Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0029463 (osteosarcoma)
16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factors I (IGF-I) and II (IGF-II) are anabolic for osteoblastic cells. Although expression of IGF-I and IGF-II mRNA has been demonstrated in rodent osteoblastic cells, little is known about IGF gene expression in human osteoblastic cell models. In this study we characterized IGF-I and -II mRNA expression in (1) normal human osteoblast-like (hOB) cells, (2) a simian virus 40 immortalized hOB (HOBIT) cell line, and (3) human osteosarcoma cell lines SaOS-2, TE-85, MG-63, and U-2. Since cross-hybridization of IGF cDNA probes with ribosomal RNA obscures detection of some of the multiple IGF transcripts in human cells, we replaced Northern analysis with the more specific ribonuclease protection assay (RPA). We also used the reverse transcriptase-polymerase chain reaction (RT-PCR) to assess whether mRNAs were present at trace levels. IGF-I mRNA expression was consistently observed in normal hOB cells only and by both RT-PCR and RPA. Among IGF-I transcript variants, Ea IGF-I mRNA was more abundant than the Eb mRNA in normal hOB cells. Trace levels of IGF-I mRNA were variably detected in SaOS-2 and U-2 osteosarcoma cells when RT-PCR was performed, but we found no IGF-I mRNA in HOBIT, TE-85, or MG-63 cells. IGF-II mRNA was expressed in normal hOB, HOBIT, TE-85, and U-2 cells as assessed by either method.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Normal human osteoblast-like cells consistently express genes for insulin-like growth factors I and II but transformed human osteoblast cell lines do not. 763 14

The overexpression of P-glycoprotein (P-Gp), encoded by the human multidrug resistant gene (MDRA), decreases lipophilic drug accumulation in multidrug resistant cells in vitro. It is still not clear whether P-Gp contribute to the problem of multidrug resistance (MDR) in osteogenic sarcoma (OS). We examined the MDR1 expression of 20 OS specimens (11 primary tumors, 10 xenografts, 1 overlapping), by Northern blotting and by the reverse transcriptase-polymerase chain reaction (RT-PCR), and evaluated by the relationship between MDR1 expression and patient prognosis. RT-PCR revealed MDR1 expression in 9/20 OS; 5/11 primary tumors and 5/10 OS-xenografts; northern blotting revealed MDR1 expression in only 5/20 OS. One primary OS specimen and its corresponding xenograft had similar levels of MDR1 expression. All 20 patients with OS were treated with chemotherapeutic protocols including doxorubicin, cisplatin, methotrexate and ifosfamide. Eight of 9 OS-patients expressing MDR1 were resistant to chemotherapy and had a poor prognosis. The relationship between MDR1 expression and poor prognosis in the 20 OS-patients was significant (p < 0.01). The results support the assumption that MDR1 expression is related to MDR in human OS.
...
PMID:Expression of the human multidrug resistance gene (MDR1) and prognostic correlation in human osteogenic sarcoma. 766 Mar 82

Previous studies using cultures of fetal rodents calvaria have indicated an important role for insulin-like growth factor-I (IGF-I) in the local control of bone formation. In this study, we have examined the expression of IGF-I in adult human osteoblast-like (hOB) cells. To detect very low levels and to distinguish between the two IGF-I mRNA transcripts Ea and Eb, which are formed by alternate splicing, we have used the reverse transcriptase-polymerase chain reaction (RT-PCR). Expression of both Ea and Eb IGF-I mRNA transcripts were found in human liver and in placenta. However, neither Ea nor Eb IGF-I mRNA could be detected under basal conditions or after stimulation with growth hormone in normal hOB cells and two human osteosarcoma cell lines with osteoblastic properties, SaOS-2 and MG-63. We conclude that adult hOB cells do not synthesize IGF-I. Thus, in contrast to its crucial role as a local regulator of skeletal remodeling in fetal rodent bone, IGF-I does not appear to have this autocrine function in adult human bone.
...
PMID:Adult human osteoblast-like cells do not express insulin-like growth factor-I. 812 49

Human SAOS-2 osteogenic sarcoma cells are not metastatic in nude mice and do not express p53. We have selected a variant line (SAOS-LM2) that is tumorigenic and metastatic in nude mice. These cells were transfected with the p53 wild-type (p53wt) or mutated (p53mut 143A) gene, whose expression was verified by reverse transcriptase PCR, cDNA sequencing, and protein immunoprecipitation. Cells were injected i.v. into nude mice, and 4 months later, the mice were necropsied. All cell lines produced a similar number of visible lung metastases, albeit of different sizes. Microscopic examination revealed that most lung metastases in mice injected with p53wt cells (but not p53mut 143A or control cells) consisted of osteoid matrix and apoptotic cells. Expression of either p53wt or p53mut 143A verified the origin of the metastases. These data suggest that transfection of SAOS-LM2 cells with p53wt is associated with in vivo induction of terminal differentiation and apoptosis that inhibit progressive growth of metastases.
...
PMID:Terminal differentiation and apoptosis in experimental lung metastases of human osteogenic sarcoma cells by wild type p53. 820 33

Trk receptors have been identified by immunohistochemical methods in primitive neuroectodermal tumor (PNET)/Ewing's sarcoma (ES). However, the presence of different members of the Trk family of receptors in PNET/ES has not been specified. We have examined whether Trk A, B, and C receptors are specifically expressed in ES both with and without features of neural differentiation. Ten ES tumors (five primary tumors of bone and five extraosseous tumors transplanted into nude mice) were investigated for expression of Trk receptors by immunohistochemistry and reverse transcription-polymerase chain reaction. One primary ES and the five grafted ES tumors exhibited signs of neural differentiation; the remaining four primaries were undifferentiated ES. Other tumor types were analyzed as controls; they included three neuroblastomas (NB), two lymphomas, and single cases of pheochromocytoma (PHEO), schwannoma (SCHW), osteosarcoma, and carcinoma of breast, colon, and kidney. Trk receptors were detected in paraffin-embedded tumor tissue sections by means of a pan-Trk polyclonal antibody raised against the 14 carboxy-terminal residues of gp140trk, and trk A, B, and C transcripts were specifically detected by polymerase chain reaction-based amplification on cDNAs derived from tumor RNA with MuLV reverse transcriptase. Reactivity to the pan-Trk antibody was exhibited by six ES tumors, the three NBs, and the single PHEO and SCHW cases; immunoreactivity was restricted to differentiated tumors, in the case of ES. Tumor types positive for immunostaining were also distinguished by containing transcripts of TRK genes. However, the trk A, B, and C expression pattern of ES differed from that of NBs, PHEO, and SCHW. Transcripts of trk A, B, and C were detected in seven, four, and one case of ES, respectively, and in five, two, and five cases of NB, PHEO, and SCHW, respectively. Interestingly, all differentiated ES tumors contained trk A transcripts. Tumors of neuroectodermal phenotype and/or derivation were thus characterized by a distinct consensus expression pattern: trk A+/B-/C+ for differentiated ES and trk A+/B-/C+ for NB-PHEO-SCHW. These results indicate that the TRK gene family is frequently activated in ES; they also suggest that Trk A receptor is a feature of ES with neural differentiation, whereas Trk B and C receptors seem to be present in undifferentiated ES.
...
PMID:Activation of TRK genes in Ewing's sarcoma. Trk A receptor expression linked to neural differentiation. 902 32

Human osteosarcoma cells secrete a novel C-X-C chemokine called granulocyte chemotactic protein-2 (GCP-2), which was previously identified by amino acid sequencing of the purified natural protein. In order to understand the role of this new protein in inflammatory reactions, we cloned GCP-2 DNA sequences to generate recombinant protein and specific DNA probes and primers. By means of PCR on cloned cDNA of osteosarcoma cells induced by interleukin-1 beta and fibroblasts induced by lipopolysaccharide plus dsRNA, the complete coding domain of GCP-2 was isolated. This sequence was cloned into the bacterial expression vector pHEN1 and, after induction, GCP-2 was secreted into the periplasm of Escherichia coli. Recombinant GCP-2 (rGCP-2) was purified and characterized by SDS/PAGE as a monomeric 6.5-kDa protein and by amino-terminal sequencing. The chemoattractive potency of GCP-2 for neutrophilic granulocytes was about 10-times less than that of interleukin-8 and the minimal effective dose was 10 ng/ml. However, at optimal dose (100 ng/ml) the maximal chemotactic response was comparable with that of interleukin-8. Both characteristics correspond with those of natural GCP-2. In addition, intracellular calcium release in neutrophils by recombinant GCP-2 was achieved with as little as 10 ng/ml. Quantitation studies using reverse transcriptase and the polymerase chain reaction revealed higher GCP-2 mRNA production in normal fibroblasts than in tumor cells. When compared with epithelial-cell-derived neutrophil-activating peptide-78 (ENA-78) mRNA, the GCP-2 mRNA levels were higher in all cell lines tested. In addition, GCP-2 and ENA-78 expression seem to be differentially regulated in that phorbol ester and lipopolysaccharide have opposing effects on their mRNA induction in diploid fibroblasts and epithelial cells, respectively. Interleukin-1 was demonstrated to be a general inducer for both chemokines, while interferon-gamma down-regulates their mRNA expression. The availability of recombinant GCP-2 together with the quantitation studies on mRNA expression will help to further elucidate the biological role of GCP-2 during the inflammatory response.
...
PMID:Cloning, bacterial expression and biological characterization of recombinant human granulocyte chemotactic protein-2 and differential expression of granulocyte chemotactic protein-2 and epithelial cell-derived neutrophil activating peptide-78 mRNAs. 905 43

The human osteosarcoma 143.98.2 cell line was found to express high levels of prostaglandin synthase-2 (PGHS-2) without detectable levels of prostaglandin synthase-1 (PGHS-1) as measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblot analysis. Maximal levels of PGHS-2 induction were attained when the cells were grown beyond confluence. The osteosarcoma cells also secrete IL-1 alpha, IL-1 beta and TNF alpha in the culture medium. PGHS-2 expression was inducible by the exogenous addition of these cytokines as well as conditioned media from auto-induced cultures and inhibitable by treatment with dexamethasone. In contrast, undifferentiated U937 cells selectively express PGHS-1 as analyzed by RT-PCR and Western blotting. The effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the cellular PGE2 production mediated by each isoform of human PGHS were determined using osteosarcoma and undifferentiated U937 cells. When cells were preincubated with inhibitors to allow time-dependent inhibition prior to arachidonic acid stimulation, NS-398, CGP 28238, L-745,337, SC-58125 all behaved as potent (IC50 = 1-30 nM) and selective inhibitors of PGHS-2, in contrast to indomethacin, flurbiprofen or diclofenac which are potent inhibitors of enzymes. DuP-697 and sulindac sulfide were also potent inhibitors of PGHS-2 but both compounds inhibited cellular PGHS-1 activity at higher doses (IC50 = 0.2-0.4 microM). Time-dependent inhibition of PGE2 production in osteosarcoma cells was observed for indomethacin, diclofenac and etodolac. The synthesis of PGE2 by U937 cells was strongly dependent on exogenous arachidonic acid (100-fold stimulation) whereas confluent osteosarcoma cells also produced PGE2 without exogenous stimulus (7-fold stimulation by arachidonic acid). Osteosarcoma cells grown beyond confluence released more PGE2 from endogenous substrate than arachidonic acid stimulated undifferentiated U937 cells. These results indicate that osteosarcoma cells selectively express PGHS-2 with an autocrine regulation and effective utilization of endogenous arachidonic acid for PGE2 synthesis.
...
PMID:Characterization of autocrine inducible prostaglandin H synthase-2 (PGHS-2) in human osteosarcoma cells. 908 44

The 'deleted in colon carcinoma' (DCC) gene has been considered a candidate tumour-suppressor gene that encodes for a transmembrane protein with strong structural similarity to members of the superfamily of neural cell adhesion molecules. It has been mapped to the chromosomal region 18q21.1 and it is implicated in cellular differentiation and developmental processes. In human osteosarcoma allelic loss frequently occurs on the long arm of chromosome 18, suggesting a possible involvement of the DCC gene in the pathogenesis of this tumour entity. In the present study the mRNA and protein expression and rearrangements at the DNA level of the DCC gene were addressed in 25 osteosarcomas and several tumour cell lines, including osteosarcoma- and colon carcinoma-derived cell lines. Using an reverse transcriptase polymerase chain reach in (RT-PCR)-based approach DCC expression was found to be lost or substantially reduced in 14 of 19 high-grade osteosarcomas, in three of six lower grade osteosarcomas and most of the tumour cell lines, in contrast to normally differentiated osteoblasts. Immunohistochemical studies on DCC protein expression of 14 selected tumours correlated well with the RT-PCR-based results. In view of the putative tumour-suppressor characteristics of the DCC gene its loss or reduction of expression could be a specific event in the development or progression of many high-grade osteosarcomas.
...
PMID:Frequent reduction or loss of DCC gene expression in human osteosarcoma. 915 51

Inactivating mutations of the neutral endopeptidase, PEX, have been identified as the cause of X-linked hypophosphatemia (XLH). Though the function of PEX is unknown, current information suggests that impaired renal phosphate conservation in XLH is due to the failure of PEX to either degrade an undefined phosphaturic factor or activate a novel phosphate-conserving hormone. The physiologically relevant target tissue for the XLH mutation has not been identified. An apparent intrinsic defect of osteoblast function in XLH implicates bone as a possible site of PEX expression. In the current investigation, we employed a polymerase chain reaction (PCR) strategy to amplify a PEX cDNA from a human bone cell cDNA library. We found that the human PEX cDNA encodes a 749 amino acid protein belonging to the type II integral membrane zinc-dependent endopeptidase family. The predicted PEX amino acid sequence shares 96.0% identify to the recently cloned mouse Pex cDNA and has 27-38% identity to other members of the metalloendopeptidase family. Using reverse transcriptase (RT)-PCR with PEX-specific primers, we detected PEX transcripts in both human osteosarcoma-derived MG-63 osteoblasts and in differentiated mouse MC3T3-E1 clonal osteoblasts but not in immature MC3T3-E1 preosteoblasts. The association of impaired mineralization of bone in XLH and the apparent developmental stage-specific expression of PEX in osteoblasts suggest that bone is a physiologically relevant site of PEX expression and that PEX may play an active role in osteoblast-mediated mineralization.
...
PMID:Cloning and sequencing of human PEX from a bone cDNA library: evidence for its developmental stage-specific regulation in osteoblasts. 919 99

This study investigates the human oncoprotein MDM2, which interferes with regulation of cell division and apoptosis. Fifteen mixed-type follicular non-Hodgkin's lymphomas, ten leukaemias, two hepatocellular carcinomas, one osteosarcoma, and ten normal cell lines (fibroblasts, osteoblasts, mesothelium, peripheral lymphocytes) were tested for MDM2 expression and MDM2 gene mutation by reverse transcriptase-polymerase chain reaction (RT-PCR), immunocytochemistry, and nucleotide sequence analysis. Two follicular lymphomas, three leukaemias, both hepatocellular carcinomas, and the osteosarcoma sample showed transcription of the activated MDM2 gene. These samples lacked amplified MDM2 genes and carried mis-sense, non-sense and frame-shift mutations in a zinc finger region of MDM2, altering the amino acid sequence or causing premature termination of transcription. The mis-sense mutations were found in tumour cells that showed significant accumulation of MDM2 and lack of nuclear p53. Non-sense mutations and frame-shift mutations were found in tumours lacking MDM2 proteins. The mutations may affect the biological properties of MDM2 proteins.
...
PMID:Point mutations and nucleotide insertions in the MDM2 zinc finger structure of human tumours. 922 42


<< Previous 1 2 3 4 5 6 7 8 Next >>

---