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 usefulness of nude rat xenograft systems in immunolocalization studies was investigated using the monoclonal antibody 9.2.27 which binds to melanomas and osteosarcomas. Three human tumors, two melanomas (LOX and FEMX-I) and one osteosarcoma (OHSX), were used. They were established as s.c. xenografts in congenitally athymic (rnu/rnu) nude rats. These serially transplantable tumors showed the same morphology, take rate and growth properties in nude rats as in nude mice. Radiolabeled 9.2.27 F(ab')2 fragments injected i.v. into nude rats were concentrated in s.c. LOX and OHSX xenografts, reaching tumor to blood ratios of up to 30 after 3-4 days. However, the injected antibody failed to concentrate in FEMX-I xenografts, in contrast to previous findings in mice. This discrepancy could be attributed neither to significant differences in in vivo distribution of the labeled antibody nor to the presence of blocking factors in the serum of nude rats. In immunoscintigraphic studies clear images of s.c. LOX tumors were obtained, whereas lung colonies were less well visualized. Biodistribution studies showed a low tumor to blood ratio of about 4 in the latter animals, suggesting a tumor site-dependent variation in homing of labeled antibodies. Radiography was found to be superior to immunoscintigraphy in detecting the lung tumors. The present findings demonstrate that results of immunolocalization studies in nude mice cannot readily be extrapolated to other species. For the purpose of preclinical evaluation of new methods in cancer diagnosis and treatment, tumor xenografts in nude rats may represent a valuable complement to nude mouse models.
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PMID:Athymic rats in preclinical immunodiagnostic studies. 206 18

Intratibial injection in nude rats of 1 x 10(6) OHS, MHMX, and LOX human tumor cells resulted in each case in progressively growing bone tumors. When the diameter of the affected leg had increased by 2-3 mm, the animals were examined for uptake of 99mTc-methylenediphosphonate. The OHS osteosarcoma tumors caused sclerotic lesions with high and uniform isotope uptake, and the MHMX unclassified sarcoma showed a mixed pattern with both sclerotic and lytic areas, whereas the LOX melanoma caused lytic bone lesions with low uptake of the radionuclide. These findings were compared with the results of analogous investigations previously performed in the patients from whom the tumor lines originated. Striking similarities in both the morphology and the scintigraphic images were observed between corresponding tumors in rats and humans, with results supporting the clinical relevance of the model systems. When the LOX model was used for therapy experiments, doxorubicin had no effect on the growth of the tibial tumors, which in the control group appeared after a latency of 13.5 days. The alkylating agent mitozolomide increased the median tumor-free latency to 47 days in 7 rats, and 5 animals did not develop tumors within the observation period of 60 days. Doxorubicin was ineffective also against the OHS tumor, whereas ifosfamide and the radionuclide 89Sr-chloride showed significant antitumor activity. The disease-free latency increased from 20 days, in the control animals, to 45 and 28.5 days, respectively, in the 2 treated groups, in which 2 of 7 and 2 of 10 rats were without tumors at 60 days. The data demonstrate that the tibial models discriminated between the action of the different therapeutic agents, and suggest that they may be useful in selecting compounds with clinical activity against skeletal tumors.
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PMID:Validity and usefulness of human tumor models established by intratibial cell inoculation in nude rats. 813 86

Halichondrin B and homohalichondrin B are novel tubulin-interacting agents isolated from marine sponges. The in vivo antitumor activities of these compounds were examined in human tumor models in immunodeficient mice and rats. In nude mice, regression or pronounced delay of subcutaneous tumor growth was obtained with both halichondrins, at a maximum tolerable dose of 20 micrograms/kg Q2Dx5, in three of four vinblastine-sensitive tumors, including two melanomas and one osteosarcoma; one small-cell lung cancer line was resistant. The halichondrins as well as vinblastine showed only marginal activity against KM20L colon carcinoma xenografts. In a LOX melanoma lung colony formation assay in groups of six nude mice, all control animals were sacrificed because of respiratory symptoms 38 days after cell injection, and likewise one vinblastine-treated mouse after 53 days. All halichondrin-treated mice in the lung colony assay appeared healthy throughout an observation period of 112 days (p = 0.002). Upon necropsy all vinblastine-treated animals, and two of six mice in the halichondrin group, had macroscopic lung tumor colonies. In a nude rat model for LOX bone marrow metastases, the mean lifespan of untreated control animals was 15 days. Whereas vinblastine had only a marginal effect (17 days) in this model, halichondrin B prolonged the lifespan of the animals to 32 days, representing a significant (p = 0.0016) difference between the two compounds. In conclusion, the halichondrins, which comprise a subtype of tubulin-interactive anti-mitotic agents, showed distinct antitumor activity profiles in human tumor models, thereby encouraging their further preclinical development and possible clinical evaluation.
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PMID:Comparative antitumor activities of halichondrins and vinblastine against human tumor xenografts. 941 95

Eradicative levels of antitumor activity by cytokines and leukocytes have not yet been reached experimentally and are needed clinically. Only a limited number of human cancers respond to therapy with interferon (IFN), other cytokines, or mononuclear leukocytes despite significant antitumor activity in vitro. We studied the IFN and monocytic cell conditions that would lead to an eradicative effect using human cells in vitro. Targets of the IFN-activated monocytic cells were either four human tumor cell lines (human osteosarcoma [HOS], LOX melanoma, A549 lung tumor, and SNB-19 glioblastoma) or two diploid cell lines (WI38 and MRC5). An average of 30-90 colony-forming tumor target cells were cultured overnight in 96-well tissue culture plates prior to treatment with serially diluted IFN with or without activated elutriation-purified monocytes or lymphocytes. The target cell colonies were treated for 3 days. The colonies were then stained with crystal violet to determine the levels of antitumor activity. IFN-activated human monocytes reached an eradicative level (95%-100%) against three of four tumor cell lines. The eradicative level (1) was induced best in human monocytes activated by combined type I and II IFNs, (2) was effective against tumor cells that were growing for 24 h, (3) was specific for human tumors, as diploid human cells were not inhibited, and (4) required contact between the macrophage and the tumor cells. Also, for the first time, the minimal effective concentration (MEC) of IFNs to activate monocytes can approach those needed for antiviral activity. To our knowledge, this is the first report of near total eradication of many tumor cells, but not diploid cells, by IFN-activated monocytes. Because of its potency and specificity, the IFN-activated monocyte arm of the innate immune system may be a candidate for therapy of established tumors.
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PMID:Clinical model: interferons activate human monocytes to an eradicative tumor cell level in vitro. 1731 43

A mixed extract containing two naturally occurring flavonoids, baicalin from Scutellaria baicalensis and catechin from Acacia catechu, was tested for cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibition via enzyme, cellular, and in vivo models. The 50% inhibitory concentration for inhibition of both ovine COX-1 and COX-2 peroxidase enzyme activities was 15 microg/mL, while the mixed extract showed a value for potato 5-LOX enzyme activity of 25 microg/mL. Prostaglandin E2 generation was inhibited by the mixed extract in human osteosarcoma cells expressing COX-2, while leukotriene production was inhibited in both human cell lines, immortalized THP-1 monocyte and HT-29 colorectal adenocarcinoma. In an arachidonic acid-induced mouse ear swelling model, the extract decreased edema in a dose-dependent manner. When arachidonic acid was injected directly into the intra-articular space of mouse ankle joints, the mixed extract abated the swelling and restored function in a rotary drum walking model. These results suggest that this natural, flavonoid mixture acts via "dual inhibition" of COX and LOX enzymes to reduce production of pro-inflammatory eicosanoids and attenuate edema in an in vivo model of inflammation.
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PMID:A medicinal extract of Scutellaria baicalensis and Acacia catechu acts as a dual inhibitor of cyclooxygenase and 5-lipoxygenase to reduce inflammation. 1788 37

It is well known that suramin influences proliferation and differentiation of tumour cells. To study whether and how suramin effects osteosarcoma (OS) cells, proliferation, differentiation, LOX mRNA expression and telomerase activity (TA) was analysed in the human MG-63 and U-2 OS, and the rat UMR-106 OS cell lines. Data show that suramin inhibited proliferation in the human cell lines and upregulated alkaline phosphatase activity. TA was attenuated in the human cells while in UMR-106 it was not changed. In UMR-106 suramin had no influence on osteocalcin and LOX expression, in the human cells however, both genes were upregulated.
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PMID:Lysyl oxidase (LOX) mRNA expression and genes of the differentiated osteoblastic phenotype are upregulated in human osteosarcoma cells by suramin. 1837 78

The 5-lipoxygenase (5-LOX) inhibitor tepoxalin has been shown to slow canine osteosarcoma (OSA) tumour xenografts growth, yet the mechanisms are poorly elucidated. Further examination of tepoxalin in canine OSA cell lines shows that tepoxalin treated cells undergo apoptosis through caspase-3 activation and annexin staining. Interestingly, apoptosis is superseded by an increase in reactive oxygen species (ROS), as measured by activation of dihydrorhodamine 123 and mitosox. This increase in ROS appears to be related to the 5-LOX inhibitor regardless of cellular 5-LOX status, and was not observed after treatment with the tepoxalin metabolite RWJ20142. Additionally, 5-LOX inhibition by tepoxalin appears to increase phosphatase and tensin (PTEN) homolog activity by preventing its alkylation or oxidation. PTEN modification or inhibition allows phosphoinositide-3 (PI3) kinase activity thereby heightening activation of protein kinase B (AKT) phosphorylation. Our data suggest that off target oxidation and LOX inhibition play roles in the apoptotic response.
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PMID:The 5-lipoxygenase inhibitor tepoxalin induces oxidative damage and altered PTEN status prior to apoptosis in canine osteosarcoma cell lines. 2481 77