Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Taxotere (RP 56976; NSC 628503; N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyl taxol) is a new microtubule stabilizing agent. It is obtained by semisynthesis from a noncytotoxic precursor extracted from the needles of the tree, Taxus baccata L. Taxotere was evaluated for antitumor activity against a variety of transplantable tumors of mice. Taxotere had no marked schedule dependency and was found active by the i.v. and the i.p. routes. Upon i.v. administration, 9 of 11 tumor models tested responded to Taxotere. B16 melanoma was found highly sensitive to Taxotere, with a tumor growth inhibition of 0% and a 3.0 log10 tumor cell kill at the maximum tolerated dose. In the same trial, taxol produced only a 1.1 log10 tumor cell kill at the maximum tolerated dose. Taxotere cured early stage pancreatic ductal adenocarcinoma 03 (6 of 6 cures) and colon adenocarcinoma 38 (7 of 7 cures). It also effected greater than 80% complete regressions of advanced stage disease with both tumors. Taxotere was active against early and advanced stage colon adenocarcinoma 51, with 2.3 and 1.7 log10 cell kill, respectively. Four other tumors responded to a lesser extent: Lewis lung (5.5% tumor growth inhibition), Glasgow osteogenic sarcoma (27.2% tumor growth inhibition), L1210 and P388 leukemias (70 and 54% increase in life span, respectively). Because of its good preclinical activity and its unique mechanism of action, Taxotere has entered Phase I clinical trials.
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PMID:Experimental antitumor activity of taxotere (RP 56976, NSC 628503), a taxol analogue. 168 23

The effect of suramin on tumor growth and morphology in two different human osteosarcoma xenografts (L-I OSM and L-II OSM) grown in BALB/cA-nu/nu mice was studied. Suramin (total dose, 720 mg/kg) given by i.p. injection (60 mg/kg/dose) for up to 9 weeks significantly inhibited osteosarcoma cell growth in both tumors, suramin-treated tumors showing only one-third or less of the volume of nontreated controls. Cell cycle distribution of tumor cells measured by DNA flow cytometry demonstrated that suramin treated caused accumulation of cells in the S and G2 phases of the cell cycle, in both L-I OSM and L-II OSM. In the aneuploid L-II OSM tumor suramin preferentially inhibited the growth of aneuploid cells, leading to a decrease in the ratio of aneuploid to diploid cells. Both osteosarcomas retained their histological appearance and the liver, spleen, heart, and kidneys of the treated animals were unaffected by suramin. These results are compatible with the view that suramin inhibits the growth of human osteosarcomas by cytostatic effects.
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PMID:Suramin inhibits growth of human osteosarcoma xenografts in nude mice. 205 94

Initial immunologic status in children suffering osteogenic sarcoma was retrospectively evaluated versus such parameters as site and extent of tumor, and clinical course. A complex of disorders in the immunologic system was established in osteogenic sarcoma patients. Such characteristics as levels of active, theophylline--sensitive and levamisole--reactivated T-cells were found clinically valuable and prognostically significant. These parameters may betray response of high- and low-affinity E-receptors of lymphocytes to serum factors of tumor growth.
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PMID:[Osteogenic sarcoma in children: clinico-immunological correlations]. 213 27

Chemotaxis is an important step in monocyte recruitment in inflammation, wound healing, and tumor growth. We reported previously that monocyte chemotactic activity secreted by malignant cells and normal smooth muscle cells is associated with a protein or family of proteins that are related to the monocyte-specific smooth muscle cell-derived chemotactic factor (SMC-CF) (Graves, D. T., Jiang, Y. L., Williamson, M. J., and Valente, A. J. (1989) Science 245, 1490-1493). Similar monocyte chemotactic proteins (MCP-1) produced by U-105MG human glioma cells have also been identified (Yoshimura, T., Robinson, E. A., Tanaka, S., Appella, E., Kuratsu, J., and Leonard, E. J. (1989) J. Exp. Med. 169, 1449-1459). We now report that the MCP-1 gene is expressed in MG-63 human osteosarcoma and vascular smooth muscle cells and that SMC-CF antiserum specifically immunoprecipitates proteins synthesized by U-105MG glioma cells. Experiments were undertaken to elucidate the processing pathway of MCP-1/SMC-CF-like proteins in each of these cell types. These experiments demonstrate that larger MCP-1/SMC-CF-like proteins are derived from a Mr = 9000 precursor. Post-translational modification involves the addition of O-linked carbohydrates and sialic acid residues. Differences in carbohydrate processing account for the heterogeneity in MCP-1/SMC-CF-like proteins produced by different cell types. Secretion of these proteins occurs rapidly following processing events in the endoplasmic reticulum-Golgi compartment.
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PMID:Post-translational modification of a monocyte-specific chemoattractant synthesized by glioma, osteosarcoma, and vascular smooth muscle cells. 221 4

Despite the fact that preoperative chemotherapy causes substantial necrosis in the primary osteosarcoma tumor, most authorities recommend resecting these lesions with a wide margin of normal tissue to avoid local recurrence. This study evaluated the effect of systemic chemotherapy (doxorubicin) on tumor growth and histology in the MGH-OGS transplantable murine model and examined whether this drug prevents local recurrence after resection of the tumor with positive microscopic margins. The results indicate that doxorubicin caused prolonged cessation of tumor growth, produced substantial necrosis within the lesion, and decreased the risk of local relapse following marginal surgery. The drug effect was dose-dependent and drug efficacy in preventing local relapse was maximal with administration prior to or at the time of surgery.
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PMID:Effect of doxorubicin on local recurrence following marginal resection in the MGH-OGS murine model. 229 25

The lung is the most frequent site of metastasis in osteosarcoma, but extensive intraluminal tumor growth in pulmonary arteries is rare. Two patients with osteosarcoma in whom the tumors grew in the pulmonary artery and caused massive pulmonary emboli are reported. Histologically the tumor emboli were myxoid and different from the primary lesion and the other metastases, which were osteoblastic in one case and chondroblastic in another case. In both cases the pulmonary tumor emboli were the cause of death.
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PMID:Massive pulmonary tumor emboli in osteosarcoma. Occult and fatal complication. 236 69

Cis-diamminedichloro platinum (II) (cis-DDP) and cis-diamminediaquo platinum (II) nitrate (cis-aq) were complexed to a macromolecular carrier carboxymethyl dextran (CM-dex). Two carriers were used in this study, one derived from dex-T-10 (Mr-10000) and the other from dex-T-40 (Mr-40000). The two platinum (II) drugs formed soluble complexes with both carriers. Uncomplexed and complexed drugs were tested and found to be cytotoxic in vitro against 5 murine and 2 human derived tumor cell lines. The two free platinum (II) drugs were cytotoxic against these cells to a similar extent. In comparison to the free drugs the complexes were somewhat less active, up to 3 fold, against murine 38C-13, L1210, EL-4 and RDM-4 leukemias, as well as against human HeLa and osteogenic sarcoma, and as active as the free drugs against murine F9 embryonal carcinoma. There were no major differences in the in vitro cytotoxic activity between CM-dex T-10 and CM-dex T-40 complexes. Differences due to the molecular size of the carrier were observed in vivo: The CM-dex T-10 complexes were significantly less toxic than the free drugs, whereas the reduction of toxicity by complexing to CM-dex T-40 was less profound. As for the efficacy, when tested in vivo against a cis-DDP sensitive tumor (F9) the T-40 complexes were equally or even more effective than the respective free drugs. The T-10 complexes were less effective than the free drugs at equal drug doses but their effectivity increased at increasing drug levels. These complexes were, however, very effective in inhibiting tumor growth upon repeated injections, leading to 100% survival.
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PMID:Cis-platinum (II) complexes of carboxymethyl-dextran as potential antitumor agents. II. In vitro and in vivo activity. 243 22

Although chemotherapeutic drugs are frequently administered to patients with osteosarcoma, there has been little research into the effect of cytotoxic drugs on osteosarcoma cell biology. The effect of two drugs (Adriamycin and bleomycin) on cell cycle kinetics was investigated in vitro in an established line of human osteosarcoma cells and in vivo using the Dunn osteosarcoma model. The cell cycle changes were consistent with G2 arrest for both drugs in vivo and in vitro. The alteration in cell cycle distribution was correlated with inhibition of 3H-thymidine incorporation in vitro. In vivo, the greater change in cell cycle distribution caused by Adriamycin was reflected in the increased inhibition of tumor growth found with this drug.
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PMID:Kinetic effects of adriamycin and bleomycin on two osteosarcoma models. 244 44

The effectiveness to reduce tumor growth by 1-(2-chloroethyl)-3-(1-oxyl-2,2,6,6-tetramethylpiperidinyl)- 1-nitrosourea (SLCNU) and N,N,N,'N'- bis(1,2-ethanediyl)-N"-(1-oxyl-2,2,6,6-tetramethyl- 2-piperidinylaminocarbonyl)-phosphoric triamide (SLDU) was studied in osteosarcoma and MNU-induced mammary carcinoma in the SD-rat. Both compounds elicited neither an inhibitory effect on these tumors nor an increase in the mean/median life span as compared to the control group.
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PMID:Evaluation of spin labeled TEPA and CCNU analogs against osteosarcoma and MNU-induced mammary carcinoma of the SD-rat. 247 94

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


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