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)

In vitro and in vivo studies have suggested synergistic anti-tumour activity of combined hyperthermia and tumour necrosis factor alpha (TNF-alpha). However, some studies indicated an increased systemic toxicity of TNF by additional hyperthermia. The aim of this study was to obtain starting dosages for a clinical phase I study on the application of deep local hyperthermia and systemic TNF. We investigated the effect of local hyperthermia on the toxicity and efficacy of systemic TNF. Rats (Wag/Rij) carrying a subcutaneously transplanted osteosarcoma in the hind leg received a single intravenous dose of recombinant human (rh) TNF-alpha, either at normothermia or at hyperthermia, by positioning the tumour bearing hind leg in a water bath of 43 degrees C. Dose-effect curves for lethality and tumour cure were established and LD50 and TCD50 values were calculated. Systemic toxicity was increased by local hyperthermia. The LD50 values (+/- s.e.) were 1088 (+/- 61) micrograms kg-1 at normothermia and 205 (+/- 23) micrograms kg-1 at hyperthermia, resulting in a thermal enhancement ratio (TER) of 5.3. Following normothermia, tumour cures were observed at TNF concentrations of 1000-1300 micrograms kg-1, while this was observed at doses of 50-300 micrograms kg-1 when combined with hyperthermia (TCD50 values of 1211 and 188 micrograms kg-1 respectively), resulting in a TER of 6.4. Systemic toxicity and anti-tumour activity of TNF are both increased by local hyperthermia. A safe starting dose for the combined clinical treatment would be 10% of the dose of TNF-alpha that has been recommended for phase II studies on intravenous bolus administration of TNF-alpha at normothermia. In view of the large variability in tumour sensitivity for TNF-alpha, the clinical usefulness of this combined treatment modality has to be determined.
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PMID:Thermal enhancement of both tumour necrosis factor alpha-induced systemic toxicity and tumour cure in rats. 777 5

The anti-caries effects of water fluoridation are well-established. The non-dental tissue effects of fluoride in drinking water, either naturally occurring or as an additive, have been too poorly studied to permit definitive conclusions to be drawn. Claims have been made that fluoride results in an increased occurrence of malignancies, particularly osteogenic sarcoma. Experimental rat data have not resolved this issue, and epidemiologic studies are equally unclear. Initial claims that fluoride offers protection against atherosclerosis remain viable, but here too, much more directed research is needed. Early studies suggested that a water fluoride content greater than 1 ppm resulted in a lower prevalence of osteoporotic fractures. Recent epidemiologic data seriously question this conclusion and raise the possibility that even this relatively low level may increase the prevalence of osteoporotic hip fractures. Other elements, including calcium and magnesium, also vary in amount as water fluoride content varies, and it has proved difficult to distinguish the independent effects of the various nutrients in water from each other. Therapeutic use of fluoride has been largely restricted to studies of its effect on the osteoporotic study, this important issue remains unresolved. This review provides an overview of these issues, focusing on the uncertainties alluded to, and attempting to develop strategies for future research.
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PMID:Non-dental tissue effects of fluoride. 799 58

Four groups of 400 12-week-old CBA/H mice were injected i.p. with 69, 139, 280 and 550 Bqg-1 224Ra. A further group of 400 mice were injected i.p. with diluting solution only. The mice were then allowed unrestricted access to food and water until they died or were killed. 53 cases of myeloid leukaemia and 22 cases of osteosarcoma were confirmed in the 2000 mice injected, and for both tumour types direct relationships were shown to exist between the amount of 224Ra administered and the incidence of tumours. It is concluded that mouse is at a greater risk from myeloid leukaemia than from osteosarcoma in the region of administered 224Ra below that which causes a maximum yield of osteosarcoma. These results are discussed in the light of the present acceptance of osteosarcoma as the major risk to man from bone-seeking alpha-particle emitters.
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PMID:Myeloid leukaemia and osteosarcoma in CBA/H mice given 224Ra. 810 48

Methotrexate (MTX) serum concentrations were measured in 7 cases (2 patients) in which a high-dose administration of MTX with citrovorum factor rescue for osteogenic sarcoma were performed for repressing activity in the original lesion and satellite micrometastasis. In the pharmacokinetic analysis, the changes of MTX serum concentrations were explained by a 2-compartment open model under the assumption that the elimination rate was proportional to both of volume of parenteral solution and the amount of water intake. It was suggested that MTX serum concentration could be controlled by adjusting the volumes of parenteral solutions. MTX amount in the peripheral compartment was found about ten times larger than that in the central compartment after about 40 h of administration. It is considered that an early increase in the volumes of parenteral solutions is effective to keep the safety level of MTX serum concentration, and continuous infusion is important for avoiding the severe side effects caused by delayed elimination of MTX.
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PMID:[A pharmacokinetic study on high-dose methotrexate administration--the effects of volume changes of parenteral solutions on the elimination rate]. 829 21

Aromatase activity was studied in cultured human osteosarcoma cell (HOS). HOS was incubated from 12 to 72 hours with 10(-10) M-10(-5) M dexamethasone. Aromatase activity was determined by measuring [3H]H2O released upon the conversion of [1 beta-3H]androstenedione to estrone. HOS showed aromatase activity, and apparent km for [1 beta-3H]androstenedione was 4.46 +/- 0.98 nm (mean +/- SD). The aromatase activity was significantly increased by 10(-9) M-10(-5) M dexamethasone in a dose-dependent manner. Dexamethasone increased Vmax of aromatase activity but did not change its km value. These results suggest that osteoblastic cells have aromatase activity which is regulated by glucocorticoid, and directly convert androgen to estrogen in itself.
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PMID:Aromatase activity in human osteoblast-like osteosarcoma cell. 844 85

It is well known that the bone matrix contains proteins which can induce ectopic endochondral bone formation in vivo. One class of these proteins is the bone morphogenetic protein (BMP). In order to investigate the physiological function of the BMP, its purification was attempted from an extract of demineralized bone matrix and its actions on the osteoblastic cell line were investigated. To isolate the BMP, a demineralized bone matrix was extracted with 4M guanidine-HCl. A water-insoluble fraction (G-WI) was separated from the demineralized bone extract by dialysis against distilled water and centrifugation. The BMP was purified from G-WI by gel filtration on Sephacryl S-200 HR, cation exchange with Mono-S, heparin affinity column and finally by C1/8 reverse phase chromatography. Peptide sequence analysis revealed that the purified BMP fraction contained "BMP-3" reported by Wozney et al. (1988). In order to investigate its function, the BMP was applied to the rat osteogenic sarcoma cell line UMR108. The BMP inhibited the growth of the UMR108 cells and enhanced the alkaline phosphatase activity in a dose-responsive manner.
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PMID:[Purification of bone morphogenetic protein and investigation of its effects on osteoblastic cell line UMR108]. 848 1

We have previously established a rat model of chronic uremia, which is suitable to investigate the effect of various treatment modalities on renal osteodystrophy [1]. After four months subsequent to 5/6 nephrectomy, some animals were treated by gavage for 9 weeks with tap water (controls), or with aluminium (Al-citrate) 3 x 25 mg/week/kg b.wt +/- subsequent deferoxamine (DFO) 3 x 50 mg/week/kg b.wt. for 4 weeks. At termination of the study, serum clinical chemistry, femoral chemical composition and mechanical properties, calvarial parathyroid hormone (PTH)-elicited adenylate cyclase (AC) and phospholipase C (PLC) activities, cross-sectional femoral area, as well as bone histomorphometry, were analyzed. Animals given Al displayed moderately enhanced serum Al and bone Al accumulation, however, DFO-treatment did not fully alleviate bone Al retainment. A small increase in serum PTH was seen in all animals rendered uremic. Furthermore, a marked fall in serum alkaline phosphatase (ALP) below normal controls was observed in Al +/- DFO-treated animals compared with uremic controls. The uremic condition led to reduced femoral ratios of hydroxyproline (HYP) over Ca(2+) and phosphate (P(i)), while Al-intoxication alone enhanced femoral Hyp contents above values seen for normal controls. The protracted ureamia caused a deterioration of long bone resilience and brittleness, however, Al +/- DFO-treatment seemed to normalize the latter. Contrastingly, Al +/- DFO-gavage enhanced time to fracture. Uremic rats intoxicated with Al showed a complete loss of calvarial PTH-sensitive AC and PLC activities. DFO-treatment normalized PTH-elicited PLC, while PTH-susceptible AC remained super-normal. Al apparently exerts a long term down-regulation of both PTH-sensitive signaling systems as evidenced by studies of rat UMR 106 osteosarcoma cells in culture. The uremic condition enhanced endosteal bone resorption as shown by femoral shaft dimension analysis, while Al +/- DFO-treatment insignificantly reversed the condition. Finally, histomorphometrical analyses showed that DFO-administration tended to normalize aberrant trabecular bone volume, while rectifying both bone resorption and degree of mineralization. In conclusion, we assert that Al-intoxication hampers both processes (i.e. formation and resorption) of bone turnover, and that DFO-treatment to a certain extent prevents the uremia- and Al-induced bone disease in rats.
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PMID:Aluminium-induced bone disease in uremic rats: effect of deferoxamine. 886 40

Monoclonal antibody HTP IV-#1 specifically recognizes a complexation-dependent neoepitope on bone acidic glycoprotein-75 (BAG-75) and a Mr = 50 kDa fragment. Complexes of BAG-75 exist in situ, as shown by immunofluorescent staining of the primary spongiosa of rat tibial metaphysis and osteosarcoma cell micromass cultures with monoclonal antibody HTP IV-#1. Incorporation of BAG-75 into complexes by newborn growth plate and calvarial tissues was confirmed with a second, anti-BAG-75 peptide antibody (#503). Newly synthesized BAG-75 immunoprecipitated from mineralizing explant cultures of bone was present entirely in large macromolecular complexes, while immunoprecipitates from monolayer cultures of osteoblastic cells were previously shown to contain only monomeric Mr = 75 kDa BAG-75 and a 50 kDa fragment. Purified BAG-75 self-associated in vitro to form large spherical aggregate structures composed of a meshwork of 10 nm diameter fibrils. These structures have the capacity to sequester large amounts of phosphate ions as evidenced by X-ray microanalysis and by the fact that purified BAG-75 preparations, even after extensive dialysis against water, retained phosphate ions in concentrations more than 1,000-fold higher than can be accounted for by exchange calculations or by electrostatic binding. The ultrastructural distribution of immunogold-labeled BAG-75 in the primary spongiosa underlying the rat growth plate is distinct from that for other acidic phosphoproteins, osteopontin and bone sialoprotein. We conclude that BAG-75 self-associates in vitro and in vivo into microfibrillar complexes which are specifically recognized by monoclonal antibody HTP IV-#1. This propensity to self-associate into macromolecular complexes is not shared with acidic phosphoproteins osteopontin and bone sialoprotein. We hypothesize that an extracellular electronegative network of macromolecular BAG-75 complexes could serve an organizational role in forming bone or as a barrier restricting local diffusion of phosphate ions.
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PMID:Bone acidic glycoprotein-75 self-associates to form macromolecular complexes in vitro and in vivo with the potential to sequester phosphate ions. 909 4

Osteosarcoma, either primary or metastatic, rarely involves the jaws. Though only a few cases of mandibular metastasis of osteosarcoma have been reported, only one case of et al maxillary involvement (Singh, 1978) has been reported. A case of 21 year old boy with metastasis of osteosarcoma to the right maxilla from primary osteosarcoma of the left femur is presented. The patient complained of pain and swelling in the left maxillary region which was earlier diagnosed as maxillary sinusitis on the basis of Water's sinus radiograph in a medical hospital. Further radiographic examination with the panoramic and intraoral periapical radiographs done by us and later by fine needle aspiration cytology led us to diagnose a secondary deposits of osteosarcoma.
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PMID:Maxillary metastasis of osteosarcoma. 949 57

The anti-tumor effects of hypoosmotic solution of MTX in distilled water (DW) on Dunn osteosarcoma were evaluated in mouse air pouches. Dunn osteosarcoma cell suspension (1 x 10[5] cells in 0.1 ml of medium) was inoculated into the mouse subcutaneous air pouch that had formed 7 days after the initial injection of air. Two hours after the inoculation of tumor cells, 5 ml of various concentrations of MTX (from 0 to 1 x 10[-3] M) dissolved in DW or PBS were injected into the air pouch. Five minutes later, the entire solution in the air pouch was aspirated. The mice were sacrificed 3 weeks after the inoculation of tumor cells and the air-pouch tissue was transected in the coronal plane with the largest area of tumor mass. The sections were stained with H&E and the area was measured with the NIH Image program. The largest area of tumor mass in the air pouch treated with 1 x 10(-3) M of MTX in DW was 11.8+/-3.4 mm2 (N = 5), which was significantly (P < 0.005) smaller than that in PBS (51.7+/-8.3 mm2). These findings suggested that hypoosmotic solution in DW might augment the anti-tumor effect of MTX on sarcoma cells.
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PMID:Augmentation of anti-tumor effects of methotrexate by distilled water on Dunn osteosarcoma in mouse air pouch. 958 66


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