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)

Clonal osteoblast-like cells derived from a rat osteogenic sarcoma (UMR 106-06) were shown to possess specific, high-affinity binding sites for insulin, with a receptor density of 22,000/cell. The hormone, at physiologic concentrations (1-10 ng/ml), was found to stimulate active K+ transport into these cells, the effect being mediated via the Na+-K+ pump. Alterations in insulin-receptor status by treatment of cells with glucocorticoids or exposure to subphysiologic pH was reflected in parallel changes in the sensitivity of the K+-uptake process to the hormone. We conclude that insulin can directly affect the metabolism of bone cells and that the hormone's action on transmembrane ion transport may be linked to interaction with its cell surface receptors.
Diabetes 1988 Jan
PMID:Insulin stimulation of Na+-K+ pump in clonal rat osteosarcoma cells. 244 38

The normal range of glucose-phosphate-isomerase (GPI) in the plasma of children during the first month of life is up to 80 U/l; until the end of the second year of life between 11 and 50 U/l; thereafter the upper limit is 46 U/l. In osteogenic sarcoma or medulloblastoma there is a good correlation between activity of GPI in plasma and clinical tumor stage. In a lot of other tumors sensitivity of this enzyme is either very low as in Ewing-sarcoma or myeloic leukemia or there is no consistent relation to the extent of the tumor. High activities of GPI are equally obtained in children suffering from cystic fibrosis, diabetes mellitus or muscular dystrophy. GPI is not valid as a tumor marker even being raised in sarcoma and medulloblastoma as mentioned. So it is not necessary to check GPI activity as a part of routine enzyme chemistry.
 ...
PMID:[Behavior of glucosephosphate isomerase in children with malignant diseases]. 346 43

Osteoporosis is a known complication of diabetes mellitus, suggesting a role for insulin in bone homeostasis. We studied insulin receptors and insulin action in the osteoblast-like rat osteogenic sarcoma cell line ROS 17/2.8. These cells share many common features with the osteoblast, such as 1,25-dihydroxyvitamin D3 receptors, PTH receptors, and 1,25-dihydroxyvitamin D3-induced modulation of alkaline phosphatase activity and osteocalcin. Competition binding studies revealed high affinity insulin receptors, with an ED50 for insulin of 1 nM. The receptors were highly specific for insulin, with 60% inhibition of insulin binding by an antireceptor antibody, no competition by epidermal growth factor, and an ED50 of 300 nM for proinsulin. Steady state maximal insulin binding was obtained by 40 min at 37 C, and insulin degradation, as measured by trichloroacetic acid solubility, was 1%/h at 37 C. ROS cells readily internalized insulin, and under steady state binding conditions at 37 C, 56% of the cell-associated radioactivity consisted of intracellular material. Chloroquine (100 microM) inhibited intracellular processing of insulin, leading to a 300% increase in cell-associated insulin by 2 h (37 C). Photoaffinity labeling of the insulin receptor with the photosensitive analog of insulin, B2 (2-nitro-4-azidophenyl-acetyl)des-pheB1-insulin, followed by solubilization and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, revealed specific bands of 125K and 430K mol wt under reducing and nonreducing conditions, respectively. Thus, the structure of insulin receptors in ROS cells appears comparable to that of insulin receptors of known target tissues. Insulin action was also examined. Insulin did not stimulate [2-3H]deoxyglucose uptake or [1-14C]leucine incorporation into protein. In contrast, physiological concentrations of insulin inhibited alkaline phosphatase activity in nonconfluent cells. After exposure to insulin for 24 h, alkaline phosphatase activity was decreased compared to basal by 39.5% and 50% with 5 and 50 ng/ml insulin, respectively. In conclusion, ROS cells bind insulin to specific receptors that are similar to insulin receptors on other target tissues; receptors internalize insulin, which is then processed through a chloroquine-sensitive pathway; insulin does not affect membrane substrate transport; and insulin does inhibit the activity of an enzyme that is important in bone metabolism. ROS cells represent a model for studying insulin effects on bone.
 ...
PMID:Demonstration of insulin receptors and modulation of alkaline phosphatase activity by insulin in rat osteoblastic cells. 353 Jul 24

Impaired bone formation due to defective osteoblast function, as reflected in a decreased serum osteocalcin (OC) concentration in the patients with diabetes, has been implicated in the development of diabetic osteopenia. The role of hyperglycemia in this decrease in serum OC concentration was investigated. 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), an active form of vitamin D3, stimulated OC secretion from the human osteosarcoma cell line MG-63 in a dose-dependent manner. Exposure of the cells to high concentrations of glucose for 7 days significantly impaired 1,25(OH)2D3-induced OC secretion as compared with that observed with cells maintained under normal glucose (5.5 mM) or high mannitol conditions. The inhibitory effect of glucose was in a dose-dependent manner up to 55 mM. High glucose (55 mM) also attenuated the 1,25(OH)2D3-induced increase in OC mRNA abundance in MG-63 cells, suggesting that the inhibition of the 1,25(OH)2D3-induced increase in OC secretion by exposure to a high concentration of glucose was, at least in part, mediated at the transcriptional level. High glucose significantly decreased the number of 1,25(OH)2D3 receptors in MG-63 cells, without any change in the dissociation constant for 1,25(OH)2D3; this effect was not mimicked by high mannitol, indicating specificity for glucose. These observations suggest that a high glucose concentration significantly impairs the ability of osteoblastic cells to synthesize OC in response to 1,25(OH)2D3 by reducing 1,25(OH)2D3 receptor number, and that impaired cell function caused by sustained exposure to high glucose contributes to the defect in bone formation observed in the patients with diabetic osteopenia.
 ...
PMID:Influence of high glucose on 1,25-dihydroxyvitamin D3-induced effect on human osteoblast-like MG-63 cells. 748 80

It is known that osteopenia is frequently associated with diabetes mellitus. Although its mechanism is not well understood, impaired bone formation due to an osteoblast deficit seems to be a major factor as reflected by a fall in serum levels of osteocalcin and by the findings of low bone formation with bone histomorphometry. In the present study, we studied the effect of high glucose conditions on osteoblast by examining the responsiveness of human osteosarcoma (MG-63) cells to human parathyroid hormone 1-34 [hPTH-(1-34)]. MG-63 cells were cultured either with 5.5 mM glucose (normal glucose), 55.0 mM glucose (high glucose) or 5.5 mM glucose plus 49.5 mM mannitol (high mannitol) condition for 7 days. Both an increase in cAMP levels and an immediate increase in [Ca2+]i, induced by hPTH(1-34), were significantly lower in high glucose-treated cells than in those treated with normal glucose or high mannitol. Basal cAMP levels in the cells after a 7-day culture in high glucose conditions were significantly higher than in those in the other two groups. We concluded that high glucose specifically impaired the response to hPTH(1-34). This impairment seemed to arise from an increase in intracellular cAMP levels, which is reported to induce downregulation of PTH receptors.
 ...
PMID:Impaired response of human osteosarcoma (MG-63) cells to human parathyroid hormone induced by sustained exposure to high glucose. 756 50

Insulin-dependent diabetes (IDDM) results from autoimmune destruction of pancreatic beta cells mediated predominantly by cellular effector mechanisms. To date, investigators have studied a limited number of islet cell proteins stimulatory to T cells. However, before development of clinical IDDM, the majority of the beta cells are impaired or destroyed. Thus, numerous proteins from lysed beta cells would be accessible to the immune system of the patient. Our goal was to investigate the PBMC reactivity of IDDM patients to the full spectrum of fractionated human pancreatic islet cell proteins to determine whether numerous islet cell proteins or a select few would be recognized. We observed that PBMCs from IDDM patients responded reproducibly (mean stimulation index, >2.0) to the proteins in all m.w. regions, whereas the mean stimulation index for controls from all m.w. regions was <2.0. Using three different islet protein preparations, PBMC responses of IDDM patients (n = 30) and controls (n = 39) to the islet cell proteins were significantly different. Dose responses were also demonstrated for the lymphocyte reactivity of the IDDM patients (n = 29) vs controls (n = 56) to the islet cell preparations. Proteins, presumably irrelevant to the IDDM disease process, from a human osteosarcoma cell line and normal human spleen cells did not stimulate PBMCs from IDDM patients or controls. Moreover, IDDM patients and controls responded similarly to mitogens and tetanus toxoid. These studies show that at the time of diagnosis of IDDM, PBMCs from IDDM patients are stimulated by a wide array of islet cell proteins.
 ...
PMID:Peripheral blood mononuclear cells of insulin-dependent diabetic patients respond to multiple islet cell proteins. 895 20

We describe a premature aging disorder in a 15-year-old girl with severe growth and developmental deficiency. Her clinical findings included osteosarcoma, nuclear and subcapsular cataracts, insulin-resistant diabetes mellitus, osteoporosis, epilepsy, foot ulcers, erythroid macrocytosis, and unusual facial appearance. Hyaluronic acid levels in serum and urine were normal. Cultured skin fibroblasts had a normal potential for in vitro growth. This finding represents a new and unique premature aging syndrome.
 ...
PMID:Premature aging syndrome with osteosarcoma, cataracts, diabetes mellitus, osteoporosis, erythroid macrocytosis, severe growth and developmental deficiency. 905 55

We described a case of Werner's syndrome associated with osteosarcoma. A 37-year-old Japanese man was diagnosed as having Werner's syndrome by the presence of juvenile cataracts, skin sclerosis and hyperpigmentation of the feet, high-pitched voice, characteristic bird-like appearance of the face with beak-shaped nose, thinning of the entire skin and hyperkeratoses on soles, hyperlipemia, hyperuricemia, diabetes melitus, and the mutated responsible gene (WRN). He had a 3-month history of a tumor on his left forearm. Histologically, the tumor included four histological patterns; a malignant fibrous histiocytoma-like, a desmoid-like, a dermatofibrosarcoma protuberans-like, and a chondrosarcoma-like pattern. Tumoral osteoid formation was also found in the tumor. Therefore, the tumor was diagnosed as osteosarcoma.
 ...
PMID:A case of Werner's syndrome associated with osteosarcoma. 1055 36

In recent years, analogs of human insulin have been engineered with the aim of improving therapy for people with diabetes. To ensure that the safety profile of the human hormone is not compromised by the molecular modifications, the toxico-pharmacological properties of insulin analogs should be carefully monitored. In this study, we compared the insulin and IGF-I receptor binding properties and metabolic and mitogenic potencies of insulin aspart (B28Asp human insulin), insulin lispro (B28Lys,B29Pro human insulin), insulin glargine (A21Gly,B31Arg,B32Arg human insulin), insulin detemir (NN304) [B29Lys(epsilon-tetradecanoyl), desB30 human insulin], and reference insulin analogs. Receptor affinities were measured using purified human receptors, insulin receptor dissociation rates were determined using Chinese hamster ovary cells overexpressing the human insulin receptor, metabolic potencies were evaluated using primary mouse adipocytes, and mitogenic potencies were determined in human osteosarcoma cells. Metabolic potencies correlated well with insulin receptor affinities. Mitogenic potencies in general correlated better with IGF-I receptor affinities than with insulin receptor off-rates. The 2 rapid-acting insulin analogs aspart and lispro resembled human insulin on all parameters, except for a slightly elevated IGF-I receptor affinity of lispro. In contrast, the 2 long-acting insulin analogs, glargine and detemir, differed significantly from human insulin. The combination of the B31B32diArg and A21Gly substitutions provided insulin glargine with a 6- to 8-fold increased IGF-I receptor affinity and mitogenic potency compared with human insulin. The attachment of a fatty acid chain to LysB29 provided insulin detemir with reduced receptor affinities and metabolic and mitogenic potencies but did not change the balance between mitogenic and metabolic potencies. The safety implications of the increased growth-stimulating potential of insulin glargine are unclear. The reduced in vitro potency of insulin detemir might explain why this analog is not as effective on a molar basis as human insulin in humans.
Diabetes 2000 Jun
PMID:Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. 1086 53

Although numerous clinical studies have demonstrated the beneficial effect of preventing postmenopausal bone loss in elder women by long-term estrogen administration, effects of estrogen at the cellular level still remain unclear. Efforts to determine the precise role of bone cells in estrogen-mediated pathways are often hampered by the lack of suitable cell culture models. Presuming that sex steroids have a direct, stimulating effect on bone cells in vitro, we investigated the influence of 17beta-estradiol, testosterone and 1,25(OH)2D, on cell proliferation and differentiation using four established human osteosarcoma (HOS) cell lines of different gender of the donors (male origin: MG 63, HOS 58; female origin: SaOS 2, TE 85). These cell lines are believed to represent different stages of osteogenic maturation. Thus, the aim of this study was to clarify if possible responses to sex steroids are related to gender or osteogenic commitment of the individual cell culture. HOS cells were cultured in six-well plates and underwent hormone treatment (1 nM and 10 nM 17beta-estradiol. 0.1 nM and I nM testosterone and 1 microM 1,25(OH)2D3) for 48 h hours. Cell proliferation was determined by measuring total cell numbers. Cell function was studied by measuring alkaline phosphatase activity and secreted osteocalcin. In this study, estrogen significantly increased proliferation of both one male (MG 63) and one female (SaOS 2) cell line, but decreased proliferation of the female HOS TE 85 cell line significantly. Testosterone treatment had a positive effect on proliferation of only one female cell line (SaOS 2). A significant increase of alkaline phosphatase activity in SaOS 2 and HOS 58 cells and of osteocalcin levels in SaOS 2 cells was detected following estrogen treatment. Administration of 1.25(OH)2D3 was followed by an increased cell proliferation in HOS 58, MG 63 and SaOS 2. Significant gender-related differences could not be demonstrated. In conclusion, response to hormonal treatment with sex steroids is not related to the gender of the osteosarcoma cell line, but rather depends on its osteoblastic commitment.
Exp Clin Endocrinol Diabetes 2000
PMID:Sex steroids and bone metabolism: comparison of in vitro effects of 17beta-estradiol and testosterone on human osteosarcoma cell lines of various gender and differentiation. 1102 55


1 2 3 4 Next >>