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)

Tumors were induced in 46 of 52 female Sprague-Dawley rats by gastric intubation of 5 mg of DMBA, dissolved in 1 ml of sesame oil, given weekly for 5 weeks. From 4 weeks after the final dose tumors were recorded and measured. Bilateral ovariectomy was done 3 days before sacrifice and assay. Excised tumors were immediately immersed in ice-cold Tris-EDTA buffer. Sections were prepared for histological examination. The assay was done by sucrose density centrifugation after administration of (2,4,6,7-tritiated)-estradiol-17beta in vivo 3 minutes before killing, and/or in vitro. For specific estrogen-binding proteins the capacity to bind (tritiated)-estradiol-17beta was not related to the growth characteristics, time of appearance, or time between ovariectomy and assay. Different tumors had estrogen-binding capacities unrelated to the percentage of neoplastic cells in the tumor, amount of inflammation, mast cell infiltration, or presence of fluid-filled cysts. The number of mitoses and the lipid content of the tumors were correlated with the estrogen-binding capacity in that it was lower in tumors with many mitoses and in those with much lipid in the epithelial cells. Of 19 adenocarcinomas, 6 did not regress after ovariectomy. In 5 of the regressed tumors a new growth phase was seen, beginning 2 months after ovariectomy. Tumors encountered, other than mammary adenocarcinomas, were an extraosseous osteosarcoma, fibroadenomas, and zymbal-gland tumors.
 ...
PMID:Morphology, growth characteristics and oestrogen-binding capacity of DMBA-induced mammary tumours from ovariectomized rats. 40 32

Except for oral administration, there was no grossly observed toxicity from carefully administered high doses of amygdalin in the experimental systems used. The compound in high doses was ineffective against the DMBA-induced rat mammary carcinoma and the following transplanted experimental tumors: Sarcoma 180, plasma cell tumor LPC-1, leukemia L1210, Mecca lymphosarcoma, Ridgway osteogenic sarcoma, sarcoma T241, mammary carcinoma E0771, Taper liver tumor, Ehrlich carcinoma (solid and ascites), and Walker carcinosarcoma 256. Amygdalin did not noticeably influence the toxicity or impair the efficacy of these chemotherapeutic agents in their respective systems: Cytosine arabinoside, methotrexate, cytoxan, or 5-fluorouracil in L1210; the latter two in LPC-1; 6-mercaptopurine in Ridgway osteogenic sarcoma; estradiol-17beta or 2alpha-methyldihydrotestosterone propionate in the DMBA-induced rat mammary carcinoma.
 ...
PMID:Antitumor tests of amygdalin in transplantable animal tumor systems. 64 16

A single, nonlethal dose of actinomycin D will cause total regression and cure of Ridgway osteogenic sarcoma in mice. A cure is not obtained with a single dose daily for 7 days, a dose regimen which kills 10% of normal C57BL/6 X DBA/2 mice. This suggests that actinomycin D is more effective on a single high-dose schedule than on chronic daily therapy. Analysis of drug exposure in Ridgway osteogenic sarcoma and normal mouse tissues following the single and multiple-dose regimens suggests the difference in therapeutic response is due to drug exposure at a higher concentration in Ridgway osteogenic sarcoma after the single high dose than after the multiple-dose regimen. This may be related to the higher drug concentration attained in blood following the single-dose regimen than is attained with the multidose regimen.
 ...
PMID:Disposition of [3H]actinomycin D in tumor-bearing mice. 106 63

Flavone acetic acid (FAA) is a new antitumor agent with broad activity against transplantable solid tumors of mice but with only scant or no activity against leukemias and lymphomas. The technique of alkaline elution was used to study DNA lesions in s.c. implanted Glasgow osteogenic sarcoma in C57BL/6 x DBA/2 F1 mice treated i.v. with FAA. At efficacious dosages (235 and 200 mg/kg), FAA produced extensive single strand breakage. Formation of single strand breaks was dependent on time of assay after exposure to FAA with only minimal damage occurring prior to 5 h posttreatment. Apparently Glasgow osteogenic sarcoma had no capacity to repair single strand breaks for at least 45 h after drug administration. Thus, FAA differs in its mechanism from other scission agents (e.g., VP-16). Neither interstrand cross-links nor DNA-protein cross-links were detected. DNA single strand breaks did not occur in the bone marrow cells or in the unresponsive P388 leukemia cells at dosages causing extensive DNA damage in solid tumor cells.
 ...
PMID:Flavone acetic acid (NSC 347512)-induced DNA damage in Glasgow osteogenic sarcoma in vivo. 342 92

This study explored whether valproic acid (VPA, a histone deacetylase inhibitor) could radiosensitize osteosarcoma and primary-culture tumor cells, and determined the mechanism of VPA-induced radiosensitization. The working system included osteosarcoma cells (U2OS) and primary-culture cells from chemical carcinogen (DMBA)-induced breast cancer in rats; and clonogenic survival, immunofluorescence, fluorescent in situ hybridization (FISH) for chromosome aberrations, and comet assays were used in this study. It was found that VPA at the safe or critical safe concentration of 0.5 or 1.0 mM VPA could result in the accumulation of more ionizing radiation (IR)-induced DNA double strand breaks, and increase the cell radiosensitivity. VPA-induced radiosensitivity was associated with the inhibition of DNA repair activity in the working systems. In addition, the chromosome aberrations including chromosome breaks, chromatid breaks, and radial structures significantly increased after the combination treatment of VPA and IR. Importantly, the results obtained by primary-culture cells from the tissue of chemical carcinogen-induced breast cancer in rats further confirmed our findings. The data in this study demonstrated that VPA at a safe dose was a radiosensitizer for osteosarcoma and primary-culture tumor cells through suppressing DNA-double strand breaks repair function.
 ...
PMID:The Effect of VPA on Increasing Radiosensitivity in Osteosarcoma Cells and Primary-Culture Cells from Chemical Carcinogen-Induced Breast Cancer in Rats. 2848 60

Mouse double minute 2 (Mdm2) is a multifaceted oncoprotein that is highly regulated with distinct domains capable of cellular transformation. Loss of Mdm2 is embryonically lethal, making it difficult to study in a mouse model without additional genetic alterations. Global overexpression through increased Mdm2 gene copy number (Mdm2Tg ) results in the development of hematopoietic neoplasms and sarcomas in adult animals. In these mice, we found an increase in osteoblastogenesis, differentiation, and a high bone mass phenotype. Since it was difficult to discern the cell lineage that generated this phenotype, we generated osteoblast-specific Mdm2 overexpressing (Mdm2TgOb ) mice in 2 different strains, C57BL/6 and DBA. These mice did not develop malignancies; however, these animals and the MG63 human osteosarcoma cell line with high levels of Mdm2 showed an increase in bone mineralization. Importantly, overexpression of Mdm2 corrected age-related bone loss in mice, providing a role for the proto-oncogenic activity of Mdm2 in bone health of adult animals.
 ...
PMID:The proto-oncogene function of Mdm2 in bone. 3001 Oct 84