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)

Various 117mSn (2+ and 4+) compounds in well defined oxidation states were studied in normal mice using whole body autoradiography (WBARG), tissue distribution and scintigraphy in animal models of vitamin A induced bone disease, fracture, infected fracture and ischemic muscle lesions. The 117mSn4+-DTPA showed high affinity to normal bone with low soft tissue concentration. Increased deposition of this compound in fractures and ischemic lesions in muscle was also demonstrated. In hypervitaminosis A, reduced bone uptake of 117mSn4+-DTPA was shown to occur. Nude mice bearing osteogenic sarcoma of human origin showed uptake in spiculated pattern. The similar distribution of 117mSn4+-DTPA which does not contain phosphate or phosphonate groups, and the 99mTc(Sn) skeletal imaging compounds may indicate that tin is important in binding to bone. 117mSn4+-DTPA may not be ideal for routine imaging except when long term follow up is required. It should however be considered for therapy of bone tumors because of the long physical half-life of 117mSn (t1/2 = 14.03 days), abundance of short-range conversion and Auger electrons and its preferential deposition in cortical bone as indicated by our results.
 ...
PMID:The development and in-vivo behavior of tin containing radiopharmaceuticals--II. Autoradiographic and scintigraphic studies in normal animals and in animal models of bone disease. 386 59

Twelve patients with osteosarcoma were evaluated by plain radiographs, radionuclide bone scans and computed tomography (CT). Plain films were the primary radiologic tool for the investigation and follow-up of the skeletal lesion and were particularly helpful for the demonstration of periosteal calcification and bone permeation. The main value of the radiophosphate scan was to detect metastatic or multifocal bone disease. CT was able to show new bone formation in the soft-tissue mass not seen on plain films, to determine proximal intramedullary extension and to assess the response of the bone lesion to preamputation chemotherapy. The lungs were followed at regular intervals with plain chest radiographs and CT scans.
 ...
PMID:Radiologic evaluation of osteosarcoma. 695 77

Bone cells respond to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) for mineral mobilization and contain receptors for 1,25(OH)2D3. We report here the expression of 25-hydroxyvitamin D3 (25 (OH)D3) metabolizing enzymes in primary cultures of human bone cells, as well as n a human osteosarcoma cell line. Human bone cells were obtained by enzyme digestion of the extracellular matrix of bone from iliac crest biopsies from 3 male patients without primary bone disease. These cells were plated (5 X 10(4)/min) in medium with 10% fetal calf serum and proliferated to confluence in 10-14 days. At confluence, the medium was replaced with serum-free medium. The cells were preincubated in this serum-free medium for 24 h prior to incubating them 2-4 h with [3H]25(OH)D3 (10-20 nM). The vitamin D metabolites synthesized during this incubation were extracted from the medium and cells with dichloromethane, then separated by chromatography on Sephadex LH-20, followed by high performance liquid chromatography. The cells synthesized 1,25(OH)2D3 and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) with the specific activities of the 1- and 24-hydroxylases similar in magnitude to those in kidney cells in vitro. The enzymes could be regulated by external perturbations, in that the activity of the 1-hydroxylase was inhibited by preincubation of the cells for 8 h with 1,25(OH)2D3 (10 nM), whereas the 24-hydroxylase was enhanced. Incubation of the cells in a low calcium medium (0.6 mM) depressed the 24-hydroxylase activity. We conclude: 1) normal human bone cells can produce 1,25(OH)2D3 and 24,25(OH)2D3 in vitro in amounts similar to kidney cells, suggesting a physiological significance and 2) this synthesis could account for the increase in osteoclast number in anephric patients with renal osteodystrophy.
 ...
PMID:Human bone cells in culture metabolize 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3. 697 69

With a brother and sister, osteosarcoma developed at the age of 11 and 14 respectively. With both there was no previous retinoblastoma or other bone disease with a proclivity to develop osteosarcoma. We discuss possible explanations for familial aggregation of osteosarcoma, citing external or genetic factors. We suggest that it is the retinoblastoma gene RB and the tumor suppressor gene p53 which play an important part in the development of osteosarcoma.
 ...
PMID:[Osteosarcoma in 2 siblings. A case report]. 750 Jun 7

Primary renal osteogenic sarcoma is a rare tumour which requires differentiation from osteoid formation in sarcomatoid variants of renal cell carcinoma. The diagnosis in this case was suggested pre-operatively by marked elevation of serum alkaline phosphatase in the absence of bone disease. The poor prognosis is emphasized.
 ...
PMID:Primary osteogenic sarcoma of the kidney. 766 14

The authors treated 18 patients with Paget's disease of bone (12 men and 6 women, age 65 +/- 5 years) with pamidronate (bisphosphonate of the second generation). Three patients from this group were treated previously without success with calcitonin or bisphosphonate of the first generation (etidronate) 50% of the patients suffered from the polyostotic form of the disease. In one patient a rare combination of primary hyperparathyroidism with Paget's bone disease was found and in another patient later an osteosarcoma developed in the affected bone. To all patients sodium pamidronate was administered (Aredia, Ciba-Geigy) 30 mg per day by i.v. infusion for 2 hours during three days. Four patients developed fever, two patients phlebitis at the site of injection. These side-effects are described by the manufacturer. Two patients developed transient regional alopecia, not described so far. Subjective pain relief of the affected skeleton occurred in one patient after one month of treatment, after three months in 78%. Laboratory manifestations of activity of the disease (serum activity of alkaline phosphatase, tartrate resistant acid phosphatase and hydroxyprolinuria) declined gradually from the 1st to the 6th month after onset of treatment. There was a less marked decline of the osteocalcin serum concentration. The concentration of calcium, phosphorus and vitamin D metabolites did not change markedly. Twelve months after treatment 14.7% of the patients were inactive according to laboratory tests, 73% however experienced another rise of parameters of osteoresorption and osteoformation. Pamidronate treatment in patients with Paget's disease of bone is effective and safe.
 ...
PMID:[Paget's disease of bone and treatment with pamidronate]. 837 65

Bone morphogenetic proteins (BMPs) are differentiative factors whose principal function is to induce transformation of undifferentiated mesenchymal cells into chondroblasts and osteoblasts in a dose-dependent manner. Bone morphogenetic proteins have been isolated postnatally in mammals from bone matrix, periosteal cells, mesenchymal cells of marrow stroma, tooth analagen, and cells of osteosarcoma and chondrosarcoma. Distribution in additional embryonic tissues implies a broader organogenic function. Bone morphogenetic proteins are the only differentiative factors able to singularly induce de novo bone formation in vitro and in vivo. Recombinant DNA technology allows their production in large and highly purified quantities. The BMPs' osteoinductive ability has been shown with a variety of carriers including collagens and polymers at heterotopic and orthotopic sites in a wide range of species. They are presently being readied for clinical use as alternatives to bone grafts. Other potential applications include use as pulp capping agents, promoters of implant osteointegration and soft tissue reunion with bone, treatments for nonadaptive bone disease, and implants for use with mitotically expanded skeletal stem cell populations. Errors in the genetic coding of BMPs may manifest as clinical disease entities.
 ...
PMID:Recombinant bone morphogenetic proteins: novel substances for enhancing bone healing. 858 49

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.
 ...
PMID:Aluminium-induced bone disease in uremic rats: effect of deferoxamine. 886 40

Paget disease of bone, or "osteitis deformans," is a bone disorder characterized by rapid bone remodeling resulting in abnormal bone formation. It is the second most common metabolic bone disease after osteoporosis, affecting 3%-5% of subjects aged >40 years. Recent evidence suggests that predisposition to Paget disease may have a genetic component. Genetic linkage analysis of families with multigenerational Paget disease shows linkage to a region of chromosome 18q near the polymorphic locus D18S42. Approximately 1% of Paget patients develop osteosarcoma, which represents an increase in risk that is several thousandfold over that of the general population. Osteosarcoma in Paget patients is the underlying basis for a significant fraction of osteosarcomas occurring after age 60 years. Our analysis of tumor-specific loss of constitutional heterozygosity (LOH) in 96 sporadic osteosarcomas has identified a putative tumor-suppressor locus that maps to chromosome 18q. We have localized this tumor-suppressor locus between D18S60 and D18S42, a region tightly linked to familial Paget disease. Analysis of osteosarcomas from patients with Paget disease revealed that these tumors also undergo LOH in this region. These findings suggest that the association between Paget disease and osteosarcoma is the result of a single gene or two tightly linked genes on chromosome 18.
 ...
PMID:Evidence for a novel osteosarcoma tumor-suppressor gene in the chromosome 18 region genetically linked with Paget disease of bone. 971 49

Lymphocytes are implicated in the pathogenesis of bone disease in chronic inflammation, osteoporosis, transplantation and osteopetrosis. The effects of lymphocytes and lymphocyte-conditioned medium on bone-resorbing activity and osteoclast function have been well studied, but there are few studies of the effects of LCM on bone formation and osteoblast function. The effects of LCM on the function of the MG-63 human osteosarcoma cell line were studied, which, when stimulated with 1,25-(OH)2D3, demonstrates many of the properties of the mature human osteoblast. Lymphocytes contain oestrogen receptors and the model was also used to test the hypothesis that the effects of oestrogen on bone cells may be mediated indirectly via lymphokines. Lymphokines were measured by ELISA in human lymphocyte conditioned medium (LCM) collected following incubation of mixed lymphocytes with or without stimulation for 72 h. Unstimulated LCM increased proliferation of MG-63 cells and this increase was not affected by neutralization of interleukin 1 (IL-1), IL-3, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF), lymphotoxin alpha, or interferon gamma (IFN-gamma). Phytohaemagglutinin-stimulated LCM decreased proliferation of MG-63 cells, as well as induced expression of IL-6 mRNA, increased alkaline phosphatase production, and inhibited osteocalcin production. The decrease in proliferation was abolished by neutralization of IFN-gamma but was unaffected by neutralization of IL-1, IL-2, IL-3, IL-4, IL-6, GM-CSF, TNF, or lymphotoxin alpha. Neutralization of IFN-gamma in stimulated LCM also partially inhibited the increase in alkaline phosphatase production but had no effects on the decrease in osteocalcin production. Although oestrogen inhibited lymphocyte proliferation, the effects of LCM collected from lymphocytes in the presence of oestrogen on MG-63 cell proliferation and function was no different than the effects of LCM collected in the absence of oestrogen. LCM has multiple effects on MG-63 cell function and gene expression. Lymphocyte stimulation during the preparation of LCM further modulates these effects. Although partially mediated by IFN-gamma, the effects of LCM on these cells cannot be completely explained by individual component lymphokines. This may have implications for understanding the pathophysiology of bone loss in inflammatory disorders as well as possible feedback loops of locally generated cytokines in bone.
 ...
PMID:Effects of human lymphocyte-conditioned medium on MG-63 human osteosarcoma cell function. 972 33


<< Previous 1 2 3 4 5 6 Next >>