonstrated that the main organs of elimination were the kidneys, when the calculation was made on the basis of surface area. On the other hand, the apparent total uptake by liver (whose projection surface--i.e. the area exposed to the lens--is greater) was higher, reaching about 25 to 30% of the injected dose. The projection surface of the tumour was able to take up radiolabelled interferon in both cases, resulting in a 4-fold increase in the external radiation count compared with the equivalent region of the contralateral limb (although it is not possible to determine whether the label is present on the tumour itself or on the surrounding inflammatory cells). Thus, interferon-alpha seems able to reach at least the immediate neighbourhood of osteosarcoma mass.
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PMID:Scintigraphic study of radiolabelled interferon-alpha in osteosarcoma patients. 231 32

This work assessed the transplantability of human osteosarcomas to immunodeficient nude mice. Osteosarcomas serially transplanted in nude mice were characterized by growth rate, histologic features, and nuclear DNA content. The osteosarcoma xenografts were used to investigate the antitumor effects of interferon (IFN). Tumor tissue from 25 primary osteosarcomas was transplanted into nude mice. All tumors were histologically of high grade (III-IV). Flow DNA cytometry disclosed that all, except 1, had a nondiploid DNA content. 14 of the 25 osteosarcomas grew in serial passage in nude mice, i.e., the take rate was 0.6. The transplantable osteosarcoma group was characterized by a predominance of Grade IV lesions, and a high proportion of proliferating cells, compared to the nontransplantable. The 14 osteosarcoma xenografts, established in nude mice, were heterogeneous with respect to growth rate, histologic subtype, DNA content, and proliferative activity. However, the osteosarcomas retained the basic characteristics of their respective original tumor; the xenografts exhibited the same histologic appearance and DNA content in the first 2 passages in nude mice. During serial transplantation of the 14 osteosarcomas, the histologic features remained unaltered from passage to passage during the observation period of up to 3 years. The aneuploid DNA content was also unchanged over time in most tumors. However, in 4 osteosarcomas with 2 aneuploid cell populations, the cell population with the higher DNA content became predominant, while the other gradually disappeared. Hence, the changes in DNA content involved polyploidization, followed by selection of the cell population with higher DNA content. At the same time growth rate increased, but histologic features were unchanged. This study of osteosarcoma, serially transplanted in nude mice, shows that growth rate, histologic appearance, and DNA content are relatively stable tumor features. The observed changes in DNA content illustrate the development of aneuploidy in malignant tumors. The antitumor effects of human nIFN-alpha were assessed in the 14 osteosarcoma xenografts. In dose-response experiments, based on 2 different tumors, 2 x 10(5) IU/day of nIFN-alpha was found to arrest tumor growth. This dose was chosen as the standard dose in subsequent experiments. Among the 14 osteosarcomas, tumor regression or growth arrest was seen in 5, whereas 8 were only partially growth inhibited with the standard dose. The remaining osteosarcoma was growth inhibited with higher nIFN-alpha doses. Hence, all 14 analyzed osteosarcomas were sensitive to the antitumor effect of nIFN-alpha.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Osteosarcoma and interferon. Studies of human xenografts in the nude mouse. 249 40

In a retrospective study of 83 osteosarcoma patients treated by surgery and adjuvant interferon from 1971 to 1986, the clinical course was related to different clinicopathologic features and tumor DNA content. DNA analysis was feasible in 60 cases. Four tumors were diploid and 56 hyperploid. The 7-year survival rate, estimated by life-table analysis, was 0.44 for the whole series. Multivariate analysis disclosed that male sex, proximal tumor location, and histologic Grade IV were independent risk factors--all approximately of equal strength. DNA analysis did not provide prognostic information, except for tumors with extreme abnormality of the DNA content, which was associated with a very poor prognosis. A prognostication model was created, based on the number of risk factors present. The 7-year survival rate for patients with none, one, two, or three risk factors was 0.80, 0.59, 0.42, and 0.13, respectively. The estimated 7-year rate of local recurrence was 0.29: 0.07 after ablative surgery and 0.54 after local surgery. Among patients who were free of metastasis 1 year after diagnosis, local recurrence reduced the 7-year survival rate from 0.86 to 0.48. In high-grade osteosarcoma, conventional clinicopathologic features and local tumor control remain the most important prognostic factors.
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PMID:Prognostication including DNA analysis in osteosarcoma. 275 May 14


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