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)

To observe the differentiation and gene expression of human osteosarcoma cell line MG-63 in culture. Alkaline phosphatase (ALP) activity was determined by p-nitrophenyl phosphate assay; bone Gla protein (BGP) was measured by radioimmunoassay; type I collagen, matrix metalloproteinase (MMP)-1, tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA were examined using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis; MG-63 cells were stained by the Van GieSon method. Type I collagen mRNA expression achieved a maximum level on the 17th day in MG-63 cells; MMP-1 mRNA was not expressed until the 5th day of culture, and gradually increased; TIMP-1 mRNA was nearly constant; ALP activity gradually up-regulated during 0-12 days, and decreased on the 18th day. By Van GieSon staining, MG-63 cells displayed nodule formation at the 12th day, and became more prominent on the 18th day. The results indicate that human osteosarcoma cell line MG-63 has the osteoblast phenotype; during the differentiation of MG-63 cells, there are the following three principle periods: proliferation, extracellular matrix maturation and mineralization.
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PMID:[Differentiation and gene expression of human osteosarcoma cell line MG-63]. 1253 36

Bone hybrids made of bioceramics seeded with mesenchymal or osteoblastic cells are very promising alternatives to autologous bone graft. Along this line, the development of in vitro models, dedicated to analyze the influence of these biomaterials on osteogenic cells, will help to improve the performance of these bone substitutes. In the present work we analyzed the effects of a macroporous biphasic calcium phosphate ceramic (BCP, Triosite) on three different human osteosarcoma cell lines and on human primary osteogenic cells and compared this culture substratum to traditional culture on plastic. We showed that all these osteoblastic cells adhere and proliferate on the trabecular BCP blocks, with a different spatial organization for osteosarcoma cells compared to normal osteogenic cells. We also demonstrated that osteoblastic marker genes such as Cbfa1, type I collagen, osteonectin, osteopontin, and osteocalcin were expressed at similar levels by these cells cultured on either substratum, suggesting that adhesion to BCP does maintain the osteoblastic phenotype of these cells. Next, we provided the first evidence of differences of cytokine expression profiles revealed on this Ca-P ceramic as compared to expression in classical culture. These modifications affected the expression of cytokines such as TGF-beta1, G-CSF, and IL-3 and were quantitatively different between osteosarcoma cells and normal osteogenic cells. Given the role of these cytokines in bone biology and in hematopoiesis, these results obtained in vitro suggest that the BCP ceramic studied here could stimulate osteogenesis in vivo by activating cellular processes during bone formation and healing. This study highlights the notion that the nature of the culture substratum must be taken into account when studying bone cell biology in vitro. Owing to the nature and spatial organization of the BCP, our hypothesis is that culture on BCP is closer to the physiological situation than culture on plastic.
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PMID:Modification of gene expression induced in human osteogenic and osteosarcoma cells by culture on a biphasic calcium phosphate bone substitute. 1281 Jan 67

A bioassay of acronycine for possible carcinogenicity was conducted by administering the test chemical by intraperitoneal injection to Sprague-Dawley rats and B6C3F1 mice. Initially, groups of 35 rats of each sex were administered acronycine at one of two doses, either 7.5 or 15 mg/kg body weight, in a vehicle composed of 0.05% polysorbate 80 in phosphate-buffered saline. Control groups of each sex consisted of 10 untreated rats (untreated controls) and 10 rats injected with the vehicle (vehicle controls). Because of high mortality rates in the dosed animals, new dosed groups of 35 rats of each sex were started later at a dose of 3.75 mg/kg. Additional groups of 10 untreated and 10 vehicle controls of each sex were also started. The rats were administered the acronycine or the vehicle for 51 or 52 weeks, then observed for an additional 28-30 weeks. All surviving rats were killed at 80-82 weeks. Initially, groups of 35 mice of each sex were administered acronycine at one of two doses, either 12.5 or 25 mg/kg body weight, in a vehicle composed of 0.05% polysorbate 80 in phosphate-buffered saline. Control groups of each sex consisted of 10 untreated mice (untreated controls) and 10 mice injected with the vehicle (vehicle controls). Because of high mortality rates in the dosed animals, two additional dosed groups were started later: 35 mice of each sex at 6 mg/kg and 40 mice of each sex at 2 mg/kg, together with 10 untreated controls and 10 vehicle controls of each sex for the groups dosed at 6 mg/kg, and 20 untreated controls and 20 vehicle controls for the groups dosed at 2 mg/kg. Periods of administration of the chemical to the mice varied from 25 weeks to 92 weeks, depending on toxicity or length of time of survival. Surviving control animals were killed at 78-105 weeks. Acronycine was toxic to rats and mice of each sex at the doses used in this bioassay, as shown by the high mortality rates in all but the low-dose groups and by the lower mean body weights in dosed rats and mice at all doses throughout most of the bioassay. Because of this high number of deaths, time-adjusted statistics are used for the analyses of all incidences of tumors. In male rats, the dose-related trend in the mid-and high-dose groups for the incidence of osteosarcoma at all sites was significant (P=0.002) using the respective vehicle-control group (vehicle controls 0/8, mid-dose 13/30, high-dose 12/18). Comparisons of the individual groups with respective control groups were also significant for the mid-dose (P=0.022) and high-dose (P=0.002) groups, but not for the low-dose group. In female rats, osteosarcoma was observed only in 1/8 high-dose animals. Sarcomas and other related tumors of the peritoneum were observed in all three dosed groups of both male and female rats, but in none of the control groups (males: low-dose 5/30, mid-dose 3/26, high-dose 7/16; females: low-dose 1/35, mid-dose 5/30, high-dose 13/28). In both sexes, the dose-related trends were significant (males, P=0.006; females, P=0.002), and the comparison of the incidences in the high-dose females with the vehicle-control group was significant (P=0.016). None of the incidences in the individual dosed groups of males were significant when compared with vehicle controls. However, since the tumors were observed in all dosed groups but did not occur in historical-control animals at this laboratory, they are considered to be related to the administration of the chemical. In female rats, the incidence of all tumors of epithelial origin of the mammary gland was significant only at the low dose (low-dose vehicle controls 1/10, low-dose 22/35, P=0.004). Adenocarcinomas of the mammary gland were observed in seven low-dose, five mid-dose, and two high-dose female rats, but in no cs, but in no control females. The reverse dose relationship of both benign and malignant tumors was probably due to the higher number of early deaths which occurred in the high-dose group. In mice, the low survival in all dosed groups except the low-dose animals precluded an evaluation of the significance of the incidences of tumors. Lymphomas occurred in low-dose groups of both males and females; however, the incidence of lymphoma in different control groups was highly variable. The high incidence in the low-dose vehicle controls may have been due to a procedural problem associated with the possibility of transfer of tumor cells or oncogenic viruses during the intraperitoneal injection of the test chemical. It is concluded that under the conditions of this bioassay, the low survival of the dosed and control mice and the possible procedural problems associated with the intraperitoneal injection of the chemical did not allow a determination to be made of the carcinogenicity of acronycine in this species. In Sprague-Dawley rats, acronycine in the vehicle of 0.05% polysorbate 80 in phosphate-buffered saline was carcinogenic, producing tumors of the mammary gland in females, osteosarcomas in males, and sarcomas and other related tumors of the peritoneum in both males and females.
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PMID:Bioassay of acronycine for possible carcinogenicity. 1284 58

Blood pH is maintained in a narrow range around pH 7.4 mainly through regulation of respiration and renal acid extrusion. The molecular mechanisms involved in pH homeostasis are not completely understood. Here we show that ovarian cancer G-protein-coupled receptor 1 (OGR1), previously described as a receptor for sphingosylphosphorylcholine, acts as a proton-sensing receptor stimulating inositol phosphate formation. The receptor is inactive at pH 7.8, and fully activated at pH 6.8-site-directed mutagenesis shows that histidines at the extracellular surface are involved in pH sensing. We find that GPR4, a close relative of OGR1, also responds to pH changes, but elicits cyclic AMP formation. It is known that the skeleton participates in pH homeostasis as a buffering organ, and that osteoblasts respond to pH changes in the physiological range, but the pH-sensing mechanism operating in these cells was hitherto not known. We detect expression of OGR1 in osteosarcoma cells and primary human osteoblast precursors, and show that these cells exhibit strong pH-dependent inositol phosphate formation. Immunohistochemistry on rat tissue sections confirms the presence of OGR1 in osteoblasts and osteocytes. We propose that OGR1 and GPR4 are proton-sensing receptors involved in pH homeostasis.
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PMID:Proton-sensing G-protein-coupled receptors. 1295 48

Oncogenic osteomalacia (OO) is a rare paraneoplastic syndrome of osteomalacia due to phosphate wasting. The phosphaturic mesenchymal tumor (mixed connective tissue variant) (PMTMCT) is an extremely rare, distinctive tumor that is frequently associated with OO. Despite its association with OO, many PMTMCTs go unrecognized because they are erroneously diagnosed as other mesenchymal tumors. Expression of fibroblast growth factor-23 (FGF-23), a recently described protein putatively implicated in renal tubular phosphate loss, has been shown in a small number of mesenchymal tumors with known OO. The clinicopathological features of 32 mesenchymal tumors either with known OO (29) or with features suggestive of PMTMCT (3) were studied. Immunohistochemistry for cytokeratin, S-100, actin, desmin, CD34, and FGF-23 was performed. The patients (13 male, 19 female) ranged from 9 to 80 years in age (median 53 years). A long history of OO was common. The cases had been originally diagnosed as PMTMCT (15), hemangiopericytoma (HPC) (3), osteosarcoma (3), giant cell tumor (2), and other (9). The tumors occurred in a variety of soft tissue (21) and bone sites (11) and ranged from 1.7 to 14 cm. Twenty-four cases were classic PMTMCT with low cellularity, myxoid change, bland spindled cells, distinctive "grungy" calcified matrix, fat, HPC-like vessels, microcysts, hemorrhage, osteoclasts, and an incomplete rim of membranous ossification. Four of these benign-appearing PMTMCTs contained osteoid-like matrix. Three other PMTMCTs were hypercellular and cytologically atypical and were considered malignant. The 3 cases without known OO were histologically identical to the typical PMTMCT. Four cases did not resemble PMTMCT: 2 sinonasal HPC, 1 conventional HPC, and 1 sclerosing osteosarcoma. Three cases expressed actin; all other markers were negative. Expression of FGF-23 was seen in 17 of 21 cases by immunohistochemistry and in 2 of 2 cases by RT-PCR. Follow-up (25 cases, 6-348 months) indicated the following: 21 alive with no evidence of disease and with normal serum chemistry, 4 alive with disease (1 malignant PMTMCT with lung metastases). We conclude that most cases of mesenchymal tumor-associated OO, both in the present series and in the reported literature, are due to PMTMCT. Improved recognition of their histologic spectrum, including the presence of bone or osteoid-like matrix in otherwise typical cases and the existence of malignant forms, should allow distinction from other mesenchymal tumors. Recognition of PMTMCT is critical, as complete resection cures intractable OO. Immunohistochemistry and RT-PCR for FGF-23 confirm the role of this protein in PMTMCT-associated OO.
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PMID:Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature. 2021 75

Alkaline phosphatases (ALPs) are a family of cell surface glycoproteins that catalyze the hydrolysis of phosphomonoesters with release of inorganic phosphate. Liver/bone/kidney (L/B/K) ALP participates in bone mineralization, but its other physiological and pathological functions remain obscure. In human osteosarcoma, an inverse relationship has been found between cellular L/B/K ALP expression and aggressiveness. To explore this relationship, we employed cDNA microarray technology to characterize and compare the gene expression profile of two U-2 OS osteosarcoma clones with high L/B/K ALP activity (U-2/ALP28 and U-2/ALP40) and one with contrasting characteristics (U-2/ALP23). We identified 79 differentially expressed genes (58 upregulated in U-2/ALP28 and U-2/ALP40 compared to U-2/ALP23). Using GenMAPP/MAPPFinder, we highlighted nine functional groups strictly related to high L/B/K ALP activity, including microtubule-based movement and cell adhesion groups, two functions well related to tumor invasiveness. Notably, cadherin 13 (CDH13) and caveolin 1 (CAV1) genes were upregulated in our cells. Since these two genes are involved in cell-cell adhesion and cell growth, their co-expression with L/B/K ALP could help explain the lower levels of malignancy found in osteosarcoma cells with high L/B/K ALP activity. Although functional studies are needed to better define the role of CDH13 and CAV1 in the malignant behavior of osteosarcoma cells, the data presented here provide an aid to understanding the biological functions of L/B/K ALP in bone tumors.
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PMID:Identification of candidate genes involved in the reversal of malignant phenotype of osteosarcoma cells transfected with the liver/bone/kidney alkaline phosphatase gene. 1505 Aug 98

A new system for the local delivery of chemotherapy to malignant solid tumors has been developed based on calcium phosphate (CaP) nanoparticles. The adsorption of the anti-neoplastic drug cis-diamminedichloroplatinum (cisplatin) was characterized on three types of apatitic CaP (poorly and well crystallized hydroxyapatite, and carbonated apatite). Adsorption isotherms obtained in chloride-free phosphate solutions at pH = 7.4 (24 and 37 degrees C) indicate that cisplatin adsorption increases with temperature and increases with decreasing crystallinity. Release studies in phosphate buffer saline (containing the chloride ion essential for release) showed that while the cumulative amount of released drug was the same for all apatites at 20 days (approximately 70% of the total bound), the least crystalline material released the drug more slowly. The drug release rate increased slightly with temperature. Cytotoxicity testing was conducted in a K8 clonal murine osteosarcoma cell line to verify that drug activity was retained after adsorption onto the apatite crystals. K8 cells were plated onto dried films of the apatite/cisplatin conjugates and after 24 h, viability was measured with tritiated uridine. The apatite/cisplatin formulations exhibited cytotoxic effects with a dose dependent diminishment of cell viability.
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PMID:Interactions of cisplatin with calcium phosphate nanoparticles: in vitro controlled adsorption and release. 1518 24

Aspiration of lytic bone lesions is an excellent diagnostic test in the initial evaluation of primary bone neoplasia. However, cytologically, it can be difficult to differentiate osteosarcoma (OSA) from other bone neoplasms, including fibrosarcoma, chondrosarcoma, synovial cell sarcoma, and plasma cell myeloma. The purpose of this study is to determine the sensitivity and specificity of alkaline phosphatase (ALP) staining to differentiate OSA from other tumors that express vimentin by immunocytochemistry or immunohistochemistry. ALP is a hydrolytic enzyme present in multiple tissues including liver, kidney, intestine, placenta, and bone. Hypothetically, neoplasms actively producing bone should be specifically positive for ALP staining. Unstained, cytologic specimens were incubated for 8-10 minutes with nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolyl phosphate toluidine salt-phosphatase substrate. A positive reaction stains the membrane of the cells gray to black. Samples were counterstained with a Romanowsky's stain to determine whether the sample was of representative cellularity. A total of 61 vimentin-positive neoplasms have been evaluated and confirmed histopathologically. Tumors that expressed vimentin and were positive for ALP included 33 OSAs, one multi-lobular tumor of bone, one amelanotic melanoma, and one chondrosarcoma. Tumors that expressed vimentin and were negative for ALP included chondrosarcomas (three of four), multiple fibrosarcomas, and multiple synovial cell sarcomas. The sensitivity is 100%, and the specificity is 89%. In conclusion, ALP appears to be a highly sensitive and fairly specific marker in the diagnosis of OSA.
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PMID:Use of alkaline phosphatase staining to differentiate canine osteosarcoma from other vimentin-positive tumors. 1575 69

An ideal gene carrier requires both safety and transfection efficiency. Polyethylenimine (PEI) is a well-known cationic polymer, which has high transfection efficiency owing to its buffering capacity. But it has been reported that PEI is cytotoxic in many cell lines and non-degradable. In this study, we synthesized degradable PEI-alt-poly(ethylene glycol) (PEG) copolymers using Michael-type addition reactions as a new gene carrier and characterized them. These copolymers were complexed with plasmid DNA and the resulting complexes were characterized by dynamic light scattering, gel retardation and atomic force microscopy to determine particle sizes, complex formation and complex shape, respectively. Cytotoxicity and transfection efficiency of the copolymers were also checked in cultured HeLa human cervix epithelial carcinoma cells, HepG2 human hepatoblastoma cell line and MG63 human osteosarcoma cells. PEG to PEI ratio in the copolymers was near 1 and the molecular weight of the copolymer ranged from around 8000 to 12,900. These copolymers degraded rapidly at 37 degrees C in 0.1 M phosphate buffered saline (PBS, pH 7.4). The complete copolymer/DNA complex was formed at an N/P ratio of 12, producing a complex resistant to DNase I. Particle sizes decreased with increasing N/P ratio and PEG molecular weight, exhibiting a minimum value of 75 nm at an N/P ratio of 45 with PEI-alt-PEG (700). Cytotoxicity study showed that copolymers exhibited no cytotoxic effects on cells even at high copolymer concentration. Also, transfection efficiency was influenced by PEG molecular weight and, in case of PEI-alt-PEG (258), the transfection efficiency was higher than that for PEI 25 K in HepG2 and MG63, whereas it was lower than that for PEI 25K in HeLa cells.
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PMID:Degradable polyethylenimine-alt-poly(ethylene glycol) copolymers as novel gene carriers. 1593 8

We investigated the renal function of pediatric and adult patients who had been submitted to chemotherapy with high-dose methotrexate (MTX), cisplatin and high-dose ifosfamide (IFO). We observed 43 osteosarcoma patients aged 4--34 years (median 16 years). The median received cumulative doses of MTX, cisplatin and IFO were 60.1 g/m, 598 mg/m and 73.5 g/m. Renal function was assessed by measurement of creatinine clearance, renal threshold for phosphate (Tmp/GFR), urinary alpha1-microglobulin (A1M):creatinine ratio, urinary albumin:creatinine ratio, 24-h glycosuria and proteinuria. The median interval between chemotherapy completion and first renal function assessment was 2 months (range 2--4 months); assessments were then performed at a median interval of 16 months (range 9--49 months). A significant decrease of TmP/GFR was observed only in the pediatric group (under 18 years): the percentage of patients with TmP/GFR<1 mmol/l increased from 21% (six of 28) at the end of treatment to 46% (13 of 28) at the late assessment. Glycosuria in 10 (67%) of 15 adults and 21 (75%) of pediatric patients was detected with an increased incidence compared to the early post-chemotherapy assessment (13% adults and 29% children). A significant increase of the albumin:creatinine ratio and A1M:creatinine ratio was observed only in adults. Overall, 21 patients had a reduced glomerular function at the latest evaluation, associated with glycosuria in 15 patients (71%), proteinuria in 14 (67%) and TmP/GFR<1 mmol/l in 11 (52%). We conclude that strict monitoring of renal function should be recommended in pediatric and adult patients after chemotherapy with high-dose MTX, cisplatin and high-dose IFO.
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PMID:Prospective evaluation of renal function in pediatric and adult patients treated with high-dose ifosfamide, cisplatin and high-dose methotrexate. 1602 21


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