Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00369 (ROS)
 19,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A highly sensitive bioassay for PTH was developed by using rat osteosarcoma cells (ROS 17/2.8). By limiting dilution, ROS cells were subcloned and the subclonal cell line (ROS 17/2.8-5) most responsive to PTH was selected. When subconfluent ROS 17/2.8-5 cells were treated with hydrocortisone for 3 days and then incubated with PTH, the cAMP response was significant at 10-40 ng/l hPTH (1-34) (4 approximately 16 X 10(-12) mol/l). Osteoclast activating factors such as human interleukin 1 alpha and beta, and tumour necrosis factor alpha did not stimulate cAMP production, whereas a conditioned medium of oesophageal carcinoma cells established from a patient with humoral hypercalcaemia stimulated cAMP production. By selecting PTH-responsive subclonal cells and treating them with hydrocortisone, the sensitivity for detecting PTH was improved approximately 15 times. This method will be useful in the characterization and purification of PTH-like factors produced by malignant tumours from hypercalcaemic patients.
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PMID:A highly sensitive bioassay for PTH using ROS 17/2.8 subclonal cells. 282 16

A new cell line, designated EC-GI, was established from a 65-year-old patient with esophageal carcinoma who developed humoral hypercalcemia. The original tumor as well as the cell line caused marked hypercalcemia in tumor-bearing nude mice, in which a marked increase in osteoclastic bone resorption was demonstrated. The conditioned medium of EC-GI cells contained potent bone resorbing activity which stimulated cyclic AMP production in parathyroid hormone (PTH)-responsive osteoblast-like cells (ROS 17/2.8). EC-GI cells will be useful for characterization and purification of the PTH-like factor responsible for humoral hypercalcemia of malignancy.
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PMID:Establishment of a parathyroid hormone-like factor-producing esophageal carcinoma cell line (EC-GI). 282 16

The mechanism of the calcium and phosphorus abnormalities associated with metastatic prostate carcinoma (CaP) is not yet understood. A tumor model was recently established in which 9479, a human CaP from a patient with prostate carcinoma-induced osteomalacia, was heterotransplanted into athymic nude mice (ANM). In the present study the effect of 9479 on ANM was evaluated. Serum calcium (Ca), phosphorus (P), parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3(1,25-(OH)2D3) and urinary cAMP were measured. Ca was markedly elevated in ANM bearing 9479 vs. age-matched controls (C); the increased Ca returned to control level after tumor removal. Serum PTH was lower in 9479-bearing ANM vs. C while urinary cAMP and serum 1,25-(OH)2D3 levels were elevated. In the ANM bearing 9479, there was a decrease in serum P vs. C which returned to normal after tumor removal. Fractional P excretion was greater in 9479 animals than C. Extracts of 9479 were examined for the presence of parathyroid hormone-like bioactivity by measuring stimulation of intracellular cAMP in ROS 17/2.8 cells. Cyclic AMP stimulation which was found was shown to be inhibited by the competitive PTH antagonist [8Nle, 18Nle, 34Tyr]bPTH-(3-34) amide. These data suggest tumor induction of parathyroid hormone-like humoral modulation of calcium, phosphate and vitamin D metabolism in vivo associated with a parathyroid hormone-like prostate carcinoma product.
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PMID:Human prostate carcinoma causes hypercalcemia in athymic nude mice and produces a factor with parathyroid hormone-like bioactivity. 300 5

The culture media of three cell lines, a human prostate carcinoma (PC3), a rat Leydig cell tumor (Rice-500), and a rat carcinosarcoma (WRC-256), that were derived from tumors associated with humoral hypercalcemia of malignancy (HHM), were examined for stimulation of adenylate cyclase in ROS 17/2.8 osteoblastic cells and for bone resorptive activity in culture. Cells from a nonhypercalcemic variant of the WRC256 tumor served as control. Extracts from three solid human tumors, a lung adenocarcinoma from a patient with HHM and two adenocarcinoma from normocalcemic patients (lung and colon), were also examined for adenylate cyclase stimulation. We found excellent correlation between stimulation of cyclic AMP accumulation in ROS 17/2.8 cells and bone resorbing activity in culture, or production of HHM in vivo. Stimulation of adenylate cyclase by HHM factors was inhibited by the parathyroid hormone competitive inhibitor, [8norleucyl, 18norleucyl, 34tyrosinyl] bovine parathyroid hormone (3-34) amide.
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PMID:Factors associated with humoral hypercalcemia of malignancy stimulate adenylate cyclase in osteoblastic cells. 668 37

The association of DNA binding proteins with the nuclear matrix may be related to a functional role of this subcellular structure in chromatin organization and gene regulation. In this study, nuclear matrix preparations from human HeLa S3 cervical carcinoma and rat ROS 17/2.8 osteosarcoma cells were assayed for the presence of DNA binding activities using consensus binding sequences of well-characterized transcription factors as probes. Competition analysis shows that each probe interacts with different nuclear matrix proteins in a sequence-specific manner and that DNA binding activities related to or identical with SP-1, ATF, CCAAT, C/EBP, OCT-1, and AP-1 are present in the nuclear matrix fraction of different cell types. Comparison of the relative abundance of these transcription factor binding activities in nuclear matrix and nonmatrix nuclear fractions suggests that the distribution between these two fractions is cell type specific, cell growth dependent, or independent of these biological parameters. These results are consistent with the postulated role of the nuclear matrix in transcriptional regulation of gene expression.
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PMID:Nuclear matrix association of multiple sequence-specific DNA binding activities related to SP-1, ATF, CCAAT, C/EBP, OCT-1, and AP-1. 835 91

Osteocalcin (OC), a noncollagenous bone matrix protein, is expressed in high levels by osteoblasts. To determine whether the OC promoter mediates cell-specific gene expression in cells of osteoblast lineage, we constructed a recombinant adenovirus, Ad-OC-TK, which contains the OC promoter that drives the expression of herpes simplex virus thymidine kinase (TK). We tested the expression of TK by this virus in osteoblast cell lines as well as in non-osteoblastic cell lines by assessing the enzyme activity of TK in vitro. Whereas the OC promoter failed to drive the expression of the TK gene in several non-osteoblastic cell lines such as WH, a human bladder transitional carcinoma, and NIH 3T3, an embryonic mouse fibroblast cell line, the OC promoter mediated high levels of expression in osteoblast cell lines including murine ROS and human MG-63 cells. The addition of acyclovir (ACV), a pro-drug for the inhibition of cell proliferation, resulted in the induction of osteoblast-specific cell death in vitro. Intratumoral injection of Ad-OC-TK into murine ROS osteosarcoma abolished tumor growth in a host treated with subsequent i.p. ACV injection in vivo. The Ad-OC-TK virus plus ACV treatment appears to be highly selective in blocking the growth of both murine and human osteosarcoma cell lines in vitro and murine osteosarcoma in vivo.
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PMID:Osteocalcin promoter-based toxic gene therapy for the treatment of osteosarcoma in experimental models. 884 Sep 73

Fibronectin (FN) is an important adhesive noncollagenous glycoprotein involved in maintenance of the extracellular matrix and cell adhesiveness, loss of which has been implicated in the metastatic potential of cells. Regulation of FN occurs at the transcriptional level by the active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). Transient transfection of homologous and heterologous promoter reporter constructs into ROS 17/2.8 (rat osteosarcoma), NIH 3T3 (mouse fibroblast), and MCF-7 (human mammary carcinoma) cell lines showed a consistent two- to threefold induction of transcription when stimulated with 1,25-(OH)2D3. These heterologous promoter transfection studies with gel shift analysis locate a third, natural DR6-type vitamin D responsive element (VDRE) at nucleotide positions -171 to -154 in the murine FN promoter. Interestingly, this VDRE is also present in rat and human FN promoters. This study shows that 1,25-(OH)2D3 induces FN transcription from an existing elevated basal transcriptional activity by acting through two putative hexameric core binding motifs which bind VDR homodimers. Furthermore, the FN VDRE is the first homodimer-type VDRE that is not overlaid by a DR3-type structure.
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PMID:Identification of a vitamin D3 response element in the fibronectin gene that is bound by a vitamin D3 receptor homodimer. 886 8

Human prostatic carcinoma frequently metastasizes to bone tissue and activates bone metabolism, especially bone formation, at the site of metastasis. It has been reported that an extract of prostatic carcinoma and conditioned medium (CM) of a human prostatic carcinoma cell line, PC-3, established from a bone metastastic lesion, stimulate osteoblastic cell proliferation. However, there is little information about the effect of PC-3 CM on the differentiation of osteoblastic cells. In this study, we investigated the effect of PC-3 CM on the differentiation of two types of osteoblastic cells, primary fetal rat calvaria (RC) cells containing many undifferentiated osteoprogenitor cells, and ROS 17/2.8, a well-differentiated rat osteosarcoma cell line. PC-3 CM inhibited bone nodule formation and the activity of alkaline phosphatase (ALPase), an osteoblastic marker enzyme, on days 7, 14, and 21 (RC cells) or 3, 6, and 9 (ROS 17/2.8 cells) in a dose-dependent manner (5-30% CM). However, the CM did not affect cell proliferation or cell viability. PC-3 CM was found to markedly block the gene expression of ALPase and osteocalcin (OCN) mRNAs but had no effect on the mRNA expression of osteopontin (OPN), the latter two being noncollagenous proteins related to bone matrix mineralization. These findings suggest that PC-3 CM contains a factor that inhibits osteoblastic cell differentiation and that this factor may be involved in the process of bone metastasis from prostatic carcinoma.
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PMID:Inhibition of osteoblastic cell differentiation by conditioned medium derived from the human prostatic cancer cell line PC-3 in vitro. 932 30

Angiogenesis is a fundamental process in skeletal development and repair, and previous studies indicate that vascular endothelial growth factor (VEGF), an endothelial cell-specific angiogenic factor, may be involved in bone formation and repair. Therefore, we studied the hormonal regulation of VEGF expression in SaOS-2 osteoblast-like cells, both at the protein level, and at the transcriptional level by transient transfection experiments. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], increased VEGF expression by approximately 3-fold, and the increase was dose dependent, with maximum stimulation between 1.0 and 10 nM of 1,25-(OH)2D3. Up-regulation of VEGF protein was detected already after 6 h of treatment. VEGF up-regulation was also observed in ROS-17/2.8 and OHS-4 osteoblast-like cells but not in MCF-7 and MDA-MB231 breast carcinoma cells. Dexamethasone (Dex) decreased VEGF expression to 40% of the control, but when added together with 1,25-(OH)2D3, had no effects on the up-regulation of VEGF by 1,25-(OH)2D3. PTH1-34 stimulated weakly VEGF expression, but combined with 1,25-(OH)2D3, resulted in a close to 5-fold stimulation. A 4-day pretreatment of the cells with Dex increased the vitamin D3 receptor expression and resulted in a stronger stimulation of VEGF by 1,25-(OH)2D3, alone or in combination with PTH1-34. The results show that the VEGF promoter is a target of 1,25-(OH)2D3 regulation in osteoblasts, despite the lack of classical vitamin D3 responsive elements. The up-regulation of VEGF in osteoblast-like cells by calciotropic hormones provides additional evidence of the involvement of VEGF in bone metabolism.
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PMID:1,25-Dihydroxyvitamin D3 induces the expression of vascular endothelial growth factor in osteoblastic cells. 937 8

Certain tumor cells, such as squamous carcinoma cells, express an increased number of epidermal growth factor (EGF) receptors. The goal of this study was the targeted delivery of the photocytotoxic compound Sn(IV)chlorine e6 monoethylenediamine++ (SnCe6(ED)) to tumors that overexpress the EGF receptor. Therefore EGF was conjugated to SnCe6(ED) through a carrier, such as dextran (Dex) and human serum albumin (HSA), followed by the evaluation of the photocytotoxicity on the EGF receptor overexpressing MDA-MB-468 cell line. The photobiologic activity of these conjugates was then compared to a conjugate of the photosensitizer to HSA or dextran, or to the photosensitizer alone. In contrast to EGF-HSA-SnCe6(ED), the affinity of EGF for its receptor was substantially impaired upon conjugation in EGF-Dex-SnCe6(ED). In correlation with these results, EGF-HSA-SnCe6(ED) displayed a high cytotoxicity (IC50, 63 nM) on MDA-MB-468 cells at a light dose of 27 kJ/m2, whereas EGF-Dex-SnCe6(ED) showed very limited photocytotoxicity. In the presence of a competing EGF concentration (10 microM), EGF-HSA-SnCe6(ED) was not cytotoxic anymore. The high photocytoxicity of EGF-HSA-SnCe6(ED) was shown to be a result of a high intracellular concentration in MDA-MB-468 cells, which could be lowered dramatically by incubating the conjugate with a competing EGF concentration. In contrast, EGF-Dex-SnCe6(ED) displayed very poor accumulation in MDA-MB-468 cells, in agreement with its low EGF receptor affinity and photocytoxicity. Besides, it could be demonstrated that EGF-HSA-SnCe6(ED) produced intracellularly ROS (reactive oxygen species) upon light irradiation, more than EGF-Dex-SnCe6(ED) did. It was concluded that, in contrast to EGF-Dex-SnCe6(ED) the photodynamic activity of the EGF-HSA conjugate of SnCe6(ED) on MDA-MB-468 breast adenocarcinoma cells is EGF-specific and more potent than free SnCe6(ED).
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PMID:[Targeting of chlorine E6 by EGF increasing its photodynamic activity in selective ways]. 1100 8


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